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...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.展开更多
基金supported by the National Natural Science Foundation of China(No.82130027,81921002,81991505,31900971)Cross Disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202128)Moreover,we thank the Electron Microscopy center of Shanghai Institute of Precision Medicine,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,for their technical support and assistance in the electron microscopy.
文摘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.
