Engineered materials for spatiotemporal regulation of monocyte and macrophage recruitment

Abstract

Significant advances have been made in the development of materials that better mimic native tissues through incorporation of biofunctionality, transplantation of exogenous cells, and recapitulation of host tissue mechanical properties. While these advances have generated promising pre-clinical results, biomaterial implantation still faces several challenges, including proper integration into host tissue, vascularization, and circumventing fibrotic responses. Materials that balance the reparative and inflammatory functions of endogenous immune cells represent a promising approach to enhance the efficacy of biomaterial-based regenerative strategies. The objective of this work was to engineer materials that tune myeloid cell recruitment and function to improve post-injury revascularization and tissue repair. We identified a population of monocytes that selectively generates alternatively activated, wound healing macrophages. Subsequently, we examined the effect of biomolecule delivery and adhesive ligand presentation on myeloid cell recruitment. Local delivery of FTY720, a small molecule agonist of sphingosine-1-phosphate receptors, enhanced accumulation of reparative monocytes and macrophages, and promoted revascularization of ischemic and volumetric muscle injuries. We also explored the temporal progression of myeloid cell recruitment in response to adhesive ligand functionalization and angiogenic growth factor delivery from degradable poly(ethylene glycol) hydrogels. These results provide new mechanistic insight and tools to leverage endogenous monocyte and macrophage populations during tissue repair.