Injectable biodegradable polysaccharide-based hydrogels for stem cell delivery and cartilage regeneration

Current knee osteoarthritis (KOA) treatments mainly provide symptom relief rather than cartilage repair. While regenerative medicine using stem cell therapy holds promise for tissue regeneration and joint function restoration, a significant challenge lies in the efficient and minimally invasive delivery of stem cells to target sites and ensuring high regenerative efficacy. This challenge stems from issues such as cell leakage and reduced cellular activity post-transplantation. In this study, we report the development of an injectable polysaccharide hydrogel (termed Ald-HA/Suc-CS), which is compatible with cells and tissues, and will be suitable to support the proliferation of human adipose-derived stem cells (hADSCs) for cartilage regeneration. The hydrogel is formed on-site at the defect site of articular cartilage by mixing two injectable polymer solutions at physiological temperature post-injection. During the gelation process, hADSCs contained in one of the polymer solutions are encapsulated in the hydrogel. The hydrogel is tailored to create a desired microenvironment with mechanical properties, pore size, and degradation rate suitable for supporting hADSC viability and function. We demonstrated that nearly all of the encapsulated hADSCs remained viable 14 days post-injection and exhibited increased expression of chondrogenic differentiation genes compared to those cultured on 2D surfaces. This hydrogel holds great promise to improve the efficacy of KOA treatment and is potentially applicable to other cell-based therapies.