Injury of articular cartilage leads to an imbalance in tissue homeostasis, and due to the poor self-healing capacity of cartilage the affected tissue often exhibits osteoarthritic changes. In recent years, injectable and highly tunable composite hydrogels for cartilage tissue engineering and drug delivery have been introduced as a desirable alternative to invasive treatments. In this study, we aimed to formulate injectable hydrogels for drug delivery and cartilage tissue engineering by combining different concentrations of hyaluronic acid-tyramine (HA-Tyr) with regenerated silk-fibroin (SF) solutions. Upon enzymatic crosslinking, the gelation and mechanical properties were characterized over time. To evaluate the effect of the hydrogel compositions and properties on extracellular matrix (ECM) deposition, bovine chondrocytes were embedded in enzymatically crosslinked HA-Tyr/SF composites (in further work abbreviated as HA/SF) or HA-Tyr hydrogels. We demonstrated that all hydrogel formulations were cytocompatible and could promote the expression of cartilage matrix proteins allowing chondrocytes to produce ECM, while the most prominent chondrogenic effects were observed in hydrogels with HA20/SF80 polymeric ratios. Unconfined mechanical testing showed that the compressive modulus for HA20/SF80 chondrocyte-laden constructs was increased almost 10-fold over 28 days of culture in chondrogenic medium which confirmed the superior production of ECM in this hydrogel compared to other hydrogels in this study. Furthermore, in hydrogels loaded with anabolic and anti-inflammatory drugs, HA20/SF80 hydrogel showed the longest and the most sustained release profile over time which is desirable for the long treatment duration typically necessary for osteoarthritic joints. In conclusion, HA20/SF80 hydrogels were successfully established as a suitable injectable biomaterial for cartilage tissue engineering and drug delivery applications.

关节软骨损伤导致组织稳态失衡，并且由于软骨的自愈能力差，受影响的组织通常表现出骨关节炎变化。近年来，已引入用于软骨组织工程和药物递送的可注射且高度可调的复合水凝胶，作为侵入性治疗的理想替代方案。在这项研究中，我们旨在通过结合不同浓度的透明质酸-酪胺（HA-Tyr）与再生的丝素蛋白（SF）溶液来配制用于药物输送和软骨组织工程的可注射水凝胶。在酶促交联时，随时间表征凝胶化和机械性能。为了评估水凝胶的组成和性质对细胞外基质（ECM）沉积的影响，将牛软骨细胞包埋在酶促交联的HA-Tyr / SF复合材料（在进一步的工作中缩写为HA / SF）或HA-Tyr水凝胶中。我们证明了所有水凝胶制剂均具有细胞相容性，并且可以促进软骨基质蛋白的表达，从而允许软骨细胞产生ECM，而在具有HA20 / SF80聚合物比例的水凝胶中观察到最显着的软骨形成作用。无限制的机械测试表明，在软骨形成培养基中培养28天后，载有HA20 / SF80软骨细胞的构建体的压缩模量几乎提高了10倍，这证实了该水凝胶中ECM的产量比本研究中的其他水凝胶优越。此外，在载有合成代谢和抗炎药的水凝胶中，随着时间的推移，HA20 / SF80水凝胶显示出最长和最持久的释放曲线，这对于骨关节炎关节通常需要的较长治疗时间是理想的。总之，HA20 / SF80水凝胶已成功建立为适合软骨组织工程和药物输送应用的可注射生物材料。