A New Way to Engineer Cell Sheets for Articular Cartilage Regeneration

(1) Background: Articular cartilage has limited self-repair capacity. While thermoresponsive pNIPAAm-based Cell Sheet Engineering (CSE) is a promising scaffold-free strategy, its inherent material properties pose limitations. This study developed and validated a novel, non-thermoresponsive CSE platform for functional cartilage regeneration. (2) Methods: A culture platform was fabricated by grafting the biocompatible polymer γ-PGA and a disulfide-containing amino acid onto porous PET membranes. This design enables intact cell sheet detachment with its native extracellular matrix (ECM) via specific cleavage of the disulfide bonds by a mild reducing agent. (3) Results: The hydrated substrate exhibited a biomimetic stiffness (~16.2 MPa) that closely mimics native cartilage. The platform showed superior biocompatibility and supported the cultivation of multi-layered rabbit chondrocyte sheets rich in Collagen II and Glycosaminoglycans. Critically, in a rabbit full-thickness defect model, transplanted autologous cell sheets successfully regenerated integrated, hyaline-like cartilage at 12 weeks, as confirmed by MRI, CT, and histological analyses. (4) Conclusions: This novel CSE platform, featuring highly biomimetic stiffness and a gentle, chemically specific detachment mechanism, represents a highly promising clinical strategy for repairing articular cartilage defects.