Bioinspired collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold biomimicking native cartilage extracellular matrix facilitates chondrogenesis of human synovium-derived stem cells

Int J Biol Macromol. 2023 Jun 15:240:124400. doi: 10.1016/j.ijbiomac.2023.124400. Epub 2023 Apr 11.

Abstract

The microenvironment plays a crucial role in stem cell differentiation, and a scaffold that mimics native cartilaginous extracellular components can promote chondrogenesis. In this study, a collagen-gelatin-hyaluronic acid-chondroitin sulfate tetra-copolymer scaffold with composition and architecture similar to those of hyaline cartilage was fabricated using a microfluidic technique and compared with a pure gelatin scaffold. The newly designed biomimetic scaffold had a swelling ratio of 1278 % ± 270 %, a porosity of 77.68 % ± 11.70 %, a compressive strength of 1005 ± 174 KPa, and showed a good resilience against compression force. Synovium-derived stem cells (SDSCs) seeded into the tetra-copolymer scaffold attached to the scaffold firmly and exhibited good mitochondrial activity, high cell survival with a pronounced glycosaminoglycan production. SDSCs cultured on the tetra-copolymer scaffold with chondrogenic induction exhibited upregulated mRNA expression of COL2A1, ChM-1, Nrf2, TGF-β1, and BMP-7. Ex vivo study revealed that the SDSC-tetra-copolymer scaffold regenerated cartilage-like tissue in SCID mice with abundant type II collagen and S-100 production. BMP7 and COL2A1 expression in the tetra-copolymer scaffold group was much higher than that in the gelatin scaffold group ex vivo. The tetra-copolymer scaffold thus exhibits strong chondrogenic capability and will facilitate cartilage tissue engineering.

Keywords: Biomimetic scaffold; Cartilage regeneration; Synovium-derived stem cells.

MeSH terms

  • Animals
  • Cartilage
  • Chondrogenesis
  • Chondroitin Sulfates* / pharmacology
  • Collagen / metabolism
  • Extracellular Matrix / metabolism
  • Gelatin / pharmacology
  • Humans
  • Hyaluronic Acid* / pharmacology
  • Mice
  • Mice, SCID
  • Stem Cells
  • Synovial Membrane / metabolism
  • Tissue Engineering / methods
  • Tissue Scaffolds

Substances

  • Hyaluronic Acid
  • Chondroitin Sulfates
  • Gelatin
  • Collagen