Institute of Translational Medicine, Shanghai University, Shanghai, 200444, China.
Organoid Research Center, Shanghai University, Shanghai, 200444, China.
Mater Horiz. 2024 Mar 18;11(6):1465-1483. doi: 10.1039/d3mh01581e.
Osteoarthritis (OA) is a common joint disease known for cartilage degeneration, leading to a substantial burden on individuals and society due to its high disability rate. However, current clinical treatments for cartilage defects remain unsatisfactory due to the unclear mechanisms underlying cartilage regeneration. Tissue engineering hydrogels have emerged as an attractive approach in cartilage repair. Recent research studies have indicated that stem cells can sense the mechanical strength of hydrogels, thereby regulating their differentiation fate. In this study, we present the groundbreaking construction of dual-network DNA-silk fibroin (SF) hydrogels with controllable surface rigidity. The supramolecular networks, formed through DNA base-pairing, induce the development of β-sheet structures by constraining and aggregating SF molecules. Subsequently, SF was cross-linked horseradish peroxidase (HRP)-mediated enzyme reactions to form the second network. Experimental results demonstrated a positive correlation between the surface rigidity of dual-network DNA-SF hydrogels and the DNA content. Interestingly, it was observed that dual-network DNA-SF hydrogels with moderate surface rigidity exhibited the highest effectiveness in facilitating the migration of bone marrow mesenchymal stem cells (BMSCs) and their chondrogenic differentiation. Transcriptome sequencing further confirmed that dual-network DNA-SF hydrogels primarily enhanced chondrogenic differentiation of BMSCs by upregulating the Wnt and TGF-β signaling pathways while accelerating collagen II synthesis. Furthermore, studies revealed that dual-network DNA-SF hydrogels with moderate surface rigidity significantly accelerated cartilage regeneration. In summary, the dual-network DNA-SF hydrogels represent a promising and novel therapeutic strategy for cartilage regeneration.
骨关节炎（OA）是一种常见的关节疾病，以软骨退化为特征，由于其高致残率，给个人和社会带来了巨大负担。然而，由于软骨再生的机制尚不清楚，目前针对软骨缺损的临床治疗方法仍不尽如人意。组织工程水凝胶已成为软骨修复的一种有吸引力的方法。最近的研究表明，干细胞可以感知水凝胶的机械强度，从而调节其分化命运。在这项研究中，我们提出了具有可控表面硬度的双网络 DNA-丝素纤维（SF）水凝胶的开创性构建。通过 DNA 碱基配对形成的超分子网络通过约束和聚集 SF 分子来诱导β-折叠结构的形成。随后，SF 通过辣根过氧化物酶（HRP）介导的酶反应交联形成第二个网络。实验结果表明，双网络 DNA-SF 水凝胶的表面硬度与 DNA 含量之间存在正相关关系。有趣的是，观察到具有中等表面硬度的双网络 DNA-SF 水凝胶在促进骨髓间充质干细胞（BMSCs）迁移及其软骨分化方面最有效。转录组测序进一步证实，双网络 DNA-SF 水凝胶主要通过上调 Wnt 和 TGF-β 信号通路，同时加速胶原 II 合成，增强 BMSCs 的软骨分化。此外，研究表明，具有中等表面硬度的双网络 DNA-SF 水凝胶可显著加速软骨再生。总之，双网络 DNA-SF 水凝胶为软骨再生提供了一种有前途的新的治疗策略。
