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Kim, Jong Min, Jun Sik Son, Seong Soo Kang, Gonhyung Kim, and Seok Hwa Choi. "Bone Regeneration of Hydroxyapatite/Alumina Bilayered Scaffold with 3 mm Passage-Like Medullary Canal in Canine Tibia Model." BioMed Research International 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/235108.
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The aim of this study was to evaluate the bone regeneration of hydroxyapatite (HA)/alumina bilayered scaffold with a 3 mm passage-like medullary canal in a beagle tibia model. A porous HA/alumina scaffold was fabricated using a polymeric template-coating technique. HA/alumina scaffold dimensions were 10 mm in outer diameter, 20 mm in length, and with either a 3 mm passage or no passage. A 20 mm segmental defect was induced using an oscillating saw through the diaphysis of the beagle tibia. The defects of six beagles were filled with HA/alumina bilayered scaffolds with a 3 mm passage or without. The segmental defect was fixated using one bone plate and six screws. Bone regeneration within the HA/alumina scaffolds was observed at eight weeks after implantation. The evaluation of bone regeneration within the scaffolds after implantation in a beagle tibia was performed using radiography, computerized tomography (CT), micro-CT, and fluorescence microscopy. New bone successfully formed in the tibia defects treated with 3 mm passage HA/alumina scaffolds compared to without-passage HA/alumina scaffolds. It was concluded that the HA/alumina bilayered scaffold with 3 mm passage-like medullary canal was instrumental in inducing host-scaffold engraftment of the defect as well as distributing the newly formed bone throughout the scaffold at 8 weeks after implantation.
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Fang, Yifei, Yong Gong, Zhijian Yang, and Yan Chen. "Repair of Osteoporotic Bone Defects Using Adipose-Derived Stromal Cells and Umbilical Vein Endothelial Cells Seeded in Chitosan/Nanohydroxyapatite-P24 Nanocomposite Scaffolds." Journal of Nanomaterials 2021 (August 21, 2021): 1–11. http://dx.doi.org/10.1155/2021/6237130.
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Background. The cell regeneration and blood supply of bone defect lesions are restricted under osteoporotic pathological conditions, which make the healing of bone defect of osteoporosis still a great challenge. The current therapeutic strategies that mainly inhibit bone resorption are not always satisfactory for osteoporotic bone defects, which make the development of new therapies an urgent need. Methods. Previously, we prepared chitosan/nanohydroxyapatite (CS/nHA) biomimetic nanocomposite scaffolds for controlled delivery of bone morphogenetic protein 2-derived peptide (P24). In this study, we determined the effect of coculturing adipose-derived stromal cells (ADSCs) and human umbilical vein endothelial cells (HUVECs) with the CS-P24/nHA nanocomposite scaffolds on osteoporotic bone defect healing. In vitro mixed coculture models were employed to assess the direct effects of coculture. Results. ADSCs cocultured with HUVECs showed significantly greater osteogenic differentiation and mineralization compared with ADSCs or HUVECs alone. The CS-P24/nHA scaffold cocultured with ADSCs and HUVECs was more effective in inducing osteoporotic bone repair, as demonstrated by micro-computed tomography and histology of critical-sized calvariae defects in ovariectomized rats. Calvariae defects treated with the CS-P24/nHA nanocomposite scaffold plus ADSC/HUVEC coculture had a greater area of repair and better reconstitution of osseous structures compared with defects treated with the scaffold plus ADSCs or the scaffold plus HUVECs after 4 and 8 weeks. Conclusion. Taken together, coculture of ADSCs and HUVECs with the CS-P24/nHA nanocomposite scaffold is an effective combination to repair osteoporotic bone defects.
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Kessler, Franziska, Kevin Arnke, Benjamin Eggerschwiler, et al. "Murine iPSC-Loaded Scaffold Grafts Improve Bone Regeneration in Critical-Size Bone Defects." International Journal of Molecular Sciences 25, no. 10 (2024): 5555. http://dx.doi.org/10.3390/ijms25105555.
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In certain situations, bones do not heal completely after fracturing. One of these situations is a critical-size bone defect where the bone cannot heal spontaneously. In such a case, complex fracture treatment over a long period of time is required, which carries a relevant risk of complications. The common methods used, such as autologous and allogeneic grafts, do not always lead to successful treatment results. Current approaches to increasing bone formation to bridge the gap include the application of stem cells on the fracture side. While most studies investigated the use of mesenchymal stromal cells, less evidence exists about induced pluripotent stem cells (iPSC). In this study, we investigated the potential of mouse iPSC-loaded scaffolds and decellularized scaffolds containing extracellular matrix from iPSCs for treating critical-size bone defects in a mouse model. In vitro differentiation followed by Alizarin Red staining and quantitative reverse transcription polymerase chain reaction confirmed the osteogenic differentiation potential of the iPSCs lines. Subsequently, an in vivo trial using a mouse model (n = 12) for critical-size bone defect was conducted, in which a PLGA/aCaP osteoconductive scaffold was transplanted into the bone defect for 9 weeks. Three groups (each n = 4) were defined as (1) osteoconductive scaffold only (control), (2) iPSC-derived extracellular matrix seeded on a scaffold and (3) iPSC seeded on a scaffold. Micro-CT and histological analysis show that iPSCs grafted onto an osteoconductive scaffold followed by induction of osteogenic differentiation resulted in significantly higher bone volume 9 weeks after implantation than an osteoconductive scaffold alone. Transplantation of iPSC-seeded PLGA/aCaP scaffolds may improve bone regeneration in critical-size bone defects in mice.
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Li, Ming, Jianheng Liu, Xiang Cui, et al. "Osteogenesis effects of magnetic nanoparticles modified-porous scaffolds for the reconstruction of bone defect after bone tumor resection." Regenerative Biomaterials 6, no. 6 (2019): 373–81. http://dx.doi.org/10.1093/rb/rbz019.
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Abstract The treatment of bone defect after bone tumor resection is a great challenge for orthopedic surgeons. It should consider that not only to inhibit tumor growth and recurrence, but also to repair the defect and preserve the limb function. Hence, it is necessary to find an ideal functional biomaterial that can repair bone defects and inactivate tumor. Magnetic nanoparticles (MNPs) have its unique advantages to achieve targeted hyperthermia to avoid damage to surrounding normal tissues and promote osteoblastic activity and bone formation. Based on the previous stage, we successfully prepared hydroxyapatite (HAP) composite poly(lactic-co-glycolic acid) (PLGA) scaffolds and verified its good osteogenic properties, in this study, we produced an HAP composite PLGA scaffolds modified with MNPs. The composite scaffold showed appropriate porosity and mechanical characteristics, while MNPs possessed excellent magnetic and thermal properties. The cytological assay indicated that the MNPs have antitumor ability and the composite scaffold possessed good biocompatibility. In vivo bone defect repair experiment revealed that the composite scaffold had good osteogenic capacity. Hence, we could demonstrate that the composite scaffolds have a good effect in bone repair, which could provide a potential approach for repairing bone defect after bone tumor excision.
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Zhou, Shuai, Shihang Liu, Yan Wang, et al. "Advances in the Study of Bionic Mineralized Collagen, PLGA, Magnesium Ionomer Materials, and Their Composite Scaffolds for Bone Defect Treatment." Journal of Functional Biomaterials 14, no. 8 (2023): 406. http://dx.doi.org/10.3390/jfb14080406.
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The healing of bone defects after a fracture remains a key issue to be addressed. Globally, more than 20 million patients experience bone defects annually. Among all artificial bone repair materials that can aid healing, implantable scaffolds made from a mineralized collagen (MC) base have the strongest bionic properties. The MC/PLGA scaffold, created by adding Poly (lactic-co-glycolic acid) copolymer (PLGA) and magnesium metal to the MC substrate, plays a powerful role in promoting fracture healing because, on the one hand, it has good biocompatibility similar to that of MC; on the other hand, the addition of PLGA provides the scaffold with an interconnected porous structure, and the addition of magnesium allows the scaffold to perform anti-inflammatory, osteogenic, and angiogenic activities. Using the latest 3D printing technology for scaffold fabrication, it is possible to model the scaffold in advance according to the requirement and produce a therapeutic scaffold suitable for various bone-defect shapes with less time and effort, which can promote bone tissue healing and regeneration to the maximum extent. This study reviews the material selection and technical preparation of MC/PLGA scaffolds, and the progress of their research on bone defect treatment.
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Lim, Jin Xi, Min He, and Alphonsus Khin Sze Chong. "3D-printed Poly-Lactic Co-Glycolic Acid (PLGA) scaffolds in non-critical bone defects impede bone regeneration in rabbit tibia bone." Bio-Medical Materials and Engineering 32, no. 6 (2021): 375–81. http://dx.doi.org/10.3233/bme-216017.
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BACKGROUND: An increasing number of bone graft materials are commercially available and vary in their composition, mechanism of action, costs, and indications. OBJECTIVE: A commercially available PLGA scaffold produced using 3D printing technology has been used to promote the preservation of the alveolar socket after tooth extraction. We examined its influence on bone regeneration in long bones of New Zealand White rabbits. METHODS: 5.0-mm-diameter circular defects were created on the tibia bones of eight rabbits. Two groups were studied: (1) control group, in which the bone defects were left empty; (2) scaffold group, in which the PLGA scaffolds were implanted into the bone defect. Radiography was performed every two weeks postoperatively. After sacrifice, bone specimens were isolated and examined by micro-computed tomography and histology. RESULTS: Scaffolds were not degraded by eight weeks after surgery. Micro-computed tomography and histology showed that in the region of bone defects that was occupied by scaffolds, bone regeneration was compromised and the total bone volume/total volume ratio (BV/TV) was significantly lower. CONCLUSION: The implantation of this scaffold impedes bone regeneration in a non-critical bone defect. Implantation of bone scaffolds, if unnecessary, lead to a slower rate of fracture healing.
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Kim, You Min, Min-Soo Ghim, Meiling Quan, Young Yul Kim, and Young-Sam Cho. "Experimental Verification of the Impact of the Contact Area between the Defect Site and the Scaffold on Bone Regeneration Efficacy." Polymers 16, no. 3 (2024): 338. http://dx.doi.org/10.3390/polym16030338.
