Ding Zhaozhao, Lu Guozhong, Cheng Weinan, Xu Gang, Zuo Baoqi, Lu Qiang, Kaplan David L
National Engineering Laboratory for Modern Silk & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, People's Republic of China.
Department of Burns and Plastic Surgery, The Affiliated Hospital of Jiangnan University, Wuxi 214041, People's Republic of China.
ACS Biomater Sci Eng. 2020 Apr 13;6(4):2357-2367. doi: 10.1021/acsbiomaterials.0c00143. Epub 2020 Mar 25.
Multiple physical cues such as hierarchical microstructures, topography, and stiffness influence cell fate during tissue regeneration. Yet, introducing multiple physical cues to the same biomaterial remains a challenge. Here, a synergistic cross-linking strategy was developed to fabricate protein hydrogels with multiple physical cues based on combinations of two types of silk nanofibers. β-sheet-rich silk nanofibers (BSNFs) were blended with amorphous silk nanofibers (ASNFs) to form composite nanofiber systems. The composites were transformed into tough hydrogels through horseradish peroxidase (HRP) cross-linking in an electric field, where ASNFs were cross-linked with HRP, while BSNFs were aligned by the electrical field. Anisotropic morphologies and higher stiffness of 120 kPa were achieved. These anisotropic hydrogels induced osteogenic differentiation and the aligned aggregation of stem cells in vitro while also exhibiting osteoinductive capacity in vivo. Improved tissue outcomes with the hydrogels suggest promising applications in bone tissue engineering, as the processing strategy described here provides options to form hydrogels with multiple physical cues.
多种物理线索，如分级微观结构、形貌和刚度，在组织再生过程中会影响细胞命运。然而，将多种物理线索引入同一生物材料仍然是一项挑战。在此，开发了一种协同交联策略，以基于两种类型的丝纳米纤维的组合来制备具有多种物理线索的蛋白质水凝胶。富含β-折叠的丝纳米纤维（BSNFs）与无定形丝纳米纤维（ASNFs）混合，形成复合纳米纤维系统。通过在电场中辣根过氧化物酶（HRP）交联，将复合材料转化为坚韧的水凝胶，其中ASNFs与HRP交联，而BSNFs则由电场排列。实现了各向异性形态和120 kPa的更高刚度。这些各向异性水凝胶在体外诱导成骨分化和干细胞的排列聚集，同时在体内也表现出骨诱导能力。水凝胶改善的组织结果表明在骨组织工程中有广阔的应用前景，因为这里描述的加工策略为形成具有多种物理线索的水凝胶提供了选择。
