Self-assembled nanoparticles of hybrid elastin-like and Oncostatin M polymers for improved wound healing.

Abstract

Oncostatin M (OSM) is a pleiotropic cytokine that can significantly enhance wound healing. Here, we report on the use of nanoparticles (NPs) formulated from a genetically engineered A200_hOSM protein polymer, which combines an elastin-like recombinamer (A200) with human OSM (hOSM) in the same molecule, aiming at enhancing wound healing processes. A200_hOSM NPs were obtained by self-assembly and evaluated for their bioactivity in human keratinocytes and fibroblasts. The NPs demonstrated superior efficacy in promoting cell proliferation in a dose-dependent manner, exhibiting nearly threefold greater proliferation at 48 and 72 h, compared to cells treated with commercial hOSM. Moreover, the NPs stimulated cell migration and collagen production through activation of JAK/STAT3 signaling. They also promoted the production of IL-6 and IL-8, pro-inflammatory cytokines with a critical role for wound healing. Promotion of keratinocyte proliferation and differentiation were further validated in non-commercial 3D skin equivalents. The A200_hOSM NPs revealed potential in accelerating wound healing, evidenced by reduced wound size and a thicker epidermal layer. This system represents a significant advancement in the field of bioinspired biomaterials by improving cytokine bioavailability, allowing for localized therapy and offering a cost-effective strategy for employing hOSM in wound healing management.