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In the field of bone tissue engineering, which is being developed for the ideal restoration of bone defects, researchers are exploring the improvement of the bone regeneration efficacy of scaffolds through various approaches involving osteoconductive, osteoinductive, and angiogenic factors. In the current trend of research, there is also a suggestion that the topological factors of recent scaffolds may influence the attachment, migration, proliferation, and differentiation of bone cells. Building upon experimental confirmation of the effect of scaffold conformity with the defect site on enhanced bone regeneration in previous studies, we conducted this research to experimentally investigate the relationship between contact area with the defect site and bone regeneration efficacy. The results demonstrated that as the contact area of the scaffold increased, not only did the resistance to bone tissue growth increase, more significant bone regeneration also occurred, as evidenced through histological analysis and micro-CT analysis. This research confirms that the contact area between the scaffold and the defect site is a critical variable affecting bone regeneration efficacy, emphasizing its importance when designing customized scaffolds. This finding holds promising implications for future studies and applications in the field.
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Chen, Shuang S., Ophir Ortiz, Alexandra K. Pastino, et al. "Hybrid Bone Scaffold Induces Bone Bridging in Goat Calvarial Critical Size Defects Without Growth Factor Augmentation." Regenerative Engineering and Translational Medicine 6, no. 2 (2020): 189–200. http://dx.doi.org/10.1007/s40883-019-00144-z.
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Abstract In the present study, a series of four different scaffolds were comparatively evaluated in a goat calvarial critical size defect model. Such studies are only rarely reported in the literature. In our work, E1001(1k), a member of a large combinational library of tyrosine-derived polycarbonates (TyrPC), was used to prepare two calcium phosphate hybrid, biodegradable bone scaffolds. In one formulation, the widely used β-tricalcium phosphate (β-TCP) was incorporated into the polymer scaffold. In the second formulation, a coating of dicalcium phosphate dihydrate (DCPD, also known as brushite) was used as the mineral phase. These scaffolds were evaluated for bone regeneration in goat calvarial 20-mm critical size defects (CSD) after 16 weeks. Results were compared with chronOS (a clinically used product) and E1001(1k)/β-TCP scaffolds, augmented with 400 μg of recombinant human bone morphogenetic protein-2 (rhBMP-2). Microcomputed tomography (micro-CT) and histomorphometry were used to assess bone regeneration within the defects. Histomorphometry showed that rhBMP-2-augmented E1001(1k)/β-TCP scaffolds completely healed the defect in all animals within 16 weeks. Among the hybrid scaffolds that were not augmented with rhBMP-2, the degree of bone regeneration within the defect area was low for the clinically used chronOS, which is a poly(lactide co-ε-caprolactone)/β-TCP hybrid scaffold. Similar results were obtained for E1001(1k)/β-TCP scaffolds, indicating that replacing poly(lactide co-ε-caprolactone) with E1001(1k) does not improve bone regeneration is this model. However, a statistically significant improvement of bone regeneration was observed for E1001(1k)/DCPD scaffolds. These scaffolds resulted in significant levels of bone regeneration in all animals and in complete bridging of the defect in three of six tests. This is the first report of a synthetic bone scaffold being able to heal a critical size calvarial defect in a large animal model without the addition of exogenous growth factors. Lay Summary Reconstruction of large bone defects is a significant clinical problem. The overwhelming majority of all research results are obtained in vitro or in small animal models (mouse, rat, rabbit) that cannot predict the clinical outcomes in humans. We address this problem by conducting our studies in a goat calvarial critical size defect model, which is widely regarded as predictive of human outcomes. Among the three rhBMP-2-free scaffolds tested, only one specific formulation, E1001(1k)/DCPD, resulted in massive bone ingrowth into the center of the defect in all animals and in complete bridging of the defect 50% of the animals. This is the first time, a synthetic bone scaffold was able to heal a critical size calvarial defect in a large animal model without the addition of biological growth factors. Given the high cost of biologically enhanced bone grafts and the regulatory complexities of their FDA market clearance, the development of E1001(1k)/DCPD hybrid scaffolds addresses a significant clinical need.
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Mi, Xue, Zhenya Su, Yu Fu, Shiqi Li, and Anchun Mo. "3D printing of Ti3C2-MXene-incorporated composite scaffolds for accelerated bone regeneration." Biomedical Materials 17, no. 3 (2022): 035002. http://dx.doi.org/10.1088/1748-605x/ac5ffe.
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Abstract Grafting of bone-substitute biomaterials plays a vital role in the reconstruction of bone defects. However, the design of bioscaffolds with osteoinductive agents and biomimetic structures for regeneration of critical-sized bone defects is difficult. Ti3C2 MXene—belonging to a new class of 2D nanomaterials—exhibits excellent biocompatibility, and antibacterial properties, and promotes osteogenesis. However, its application in preparing 3D-printed tissue-engineered bone scaffolds for repairing bone defects has not been explored. In this work, Ti3C2 MXene was incorporated into composite scaffolds composed of hydroxyapatite and sodium alginate via extrusion-based 3D printing to evaluate its potential in bone regeneration. MXene composite scaffolds were fabricated and characterized by SEM, XPS, mechanical properties and porosity. The biocompatibility and osteoinductivity of MXene composite scaffolds were evaluated by cell adhesion, cell counting kit-8 test, quantitative real-time polymerase chain reaction, alkaline phosphatase activity and alizarin red S tests of bone mesenchymal stem cells (BMSCs). A rat calvarial defect model was performed to explore the osteogenic activity of the MXene composite scaffolds in vivo. The results showed the obtained scaffold had a uniform structure, macropore morphology, and high mechanical strength. In vitro experimental results revealed that the scaffold exhibited excellent biocompatibility with BMSCs, promoted cell proliferation, upregulated osteogenic gene expression, enhanced alkaline phosphatase activity, and promoted mineralized-nodule formation. The experimental results confirmed that the scaffold effectively promoted bone regeneration in a model of critical-sized calvarial- bone-defect in vivo and promoted bone healing to a significantly greater degree than scaffolds without added Ti3C2 MXene did. Conclusively, the Ti3C2 MXene composite 3D-printed scaffolds are promising for clinical bone defect treatment, and the results of this study provide a theoretical basis for the development of practical applications for tissue-engineered bone scaffolds.
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Bergmann, Christian J. D., Jim C. E. Odekerken, Tim J. M. Welting, et al. "Calcium Phosphate Based Three-Dimensional Cold Plotted Bone Scaffolds for Critical Size Bone Defects." BioMed Research International 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/852610.
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Bone substitutes, like calcium phosphate, are implemented more frequently in orthopaedic surgery to reconstruct critical size defects, since autograft often results in donor site morbidity and allograft can transmit diseases. A novel bone cement, based onβ-tricalcium phosphate, polyethylene glycol, and trisodium citrate, was developed to allow the rapid manufacturing of scaffolds, by extrusion freeform fabrication, at room temperature. The cement composition exhibits good resorption properties and serves as a basis for customised (e.g., drug or growth factor loaded) scaffolds for critical size bone defects.In vitrotoxicity tests confirmed proliferation and differentiation of ATDC5 cells in scaffold-conditioned culture medium. Implantation of scaffolds in the iliac wing of sheep showed bone remodelling throughout the defects, outperforming the empty defects on both mineral volume and density present in the defect after 12 weeks. Both scaffolds outperformed the autograft filled defects on mineral density, while the mineral volume present in the scaffold treated defects was at least equal to the mineral volume present in the autograft treated defects. We conclude that the formulated bone cement composition is suitable for scaffold production at room temperature and that the established scaffold material can serve as a basis for future bone substitutes to enhancede novobone formation in critical size defects.
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Canciani, Elena, Paola Straticò, Vincenzo Varasano, et al. "Polylevolysine and Fibronectin-Loaded Nano-Hydroxyapatite/PGLA/Dextran-Based Scaffolds for Improving Bone Regeneration: A Histomorphometric in Animal Study." International Journal of Molecular Sciences 24, no. 9 (2023): 8137. http://dx.doi.org/10.3390/ijms24098137.
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The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-based scaffold loaded with Polylevolysine (PLL) and fibronectin (FN), intended for bone regeneration of a critical-size tibial defect, using an ovine model. After physicochemical characterization, the scaffolds were implanted in vivo, producing two monocortical defects on both tibiae of ten adult sheep, randomly divided into two groups to be euthanized at three and six months after surgery. The proximal left and right defects were filled, respectively, with the test scaffold (nano-HA/PGLA/dextran-based scaffold loaded with PLL and FN) and the control scaffold (nano-HA/PGLA/dextran-based scaffold not loaded with PLL and FN); the distal defects were considered negative control sites, not receiving any scaffold. Histological and histomorphometric analyses were performed to quantify the bone ingrowth and residual material 3 and 6 months after surgery. In both scaffolds, the morphological analyses, at the SEM, revealed the presence of submicrometric crystals on the surfaces and within the scaffolds, while optical microscopy showed a macroscopic 3D porous architecture. XRD confirmed the presence of nano-HA with a high level of crystallinity degree. At the histological and histomorphometric evaluation, new bone formation and residual biomaterial were detectable inside the defects 3 months after intervention, without differences between the scaffolds. At 6 months, the regenerated bone was significantly higher in the defects filled with the test scaffold (loaded with PLL and FN) than in those filled with the control scaffold, while the residual material was higher in correspondence to the control scaffold. Nano-HA/PGLA/dextran-based scaffolds loaded with PLL and FN appear promising in promoting bone regeneration in critical-size defects, showing balanced regenerative and resorbable properties to support new bone deposition.
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Semyari, Hossein, Majid Salehi, Ferial Taleghani, et al. "Fabrication and characterization of collagen–hydroxyapatite-based composite scaffolds containing doxycycline via freeze-casting method for bone tissue engineering." Journal of Biomaterials Applications 33, no. 4 (2018): 501–13. http://dx.doi.org/10.1177/0885328218805229.
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In this study, hydroxyapatite nanoparticles containing 10% doxycycline, a structural isomer of tetracycline, was prepared by the co-precipitation method. It was added to collagen solution for the preparation of the scaffold with freeze-casting method in order to develop a composite scaffold with both antibacterial and osteoinductive properties for repairing bone defects. The scaffolds were evaluated regarding their morphology, porosity, degradation and cellular response. The scaffolds for further investigation were added in a rat calvaria defect model. The study showed that after eight weeks, the bone formation was relatively higher in the collagen/nano-hydroxyapatite/doxycycline group with completely filled defect when compared with other groups. Histopathological evaluation showed that the defect in the collagen/nano-hydroxyapatite/doxycycline group was fully replaced by the new bone and connective tissue. Our results provide evidence supporting the possible applicability of doxycycline-containing scaffolds for successful bone regeneration.
