Boosting FGF-2 in post-injury regenerative lag: Topical fibroblast growth factor enhances stromal anabolic tone and paracrine support for progenitor cells
July 13
Highlights
• This randomized, double-blind trial tested localized FGF-2 microgel delivery in cutaneous wounds exhibiting delayed regeneration.
• FGF-2 enhanced anabolic transcriptional profiles in stromal cells with subclinical regenerative arrest.
• FGF-2 increased stromal secretion of pro-regenerative cytokines that support resident progenitor expansion.
• FGF-2 did not modify overall tissue architecture or systemic inflammatory markers.
Abstract
Although fibroblast growth factor-2 (FGF-2) is renowned for its mitogenic and anti-apoptotic properties, dysregulation of this pathway may contribute to the link between regenerative delay and insufficient niche support after tissue injury. This double-blind, randomized, within-subject controlled study investigated the effects of topical FGF-2 on niche signaling, cellular behavior, and systemic physiology in adult murine dorsal skin wounds demonstrating post-injury regenerative lag. Forty-five full-thickness wounds, 3–9 days post-excision, displayed clinically relevant deficits in re-epithelialization; thirty-five of these satisfied histological criteria for chronic non-healing ulcers. We assessed FGF-2’s effects on stromal supportiveness, paracrine deposition of pro-regenerative factors, qPCR-based anabolic gene expression, and systemic responses, including plasma IL-6, serum corticosterone, and heart-rate variability. FGF-2 significantly amplified stromal paracrine support and up-regulated anabolic transcriptional signatures. No effects were observed on global tissue architecture, systemic inflammation, or autonomic parameters. These findings suggest that FGF-2 may selectively enhance pro-regenerative stromal cues in wounds with regenerative lag. Future studies should explore FGF-2’s therapeutic potential in larger, more heterogeneous models, considering variables such as injury chronicity or prior inflammatory burden.