TGF-1-Modified Hyaluronic Acid/Poly(glycidol) Hydrogels for Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

In cartilage regeneration, the biomimetic functionalization of hydrogels with growth factors is a promising approach to improve the in vivo performance and furthermore the clinical potential of these materials. In order to achieve this without compromising network properties, multifunctional linear poly(glycidol) acrylate (PG-Acr) is synthesized and utilized as crosslinker for hydrogel formation with thiol-functionalized hyaluronic acid via Michael-type addition. As proof-of-principle for a bioactivation, transforming growth factor-beta 1 (TGF-1) is covalently bound to PG-Acr via Traut's reagent which does not compromise the hydrogel gelation and swelling behavior. Human mesenchymal stromal cells (MSCs) embedded within these bioactive hydrogels show a distinct dose-dependent chondrogenesis. Covalent incorporation of TGF-1 significantly enhances the chondrogenic differentiation of MSCs compared to hydrogels with supplemented noncovalently bound TGF-1. The observed chondrogenic response is similar to standard cell culture with TGF-1 addition with each medium change. In general, multifunctional PG-Acr offers the opportunity to introduce a range of biomimetic modifications (peptides, growth factors) into hydrogels and, thus, appears as an attractive potential material for various applications in regenerative medicine.