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Yun, JW, SY Heo, MH Lee, and HB Lee. "Evaluation of a poly(lactic-acid) scaffold filled with poly(lactide-co-glycolide)/hydroxyapatite nanofibres for reconstruction of a segmental bone defect in a canine model." Veterinární Medicína 64, No. 12 (2019): 531–38. http://dx.doi.org/10.17221/80/2019-vetmed.
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Critical-sized bone defects are a difficult problem in both human and veterinary medicine. To address this issue, synthetic graft materials have been garnering attention. Abundant in vitro studies have proven the possibilities of poly(lactic-acid) (PLA) scaffolds and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) nanofibres for treating bone defects. The present study aimed at conducting an in vivo assessment of the biological performance of a three dimensional (3D)-printed PLA scaffold filled with a PLGA/HAp nanofibrous scaffold to estimate its potential applications in bone defect reconstruction surgery. Defects were created in a 20 mm-long region of the radius bone. The defects created on the right side in six Beagle dogs (n = 6) were left untreated (Group 1). The defects on the left side (n = 6) were filled with 3D-printed PLA scaffolds incorporated with PLGA/Hap nanofibres with gelatine (Group 2). The other six Beagle dog defects were made bilaterally (n = 12) and filled with the same material as that used in Group 2 along with recombinant bone morphogenetic protein 2 (rhBMP-2) (Group 3). Both the radiological and histological examinations were performed for observing the reaction of the scaffold and the bone. Micro-computed tomography (CT) was utilised for the evaluation of the bone parameters 20 weeks after the experiment. The radiological and histological results revealed that the scaffold was biodegradable and was replaced by new bone tissue. The micro-CT revealed that the bone parameters were significantly (P < 0.05) increased in Group 3. Based on these results, our study serves as a foundation for future studies on bone defect treatment using synthetic polymeric scaffolds.
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Ronca, Alfredo, Vincenzo Guarino, Maria Grazia Raucci, et al. "Large defect-tailored composite scaffolds for in vivo bone regeneration." Journal of Biomaterials Applications 29, no. 5 (2014): 715–27. http://dx.doi.org/10.1177/0885328214539823.
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The discovery of new strategies to repair large segmental bone defects is currently an open challenge for worldwide clinicians. In the treatment of critical-sized bone defects, an alternative strategy to traditional bone grafting is always more frequently the use of tailor-made scaffolds modelled on the final size and shape of the implant site. Here, poly-ε-caprolactone-based composite scaffolds including poly-l-lactic acid continuous fibres and hyaluronan derivates (i.e. HYAFF11®) have been investigated for the peculiar 3D architecture characterized by interconnected macroporous networks and tunable mechanical properties. Composite scaffolds were immersed in simulated body fluid solution in order to support in vivo tissue in-growth. Scaffolds loaded with autologous cells (bone marrow stromal cells) plus platelet-rich plasma and osteoconductive protein such bone morphogenetic protein-7 were also tested to evaluate eventual enhancement in bone regeneration. The morphological and mechanical properties of poly-l-lactic acid-reinforced composite scaffolds have been studied to identify the optimal scaffold design to match the implant-site requirements of sheep metatarsal defects. Dynamic mechanical tests allowed to underline the viscoelastic response of the scaffold – resulting in elastic moduli from 2.5 to 1.3 MPa, suitable to temporarily support the structural function of damaged bone tissue. In vivo preliminary investigations in a sheep model of metatarsus shaft defect also showed the attitude of the scaffold to promote osteogenesis, preferentially in association with bone marrow stromal cell and platelet-rich plasma, even if the highest amount of mature bone was reached in the case of scaffold loaded with human bone morphogenetic protein-7 released via hydrolytic degradation of HYAFF11® phases in the implant site.
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Vigni, Giulio Edoardo, Mariano Licciardi, Lorenzo D’itri, et al. "Improved Bone Regeneration Using Biodegradable Polybutylene Succinate Artificial Scaffold with BMP-2 Protein in a Rabbit Model." Materials 18, no. 10 (2025): 2234. https://doi.org/10.3390/ma18102234.
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Extensive bone loss represents a great challenge for orthopedic and reconstructive surgery. On an in vivo rabbit model, the healing of two bone defects on a long bone, tibia, was studied. A polybutylene succinate (PBS) microfibrillar scaffold was implemented with BMP-2 protein and hydroxyapatite (HA) as potential osteogenic factors. The present study was carried out on 6 male New Zealand white (4–6 months old) rabbits in vivo model. One bone defect was created in each subject on the tibia. The controls were left to heal spontaneously while the study samples were treated with the polybutylene succinate (PBS) microfibrillar scaffolds doped with BMP-2 and HA. Histological and immunohistochemical analyses were performed after euthanasia at 3 and 6 months. The bone defect treated with the BMP-2 PBS scaffold shows, from 3 months, a significantly increased presence of activated osteoblasts with mineralized bone tissue deposition. This study confirms the great potential of PBS scaffolds in the clinical treatment of bone defects.
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Schlichting, Karin, Hanna Schell, Ralf U. Kleemann, et al. "Influence of Scaffold Stiffness on Subchondral Bone and Subsequent Cartilage Regeneration in an Ovine Model of Osteochondral Defect Healing." American Journal of Sports Medicine 36, no. 12 (2008): 2379–91. http://dx.doi.org/10.1177/0363546508322899.
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Background In osteochondral defects, subchondral bone, as a load-bearing structure, is believed to be important for bone and cartilage regeneration. Hypothesis A stiff scaffold creates better conditions for bone formation and cartilage regeneration than does a softer one. Study Design Controlled laboratory study. Methods Critical osteochondral defects were created in the femoral condyles of 24 sheep. Subchondral bone was reconstructed with a stiff scaffold or a modified softer one, with untreated defects serving as controls. The repair response was evaluated with mechanical, histological, and histomorphometrical techniques at 3 and 6 months postoperatively. Results The elastic modulus of regenerated fibrocartilage over the stiff scaffold tended to be higher than in the soft scaffold group (61 % vs 46% of healthy cartilage) at 3 months. No difference was determined at 6 months; all were well below healthy cartilage. Treated defects showed substantial degradation of the soft scaffold with surrounding sclerotic bone at 3 and 6 months. In contrast, degradation of the stiff scaffold was slower and occurred together with continuous osseous replacement. Conclusion Stiff scaffolds were found to improve bone regeneration. In contrast, soft scaffolds provided less support, and consequently subchondral bone became sclerotic. Although regenerated cartilage formed over the stiff scaffolds at 3 months, and these exhibited better mechanical properties than did the soft scaffold group, the mechanical properties in both treated groups were the same at 6 months, not dissimilar to that of tissue formed in the untreated specimens and inferior to native articular cartilage. Clinical Relevance The results imply that subchondral defect filling in clinical settings advances bone regeneration and should have a comparable stiffness to that of healthy subchondral bone rather than being too flexible. Degradation of resorbable materials and consequently the loss of stiffness may compromise the healing of critical defects.
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Wang, Wenzhao, Boqing Zhang, Lihong Zhao, et al. "Fabrication and properties of PLA/nano-HA composite scaffolds with balanced mechanical properties and biological functions for bone tissue engineering application." Nanotechnology Reviews 10, no. 1 (2021): 1359–73. http://dx.doi.org/10.1515/ntrev-2021-0083.
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Abstract Repair of critical bone defects is a challenge in the orthopedic clinic. 3D printing is an advanced personalized manufacturing technology that can accurately shape internal structures and external contours. In this study, the composite scaffolds of polylactic acid (PLA) and nano-hydroxyapatite (n-HA) were manufactured by the fused deposition modeling (FDM) technique. Equal mass PLA and n-HA were uniformly mixed to simulate the organic and inorganic phases of natural bone. The suitability of the composite scaffolds was evaluated by material characterization, mechanical property, and in vitro biocompatibility, and the osteogenesis induction in vitro was further tested. Finally, the printed scaffold was implanted into the rabbit femoral defect model to evaluate the osteogenic ability in vivo. The results showed that the composite scaffold had sufficient mechanical strength, appropriate pore size, and biocompatibility. Most importantly, the osteogenic induction performance of the composite scaffold was significantly better than that of the pure PLA scaffold. In conclusion, the PLA/n-HA scaffold is a promising composite biomaterial for bone defect repair and has excellent clinical transformation potential.
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Shah, Sarav S., Haixiang Liang, Sandeep Pandit, et al. "Optimization of Degradation Profile for New Scaffold in Cartilage Repair." CARTILAGE 9, no. 4 (2017): 438–49. http://dx.doi.org/10.1177/1947603517700954.
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Objective To establish whether a novel biomaterial scaffold with tunable degradation profile will aid in cartilage repair of chondral defects versus microfracture alone in vitro and in a rat model in vivo. Design In vitro—Short- and long-term degradation scaffolds were seeded with culture expanded articular chondrocytes or bone marrow mesenchymal stem cells. Cell growth and differentiation were evaluated with cell morphological studies and gene expression studies. In vivo—A microfracture rat model was used in this study to evaluate the repair of cartilage and subchondral bone with the contralateral knee serving as the empty control. The treatment groups include (1) empty osteochondral defect, (2) polycaprolactone copolymer–based polyester polyurethane–urea (PSPU-U) caffold short-term degradative profile, and (3) PSPU-U scaffold long-term degradative profile. After placement of the scaffold, the rats were then allowed unrestricted activity as tolerated, and histological analyses were performed at 4, 8, and 16 weeks. The cartilage defect was measured and compared with the contralateral control side. Results In vitro—Long-term scaffolds showed statistically significant higher levels of aggrecan and type II collagen expression compared with short-term scaffolds. In vivo—Within 16 weeks postimplantation, there was new subchondral bone formation in both scaffolds. Short-term scaffolds had a statistically significant increase in defect filling and better qualitative histologic fill compared to control. Conclusions The PSPU short-term degradation scaffold may aid in cartilage repair by ultimately incorporating the scaffold into the microfracture procedure.
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Sithole, Mduduzi N., Pradeep Kumar, Lisa C. Du Toit, Kennedy H. Erlwanger, Philemon N. Ubanako, and Yahya E. Choonara. "A 3D-Printed Biomaterial Scaffold Reinforced with Inorganic Fillers for Bone Tissue Engineering: In Vitro Assessment and In Vivo Animal Studies." International Journal of Molecular Sciences 24, no. 8 (2023): 7611. http://dx.doi.org/10.3390/ijms24087611.
