Project description:BackgroundAlveolar bone destruction due to periodontal disease often requires a bone graft substitute to reconstruct the anatomical structures and biological functions of the bone tissue. Despite significant advances in the development of foreign ion-doped nonstoichiometric wollastonite bioceramics (CaSiO3, nCSi) for alveolar bone regeneration over the past decade, the in vivo biosafety and osteogenesis of nCSi scaffolds remain uncertain. In this study, we developed a customized porous nCSi scaffold to investigate the in vivo biocompatibility and osteogenic properties of nCSi bioceramics.MethodsSix percent Mg-doped nCSi bioceramic scaffolds were fabricated by digital light processing (DLP), and the scaffold morphology, pore architecture, compressive strength, in vitro biodegradation, and apatite-forming ability of the bioceramic scaffolds were investigated systematically. Subsequently, an alveolar bone defect rabbit model was used to evaluate the biocompatibility and osteogenic efficacy of the nCSi bioceramics. Animal weight, hematological test, blood biochemical test, wet weight of the main organs, and pathological examination of the main organs were conducted. Micro-CT and histological staining were performed to analyze the osteogenic potential of the personalized bioceramic scaffolds.ResultsThe nCSi scaffolds exhibited appreciable initial compressive strength (>30 MPa) and mild mechanical decay over time during in vitro biodissolution. In addition, the scaffolds induced apatite remineralization in SBF. Bioceramic scaffolds have been proven to have good biocompatibility in vivo after implantation into the alveolar bone defect of rabbits. No significant effects on the hematological indices, blood biochemical parameters, organ wet weight, or organ histopathology were detected from 3 to 180 days postoperatively. The porous scaffolds exhibited strong bone regeneration capability in the alveolar bone defect model of rabbits. Micro-CT and histological examination showed effective maintenance of bone morphology in the bioceramic scaffold group; however, depressed bone tissue was observed in the control group.ConclusionsOur results suggest that personalized nCSi bioceramic scaffolds can be fabricated using the DLP technique. These newly developed strong bioceramic scaffolds exhibit good biocompatibility and osteogenic capability in vivo and have excellent potential as next-generation oral implants.The translational potential of this articleTissue-engineered strategies for alveolar bone repair require a bone graft substitute with appreciable biocompatibility and osteogenic capability. This article provides a systematic investigation of the in vivo biosafety and osteogenic property of nCSi to further development of a silicate-based bioceramics materials for clinical applications.

Project description:BackgroundThe bone regeneration of artificial bone grafts is still in need of a breakthrough to improve the processes of bone defect repair. Artificial bone grafts should be modified to enable angiogenesis and thus improve osteogenesis. We have previously revealed that crystalline Ca10Li(PO4)7 (CLP) possesses higher compressive strength and better biocompatibility than that of pure beta-tricalcium phosphate (β-TCP). In this work, we explored the possibility of cobalt (Co), known for mimicking hypoxia, doped into CLP to promote osteogenesis and angiogenesis.MethodsWe designed and manufactured porous scaffolds by doping CLP with various concentrations of Co (0, 0.1, 0.25, 0.5, and 1 mol%) and using 3D printing techniques. The crystal phase, surface morphology, compressive strength, in vitro degradation, and mineralization properties of Co-doped and -undoped CLP scaffolds were investigated. Next, we investigated the biocompatibility and effects of Co-doped and -undoped samples on osteogenic and angiogenic properties in vitro and on bone regeneration in rat cranium defects.ResultsWith increasing Co-doping level, the compressive strength of Co-doped CLP scaffolds decreased in comparison with that of undoped CLP scaffolds, especially when the Co-doping concentration increased to 1 mol%. Co-doped CLP scaffolds possessed excellent degradation properties compared with those of undoped CLP scaffolds. The (0.1, 0.25, 0.5 mol%) Co-doped CLP scaffolds had mineralization properties similar to those of undoped CLP scaffolds, whereas the 1 mol% Co-doped CLP scaffolds shown no mineralization changes. Furthermore, compared with undoped scaffolds, Co-doped CLP scaffolds possessed excellent biocompatibility and prominent osteogenic and angiogenic properties in vitro, notably when the doping concentration was 0.25 mol%. After 8 weeks of implantation, 0.25 mol% Co-doped scaffolds had markedly enhanced bone regeneration at the defect site compared with that of the undoped scaffold.ConclusionIn summary, CLP doped with 0.25 mol% Co2+ ions is a prospective method to enhance osteogenic and angiogenic properties, thus promoting bone regeneration in bone defect repair.

