A hierarchical biomimetic periosteum combined immunomodulatory and osteogenic functions for bone regeneration
A hierarchical biomimetic periosteum combined immunomodulatory and osteogenic functions for bone regeneration
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DOI：
10.1016/j.compositesb.2022.110099
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发表时间：
2022-07
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影响因子：
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通讯作者：
Xiaoming Li;Shuang Yang;ShaoChuang Wang;Shidan Li;Hao Jiang;Wenhui Hu;Ping Liu;Qijie Dai;Bo Zhang;Yanfeng Luo;S. Dong
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作者：
Xiaoming Li;Shuang Yang;ShaoChuang Wang;Shidan Li;Hao Jiang;Wenhui Hu;Ping Liu;Qijie Dai;Bo Zhang;Yanfeng Luo;S. Dong
在骨再生过程中，骨膜在免疫调节和成骨方面起着不可或缺的作用。天然骨膜具有分层结构，其中外部纤维层由平行排列的纤维组织组成，而在内部形成层中发现无序的纳米纤维。在此，受骨膜的纳米结构/功能的启发，我们设计了一种以定向方式排列的胶原蛋白膜（CMalig），以模拟天然骨膜的纤维层，从而促进M1-M2表型巨噬细胞的转变。随机取向的细胞膜（CMrand）模拟形成层，促进内源性骨祖细胞的成骨分化。CMalig可诱导RAW 264.7细胞M2极化，在股骨缺损处可见大量的CD 206 +F4/80+细胞。CMrand促进骨膜干细胞的成骨分化和异位骨形成。这些异位骨化也在大鼠跟腱缺损模型中得到验证。具有层次结构的仿生骨膜显著促进大鼠股骨缺损模型中新骨的形成。这些结果表明，具有免疫调节和成骨功能的分层结构仿生骨膜可以作为自体骨膜移植的替代品。
The periosteum plays an indispensable role in immunomodulation and osteogenesis during bone regeneration. The natural periosteum has a hierarchical structure, in which the outer fibrous layer is composed of fibrous tissue arranged in parallel, while disorganized nanofibers are found in the inner cambium layer. Herein, inspired by the nanostructure/function of the periosteum, we designed a collagen membrane aligned in an oriented manner (CMalig) to mimic the fibrous layer of the natural periosteum and thereby facilitate the M1-to-M2 phenotypic macrophage transition. The randomly oriented nanofiber membrane (CMrand) simulated the cambium layer and promoted the osteogenic differentiation of endogenous bone progenitor cells. CMaliginduced the M2 polarization of RAW 264.7 cellsin vitro, and numerous CD206+F4/80+cells were observed at femur defect sites after CMaligtreatment. CMrandpromoted the osteogenic differentiation of periosteal stem cells and ectopic bone formation in a subcutaneous implantation model. These heterotopic ossifications were also verified in a rat Achilles tendon defect model. The biomimetic periosteum with a hierarchical structure significantly accelerated new bone formation in the rat femur defect model. These results suggest that the hierarchically structured biomimetic periosteum with immunomodulatory and osteogenic functions can be used as an alternative to periosteal autografts.