Carbon monoxide-releasing Vehicle CO@TPyP-FeMOFs modulating macrophages phenotype in inflammatory wound healing

Abstract

Healing of chronic wounds has been critically limited by prolonged inflammation. Carbon monoxide (CO) is a biologically active molecule with high potential based on its efficacy in modulating inflammation, promoting wound healing and tissue remodeling. Strategies to use CO as a gaseous drug to chronic wounds have emerged, but controlling the sustained release of CO at the wound site remains a major challenge. In this work, a porphyrin-Fe based metal organic frameworks, TPyP-FeMOFs was prepared. The synthesized TPyP-FeMOFs was high-temperature vacuum activated (AcTPyP-FeMOFs) and AcTPyP-FeMOFs had a relatively high Fe (II) content. CO sorption isotherms showed that AcTPyP-FeMOFs chemisorbed CO and thus CO release was sustained and prolonged. In vitro evaluation results showed that CO@TPyP-FeMOFs reduced the inflammatory level of lipopolysaccharide (LPS) activated macrophages, polarized macrophages to M2 anti-inflammatory phenotype, and promoted the proliferation of fibroblasts by altering the pathological microenvironment. In vivo study confirmed CO@TPyP-FeMOFs promoted healing in a LPS model of delayed cutaneous wound repair and reduced macrophages and neutrophils recruitment. Both in vitro and in vivo studies verified that CO@TPyP-FeMOFs acted on macrophages by modulating phenotype and inflammatory factor expression. Thus, CO release targeting macrophages and pathological microenvironment modulation presented a promising strategy for wound healing.