The mitochondrial protectant SS31 optimized decellularized Wharton's jelly scaffold improves allogeneic chondrocyte implantation-mediated articular cartilage repair

• Published in: Journal of Orthopaedic Translation
• Main Authors: Chao Wang, Hao Li, Fakai Li, Yongkang Yang, Ziheng Xu, Tianze Gao, Runmeng Li, Ruiyang Zhang, Yuhao Mu, Zheng Guo, Quanyi Guo, Shuyun Liu
• Format: Article
• Language: English
• Published: Elsevier 2025-05-01
• Subjects: Articular cartilage; Decellularized Wharton jelly; SS31 peptide; ACI; Regenerative medicine
• Online Access: http://www.sciencedirect.com/science/article/pii/S2214031X25000592

Background: The process of allogeneic chondrocyte implantation entails obtaining donor chondrocytes, culturing them in a medium enriched with growth factors, and then introducing them-either individually or in conjunction with biocompatible scaffolds-into areas of cartilage damage. While promising, this approach is hindered by mitochondrial dysfunction in the implanted chondrocytes. Methods: This research introduced an innovative approach by creating a new type of scaffold derived from Decellularized Umbilical Cord Wharton's Jelly (DUCWJ) extracted from human umbilical cords. The scaffold was manufactured using procedures involving decellularization and lyophilization. The resulting scaffold demonstrated superior characteristics, including high porosity, hydrophilic properties, and excellent biocompatibility. To enhance its function, SS31 peptides, known for their mitochondrial-protective properties, were chemically bonded to the scaffold surface, creating an SS31@DUCWJ system. This system aims to protect chondrocytes and regulate the mitochondrial respiratory chain (MRC), thereby improving cartilage repair mediated by allogeneic chondrocyte implantation. Results: In vitro studies have shown that SS31 effectively attenuates metabolic dysfunction, extracellular matrix degradation, oxidative stress, inflammation, and mitochondrial damage induced by serial cell passages. Complementary in vivo experiments showed that the SS31@DUCWJ scaffold promoted regeneration of healthy articular cartilage in femoral condylar defects in rabbits. Conclusions: This SS31-modified porous decellularized scaffold represents an innovative biomaterial with anti-inflammatory properties and targeted mitochondrial regulation. It offers a promising new approach for treating articular cartilage injuries. The translational potential of this article: Our study was the first to successfully load the mitochondrial protectant SS31 onto a DUCWJ hydrogel scaffold for localized drug delivery. This method is highly efficacious in repairing cartilage defects and offers a promising new avenue for the treatment of such conditions.