The Polymer Society of Korea

Abstract

Fibrotic lung disease has limited therapies, and delivered mesenchymal stromal cells (MSCs) are rapidly phagocytosed by alveolar macrophages. We encapsulated single MSCs in soft (~3 µm, ~2 kPa) RGD-alginate microgels bearing a CD47 agonist peptide (pCD47), combining a compliant niche with a “don’t-eat-me” signal. In bleomycin-injured mice with acute or chronic fibrosis, pCD47 increased MSC lung half-life from ~13 h to ~100 h via SIRPα, SIRPα blockade removed retention. One dose reduced collagen and improved lung mechanics, whereas unmodified gels were ineffective. scRNA-seq (>20,000 CD45⁺ cells) showed depletion of profibrotic Spp1^hi alveolar macrophages and expansion of a Cd74^hi MHC-II^hi antigen-presenting subset, MHC-II blockade prevented collagen resolution. Soft pCD47 microgels thus prolong MSC residence and reprogram macrophages to reverse established fibrosis. References: Cho et al., Advanced Materials (2025).