基于干细胞的疗法在治疗膝骨关节炎(KOA)中有望实现软骨再生。已经开发了可注射水凝胶来模拟细胞外基质(ECM)并促进干细胞生长,扩散,和差异化。然而,这些水凝胶面临的限制,如机械强度差,生物相容性不足,和次优的生物降解性,共同阻碍它们在软骨再生中的有效性。这项研究介绍了一种注射剂,可生物降解,以及由壳聚糖-PEG和PEG-二醛组成的用于干细胞递送的自修复水凝胶。这种水凝胶可以通过在生理温度下注射混合两种聚合物溶液而原位形成,在凝胶化过程中封装人脂肪来源的干细胞(hADSC)。具有大孔径的3D多孔结构,最佳机械性能,生物降解性,易于注射,和快速的自我修复能力,水凝胶支持生长,扩散,和hADSC的分化。值得注意的是,封装的hADSC在增殖过程中形成3D球状体,随着水凝胶降解,它们的尺寸随时间增加,同时保持高活力至少10天。此外,与在2D表面上培养的那些相比,封装在该水凝胶中的hADSC表现出软骨形成分化基因和蛋白质的上调表达。这些特性使得壳聚糖-PEG/PEG-二醛水凝胶-干细胞构建体适于通过微创注射直接植入,增强KOA和其他基于细胞的治疗的基于干细胞的治疗。
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.