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The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro. Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo. The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation (p < 0.05) compared to pure titanium alloy scaffolds in vitro. Furthermore, the composite scaffold can exhibit significant osteogenic differentiation (p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds (p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups (p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration.

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo. Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering.

Exploration for ideal bone regeneration materials still remains a hot research topic due to the unmet clinical challenge of large bone defect healing. Bone grafting materials have gradually evolved from single component to multiple-component composite, but their functions during bone healing still only regulate one or two biological processes. Therefore, there is an urgent need to develop novel materials with more complex composition, which convey multiple biological functions during bone regeneration. Here, we report an naturally nanostructured ECM based composite scaffold derived from fish air bladder and combined with dicalcium phosphate (DCP) microparticles to form a new type of bone grafting material. The DCP/acellular tissue matrix (DCP/ATM) scaffold demonstrated porous structure with porosity over 65% and great capability of absorbing water and other biologics. In vitro cell culture study showed that DCP/ATM scaffold could better support osteoblast proliferation and differentiation in comparison with DCP/ADC made from acid extracted fish collagen. Moreover, DCP/ATM also demonstrated more potent bone regenerative properties in a rat calvarial defect model, indicating incorporation of ECM based matrix in the scaffolds could better support bone formation. Taken together, this study demonstrates a new avenue toward the development of new type of bone regeneration biomaterial utilizing ECM as its key components.

The repair and reconstruction of bone defects remain a challenge in orthopedics. The present study offers a solution to this problem by developing a vascular endothelial growth factor (VEGF)/bone morphogenetic protein 2 (BMP-2) shell-core microspheres loaded on 3D-printed porous titanium alloy via gelatin coating to prepare a titanium-alloy microsphere scaffold release system. The composite scaffold was characterized via scanning electron microscope (SEM) and energy disperse spectroscopy (EDS), and the effect of the composite scaffold on the adhesion, proliferation, and differentiation of osteoblasts were determined in vitro . Furthermore, a rabbit femoral defect model was established to verify the effect of the composite scaffold on osteogenesis and bone formation in vivo . The results demonstrated that the composite scaffold could release VEGF and BMP-2 sequentially. Meanwhile, the composite scaffold significantly promoted osteoblast adhesion, proliferation, and differentiation ( p < 0.05) compared to pure titanium alloy scaffolds in vitro . Furthermore, the composite scaffold can exhibit significant osteogenic differentiation ( p < 0.05) than gelatin-coated titanium alloy scaffolds. The in vivo X-rays demonstrated that the implanted scaffolds were in a good position, without inflammation and infection. Micro-CT and quantitative results of new bone growth illustrated that the amount of new bone in the composite scaffold is significantly higher than that of the gelatin-coated and pure titanium alloy scaffolds ( p < 0.05). Similarly, the fluorescence labeling and V-G staining of hard tissue sections indicated that the bone integration capacity of the composite scaffold was significantly higher than the other two groups ( p < 0.05). This research suggests that VEGF/BMP-2 shell-core microspheres loaded on 3D-printed titanium alloy porous scaffold through gelatin hydrogel coating achieved the sequential release of VEGF and BMP-2. Most importantly, the in vitro and in vivo study findings have proven that the system could effectively promote osteogenic differentiation and osseointegration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial elationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Xu, Wang, Zhang, Wu, Jiang and Jia.)

Repair of articular cartilage defects is a challenging aspect of clinical treatment. Kartogenin (KGN), a small molecular compound, can induce the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) into chondrocytes. Here, we constructed a scaffold based on chondrocyte extracellular matrix (CECM) and poly(lactic-co-glycolic acid) (PLGA) microspheres (MP), which can slowly release KGN, thus enhancing its efficiency. Cell adhesion, live/dead staining, and CCK-8 results indicated that the PLGA(KGN)/CECM scaffold exhibited good biocompatibility. Histological staining and quantitative analysis demonstrated the ability of the PLGA(KGN)/CECM composite scaffold to promote the differentiation of BMSCs. Macroscopic observations, histological tests, and specific marker analysis showed that the regenerated tissues possessed characteristics similar to those of normal hyaline cartilage in a rabbit model. Use of the PLGA(KGN)/CECM scaffold may mimic the regenerative microenvironment, thereby promoting chondrogenic differentiation of BMSCs in vitro and in vivo . Therefore, this innovative composite scaffold may represent a promising approach for acellular cartilage tissue engineering., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Zhao, Zhao, Zhang, Huang, Li, Shan, Zhong, Xing, Wang, Zhang and Zhao.)

Exploration for ideal bone regeneration materials still remains a hot research topic due to the unmet clinical challenge of large bone defect healing. Bone grafting materials have gradually evolved from single component to multiple-component composite, but their functions during bone healing still only regulate one or two biological processes. Therefore, there is an urgent need to develop novel materials with more complex composition, which convey multiple biological functions during bone regeneration. Here, we report an naturally nanostructured ECM based composite scaffold derived from fish air bladder and combined with dicalcium phosphate (DCP) microparticles to form a new type of bone grafting material. The DCP/acellular tissue matrix (DCP/ATM) scaffold demonstrated porous structure with porosity over 65% and great capability of absorbing water and other biologics. In vitro cell culture study showed that DCP/ATM scaffold could better support osteoblast proliferation and differentiation in comparison with DCP/ADC made from acid extracted fish collagen. Moreover, DCP/ATM also demonstrated more potent bone regenerative properties in a rat calvarial defect model, indicating incorporation of ECM based matrix in the scaffolds could better support bone formation. Taken together, this study demonstrates a new avenue toward the development of new type of bone regeneration biomaterial utilizing ECM as its key components., (Copyright © 2020 Wang, Chen, Ran, He, Jiang, Li and Yu.)