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This research aimed to substantiate the potential practicality of utilizing a matrix-like platform, a novel 3D-printed biomaterial scaffold, to enhance and guide host cells’ growth for bone tissue regeneration. The 3D biomaterial scaffold was successfully printed using a 3D Bioplotter® (EnvisionTEC, GmBH) and characterized. Osteoblast-like MG63 cells were utilized to culture the novel printed scaffold over a period of 1, 3, and 7 days. Cell adhesion and surface morphology were examined using scanning electron microscopy (SEM) and optical microscopy, while cell viability was determined using MTS assay and cell proliferation was evaluated using a Leica microsystem (Leica MZ10 F). The 3D-printed biomaterial scaffold exhibited essential biomineral trace elements that are significant for biological bone (e.g., Ca-P) and were confirmed through energy-dispersive X-ray (EDX) analysis. The microscopy analyses revealed that the osteoblast-like MG63 cells were attached to the printed scaffold surface. The viability of cultured cells on the control and printed scaffold increased over time (p < 0.05); however, on respective days (1, 3, and 7 days), the viability of cultured cells between the two groups was not significantly different (p > 0.05). The protein (human BMP-7, also known as growth factor) was successfully attached to the surface of the 3D-printed biomaterial scaffold as an initiator of osteogenesis in the site of the induced bone defect. An in vivo study was conducted to substantiate if the novel printed scaffold properties were engineered adequately to mimic the bone regeneration cascade using an induced rabbit critical-sized nasal bone defect. The novel printed scaffold provided a potential pro-regenerative platform, rich in mechanical, topographical, and biological cues to guide and activate host cells toward functional regeneration. The histological studies revealed that there was progress in new bone formation, especially at week 8 of the study, in all induced bone defects. In conclusion, the protein (human BMP-7)-embedded scaffolds showed higher regenerative bone formation potential (week 8 complete) compared to the scaffolds without protein (e.g., growth factor; BMP-7) and the control (empty defect). At 8 weeks postimplantation, protein (BMP-7) significantly promoted osteogenesis as compared to other groups. The scaffold underwent gradual degradation and replacement by new bones at 8 weeks in most defects.
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Charbonnier, B., L. Guyon, N. Touya, et al. "MECHANICALLY EVOLUTIVE 3D-PRINTED SCAFFOLDS FOR BONE REGENERATION." Orthopaedic Proceedings 106-B, SUPP_1 (2024): 63. http://dx.doi.org/10.1302/1358-992x.2024.1.063.
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Developments in the field of additive manufacturing have allowed significant improvements in the design and production of scaffolds with biologically relevant features to treat bone defects. Unfortunately, the workflow to generate personalized scaffolds is source of inaccuracies leading to a poor fit between the implant and patients' bone defects. In addition, scaffolds are often brittle and fragile, uneasing their handling by surgeons, with significant risks of fracture during their insertion in the defect. Consequently, we developed organo-mineral cementitious scaffolds displaying evolutive mechanical properties which are currently being evaluated to treat maxillofacial bone deformities in veterinary clinics. Treatment of dog patients was approved by ethic and welfare committees (CERVO-2022-14-V). To date, 8 puppies with cleft palate/lip deformities received the following treatment. Two weeks prior surgery, CT-scan of patient's skull was performed to allow for surgical planning and scaffold designing. Organo-mineral printable pastes were formulated by mixing an inorganic cement precursor (α-Ca3(PO4)2) to a self-reticulating hydrogel (silanized hyaluronic acid) supplemented with a viscosifier (hydroxymethylpropylcellulose). Scaffolds were produced by robocasting of these pastes. Surgical interventions included the reconstruction of soft tissues, and the insertion of the scaffold soaked with autologous bone marrow. Bone formation was monitored 3 and 6 months after reconstruction, and a biopsy at 6 months was performed for more detailed analyses. Scaffolds displayed great handling properties and were inserted within bone defects without significant issue with a relevant bone edges/scaffold contact. Osteointegration of the scaffolds was observed after 3 months, and regeneration of the defect at 6 months seemed quite promising. Preliminary results have demonstrated a potential of the set-up strategy to treat cleft lip/palate deformities in real, spontaneous clinical setting. Translation of these innovative scaffolds to orthopedics is planned for a near future.
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Peña, Gonzalo de la, Lorena Gallego, Luis M. Redondo, Luis Junquera, Javier F. Doval, and Álvaro Meana. "Comparative analysis of plasma-derived albumin scaffold, alveolar osteoblasts and synthetic membrane in critical mandibular bone defects: An experimental study on rats." Journal of Biomaterials Applications 36, no. 3 (2021): 481–91. http://dx.doi.org/10.1177/0885328221999824.
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Repair of bone deficiencies in the craniofacial skeleton remains a challenging clinical problem. The aim of this study was to evaluate and compare the effects of a plasma-derived albumin scaffold, alveolar osteoblasts and synthetic membrane implanted into experimental mandibular defects. Bilateral mandibular defects were created in twelve immunodeficient rats. The bone defect was filled with serum scaffold alone in left sides and scaffold combined with human alveolar osteoblast in right side defects. Implanted areas were closed directly in Group 1 ( n = 6) and covered by a resorbable polyglycolic-polylactic acid membrane in Group 2 ( n = 6). Bone regeneration was determined at 12 weeks as measured by and exhaustive multiplanar computed tomography analysis and histological examination. No significant differences in bone density were observed between defects transplanted with scaffold alone or scaffold seeded with osteoblasts. The use of membrane did not result in a determining factor in the grade of bone regeneration between Groups 1 and 2. Based on these results, it could be concluded that the albumin scaffold alone has osteoinductive capacity but presence of seeded ostogenic cells accelerates defect repair without being significantly influenced by covering the defect with a resorbable membrane.
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Wang, Xiaoyang, Shuqing Tong, Shengyun Huang, Li Ma, Zhenxing Liu, and Dongsheng Zhang. "Application of a New Type of Natural Calcined Bone Repair Material Combined with Concentrated Growth Factors in Bone Regeneration in Rabbit Critical-Sized Calvarial Defect." BioMed Research International 2020 (November 24, 2020): 1–6. http://dx.doi.org/10.1155/2020/8810747.
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Purpose. This study is aimed at investigating bone regeneration in critical-sized defects in rabbit calvarium using a novel nano- (n-) hydroxyapatite hybrid scaffold with concentrated growth factors (CGFs). Methods. Twenty-four male adult rabbits were chosen to establish a critical-sized bone defect model and randomly divided into two groups. Two defects of 15 mm diameter each were created in the parietal bone of each animal. Group A had n-hydroxyapatite hybrid scaffold placed in the experimental defect on the right, and the left defect was unfilled as blank. Group B had hydroxyapatite hybrid scaffold mixed with CGF placed in the right defect and CGF on the left. Six animals in each group were sacrificed after 6 and 12 weeks. Cone-beam computed tomography system scanning and hematoxylin and eosin (HE) staining were used to detect osteogenesis within the defects. Results. The treatment with n-hydroxyapatite hybrid scaffold along with CGF resulted in a significantly higher amount of new bone at 6 and 12 weeks compared to the treatment with CGF alone and the controls. No apparent inflammation and foreign body reaction were observed through HE staining. Conclusions. The new synthesized n-hydroxyapatite hybrid scaffold and CGF can be applied for bone defect regeneration to promote the process to a certain extent.
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Gabor, Alin, Tiberiu Hosszu, Cristian Zaharia, et al. "3D Printing of a Mandibular Bone Deffect." Materiale Plastice 54, no. 1 (2017): 29–31. http://dx.doi.org/10.37358/mp.17.1.4778.
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The aim of this study was to achieve a polymeric scaffold, ex-vivo, using 3D printing technology and then subjecting it to various tests to check its optimal property. Initially there was selected a lower jaw with a bone defect that would have prevented any treatment based prosthetic implant. The mandible was first scanned using an optical scanner (MAESTRO DENTAL SCANNER MDS400). The scanning parameters using optical scanning system are: 10 micron accuracy, resolution 0.07 mm, 2 rooms with High-Resolution LED structured light, two axes. The scan time of the mandible was 4-5 min. Later the same mandible was scanned using CBCT�s CRANEX 3DX. The images obtained using CBCT�s were correlated with those obtained by optical scanning. Further on, there was achieved the digital design of the future scaffold with the conventional technique of wax addition directly on the mandibular bone defect. After that, this was again scanned using scanning system MAESTRO DENTAL SCANNER MDS400, and using CBCT�s CRANEX 3DX. The images obtained were correlated with all the scanned images of original mandible bone defects. There were made two polymeric scaffolds using 3D printing system an (D20 Digital Wax System 3D Printer). After printing, scaffold sites were introduced for 30 minutes in an oven curing. Later the pieces obtained were processed to remove small excesses of work. There were obtained 3 blocks of polymers that have a good adaptation to the bone profile. Often, in oral implantology and maxillofacial surgery appear bone defects. They prevent an optimal treatment of bio-functional and aesthetic restoration. Using 3D printing technology one can achieve scaffold sites of different biocompatible materials that have optimal properties to replace bone defect and restore the defective area. These scaffold sites have an intimate adaptation to the defect. 3D printing techniques used to restore bone defects can quickly and efficiently give the possibility to have a successful implantology prosthetics treatment.
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Alonso-Fernández, Iván, Håvard Jostein Haugen, Liebert Parreiras Nogueira, et al. "Enhanced Bone Healing in Critical-Sized Rabbit Femoral Defects: Impact of Helical and Alternate Scaffold Architectures." Polymers 16, no. 9 (2024): 1243. http://dx.doi.org/10.3390/polym16091243.
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This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid–bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.
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Unni, Ashok R., Syam K. Venugopal, K. D. John Martin, S. Anoop, S. Maya Maya та B. Dhanush Krishna. "Serum biochemical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds". Journal of Veterinary and animal sciences 55, № 3 (2024): 586–92. http://dx.doi.org/10.51966/jvas.2024.55.3.586-592.
