Although bone is regenerative, its regeneration capacity is limited. For bone defects beyond a critical size, further intervention is required. As an attractive strategy, bone tissue engineering (bone TE) has been widely investigated to repair bone defects. However, the rapid and effective bone regeneration of large non-healing defects is still a great challenge. Multifunctional scaffolds having osteoinductivity and osteoconductivity are desirable to fasten functional bone tissue regeneration. In the present study, biomimetic composite scaffolds of collagen and biphasic calcium phosphate nanoparticles (BCP NPs) with a controlled release of dexamethasone (DEX) and the controlled pore structures were prepared for bone TE. DEX was introduced in the BCP NPs during preparation of the BCP NPs and hybridized with collagen scaffolds, which pore structures were controlled by using pre-prepared ice particulates as a porogen material. The composite scaffolds had well controlled and interconnected pore structures, high mechanical strength and a sustained release of DEX. The composite scaffolds showed good biocompatibility and promoted osteogenic differentiation of hMSCs when used for three-dimensional culture of human bone marrow-derived mesenchymal stem cells. Subcutaneous implantation of the composite scaffolds at the dorsa of athymic nude mice demonstrated that they facilitated the ectopic bone tissue regeneration. The results indicated the DEX-loaded BCP NPs/collagen composite scaffolds had high potential for bone TE.

Statement of significance

Scaffolds play a crucial role for regeneration of large bone defects. Biomimetic scaffolds having the same composition of natural bone and a controlled release of osteoinductive factors are desirable for promotion of bone regeneration. In this study, composite scaffolds of collagen and biphasic CaP nanoparticles (BCP NPs) with a controlled release nature of dexamethasone (DEX) were prepared and their porous structures were controlled by using ice particulates. In vitro cell culture and in vivo implantation experiments demonstrated the composite scaffolds exerted synergistic effects on the osteogenic differentiation of hMSCs and bone regeneration. The composite scaffolds also showed promotive effect on the formation of capillary blood vessels in the regenerated bone. This study is the first research to prepare DEX-loaded BCP NPs/collagen porous composite scaffolds. The superior performance of the composite scaffolds indicates the composite scaffolds should be useful for bone tissue engineering.

中文翻译：

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地塞米松双相磷酸钙纳米粒子/胶原蛋白多孔复合支架的制备及其在骨组织工程中的应用

尽管骨骼是可再生的，但其再生能力有限。对于超过临界尺寸的骨缺损，需要进一步的干预。作为一种有吸引力的策略，已经广泛研究了骨组织工程（骨TE）以修复骨缺损。但是，快速有效地修复大的非愈合性缺损仍然是一个巨大的挑战。具有骨诱导能力和骨传导能力的多功能支架对于固定功能性骨组织再生是理想的。在本研究中，为骨TE准备了胶原和双相磷酸钙纳米颗粒（BCP NPs）的仿生复合支架，并控制了地塞米松（DEX）的释放和受控的孔结构。在制备BCP NP的过程中，将DEX引入BCP NP中，并与胶原蛋白支架杂交，通过使用预制备的冰粒作为致孔剂材料来控制哪些孔结构。复合支架具有良好控制和相互连接的孔结构，高机械强度和DEX的持续释放。当用于人骨髓来源的间充质干细胞的三维培养时，该复合支架显示出良好的生物相容性并促进了hMSC的成骨分化。在无胸腺裸鼠的背部皮下植入复合支架表明，它们促进了异位骨组织的再生。结果表明，装有DEX的BCP NPs /胶原蛋白复合支架具有很高的骨TE潜力。高机械强度和DEX的持续释放。当用于人骨髓来源的间充质干细胞的三维培养时，该复合支架显示出良好的生物相容性并促进了hMSC的成骨分化。在无胸腺裸鼠的背部皮下植入复合支架表明，它们促进了异位骨组织的再生。结果表明，装有DEX的BCP NPs /胶原蛋白复合支架具有很高的骨TE潜力。高机械强度和DEX的持续释放。当用于人骨髓来源的间充质干细胞的三维培养时，该复合支架显示出良好的生物相容性并促进了hMSC的成骨分化。在无胸腺裸鼠的背部皮下植入复合支架表明，它们促进了异位骨组织的再生。结果表明，装有DEX的BCP NPs /胶原蛋白复合支架具有很高的骨TE潜力。在无胸腺裸鼠的背部皮下植入复合支架表明，它们促进了异位骨组织的再生。结果表明，装有DEX的BCP NPs /胶原蛋白复合支架具有很高的骨TE潜力。在无胸腺裸鼠的背部皮下植入复合支架表明，它们促进了异位骨组织的再生。结果表明，装有DEX的BCP NPs /胶原蛋白复合支架具有很高的骨TE潜力。

重要声明

支架在大骨缺损的再生中起着至关重要的作用。具有相同的天然骨组成和受控释放的骨诱导因子的仿生支架对于促进骨再生是理想的。在这项研究中，制备了具有地塞米松（DEX）控释性质的胶原蛋白和双相CaP纳米颗粒（BCP NPs）复合支架，并使用冰颗粒控制了它们的多孔结构。体外细胞培养和体内植入实验表明，复合支架对hMSCs的成骨分化和骨再生具有协同作用。复合支架还显示出对再生骨中毛细血管形成的促进作用。这项研究是制备载有DEX的BCP NP /胶原多孔复合支架的第一项研究。复合支架的优越性能表明复合支架应可用于骨组织工程。