Scaffold-mediated delivery of a miRNA-29b mimic mitigates excessive extracellular matrix deposition and matrix contraction in wound healing applications

Scaffolds delivering microRNA-29b promise to reduce excessive extracellular matrix production and healing complications in wounds. Disruption of the normal wound healing process can lead to fibrosis, a condition caused by overactive myofibroblasts depositing collagen. While existing treatments for fibrosis have varied results, new strategies combining scaffolds with gene delivery hold promise.

MicroRNA-29b, a key regulator of fibrotic signaling, downregulates the production of pro-fibrotic genes and reduces extracellular matrix buildup, thereby limiting the overactivation of fibroblasts and myofibroblasts. In this study, a collagen-GAG scaffold platform was developed to deliver miRNA-29b complexed with GET nanoparticles, targeting fibrosis.

Bioinformatics analysis confirmed miRNA-29b's involvement in ECM-related pathways, and the nanoparticles were successfully internalized in primary dermal fibroblasts. The optimised miRNA-29b formulation demonstrated significant reductions in collagen deposition and -SMA expression, key indicators of myofibroblast differentiation and fibrosis.

The formulation was then incorporated into porous collagen-GAG scaffolds, which modulated fibrotic gene expression while maintaining the necessary scaffold structure for fibroblast and myofibroblast infiltration and proliferation. Functional results in seeded TGF-beta-stimulated fibroblasts showed reduced matrix contraction, -SMA expression, and ECM deposition, similar to non-fibrotic conditions.

These findings indicate that scaffold-mediated miRNA-29b delivery could be a promising anti-fibrotic approach for wound healing by inhibiting myofibroblast activation, limiting matrix contraction, and preventing pathological ECM accumulation.