Work

Injectable Dendritic Hydrogels Curable by High-Energy Visible Light for Cell Delivery in Bone Regeneration

Year: 2025

Type: article

Abstract: Hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) have emerged as a promising alternative to grafting for bone regeneration in critical-sized fractures and defects. Here, we present a platform for an injectable bone scaffold hydrogel that cures in situ via high-energy visible (HEV) light-induced thiol-ene coupling (TEC) chemistry. The hydrogel platform consists of branched allyl-functionalized dendritic-linear-dendritic (DLD) copolymers, constructed from poly(ethylene glycol) (PEG) and 2,2-bis(hydroxymethyl)propionic acid (bis-MPA), and thiolated cross-linkers. The hydrogels' stability, swelling behavior, and modulus can be finely tuned by varying the DLD generation, cross-linker valency and length, and dry weight content. In vitro cytocompatibility assessments reveal that the platform supports BMSC viability and interactions, comparable to those of a control hydrogel gelatin methacryloyl (GelMA). Further evaluation of the best-performing hydrogels composed of the second-generation PEG10k-G2-BAPA DLD with either dl-dithiothreitol (DTT) or PEG1k-SH cross-linkers demonstrates similar cell metabolic activity to GelMA after 7 days and significant calcium deposition after 14 and 21 days in osteogenic medium. The preferred gel, incorporating DTT, also shows a high capacity for functionalization with inorganic fillers (e.g., hydroxyapatite) and biopolymers (e.g., collagen). Collectively, the results highlight, for the first time, the broad potential of bis-MPA-based dendritic hydrogels as versatile soft biomaterials for regenerative medicine applications.

Source: Chemistry of Materials

DOI: 10.1021/acs.chemmater.5c00063