Project description:BackgroundThree-dimensional printed bioceramic scaffolds composed of 100% β-tricalcium phosphate augmented with dipyridamole (3DPBC-DIPY) can regenerate bone across critically sized defects in skeletally mature and immature animal models. Before human application, safe and effective bone formation should be demonstrated in a large translational animal model. This study evaluated the ability of 3DPBC-DIPY scaffolds to restore critically sized calvarial defects in a skeletally immature, growing minipig.MethodsUnilateral calvarial defects (~1.4 cm) were created in 6-week-old Göttingen minipigs ( n = 12). Four defects were filled with a 1000 μm 3DPBC-DIPY scaffold with a cap (a solid barrier on the ectocortical side of the scaffold to prevent soft-tissue infiltration), four defects were filled with a 1000 μm 3DPBC-DIPY scaffold without a cap, and four defects served as negative controls (no scaffold). Animals were euthanized 12 weeks postoperatively. Calvariae were subjected to micro-computed tomography, 3D reconstruction with volumetric analysis, qualitative histologic analysis, and nanoindentation.ResultsScaffold-induced bone growth was statistically greater than in negative controls ( P ≤ 0.001), and the scaffolds with caps produced significantly more bone generation compared with the scaffolds without caps ( P ≤ 0.001). Histologic analysis revealed woven and lamellar bone with haversian canals throughout the regenerated bone. Cranial sutures were observed to be patent, and there was no evidence of ectopic bone formation or excess inflammatory response. Reduced elastic modulus and hardness of scaffold-regenerated bone were found to be statistically equivalent to native bone ( P = 0.148 for reduced elastic modulus of scaffolds with and without caps and P = 0.228 and P = 0.902 for hardness of scaffolds with and without caps, respectively).Conclusion3DPBC-DIPY scaffolds have the capacity to regenerate bone across critically sized calvarial defects in a skeletally immature translational pig model.Clinical relevance statementThis study assessed the bone generative capacity of 3D-printed bioceramic scaffolds composed of 100% β-tricalcium phosphate and augmented with dipyridamole placed within critical-sized calvarial defects in a growing porcine model.

Project description:With advances in bone tissue engineering, various materials and methods have been explored to find a better scaffold that can help in improving bone growth and regeneration. Three-dimensional (3D) printing by fused deposition modeling can produce customized scaffolds from biodegradable polyesters such as polycaprolactone (PCL). Although the fabricated PCL scaffolds exhibited a lack of bioactivity and poor cell attachment on their surfaces, herein, using a simple postfabrication modification method with hydroxyapatite (HA) and bioglasses (BGs), we obtained better cell proliferation and attachment. Biological behavior and osteosupportive capacity of the 3D-printed scaffolds including PCL, PCL/HA, PCL/BG, and PCL/HA/BG were evaluated in this study, while human adipose tissue-derived mesenchymal stem cells (hADSCs) were cultured on the scaffolds. The cell morphology, attachment, and proliferation were investigated using scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, and 4',6-diamidino-2-phenylindole (DAPI) staining. In the next step, the ability of stem cells to differentiate into osteoblasts was evaluated by measuring alkaline phosphatase (ALP) activity, calcium deposition, and bone-related gene and protein expression. In the end, the expression levels of miR-20a, miR-125a, and their target genes were also investigated as positive and negative regulators in osteogenesis pathways. The results showed that the coated scaffolds with bioceramics present a more appropriate surface for cell adhesion and proliferation, as well as efficient potential in inducing osteoconduction and osteointegration compared to PCL alone and control. The PCL/HA/BG scaffold exhibited higher in vitro cell viability and bone formation compared to the other groups, which can be due to the synergistic effect of HA and BG. On the whole, this tricomponent 3D-printing scaffold has a promising prospect for bone tissue engineering applications.

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Comparison of osteogenic capability of 3D-printed bioceramic scaffolds and granules with different porosities for clinical translation

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