National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
J Mater Chem B. 2022 Jul 6;10(26):5045-5057. doi: 10.1039/d2tb00564f.
Cartilage tissue has limited self-regeneration capacity and current treatment methods often result in fibrocartilage formation. Although collagen has shown the ability to induce chondrogenesis of mesenchymal stem cells (MSCs) and regenerate hyaline cartilage, the application of a pure collagen hydrogel is inherently limited by its fast degradation, poor mechanical properties and excessive cell-mediated shrinkage. To overcome this challenge, we developed a sonication-induced silk-collagen composite hydrogel (COL + SF(S)) and investigated its physicochemical and biological properties compared with a collagen hydrogel (COL) and a non-sonicated silk-collagen composite hydrogel (COL + SF(NS)). The results showed that the sonication treatment of silk fibroin induced antiparallel β-sheet formation and a stronger negative charge on the silk fibroin molecule, which resulted in improved mechanical properties of the COL + SF(S) hydrogel. The COL + SF(S) hydrogel exhibited superior stability during cell culture and promoted the gene expression of SOX9 at the early stage and sulfated glycosaminoglycan (sGAG) deposition without any exogenous growth factor. Moreover, the cartilage regeneration capacity of the COL + SF(S) group was evaluated in rabbit knee defects. The COL + SF(S) group exhibited well-integrated articular hyaline cartilage closely resembling native articular cartilage after 6 months. Overall, the COL + SF(S) hydrogel holds great potential as a scaffold material to regenerate functional hyaline cartilage.
软骨组织的自我再生能力有限，目前的治疗方法往往导致纤维软骨形成。尽管胶原蛋白已显示出诱导间充质干细胞（MSCs）软骨分化和再生透明软骨的能力，但纯胶原蛋白水凝胶的应用由于其快速降解、较差的机械性能和过度的细胞介导收缩而受到固有限制。为了克服这一挑战，我们开发了一种超声诱导的丝胶原复合水凝胶（COL + SF（S）），并研究了其理化和生物学性质，与胶原蛋白水凝胶（COL）和未经超声处理的丝胶原复合水凝胶（COL + SF（NS））相比。结果表明，丝素蛋白的超声处理诱导了反平行β-折叠形成和丝素蛋白分子上更强的负电荷，从而提高了 COL + SF（S）水凝胶的机械性能。在细胞培养过程中，COL + SF（S）水凝胶表现出更好的稳定性，并在早期促进 SOX9 基因表达和硫酸化糖胺聚糖（sGAG）沉积，而无需任何外源性生长因子。此外，还评估了 COL + SF（S）水凝胶在兔膝关节缺损中的软骨再生能力。COL + SF（S）组在 6 个月后表现出与天然关节软骨紧密结合的整合良好的关节透明软骨。总体而言，COL + SF（S）水凝胶作为一种再生功能性透明软骨的支架材料具有很大的潜力。
