Despite advances in the development of osteo-regenerative biomaterials, current products are vulnerable to stress-induced formation of cracks, resulting in the loss of functionality and a limited lifespan. In the present study, a strategy based on host-guest assembly was developed to fabricate a silk fibroin-based inorganic-organic hybrid hydrogel (termed SF@HG@HA) in which silk fibroin was used as a polymer template to tether host (β-cyclodextrin) and guest (cholesterol) monomers, respectively. Due to dynamic host-guest interactions, the prepared hydrogel could repair itself spontaneously when damaged, without the assistance of any external stimuli, mimicking the self-healing characteristics of native bone tissue. Furthermore, the efficient energy dissipation mechanism provided by the host-guest crosslinking strategy endowed the hydrogel with robust mechanical properties to bear substantial mechanical loading. SF@HG@HA was shown to support cell proliferation and osteogenic differentiation in vitro and accelerate bone regeneration in critical-size rat femoral defects in vivo. Together, the silk fibroin-based self-healing hydrogel with robust mechanical properties shows potential applications in the reconstruction of bone defects, which may provide new directions for the design of functional biomaterials for tissue regeneration.

尽管骨再生生物材料的开发取得了进展，但当前的产品仍容易受到应力诱导的裂纹形成，从而导致功能丧失和使用寿命有限。在本研究中，开发了一种基于宿主-客体组装的策略来制备基于丝素蛋白的无机-有机杂化水凝胶（称为SF @ HG @ HA），其中将丝素蛋白用作拴系宿主的聚合物模板（β -环糊精）和客体（胆固醇）单体。由于动态的主客体相互作用，制得的水凝胶在受损时可以自发修复，而无需任何外部刺激，可以模仿天然骨组织的自我修复特性。此外，主客体交联策略提供的高效能量耗散机制使水凝胶具有强大的机械性能，可以承受较大的机械负荷。SF @ HG @ HA被证明支持细胞增殖和成骨分化在体外并加速体内临界大小大鼠股骨缺损的骨再生。总之，具有强大机械性能的基于丝素蛋白的自修复水凝胶在重建骨缺损中显示出潜在的应用前景，这可能为组织再生的功能性生物材料设计提供新的方向。