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Critical-sized long bone defects are those that would not heal spontaneously despite surgical stabilisation. The use of bioceramic scaffold has shown promising results in the repair of bone defects. The present study was undertaken to evaluate the serum biochemical parameters of Wistar rats treated for critical-sized segmental bone loss using biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds. The study was conducted in eighty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized segmental defects in the femur. A 6 mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with bioceramic scaffolds and retained in position with microplate and screws. Serum biochemical parameters serum calcium, phosphorous, acid phosphatase and alkaline phosphatase were evaluated four weeks before surgery, immediately after surgery and 4th, 8th, 12th, and 16th week after surgery. The evaluation of both serum calcium and phosphorous were found to be reliable indicators of new bone formation and mineralisation, whereas the evaluation of both serum acid phosphatase and alkaline phosphatase were found to be reliable indicators of bone healing during the treatment of critical-sized long bone defects in rats using biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds Keywords: Beta-tricalcium phosphate, bioceramic scaffold, hydroxyapatite, serum acid phosphatase, serum alkaline phosphatase, serum calcium, serum phosphorous
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Lee, Ming-Chan, Cheng-Tang Pan, Wen-Fan Chen, Meng-Chi Lin, and Yow-Ling Shiue. "Design, Manufacture, and Characterization of a Critical-Sized Gradient Porosity Dual-Material Tibial Defect Scaffold." Bioengineering 11, no. 4 (2024): 308. http://dx.doi.org/10.3390/bioengineering11040308.
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This study proposed a composite tibia defect scaffold with radial gradient porosity, utilizing finite element analysis to assess stress in the tibial region with significant critical-sized defects. Simulations for scaffolds with different porosities were conducted, designing an optimal tibia defect scaffold with radial gradient porosity for repairing and replacing critical bone defects. Radial gradient porosity scaffolds resulted in a more uniform stress distribution, reducing titanium alloy stiffness and alleviating stress shielding effects. The scaffold was manufactured using selective laser melting (SLM) technology with stress relief annealing to simplify porous structure fabrication. The study used New Zealand white rabbits’ tibia defect sites as simulation parameters, reconstructing the 3D model and implanting the composite scaffold. Finite element analysis in ANSYS-Workbench simulated forces under high-activity conditions, analyzing stress distribution and strain. In the simulation, the titanium alloy scaffold bore a maximum stress of 122.8626 MPa, while the centrally encapsulated HAp material delivered 27.92 MPa. The design demonstrated superior structural strength, thereby reducing stress concentration. The scaffold was manufactured using SLM, and the uniform design method was used to determine a collection of optimum annealing parameters. Nanoindentation and compression tests were used to determine the influence of annealing on the elastic modulus, hardness, and strain energy of the scaffold.
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Gani, Maria Apriliani, Aniek Setiya Budiatin, Dewi Wara Shinta, Chrismawan Ardianto, and Junaidi Khotib. "Bovine hydroxyapatite-based scaffold accelerated the inflammatory phase and bone growth in rats with bone defect." Journal of Applied Biomaterials & Functional Materials 21 (January 2023): 228080002211491. http://dx.doi.org/10.1177/22808000221149193.
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Hydroxyapatite (HA) is a biomaterial widely used to treat bone defect, such as due to traffic accident. The HA scaffold is obtained from synthetic HA or natural sources, such as bovine hydroxyapatite (BHA). This study aims to compare the characteristics and in vivo performance of BHA-based and HA-based scaffolds. For this purpose, the scaffold was formulated with gelatin (GEL) and characterised by SEM-EDX, FTIR and mini autograph. The defect model was carried out on the femur area of Wistar rats classified into three animal groups: defect, HA-GEL and BHA-GEL. Postoperatively (7, 14 and 28 days), the bone was radiologically evaluated, and stained with haematoxylin–eosin, anti-CD80 and anti-CD163. The BHA-GEL scaffold showed a regular surface and spherical particle shape, whereas the HA-GEL scaffold exhibited irregular surface. The BHA-GEL scaffold had higher pore size and compressive strength and lower calcium-to-phosphorus ratio than the HA-GEL scaffold. In vivo study showed that the expression of CD80 in the three experimental groups was not significantly different. However, the expression of CD163 differed significantly between the groups. The BHA-GEL group showed robust expression of CD163 on day 7, which rapidly decreased over time. It also showed increased osteoclasts, osteoblasts and osteocytes cell count that contributed to the integrity of the defect area. In conclusion, the BHA-based scaffold exhibited the desired physical and chemical characteristics that benefit in vivo performance versus the HA-based scaffold. Thus, the BHA-based scaffold may be used as a bone graft.
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Dombrovskaya, Yu A., N. I. Enukashvili, R. E. Banashkov, N. Yu Semenova, I. A. Karabak, and A. V. Silin. "Prospects for the use of fibrin scaffolds populated with pulp and periodontal stem cells: an experimental study." Parodontologiya 26, no. 2 (2021): 96–103. http://dx.doi.org/10.33925/1683-3759-2021-26-2-96-103.
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Relevance. Creating three-dimensional scaffolds from biodegradable materials and seeding them with stem cells derived from the oral tissues is a promising tool for guided tissue regeneration. Pulp and periodontal stem cells have a high potential for osteogenic differentiation, which biologically determines their use in surgical bone reconstruction. The experiment shows the result of using fibrin glue seeded with pulp and periodontal stem cells on the mandible of laboratory mice. The article presents the results of computed tomography and histological examination. The data provide evidence of the influence of seeded scaffolds on bone remodeling in the area of the defect.Materials and methods. The Local Ethics Committee of the North-Western State Medical University named after I.I. Mechnikov gave permission for the practical part of the research work. The study included 29 white laboratory mice. Molars were extracted and a bone defect was formed. Pulp and periodontal stem cells were obtained and cell-seeded scaffolds were made, then they were introduced into the defect area. The animals were euthanized, maxillofacial CT scan and histology of the defect area were performed 28 days after the molar extraction.Results. The oral cavity of mice was examined, molars were extracted, and teeth were morphologically examined under anesthesia. Scaffolds were synthesized and bone defects were filled. CT scans and histology results were analyzed. The bone volume increased in the main group compared to the control group.Conclusion. The fibrin glue can be used to obtain a material with mechanical characteristics sufficient for a stable shape scaffold. The study proved that the pulp stem cells enclosed in a fibrin glue-based scaffold can maintain the ability to proliferate and osteogenically differentiate. The scaffold based on fibrin glue, which we used, affected the bone remodeling process in the area of jaw defects.
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Yoon, Sun Jung, Ki Suk Park, Bang Sil Choi, et al. "Effect of DBP/PLGA Hybrid Scaffold on Angiogenesis during the Repair of Calvarial Bone Defect." Key Engineering Materials 342-343 (July 2007): 161–64. http://dx.doi.org/10.4028/www.scientific.net/kem.342-343.161.
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This study was designed to investigate the influence of demineralized bone particles (DBP)/PLGA hybrid scaffold on angiogenesis and osteogenesis in a calvarial defect model. DBP/PLGA scaffolds were manufactured by solvent casting/salt leaching method, and each scaffold contained 0, 10, 20, 40, and 80 wt% DBP of PLGA, respectively. A total of 34 rats were operated and bicortical holes were placed on their calvaria. The defects were filled with different ratio DBP/PLGA scaffolds. After 3, 7, 14, and 28 days, specimens were taken and, histologic, immunohistologic and RT-PCR analyses were carried out concerning number of vessels and density of regenerated bone, and angiogenic activation. On days 7, in all experimental groups, bone formation occurred in a direction from defected margin of calvarium to center of implanted scaffold and new vessel formation took place in front of the osteogenic regeneration front. We found that the 20 and 40 wt% DBP/PLGA scaffold was superior in its ability to regenerate new bone, induced more intensive formation of microvasculature and expressed in a higher level of osteocalcin mRNA than other groups.
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Weng, Weizong, Shaojun Song, Liehu Cao, et al. "A Comparative Study of Bioartificial Bone Tissue Poly-L-lactic Acid/Polycaprolactone and PLLA Scaffolds Applied in Bone Regeneration." Journal of Nanomaterials 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/935149.
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Bioartificial bone tissue engineering is an increasingly popular technique to repair bone defect caused by injury or disease. This study aimed to investigate the feasibility of PLLA/PCL (poly-L-lactic acid/polycaprolactone) by a comparison study of PLLA/PCL and PLLA scaffolds applied in bone regeneration. Thirty healthy mature New Zealand rabbits on which 15 mm distal ulna defect model had been established were selected and then were divided into three groups randomly: group A (repaired with PLLA scaffold), group B (repaired with PLLA/PCL scaffold), and group C (no scaffold) to evaluate the bone-remodeling ability of the implants. Micro-CT examination revealed the prime bone regeneration ability of group B in three groups. Bone mineral density of surgical site in group B was higher than group A but lower than group C. Meanwhile, the bone regeneration in both groups A and B proceeded with signs of inflammation for the initial fast degradation of scaffolds. As a whole, PLLA/PCL scaffoldsin vivoinitially degrade fast and were better suited to repair bone defect than PLLA in New Zealand rabbits. Furthermore, for the low mineral density of new bone and rapid degradation of the scaffolds, more researches were necessary to optimize the composite for bone regeneration.
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Verykokou, Styliani, Charalabos Ioannidis, Sofia Soile, et al. "The Role of Cone Beam Computed Tomography in Periodontology: From 3D Models of Periodontal Defects to 3D-Printed Scaffolds." Journal of Personalized Medicine 14, no. 2 (2024): 207. http://dx.doi.org/10.3390/jpm14020207.
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The treatment of osseous defects around teeth is a fundamental concern within the field of periodontology. Over the years, the method of grafting has been employed to treat bone defects, underscoring the necessity for custom-designed scaffolds that precisely match the anatomical intricacies of the bone cavity to be filled, preventing the formation of gaps that could allow the regeneration of soft tissues. In order to create such a patient-specific scaffold (bone graft), it is imperative to have a highly detailed 3D representation of the bone defect, so that the resulting scaffold aligns with the ideal anatomical characteristics of the bone defect. In this context, this article implements a workflow for designing 3D models out of patient-specific tissue defects, fabricated as scaffolds with 3D-printing technology and bioabsorbable materials, for the personalized treatment of periodontitis. The workflow is based on 3D modeling of the hard tissues around the periodontal defect (alveolar bone and teeth), scanned from patients with periodontitis. Specifically, cone beam computed tomography (CBCT) data were acquired from patients and were used for the reconstruction of the 3D model of the periodontal defect. The final step encompasses the 3D printing of these scaffolds, employing Fused Deposition Modeling (FDM) technology and 3D-bioprinting, with the aim of verifying the design accuracy of the developed methodοlogy. Unlike most existing 3D-printed scaffolds reported in the literature, which are either pre-designed or have a standard structure, this method leads to the creation of highly detailed patient-specific grafts. Greater accuracy and resolution in the macroarchitecture of the scaffolds were achieved during FDM printing compared to bioprinting, with the standard FDM printing profile identified as more suitable in terms of both time and precision. It is easy to follow and has been successfully employed to create 3D models of periodontal defects and 3D-printed scaffolds for three cases of patients, proving its applicability and efficiency in designing and fabricating personalized 3D-printed bone grafts using CBCT data.
