Hydrogels with tunable modulus regulate chondrocyte microaggregates growth for cartilage repair.
Jing ChenPeng AnHua ZhangYansheng ZhangHua WeiYang ZhouYabin ZhuPublished in: Biomedical materials (Bristol, England) (2021)
Chondrocyte spheroids in 3D hydrogel are more beneficial to improve their survival and maintain chondrogenic phenotype comparing to dissociated chondrocytes. However, in-situ inducing cell into spheroids rather than encapsulating spheroids in a hydrogel remains a tremendous challenge because of the limitations of biochemical and viscoelastic controllability for hydrogel. Herein, a hydrogel consisting of photo-crosslinkable chitosan methacrylate (CHMA) and semi-interpenetrating polyvinyl alcohol (PVA) is developed as a cell-responsive matrix with controllable viscoelastic properties. The proposed CHMA-PVA precursor preferentially exhibits a weak gel-like state with a storage modulus of 16.9 Pa, loss modulus of 13.0 Pa and yielding stain of 1%, which could allow chondrocyte to vigorously move and assemble but hinder their precipitation before crosslinking. The chondrocytes could form microaggregates within 8 h in vitro and keep high viability. Moreover, subcutaneous implantation experiments demonstrate that the CHMA/PVA hydrogels are biocompatible and degrade within five weeks in vivo. The cell-free hydrogels are further placed in cylindrical cartilage defects in the rabbit femoral condyle and examined 8 weeks postoperatively. Gross, histological and immunohistochemical analyses reveal a significant acceleration for the cartilage regeneration. These findings suggest that this novel cell adhesion-responsive and histo-compatible hydrogel is promising for cartilage regeneration.
Keyphrases
- wound healing
- hyaluronic acid
- drug delivery
- extracellular matrix
- tissue engineering
- cancer therapy
- cell free
- single cell
- drug release
- cell adhesion
- stem cells
- cell therapy
- mesenchymal stem cells
- genome wide
- atomic force microscopy
- gene expression
- mass spectrometry
- dna methylation
- high resolution
- circulating tumor
- quantum dots