Cell-based cytokine patch for localized immunomodulation and accelerated healing in rodent and porcine wounds

Abstract

Wounds can become chronic if the biological processes that coordinate tissue repair, including immune cell activity and matrix remodelling, become dysregulated. Current treatments mainly focus on a wound’s physical properties, such as moisture and pressure, and do not restore the disrupted molecular pathways. Here we show a removable patch containing engineered human cells that continuously release native cytokines and that can accelerate healing in rodent and porcine full-thickness wounds. The patch is a polydimethylsiloxane structure that houses alginate-encapsulated human retinal epithelial cells engineered to secrete individual cytokines relevant to tissue repair. Once placed on the wound bed, the cells remain viable and locally release the cytokines over several days. Delivery of interleukin 10, interleukin 12 and transforming growth factor-beta accelerates wound healing in mice and pigs, with accompanying changes in gene expression linked to tissue repair, including pathways involved in skin development and collagen organization. This work suggests that localized, cell-based cytokine delivery may enable future wound treatments that directly modulate the cellular programs governing tissue repair.