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Lesci, Isidoro Giorgio, Leonardo Ciocca, Odila Mezini, and Norberto Roveri. "Synthetic Biomimetic HA Composite Scaffolds for the Bone Regenerative Medicine Using CAD-CAM Technology." Key Engineering Materials 672 (January 2016): 235–46. http://dx.doi.org/10.4028/www.scientific.net/kem.672.235.
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The study of nanocrystalline calcium phosphate physical-chemical characteristics and, thereafter, the possibility to imitate bone mineral for the development of new advanced biomaterials is constantly growing. The availability to use synthetic biomimetic hydroxylapatites (HA), since they are the most important inorganic constituents of hard tissues in vertebrates, represents a great turning point in bone tissue engineering because of their chemical similarity to the biological mineral component. The ability to control the architecture and strength of a bone tissue engineering scaffold is critical to achieve a harmony between the scaffold and the host tissue. The scaffold attempts to mimic the function of the natural extracellular matrix, providing a temporary template for the growth of target tissues. Scaffolds should have suitable architecture and strength to serve their intended function. Rapid prototyping (RP) technique is applied to tissue engineering to satisfy this need and to create a scaffold with fully interconnected pore structure directly from the scanned and digitized image of the defect site. In this study, we developed a biomimetic mineralized collagen/Polycaprolactone composite by self-assembling process of collagen fibers and nucleation of a nanostructured HA mimicking the natural bone. This new solution provides a hybrid material, based on natural components of bone (collagen and HA) and the support of the widely-tested PCL (polycaprolactone) giving the scaffolds ideal characteristics such as resorption, biocompatibility and 3-D printability. CAD design of the microstructure and bioprinting fulfills the need to finely control the scaffold’s shape to best fit the anatomical defect, the possibility of customization and the ability to perfectly control spatial distribution of pores and their morphology. The results allowed the conclusion that these scaffolds are biocompatible and allow the colonization and proliferation of MSC (mesenchymal stem cell). The in vivo results confirm the scaffold’s biocompatibility and its composition and structure create the basis for bone tissue regeneration.
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Cristescu, Ioan, Lucian Marina, Daniel Vilcioiu, F. Safta, M. Istodorescu, and A. Stere. "The Potential of Antibiotic Collagen Based Biocomposites for the Treatment of Bone Defects." Key Engineering Materials 587 (November 2013): 404–11. http://dx.doi.org/10.4028/www.scientific.net/kem.587.404.
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Antibiotic delivery systems used in the past have consisted primarily of impregnated cement beads that required routine removal once the antibiotic had eluded completely. With the development of collagen scaffolds that could be used to fill bony defects the antibiotic cold be delivered from the scaffold used to sustain local bone growth. Over the course of two years antibiotic loaded collagen scaffolds were used in the local treatment of 21patients suffering of complicated fractures including bone defects, infections or pseudoarthrosis, all of them of traumatic nature. At the time of the initial surgical debridement or at subsequent second look procedures once local tissue viability was observed the antibiotic loaded collagen scaffold was inserted in the tissue defect and never removed. Excellent results were obtained and the infection was brought under control by use of both surgical and antibiotic modalities. Bone grafting was used in 6 cases where the defects were extensive. Where there was less extensive bone destruction the scaffold was a good adjuvant in new bone formation. Use of antibiotic loaded collagen scaffolds is a reliable and effective means of local antibiotic delivery system combining both the new bone formation capacity of the scaffold to hold osteoblasts with the ability to deliver high doses of antibiotic in the local tissue environment and thus avoiding the systemic toxicity.
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Zhu, Hong, Ziheng Lin, Qifei Luan, et al. "Angiogenesis-promoting composite TPMS bone tissue engineering scaffold for mandibular defect regeneration." International Journal of Bioprinting 10, no. 1 (2023): 0153. http://dx.doi.org/10.36922/ijb.0153.
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Mandibular defects severely impact the patient&rsquo;s quality of life and are difficult problems to treat in the clinical setting. Due to the limitations of current gold-standard therapies, there is a tremendous need for tissue engineering approaches to meet this rising clinical demand. Injectable platelet-rich fibrin (I-PRF) containing a variety of pro-regenerative growth factors and stromal cell-derived factor-1 (SDF-1) has been shown to be beneficial in stimulating angiogenesis. In this study, we developed a three-cycle minimally curved biomimetic bone tissue engineering scaffold made of &beta;-tricalcium phosphate, modified with I-PRF and SDF-1. I-PRF was loaded at a concentration of 5% onto a triply periodic minimal surface (TPMS) scaffold with a porosity of 70%. CCK-8 experiments and live-dead staining confirmed the scaffold&rsquo;s good biocompatibility and its ability to promote cell proliferation. Wound healing assays showed that the TPMS scaffold loaded with I-PRF and SDF-1 (SIT) enhanced cell migration of MC3T3 cells. Moreover, angiogenesis experiments showed that the SIT scaffold promoted angiogenesis. Importantly, alkaline phosphatase and alizarin red staining confirmed that the bone scaffold accelerated MC3T3 cells&rsquo; osteogenic differentiation and mineralization. The SIT bone scaffold was then implanted into a rabbit mandible defect model. After a 2-month post-implantation period, micro- CT analysis revealed the growth of new bone tissue around the SIT construct, while histological analysis which included hematoxylin-eosin (H&E) staining and masson&rsquo;s trichrome staining, alkaline phosphatase (ALP) staining, osteoprotegerin (OPG) staining demonstrated that the SIT scaffold substantially promoted the growth of a highly vascularized fibrous and bone tissue in the defect site. Taken together, these findings demonstrate the considerable potential of TPMS scaffolds loaded with I-PRF and SDF-1 in promoting the repair of mandible defects.
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Fauzan, Fauzan. "Effect of Human Adipose-Derived Mesenchymal Stem Cell (HADMSC) With Chitosan Scaffold on Bone Defect White Rats (Rattus Norvegicus) on Serum Alkaline Phosphatase (ALP) Levels." Journal of Stem Cell Research and Tissue Engineering 6, no. 1 (2022): 39–47. http://dx.doi.org/10.20473/jscrte.v6i1.37514.
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Bone defect is one of the challenges for dentists in the process of healing bone tissue. Bone defect can occur in alveolar bone with the etiology of microorganisms and cyst expansion. In addition, cases of bone defects in alveolar bone are also often found in cases with treatment of apex resection and hemisection. Autologous bone graft is a clinical gold standard in the treatment of bone defect. However, the use of bone graft has a limited number of growth factors produced. Tissue engineering is the latest method in terms of bone regeneration. Tissue engineering has three main components; stem cell, growth factor, and scaffold. Stem cells will increase osteoblastogenesis and chitosan scaffold will immobilize alkaline phosphatase (ALP) so that serum ALP levels decrease and bone regeneration and mineralization processes become faster. The aim of this study is analyzing the effect of human adipose-derived mesenchymal stem cell (HADMSC) with chitosan scaffold (CS) in bone defect on serum alkaline phosphatase (ALP) levels. This research was a in vivo laboratory experimental study. Bone defects are planted with chitosan scaffold (CS) and a combination of human adipose-derived mesenchymal stem cells (HADMSC) with chitosan scaffold. Measurement of ALP levels was carried out by the International Federation of Clinical Chemistry (IFCC) method using an analyzer on the 1st, 3rd, 7th and 14th days. Research data were analyzed using multivariate analysis of variance (MANOVA) and Bonferroni tests. The results of the data analysis showed that there were significant differences in ALP levels with CS planting and the combination of HADMSC and CS. the effect of human adipose- derived mesenchymal stem cell (HADMSC) with chitosan scaffold (CS) on bone defect reduces serum alkaline phosphatase (ALP) levels on the 3th and 14th days.
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Chen, Chiu-Fang, Ya-Shuan Chou, Tzer-Min Lee, et al. "The Uniform Distribution of Hydroxyapatite in a Polyurethane Foam-Based Scaffold (PU/HAp) to Enhance Bone Repair in a Calvarial Defect Model." International Journal of Molecular Sciences 25, no. 12 (2024): 6440. http://dx.doi.org/10.3390/ijms25126440.
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Polyurethane (PU) is a promising material for addressing challenges in bone grafting. This study was designed to enhance the bone grafting capabilities of PU by integrating hydroxyapatite (HAp), which is known for its osteoconductive and osteoinductive potential. Moreover, a uniform distribution of HAp in the porous structure of PU increased the effectiveness of bone grafts. PEG/APTES-modified scaffolds were prepared through self-foaming reactions. A uniform pore structure was generated during the spontaneous foaming reaction, and HAp was uniformly distributed in the PU structure (PU15HAp and PU30HAp) during foaming. Compared with the PU scaffolds, the HAp-modified PU scaffolds exhibited significantly greater protein absorption. Importantly, the effect of the HAp-modified PU scaffold on bone repair was tested in a rat calvarial defect model. The microstructure of the newly formed bone was analyzed with microcomputed tomography (μ-CT). Bone regeneration at the defect site was significantly greater in the HAp-modified PU scaffold group than in the PU group. This innovative HAp-modified PU scaffold improves current bone graft materials, providing a promising avenue for improved bone regeneration.
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V., Sasi Kumar, Beeula A., Praveen Kumar та Naveen Kumar. "Influence of typographic biocomposite scaffold in facilitating biomineralization to progress complex hard tissue repair". BOHR Journal of Material Sciences and Engineering (BIJMSE) 1, № 1 (2023): 7–10. http://dx.doi.org/10.54646/bjmse.2023.02.
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Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties (1).
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Kumar, V. Sasi, A. Beeula, Praveen Kumar, and Naveen Kumar. "Influence of Typographic Biocomposite Scaffold in Facilitating Biomineralization to Progress Complex Hard Tissue Repair." BOHR International Journal of Material Sciences and Engineering 1, no. 1 (2022): 7–10. http://dx.doi.org/10.54646/bijmse.002.
