Department of Chemical and Biological Engineering, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China; Polymeric Materials Research Group, Department of Materials Science and Engineering, Sharif University of Technology, Tehran, P.O. Box 11155-9466, Iran.
Department of Physics, Department of Materials Science and Engineering, Department of Biomedical Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China.
Int J Biol Macromol. 2022 Apr 30;205:638-650. doi: 10.1016/j.ijbiomac.2022.02.115. Epub 2022 Feb 23.
We report a chitosan-based nanocomposite thermogel with superior shear modulus resembling that of cartilage and dual pro-chondrogenic and anti-inflammatory functions. Two therapeutic agents, kartogenin (KGN) and diclofenac sodium (DS), are employed to promote chondrogenesis of stem cells and suppress inflammation, respectively. To extend the release time in a controlled manner, KGN is encapsulated in the uniform-sized starch microspheres and DS is loaded into the halloysite nanotubes. Both drug carriers are doped into the maleimide-modified chitosan hydrogel to produce a shear modulus of 167 ± 5 kPa that is comparable to that of articular cartilage (50-250 kPa). Owing to the hydrogel injectability and relatively suitable gelation time (5 ± 0.5 min) at 37 °C, this system potentially constitutes a manageable platform for clinical practice. Moreover, sustained linear drug release for over a month boosts chondro-differentiation of stem cells to eliminate the necessity for multiple administrations. Considering virtues such as thermogel strength and ability to co-deliver anti-inflammatory and chondro-inductive biomolecules continuously, the materials and strategy have promising potential in functional cartilage tissue engineering.
我们报告了一种壳聚糖基纳米复合温敏水凝胶，其具有类似于软骨的优异剪切模量和双重促软骨生成和抗炎功能。两种治疗剂，即 Kartogenin（KGN）和双氯芬酸钠（DS），分别用于促进干细胞的软骨生成和抑制炎症。为了以可控的方式延长释放时间，将 KGN 包封在均匀尺寸的淀粉微球中，将 DS 载入到埃洛石纳米管中。将两种药物载体掺杂到马来酰亚胺修饰的壳聚糖水凝胶中，产生的剪切模量为 167 ± 5 kPa，与关节软骨（50-250 kPa）相当。由于水凝胶的可注射性和在 37°C 时相对合适的凝胶时间（5 ± 0.5 分钟），该系统有可能成为临床实践的可控平台。此外，超过一个月的持续线性药物释放促进了干细胞的软骨分化，从而消除了多次给药的必要性。考虑到温敏水凝胶的强度以及能够持续共递送抗炎和软骨诱导生物分子的能力等优点，这些材料和策略在功能性软骨组织工程中具有广阔的应用前景。
