A New Way to Engineer Cell Sheets for Articular Cartilage Regeneration
Journal
Journal of Functional Biomaterials
Journal Volume
16
Journal Issue
12
Start Page
437
ISSN
2079-4983
Date Issued
2025-11-25
Author(s)
Tan, Ta-Lun
Tseng, Yuan
Li, Jia-Wei
Yang, Cheng-Tse
Lee, Her-I
Liu, Jun-Jen
Yang, Yi-Yuan
Tseng, How
Abstract
Background: Articular cartilage has limited self-repair capacity. While thermoresponsive poly N-isopropyl acrylamide (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. Methods: A culture platform was fabricated by grafting the biocompatible polymer poly gamma-glutamic acid (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. 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. 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.
Subjects
osteoarthritis
cell sheet engineering
non-thermoresponsive
extracellular matrix
Publisher
MDPI AG
Type
journal article