Enhanced scar mitigation via hyperbaric oxygen therapy and immune modulation using nanoparticle-orchestrated photosynthetic chlorella in polysaccharide hydrogels

Immunotherapy for fibroproliferative disorders shows great promise but is often limited by insufficient induction of immune responses. In this study, Chlorella (CHL) stimulates the immune response by activating photosynthetic and oxygen signaling pathways in macrophages, leading to the production of immunostimulatory factors. These processes ultimately led to the inactivation of abnormal fibroblasts by promoting macrophage (M1) infiltration. To further enhance scar immunogenicity, CHL was engineered with cationic nanoparticles (polyethyleneimine (PEI)-polypyrrole (PPy) NPs) and assembled into hyaluronic acid (HA) hydrogels, referred to as HA-CHL-PEI-PPy NPs. Incorporating PEI-PPy NP endowed the resulting HA-CHL-PEI-PPy NPs with photosynthetic capabilities, thereby enhancing the immunogenicity required to eradicate scars. Importantly, the surface-rich reactive sites in the HA-CHL-PEI-PPy NPs hydrogels produced oxygen upon photoirradiation (λ = 660 nm), facilitating mechanically hyperbaric oxygen therapy and enhancing the immune response for advanced anti-scar therapy. Topical administration of HA-CHL-PEI-PPy NPs hydrogels in a single dose effectively managed scars. Collectively, HA-CHL-PEI-PPy NPs hydrogels offer a promising anti-scar treatment by augmenting scar immunogenicity and activating the immune response.