Sponge-Like Microneedles Spatially Sequester Chemokines and Deplete Monocytes to Alleviate Inflammatory Skin Disorders

Abstract

Persistent inflammation, characterized by the intense interplay of inflammatory chemokine secretion and immune cell infiltration, is a hallmark of many skin disorders including diabetic wounds and psoriasis with inadequate therapeutic interventions. Monocyte chemotactic protein-1 (MCP-1) is an inflammatory chemokine that plays a key role in recruiting and polarizing monocytes into pro-inflammatory macrophages to establish a vicious cycle that worsens the inflamed tissue microenvironment. Here, the sponge-like microneedles (HPMN) technology is described to alleviate inflammatory skin disorders. Heparin/4-arm PEG-NH2 network crosslinked onto microneedle surface spatially attracted and sequestered multiple inflammatory chemokines including MCP-1. Enrichment of MCP-1 on microneedles recruits and traps inflammatory monocytes within the porous structure of microneedles. Subsequent removal of microneedles not only depletes inflammatory chemokine, MCP-1, but also its cellular source. As a result, HPMN treatment facilitates 47.1% smaller open wound area in mice and 27.2% shorter wound length in pigs. To demonstrate the versatility of the HPMN technology, it is also shown that combining the method with standard-of-care immunosuppressants reduces 45.1% epidermis thickening and attenuated immune cell influx in a mouse psoriasis model. Overall, the HPMN technology is a novel demonstration of employing inflammatory chemokine and cell extraction to treat a broad range of inflammatory skin disorders.