Systemic Humoral Activation Facilitates Tissue Regeneration by D-Chiral Biomaterial Scaffolds

The study demonstrates that D-chiral Microporous Annealed Particle (DMAP) scaffolds can promote dermal appendage regeneration by engaging humoral immunity, rather than relying solely on T lymphocyte responses. In a full-thickness wound model, DMAP scaffolds facilitated regeneration even with limited lymphocyte infiltration, indicating that adaptive immune cells are not essential. Instead, DMAP activated B cells in skin-draining lymph nodes, leading to germinal center formation and production of biomaterial-specific antibodies and pro-regenerative systemic factors. This systemic response was sufficient for regenerative healing in wounds treated with biomaterials that support collagen repair but not hair follicle regeneration. The findings highlight the role of humoral immunity in biomaterial-induced regeneration and suggest new avenues for leveraging systemic factors in tissue repair.