Adequate bone regeneration has been difficult to achieve at segmental bone defects caused by disease. The surface structure and phase composition of calcium phosphate bioceramic are crucial for its bioactivity and osteoinductivity. In the present study, biphasic calcium phosphate (BCP) bioceramics composed of micro-whiskers and nanoparticles hybrid-structured surface (hBCP) were fabricated via a hydrothermal reaction. The in vivo long bone defect model of beagle dogs implanted with hBCP bioceramics achieved a higher quality regenerated bone as compared to the traditional smooth-surface BCP control group. After a 12-week implantation period, more new bone formation within the implanted material and a higher fracture load were observed in the hBCP group (p < 0.05 vs. control). In addition, the local bone integration efficacy, as determined by nanoindentation, showed a significantly closer elastic modulus of the implanted hBCP bioceramics to that of the natural bone adjacent. Finally, in vitro gene microarray analysis of the mesenchymal stem cells (MSCs) co-cultured with two bioceramics showed that the hBCP group induced a drastic downregulation of the genes associated with inflammatory response, which was never documented in previous studies regarding biomaterials with a micro/nano hybrid structure. The tumor necrosis factor (TNF) signalling pathway was the most involved and preferentially inhibited by the hBCP material. Collectively, the findings suggested that the micro/nano hybrid-structured bioceramics augmented local bone regeneration at segmental bone defects and presented a potential alternative to autologous bone grafts.

中文翻译：

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微/纳米混合结构双相磷酸钙生物陶瓷在节段性骨缺损中的骨再生和诱导的MSCs免疫调节

在由疾病引起的节段性骨缺损方面，很难实现足够的骨再生。磷酸钙生物陶瓷的表面结构和相组成对其生物活性和骨诱导能力至关重要。在本研究中，通过水热反应制备了由微晶须和纳米颗粒杂化结构表面（hBCP）组成的双相磷酸钙（BCP）生物陶瓷。在体内与传统的光滑表面BCP对照组相比，植入hBCP生物陶瓷的比格犬长骨缺损模型获得了更高质量的再生骨。植入12周后，在hBCP组中观察到植入材料中更多的新骨形成和更高的骨折负荷（与对照组相比，p <0.05）。另外，通过纳米压痕确定的局部骨整合功效显示，所植入的hBCP生物陶瓷的弹性模量与相邻的天然骨的弹性模量显着接近。最后，体外与两个生物陶瓷共培养的间充质干细胞（MSC）的基因芯片分析表明，hBCP组诱导了与炎症反应相关的基因的急剧下调，这在以前有关具有微/纳米杂化结构的生物材料的研究中从未见过。肿瘤坏死因子（TNF）信号传导途径是最受牵连的，并且优先被hBCP物质抑制。总的来说，研究结果表明，微/纳米混合结构生物陶瓷增强了节段性骨缺损处的局部骨再生，并提供了自体骨移植物的潜在替代物。