Injectable Dendritic Hydrogels Curable by High-Energy Visible Light for Cell Delivery in Bone Regeneration
Noemí Molina, Francesco Torelli, Samih Mohamed‐Ahmed, Daniel J. Hutchinson, Cecilie Gjerde, Ahmad Rashad, Kamal Mustafa, Michael Malkoch
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.