Growth factor–loaded sulfated microislands in granular hydrogels promote hMSCs migration and chondrogenic differentiation
Open access
Date
2023-08Type
- Journal Article
Abstract
Cell-based therapies for articular cartilage lesions are expensive and time-consuming; clearly, a one-step procedure to induce endogenous repair would have significant clinical benefits. Acellular heterogeneous granular hydrogels were explored for their injectability, cell-friendly cross-linking, and ability to promote migration, as well as to serve as a scaffold for depositing cartilage extracellular matrix. The hydrogels were prepared by mechanical sizing of bulk methacrylated hyaluronic acid (HAMA) and bulk HAMA incorporating sulfated HAMA (SHAMA). SHAMA's negative charges allowed for the retention of positively charged growth factors (GFs) (e.g., TGFB3 and PDGF-BB). Mixtures of HAMA and GF-loaded SHAMA microgels were annealed by enzymatic cross-linking, forming heterogeneous granular hydrogels with GF deposits. The addition of GF loaded sulfated microislands guided cell migration and enhanced chondrogenesis. Granular heterogeneous hydrogels showed increased matrix deposition and cartilage tissue maturation compared to bulk or homogeneous granular hydrogels. This advanced material provides an ideal 3D environment for guiding cell migration and differentiation into cartilage. Statement of significance: Acellular materials which promote regeneration are of great interest for repair of cartilage defects, and they are more cost- and time-effective compared to current cell-based therapies. Here we develop an injectable, granular hydrogel system which promotes cell migration from the surrounding tissue, facilitating endogenous repair. The hydrogel architecture and chemistry were optimized to increase cell migration and extracellular matrix deposition. The present study provides quantitative data on the effect of microgel size and chemical modification on cell migration, growth factor retention and tissue maturation. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000622910Publication status
publishedExternal links
Journal / series
Acta BiomaterialiaVolume
Pages / Article No.
Publisher
ElsevierSubject
Microgels; Cartilage; Regeneration; Growth factors; Cell migration; HydrogelsOrganisational unit
03949 - Zenobi-Wong, Marcy / Zenobi-Wong, Marcy
Funding
885797 - AptoGEL: A 3D Platform for Mesenchymal Stem Cell Homing (EC)
192656 - Zwitterionic Materials for Treatment of Osteoarthritis (SNF)
More
Show all metadata