Mechanical Signal-Tailored Hydrogel Microspheres Recruit and Train Stem Cells for Precise Differentiation

Adv Mater. 2023 Oct;35(40):e2300180. doi: 10.1002/adma.202300180. Epub 2023 Jun 4.

Abstract

The aberrant mechanical microenvironment in degenerated tissues induces misdirection of cell fate, making it challenging to achieve efficient endogenous regeneration. Herein, a hydrogel microsphere-based synthetic niche with integrated cell recruitment and targeted cell differentiation properties via mechanotransduction is constructed . Through the incorporation of microfluidics and photo-polymerization strategies, fibronectin (Fn) modified methacrylated gelatin (GelMA) microspheres are prepared with the independently tunable elastic modulus (1-10Kpa) and ligand density (2 and 10 µg mL-1 ), allowing a wide range of cytoskeleton modulation to trigger the corresponding mechanobiological signaling. The combination of the soft matrix (2Kpa) and low ligand density (2 µg mL-1 ) can support the nucleus pulposus (NP)-like differentiation of intervertebral disc (IVD) progenitor/stem cells by translocating Yes-associated protein (YAP), without the addition of inducible biochemical factors. Meanwhile, platelet-derived growth factor-BB (PDGF-BB) is loaded onto Fn-GelMA microspheres (PDGF@Fn-GelMA) via the heparin-binding domain of Fn to initiate endogenous cell recruitment. In in vivo experiments, hydrogel microsphere-niche maintained the IVD structure and stimulated matrix synthesis. Overall, this synthetic niche with cell recruiting and mechanical training capabilities offered a promising strategy for endogenous tissue regeneration.

Keywords: cell recruitment; hydrogel microspheres; mechanotransduction; microfluidics; stem cell differentiation.

MeSH terms

  • Cell Differentiation
  • Gelatin / chemistry
  • Hydrogels* / chemistry
  • Ligands
  • Mechanotransduction, Cellular*
  • Microspheres
  • Stem Cells

Substances

  • Hydrogels
  • Ligands
  • Gelatin