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Biomaterial modifications and scaffold fabrication methods in hard tissue engineering applications have seen enormous growth. However, clinical demand in treating and regenerating large bone defects is intricate, as current methods fail to meet requirements such as regenerating bone with optimal physical and mechanical properties in complex bone repair due to poor scaffold design and less bioactivity. To meet such clinical expectations, biomaterials are combined to create a 3D bone composite scaffold to improve the quality of the regenerated bone by improving bioactivity through biomineralization. To advance this process, accelerated and homogenous biomineralization is facilitated by the scaffold with increased surface area and active molecules to progress the repair of large bone defect. This facilitation of biomineralization leads to minerals deposition as a layer on the substrate when 3D-printed porous scaffolds made of biocomposite are exposed to body fluid at the repair site where the substrate degrades and releases active biomolecules. These released molecules crystallized evenly to form an apatite layer on the scaffold surface, where bone-forming cells attach, grow, and regenerate bone. Additionally, the formation of the apatite layer through biomineralization to repair lost structure is also governed by the following factors, which include macromolecules and an active site present between collagen molecules in the bone. In this review, we explore the advantages of biocomposite materials and 3D-printed scaffold design in accelerating biomineralization at the bone defect area to facilitate the formation of an apatite layer to progress complex hard tissue regeneration with optimal properties [1].
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Hung, Kuo-Sheng, May-Show Chen, Wen-Chien Lan, et al. "Three-Dimensional Printing of a Hybrid Bioceramic and Biopolymer Porous Scaffold for Promoting Bone Regeneration Potential." Materials 15, no. 5 (2022): 1971. http://dx.doi.org/10.3390/ma15051971.
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In this study, we proposed a three-dimensional (3D) printed porous (termed as 3DPP) scaffold composed of bioceramic (beta-tricalcium phosphate (β-TCP)) and thermoreversible biopolymer (pluronic F-127 (PF127)) that may provide bone tissue ingrowth and loading support for bone defect treatment. The investigated scaffolds were printed in three different ranges of pore sizes for comparison (3DPP-1: 150–200 μm, 3DPP-2: 250–300 μm, and 3DPP-3: 300–350 μm). The material properties and biocompatibility of the 3DPP scaffolds were characterized using scanning electron microscopy, X-ray diffractometry, contact angle goniometry, compression testing, and cell viability assay. In addition, micro-computed tomography was applied to investigate bone regeneration behavior of the 3DPP scaffolds in the mini-pig model. Analytical results showed that the 3DPP scaffolds exhibited well-defined porosity, excellent microstructural interconnectivity, and acceptable wettability (θ < 90°). Among all groups, the 3DPP-1 possessed a significantly highest compressive force 273 ± 20.8 Kgf (* p < 0.05). In vitro experiment results also revealed good cell viability and cell attachment behavior in all 3DPP scaffolds. Furthermore, the 3DPP-3 scaffold showed a significantly higher percentage of bone formation volume than the 3DPP-1 scaffold at week 8 (* p < 0.05) and week 12 (* p < 0.05). Hence, the 3DPP scaffold composed of β-TCP and F-127 is a promising candidate to promote bone tissue ingrowth into the porous scaffold with decent biocompatibility. This scaffold particularly fabricated with a pore size of around 350 μm (i.e., 3DPP-3 scaffold) can provide proper loading support and promote bone regeneration in bone defects when applied in dental and orthopedic fields.
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Zhang, Wang, Fu, Ye, Wang, and Zhou. "Fabrication and Application of Novel Porous Scaffold in Situ-Loaded Graphene Oxide and Osteogenic Peptide by Cryogenic 3D Printing for Repairing Critical-Sized Bone Defect." Molecules 24, no. 9 (2019): 1669. http://dx.doi.org/10.3390/molecules24091669.
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Osteogenic peptides have been reported as highly effective in directing mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo. Therefore, developing novel biomaterials for the controlled delivery of osteogenic peptides in scaffolds without lowering the peptide’s biological activity is highly desirable. To repair a critical-sized bone defect to efficiently achieve personalized bone regeneration, a novel bioactive poly(lactic-co-glycolic acid) (PLGA)/β-tricalcium phosphate (β-TCP) composite scaffold, in which graphene oxide (GO) and bone morphogenetic protein (BMP)-2-like peptide were loaded in situ (PTG/P), was produced by an original cryogenic 3D printing method. The scaffolds were mechanically comparable to human cancellous bone and hierarchically porous. The incorporation of GO further improved the scaffold wettability and mechanical strength. The in situ loaded peptides retained a high level of biological activity for an extended time, and the loading of GO in the scaffold further tuned the peptide release so that it was more sustained. Our in vitro study showed that the PTG/P scaffold promoted rat bone marrow-derived mesenchymal stem cell ingrowth into the scaffold and enhanced osteogenic differentiation. Moreover, the in vivo study indicated that the novel PTG/P scaffold with sustained delivery of the peptide could significantly promote bone regeneration in a critical bone defect. Thus, the novel bioactive PTG/P scaffold with a customized shape, improved mechanical strength, sustainable peptide delivery, and excellent osteogenic ability has great potential in bone tissue regeneration.
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Yang, Changsheng, Lei Zhou, Xiaodan Geng, Hui Zhang, Baolong Wang, and Bin Ning. "New dual-function in situ bone repair scaffolds promote osteogenesis and reduce infection." Journal of Biological Engineering 16, no. 1 (2022). http://dx.doi.org/10.1186/s13036-022-00302-y.
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Abstract Background The treatment of infectious bone defects is a difficult problem to be solved in the clinic. In situ bone defect repair scaffolds with anti-infection and osteogenic abilities can effectively deal with infectious bone defects. In this study, an in situ polycaprolactone (PCL) scaffold containing ampicillin (Amp) and Mg microspheres was prepared by 3D printing technology. Results Mg and Amp were evenly distributed in PCL scaffolds and could be released slowly to the surrounding defect sites with the degradation of scaffolds. In vitro experiments demonstrated that the PCL scaffold containing Mg and Amp (PCL@Mg/Amp) demonstrated good cell adhesion and proliferation. The osteogenic genes collagen I (COL-I) and Runx2 were upregulated in cells grown on the PCL@Mg/Amp scaffold. The PCL@Mg/Amp scaffold also demonstrated excellent antibacterial ability against E. coli and S. aureus. In vivo experiments showed that the PCL@Mg/Amp scaffold had the strongest ability to promote tibial defect repair in rats compared with the other groups of scaffolds. Conclusions This kind of dual-function in situ bone repair scaffold with anti-infection and osteogenic abilities has good application prospects in the field of treating infectious bone defects.
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Jaber, Mahdi, Patrina S. P. Poh, Georg N. Duda, and Sara Checa. "PCL strut-like scaffolds appear superior to gyroid in terms of bone regeneration within a long bone large defect: An in silico study." Frontiers in Bioengineering and Biotechnology 10 (September 23, 2022). http://dx.doi.org/10.3389/fbioe.2022.995266.
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The treatment of large bone defects represents a major clinical challenge. 3D printed scaffolds appear as a promising strategy to support bone defect regeneration. The 3D design of such scaffolds impacts the healing path and thus defect regeneration potential. Among others, scaffold architecture has been shown to influence the healing outcome. Gyroid architecture, characterized by a zero mean surface curvature, has been discussed as a promising scaffold design for bone regeneration. However, whether gyroid scaffolds are favourable for bone regeneration in large bone defects over traditional strut-like architecture scaffolds remains unknown. Therefore, the aim of this study was to investigate whether gyroid scaffolds present advantages over more traditional strut-like scaffolds in terms of their bone regeneration potential. Validated bone defect regeneration principles were applied in an in silico modeling approach that allows to predict bone formation in defect regeneration. Towards this aim, the mechano-biological bone regeneration principles were adapted to allow simulating bone regeneration within both gyroid and strut-like scaffolds. We found that the large surface curvatures of the gyroid scaffold led to a slower tissue formation dynamic and conclusively reduced bone regeneration. The initial claim, that an overall reduced zero mean surface curvature would enhance bone formation, could not be confirmed. The here presented approach illustrates the potential of in silico tools to evaluate in pre-clinical studies scaffold designs and eventually lead to optimized architectures of 3D printed implants for bone regeneration.
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Liu, Bingchuan, Guojin Hou, Zhongwei Yang, et al. "Repair of critical diaphyseal defects of lower limbs by 3D printed porous Ti6Al4V scaffolds without additional bone grafting: a prospective clinical study." Journal of Materials Science: Materials in Medicine 33, no. 9 (2022). http://dx.doi.org/10.1007/s10856-022-06685-0.
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AbstractThe repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting.
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Singh, Srujan, Yuxiao Zhou, Ashley L. Farris, et al. "Geometric Mismatch Promotes Anatomic Repair in Periorbital Bony Defects in Skeletally Mature Yucatan Minipigs." Advanced Healthcare Materials, August 10, 2023. http://dx.doi.org/10.1002/adhm.202301944.
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AbstractPorous tissue‐engineered 3D‐printed scaffolds are a compelling alternative to autografts for the treatment of large periorbital bone defects. Matching the defect‐specific geometry has long been considered an optimal strategy to restore pre‐injury anatomy. However, studies in large animal models have revealed that biomaterial‐induced bone formation largely occurs around the scaffold periphery. Such ectopic bone formation in the periorbital region can affect vision and cause disfigurement. To enhance anatomic reconstruction, we introduced geometric mismatches in the scaffolds used to treat full thickness zygomatic defects created bilaterally in adult Yucatan minipigs. We used 3D‐printed, anatomically‐mirrored scaffolds in combination with autologous stromal vascular fraction of cells (SVF) for treatment. We developed an advanced image‐registration workflow to quantify the post‐surgical geometric mismatch and correlate it with the spatial pattern of the regenerating bone. Osteoconductive bone growth on the dorsal and ventral aspect of the defect enhanced scaffold integration with the native bone while medio‐lateral bone growth led to failure of the scaffolds to integrate. We found a strong positive correlation between geometric mismatch and orthotopic bone deposition at the defect site. The data suggested that strategic mismatch >20% could improve bone scaffold design to promote enhanced regeneration, osseointegration and long‐term scaffold survivability.This article is protected by copyright. All rights reserved
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Huiwen, Wu, Liang Shuai, Xie Jia, et al. "3D-printed nanohydroxyapatite/methylacrylylated silk fibroin scaffold for repairing rat skull defects." Journal of Biological Engineering 18, no. 1 (2024). http://dx.doi.org/10.1186/s13036-024-00416-5.
