Type II collagen as a material-mediated instructive platform: Cartilage regeneration and fibrosis suppression via the Tp63-Cytl1 axis.

Authors

Weicong Zhu, Shaojie Liu, Yusheng Liu, Qiguang Zhong, Hanshuo Zhang, Xiaohang Zheng, Jiake Xu, Xiaohong Yang

Published in

Materials today. Bio. Volume 41. Pages 103700. Epub Sep 23, 2026.

Abstract

A major challenge in cartilage regeneration is maintaining the hyaline cartilage phenotype and matrix over time while limiting hypertrophy and fibrosis. Here, type II collagen (Col2)-hyaluronic acid (Col2H) and type I collagen-hyaluronic acid (Col1H) sponges were compared using long-term three-dimensional chondrocyte culture, cross-species transcriptomic analysis, and functional experiments. Col2H supported longer-term chondrocyte phenotype and matrix retention than Col1H. Cytl1 was prioritized because it ranked highly in Col2H-associated analysis and was consistently downregulated during chondrocyte dedifferentiation in human and rat datasets. Functional assays, ChIP-qPCR, and co-immunoprecipitation supported involvement of an Itgb8-Nov-Tp63-Cytl1 regulatory network in the Col2-associated response. Col2H also showed preliminary cartilage-repair potential in a rabbit defect model. In human osteoarthritis cartilage, a five-gene signature comprising Cytl1, Tp63, Nov, Itgb8, and TIMP3 showed internal stability and an association with histological severity. These findings support a material-associated regulatory role for Col2H in chondrocyte phenotype and matrix maintenance.

PMID:
42861271
Bibliographic data and abstract were imported from PubMed on 12 Oct 2026.

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