Work

Axolotl-derived decellularized skin ECM as a pro-regenerative scaffold for attenuating fibrotic wound healing

Year: 2025

Type: article

Abstract: Conventional wound healing in mammals often results in fibrosis, leading to permanent scarring and compromised skin function. Inspired by the remarkable regenerative capacity of axolotls, we developed an axolotl skin decellularized extracellular matrix (A-dECM) as a pro-regenerative scaffold for mammalian wound healing. A-dECM retained its native ECM composition, including a glycosaminoglycan-rich and collagen-dense profile, while effectively eliminating cellular and immunogenic components, as confirmed by histological staining and DNA quantification. Whole scanning electron microscopy revealed a highly organized ultrastructure in intact A-dECM. To improve biocompatibility, potentially cytotoxic ∼40 kDa protein fractions were removed from A-dECM via size-exclusion chromatography, and the fractionated A-dECM promoted enhanced proliferation of HaCaT keratinocytes. In a murine burn model, A-dECM significantly enhanced re-epithelialization, dermal remodeling, and collagen organization compared to murine dECM and PBS controls. Moreover, A-dECM reduced expression of fibrotic markers (α-SMA, TXNDC5), suppressed inflammatory cytokines (IL-1β, TNF-α), and inhibited M1 macrophage polarization. These molecular changes correlated with improved restoration of key skin features, including epidermal rete ridge formation and partial hair follicle regeneration. This work demonstrates that decellularized axolotl ECM can guide mammalian tissue regeneration, highlighting its potential as an evolution-inspired biomaterial for clinical translation. • Supports reduced-scarring wound regeneration in mammals • Accelerates re-epithelialization and enhances dermal remodeling • Reduces fibrosis by limiting myofibroblast activation and ECM deposition • Selectively inhibits M1 macrophage polarization to resolve inflammation • Preserves structural and biochemical cues essential for physiological skin regeneration

Source: Materials Today Bio

DOI: 10.1016/j.mtbio.2025.102443

Authors: Mu-Hui Wang, Chen-Hsiang Kuan, Hsu Ma, Nai-Chen Cheng

Institutions: National Taiwan University, National Taiwan University Hospital, Chang Bing Show Chwan Memorial Hospital

Language: English

Topic: Tissue Engineering and Regenerative Medicine

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,400