Exploring the Role of Spatial Confinement in Immune Cell Recruitment and Regeneration of Skin Wounds

Abstract Microporous annealed particle (MAP) scaffolds are injectable granular materials comprised of micron sized hydrogel particles (microgels). The diameter of these microgels directly determines the size of the interconnected void space between particles where infiltrating or encapsulated cells reside. This tunable porosity allows the authors to use MAP scaffolds to study the impact of spatial confinement (SC) on both cellular behaviors and the host response to biomaterials. Despite previous studies showing that pore size and SC influence cellular phenotypes, including mitigating macrophage inflammatory response, there is still a gap in knowledge regarding how SC within a biomaterial modulates immune cell recruitment in vivo in wounds and implants. Thus, the immune cell profile within confined and unconfined biomaterials is studied using small (40 µm), medium (70 µm), and large (130 µm) diameter spherical microgels, respectively. This work uncovered that MAP scaffolds impart regenerative wound healing with an IgG1‐biased Th2 response. MAP scaffolds made with large microgels promote a balanced pro‐regenerative macrophage response, resulting in enhanced wound healing with mature collagen regeneration and reduced inflammation levels.