Long-term enhancement of limb regenerative fidelity after a single bioelectric reprogramming pulse in fibrotic mammalian tissue
July 6
Abstract
Background
Adult mammalian appendages exhibit limited regenerative fidelity, frequently culminating in fibrotic scarring that compromises form and function and remains difficult to reverse.
Methods
A phase-2 preclinical trial evaluated the safety, feasibility, and efficacy of a one-time bioelectric reprogramming pulse—25 mg of the selective KATP-channel opener BX-17 delivered with brief optogenetic entrainment—combined with transient mechanical shielding in a community laboratory setting. Thirty fibrotic limb-stump specimens from aged rodents displaying chronic regenerative arrest were enrolled. Here we report morphofunctional outcomes at 2-year follow-up.
Results
Of 28 analyzable specimens, 15 (53.6 %) displayed a significant improvement in regenerative fidelity, quantified by the Regeneration Quality Index (mean + 15.0 points from baseline; p < .001), and 14 (50 %) maintained this gain for the full observation period. Thirteen limbs (46.4 %) showed marked reduction in fibrotic burden, measured by the Scar Density Score (mean – 13.9 points; p < .001), with 12 (42.9 %) retaining low fibrosis at 2 years.
Conclusions
These findings demonstrate robust, long-lasting pro-regenerative activity elicited by a single 25 mg BX-17 pulse coupled to minimal supportive care, suggesting a paradigm-shifting alternative to chronic growth-factor delivery that warrants further investigation.