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

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 novel 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 crosslinkers. The hydrogels’ stability, swelling behavior, and modulus can be finely tuned by varying the DLD generation, crosslinker valency and length, and dry weight content. In vitro cytocompatibility assessments reveal that the platform supports BMSC viability and interactions, comparable to a control hydrogel gelatin methacryloyl (GelMA). Further evaluation of the best-performing hydrogels composed of second-generation PEG10k-G2-BAPA DLD with either DL-dithiothreitol (DTT) or PEG1k-SH crosslinkers 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 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.