Lin Xiaojie, Liu Ruofan, Beitzel Jacob, Zhou Yang, Lagadon Chloe, Zhang Miqin
Department of Materials Science and Engineering, University of Washington, Seattle, WA 98195, USA.
Department of Neurological Surgery, University of Washington, Seattle, WA 98195, USA.
Gels. 2024 Aug 1;10(8):508. doi: 10.3390/gels10080508.
Stem cell-based therapy holds promise for cartilage regeneration in treating knee osteoarthritis (KOA). Injectable hydrogels have been developed to mimic the extracellular matrix (ECM) and facilitate stem cell growth, proliferation, and differentiation. However, these hydrogels face limitations such as poor mechanical strength, inadequate biocompatibility, and suboptimal biodegradability, collectively hindering their effectiveness in cartilage regeneration. This study introduces an injectable, biodegradable, and self-healing hydrogel composed of chitosan-PEG and PEG-dialdehyde for stem cell delivery. This hydrogel can form in situ by blending two polymer solutions through injection at physiological temperature, encapsulating human adipose-derived stem cells (hADSCs) during the gelation process. Featuring a 3D porous structure with large pore size, optimal mechanical properties, biodegradability, easy injectability, and rapid self-healing capability, the hydrogel supports the growth, proliferation, and differentiation of hADSCs. Notably, encapsulated hADSCs form 3D spheroids during proliferation, with their sizes increasing over time alongside hydrogel degradation while maintaining high viability for at least 10 days. Additionally, hADSCs encapsulated in this hydrogel exhibit upregulated expression of chondrogenic differentiation genes and proteins compared to those cultured on 2D surfaces. These characteristics make the chitosan-PEG/PEG-dialdehyde hydrogel-stem cell construct suitable for direct implantation through minimally invasive injection, enhancing stem cell-based therapy for KOA and other cell-based treatments.
基于干细胞的疗法有望用于治疗膝关节骨关节炎（KOA）的软骨再生。已开发出可注射水凝胶来模拟细胞外基质（ECM），并促进干细胞的生长、增殖和分化。然而，这些水凝胶存在机械强度差、生物相容性不足和生物降解性欠佳等局限性，共同阻碍了它们在软骨再生中的有效性。本研究介绍了一种由壳聚糖-聚乙二醇（chitosan-PEG）和聚乙二醇二醛（PEG-dialdehyde）组成的可注射、可生物降解且能自我修复的水凝胶，用于干细胞递送。这种水凝胶可通过在生理温度下注射将两种聚合物溶液混合原位形成，在凝胶化过程中包裹人脂肪来源干细胞（hADSCs）。该水凝胶具有大孔径的三维多孔结构、最佳机械性能、生物降解性、易于注射性和快速自我修复能力，支持hADSCs的生长、增殖和分化。值得注意的是，包裹的hADSCs在增殖过程中形成三维球体，其大小随时间增加，同时水凝胶降解，且至少10天内保持高活力。此外，与在二维表面培养的hADSCs相比，包裹在这种水凝胶中的hADSCs软骨分化基因和蛋白的表达上调。这些特性使得壳聚糖-PEG/聚乙二醇二醛水凝胶-干细胞构建体适合通过微创注射直接植入，增强了基于干细胞的KOA治疗及其他基于细胞的治疗。
