J Biomed Mater Res A. 2026 Nov;114(11):e70182. doi: 10.1002/jbm.a.70182.
ABSTRACT
Enzyme therapeutics are often limited by poor stability, rapid clearance, and systemic effects that reduce therapeutic efficacy and necessitate high dosing. Enzyme-biomaterial conjugation can address these limitations and improve outcomes by localizing therapeutics at the tissue site of intended action. In particular, indoleamine 2,3-dioxygenase (IDO), a potent immunomodulatory enzyme, has demonstrated therapeutic effectiveness when retained locally at sites of inflammation through fusion to a carbohydrate-binding protein. Here, we report a complementary biomaterial-mediated delivery strategy to prolong retention time and investigate efficacy in an imiquimod-induced model of psoriasis. IDO maintained enzyme activity after bioconjugation to polyethylene glycol maleimide (PEG-MAL) microgels. Localized delivery of IDO-conjugated microgels reduced psoriatic scores compared to soluble IDO or unconjugated microgels. Additionally, fibrotic capsule thickness decreased 30% in the IDO-conjugated microgel group compared to the unconjugated microgel. These findings demonstrate the efficacy of localized IDO delivery via covalent attachment to granular hydrogels, which may serve as a platform for other immunomodulatory enzymes.
PMID:42968485 | DOI:10.1002/jbm.a.70182