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AbstractThe repair of bone defects remains a major challenge in the clinic, and treatment requires bone grafts or bone replacement materials. Existing biomaterials have many limitations and cannot meet the various needs of clinical applications. To treat bone defects, we constructed a nanohydroxyapatite (nHA)/methylacrylylated silk fibroin (MASF) composite biological scaffold using photocurable 3D printing technology. In this study, scanning electron microscopy (SEM) was used to detect the changes in the morphological structure of the composite scaffold with different contents of nanohydroxyapatite, and FTIR was used to detect the functional groups and chemical bonds in the composite scaffold to determine the specific components of the scaffold. In in vitro experiments, bone marrow mesenchymal stem cells from SD rats were cocultured with scaffolds soaking solution, and the cytotoxicity, cell proliferation, Western blot analysis, Quantitative real-time PCR analysis, bone alkaline phosphatase activity and alizarin red staining of scaffolds were detected to determine the biocompatibility of scaffolds and the effect of promoting proliferation and osteogenesis of bone marrow mesenchymal stem cells in vitro. In the in vivo experiment, the skull defect was constructed by adult SD rats, and the scaffold was implanted into the skull defect site. After 4 weeks and 8 weeks of culture, the specific osteogenic effect of the scaffold in the skull defect site was detected by animal micro-CT, hematoxylin and eosin (HE) staining and Masson's staining. Through the analysis of the morphological structure of the scaffold, we found that the frame supported good retention of the lamellar structure of silk fibroin, when mixed with nHA, the surface of the stent was rougher, the cell contact area increased, and cell adhesion and lamellar microstructure for cell migration and proliferation of the microenvironment provided a better space. FTIR results showed that the scaffold completely retained the β -folded structure of silk fibroin, and the scaffold composite was present without obvious impurities. The staining results of live/dead cells showed that the constructed scaffolds had no significant cytotoxicity, and thw CCK-8 assay also showed that the constructed scaffolds had good biocompatibility. The results of osteogenic induction showed that the scaffold had good osteogenic induction ability. Moreover, the results also showed that the scaffold with a MASF: nHA ratio of 1: 0.5 (SFH) showed better osteogenic ability. The micro-CT and bone histometric results were consistent with the in vitro results after stent implantation, and there was more bone formation at the bone defect site in the SFH group.This research used photocurable 3D printing technology to successfully build an osteogenesis bracket. The results show that the constructed nHA/MASF biological composite material, has good biocompatibility and good osteogenesis function. At the same time, in the microenvironment, the material can also promote bone defect repair and can potentially be used as a bone defect filling material for bone regeneration applications.
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Rothweiler, R., S. Kuhn, T. Stark, et al. "Development of a new critical size defect model in the paranasal sinus and first approach for defect reconstruction—An in vivo maxillary bone defect study in sheep." Journal of Materials Science: Materials in Medicine 33, no. 11 (2022). http://dx.doi.org/10.1007/s10856-022-06698-9.
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AbstractFractures of the paranasal sinuses often require surgical intervention. Persisting bone defects lead to permanent visible deformities of the facial contours. Bone substitutes for reconstruction of defects with simultaneous induction of new bone formation are not commercially available for the paranasal sinus. New materials are urgently needed and have to be tested in their future area of application. For this purpose critical size defect models for the paranasal sinus have to be developed. A ≥2.4 cm large bilateral circular defect was created in the anterior wall of the maxillary sinus in six sheep via an extraoral approach. The defect was filled with two types of an osteoconductive titanium scaffold (empty scaffold vs. scaffold filled with a calcium phosphate bone cement paste) or covered with a titanium mesh either. Sheep were euthanized after four months. All animals performed well, no postoperative complications occured. Meshes and scaffolds were safely covered with soft tissue at the end of the study. The initial defect size of ≥2.4 cm only shrunk minimally during the investigation period confirming a critical size defect. No ingrowth of bone into any of the scaffolds was observed. The anterior wall of the maxillary sinus is a region with low complication rate for performing critical size defect experiments in sheep. We recommend this region for experiments with future scaffold materials whose intended use is not only limited to the paranasal sinus, as the defect is challenging even for bone graft substitutes with proven osteoconductivity.
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Suzuki, Shigeto, Venkata Suresh Venkataiah, Yoshio Yahata, et al. "Correction of large jaw bone defect in the mouse using immature osteoblast-like cells and a three dimensional polylactic acid scaffold." PNAS Nexus, August 8, 2022. http://dx.doi.org/10.1093/pnasnexus/pgac151.
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Abstract Bone tissue engineering has been developed using a combination of mesenchymal stem cells (MSCs) and calcium phosphate-based scaffolds. However, these complexes cannot regenerate large jawbone defects. To overcome this limitation of MSCs and ceramic scaffolds, a novel bone regeneration technology must be developed using cells possessing high bone forming ability and a scaffold that provides space for vertical bone augmentation. To approach this problem in our study, we developed alveolar bone-derived immature osteoblast-like cells (HAOBs), which have the bone regenerative capacity to correct a large bone defect when used as a grafting material in combination with polylactic acid fibers that organize the three-dimensional structure and increase the strength of the scaffold material (3DPL). HAOB-3DPL constructs could not regenerate bone via xenogeneic transplantation in a micromini pig alveolar bone defect model. However, the autogenic transplantation of mice calvaria-derived immature osteoblast like cells (MCOBs) isolated using the identical protocol for HAOBs and mixed with 3DPL scaffolds successfully regenerated the bone in a large jawbone defect mouse model, compared to the 3DPL scaffold alone. Nanoindentation analysis indicated that the regenerated bone had a similar micromechanical strength to native bone. In addition, this MCOB-3DPL regenerated bone possesses osseointegration ability wherein a direct structural connection is established with the titanium implant surface. Hence, a complex formed between a 3DPL scaffold and immature osteoblast-like cells such as MCOBs represents a novel bone tissue engineering approach that enables the formation of vertical bone with the micromechanical properties required to treat large bone defects.
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Tao, Yuan, Meng Jia, Yang Shao-Qiang, et al. "A novel fluffy PLGA/HA composite scaffold for bone defect repair." Journal of Materials Science: Materials in Medicine 35, no. 1 (2024). http://dx.doi.org/10.1007/s10856-024-06782-2.
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AbstractTreatment of bone defects remains crucial challenge for successful bone healing, which arouses great interests in designing and fabricating ideal biomaterials. In this regard, the present study focuses on developing a novel fluffy scaffold of poly Lactide-co-glycolide (PLGA) composites with hydroxyapatite (HA) scaffold used in bone defect repair in rabbits. This fluffy PLGA/HA composite scaffold was fabricated by using multi-electro-spinning combined with biomineralization technology. In vitro analysis of human bone marrow mesenchymal stem cells (BMSCs) seeded onto fluffy PLGA/HA composite scaffold showed their ability to adhere, proliferate and cell viability. Transplant of fluffy PLGA/HA composite scaffold in a rabbit model showed a significant increase in mineralized tissue production compared to conventional and fluffy PLGA/HA composite scaffold. These findings are promising for fluffy PLGA/HA composite scaffolds used in bone defects. Graphical Abstract
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Jahromi, Hossein Kargar, Morteza Alizadeh, Arian Ehterami та ін. "EVALUATION OF THE EFFECT OF POLY (𝜀-CAPROLACTONE)/POLY (L-LACTIC) ACID/GELATIN NANOFIBER 3D SCAFFOLD CONTAINING RESVERATROL ON BONE REGENERATION". Biomedical Engineering: Applications, Basis and Communications 35, № 05 (2023). http://dx.doi.org/10.4015/s1016237223500278.
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Bone defects affect many people and impose expenses of costly treatment with possible complications. This study aims to investigate a novel Poly ([Formula: see text]-caprolactone)/Poly (L-lactic) acid/Gelatin nanofiber [PCL/PLA/GNF] scaffold containing 5% resveratrol (Resv) which was manufactured via thermally induced phase separation technique (TIPS), and its applicability for bone defect treatment. Gelatin nanofiber (GNF) was synthesized via the electrospinning method and mixed with PCL/PLA solution and then 5% resveratrol was added to fabricate a 3D scaffold via the TIPS technique. The prepared scaffolds were evaluated regarding their porosity, morphology, contact angle, degradation properties, biomechanical, blood compatibility, and cell viability via MTT assay. The scaffolds were further investigated by implantation in a rat femur defect model. PCL/PLA/GNF with 5% Resv showed a cancellated structure with irregular-shaped pores. The mean pore size was estimated to be 160 [Formula: see text]m and the porosity was 80.56 ± 2.68%. The contact angle of the fabricated scaffold was 95.4 ± 3.4, which determines the hydrophobic nature of the scaffold. Increased cell viability in scaffolds was observed by adding resveratrol. Twelve weeks after the implantation of the scaffold into the bone defect, the defects filled with PCL/PLA/GNF-resveratrol contained scaffold were remarkably better than PCL/PLA/GNF and negative control group (89.23 ± 6.34% in 12 weeks), and the difference was significant (p ¡ 0.05). In conclusion, the PCL/PLA/GNF scaffold containing 5% of resveratrol demonstrated adequate mechanical and physical properties. There is possible applicability of PCL/PLA/GNF scaffold containing 5% of resveratrol for surgical treatment of bone defects.
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Ma, Lan, Yijun Yu, Hanxiao Liu, et al. "Berberine-releasing electrospun scaffold induces osteogenic differentiation of DPSCs and accelerates bone repair." Scientific Reports 11, no. 1 (2021). http://dx.doi.org/10.1038/s41598-020-79734-9.
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AbstractThe repair of skeletal defects in maxillofacial region remains an intractable problem, the rising technology of bone tissue engineering provides a new strategy to solve it. Scaffolds, a crucial element of tissue engineering, must have favorable biocompatibility as well as osteoinductivity. In this study, we prepared berberine/polycaprolactone/collagen (BBR/PCL/COL) scaffolds with different concentrations of berberine (BBR) (25, 50, 75 and 100 μg/mL) through electrospinning. The influence of dosage on scaffold morphology, cell behavior and in vivo bone defect repair were systematically studied. The results indicated that scaffolds could release BBR stably for up to 27 days. Experiments in vitro showed that BBR/PCL/COL scaffolds had appropriate biocompatibility in the concentration of 25–75 μg/mL, and 50 and 75 μg/mL scaffolds could significantly promote osteogenic differentiation of dental pulp stem cells. Scaffold with 50 μg/mL BBR was implanted into the critical bone defect of rats to evaluate the ability of bone repair in vivo. It was found that BBR/PCL/COL scaffold performed more favorable than polycaprolactone/collagen (PCL/COL) scaffold. Overall, our study is the first to evaluate the capability of in vivo bone repair of BBR/PCL/COL electrospun scaffold. The results indicate that BBR/PCL/COL scaffold has prospective potential for tissue engineering applications in bone regeneration therapy.