The healing process of critical-sized bone defects urges for a suitable biomineralization environment. However, the unsatisfying repair outcome usually results from a disturbed intricate milieu and the lack of in situ mineralization resources. In this work, we have developed a composite hydrogel that mimics the natural bone healing processes and serves as a seedbed for bone regeneration. The oxidized silk fibroin and fibrin are incorporated as rigid geogrids, and amorphous calcium phosphate (ACP) and platelet-rich plasma serve as the fertilizers and loam, respectively. Encouragingly, the seedbed hydrogel demonstrates excellent mechanical and biomineralization properties as a stable scaffold and promotes vascularized bone regeneration in vivo. Additionally, the seedbed serves a succinate-like function via the PI3K-Akt signaling pathway and subsequently orchestrates the mitochondrial calcium uptake, further converting the exogenous ACP into endogenous ACP. Additionally, the seedbed hydrogel realizes the succession of calcium resources and promotes the evolution of the biotemplate from fibrin to collagen. Therefore, our work has established a novel silk-based hydrogel that functions as an in-situ biomineralization seedbed, providing a new insight for critical-sized bone defect regeneration.

中文翻译：

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一种可注射的丝基水凝胶作为用于临界尺寸骨缺损再生的新型生物矿化苗床

临界尺寸骨缺损的愈合过程迫切需要合适的生物矿化环境。然而，修复效果并不令人满意，通常是由于复杂的环境干扰和原位矿化资源的缺乏造成的。在这项工作中，我们开发了一种复合水凝胶，可以模仿自然骨愈合过程，并作为骨再生的苗床。氧化丝素蛋白和纤维蛋白被纳入刚性土工格栅，无定形磷酸钙（ACP）和富含血小板的血浆分别用作肥料和壤土。令人鼓舞的是，苗床水凝胶作为稳定的支架表现出优异的机械和生物矿化特性，并促进体内血管化骨再生。此外，苗床通过 PI3K-Akt 信号通路发挥类似琥珀酸的功能，随后协调线粒体钙吸收，进一步将外源 ACP 转化为内源 ACP。此外，苗床水凝胶实现了钙资源的连续性，促进了生物模板从纤维蛋白到胶原蛋白的进化。因此，我们的工作建立了一种新型丝基水凝胶，可作为原位生物矿化苗床，为临界尺寸的骨缺损再生提供新的见解。