Assembled granular hydrogels loaded with growth factors for enhanced mesenchymal stem cell therapy in abdominal wall defect repair

Abdominal wall defects caused by trauma, congenital rupture, and intra-abdominal infection remain challenging due to the large wound area and complex complications. Herein, an assembled mesenchymal stem cell (MSCs)-laden granular hydrogel (termed assembled GSD@FPs), loaded with basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), is developed. This hydrogel is constructed through dynamic covalent cross-linking ( via borate ester bonds) among dopamine-grafted gelatin methacrylamide (GelMA-DA), phenylborate-modified hyaluronic acid (HA-PBA), and epigallocatechin-3-gallate (EGCG), serving as multifunctional bulk building blocks for cell delivery and abdominal wall repair. The designed assembled granular hydrogels possess good rheological properties, self-healing, injectability, and tissue-adhesion properties. Detailed in vitro cell experiments are conducted, revealing that the GSD@FPs granular hydrogels can effectively promote cell proliferation, cell migration and angiogenesis. Furthermore, in abdominal wall defects, assembled GSD@FPs significantly accelerates the tissue healing process by simultaneously inhibiting the inflammatory response, promoting collagen deposition, and promoting cell proliferation and angiogenesis. Importantly, the assembled GSD@FPs granular hydrogels can also provide mechanical support and increase the thickness of regenerated tissue (1727.8 ± 169.6 μm for the control group, 3204.2 ± 278.5 μm for the assembled GSD@FPs group at 14 d). Eventually, the GSD granular hydrogels biodegraded, facilitating tissue remodeling and generating new muscle tissues. Therefore, this study provides a promising strategy with great potential for application in abdominal wall repair.