# miR‐185‐5p Derived From hUC‐MSC Exosomes via Suspension Culture Under Hypoxic Conditions Promotes Scarless Wound Healing in Mice by Precisely Regulating Collagen I/III Regeneration

## TL;DR

A new method using exosomes from stem cells under hypoxic conditions promotes scarless wound healing by regulating collagen types in mice.

## Contribution

This is the first study to show miR-185-5p in exosomes from hUC-MSCs under hypoxia regulates collagen balance for scarless healing.

## Key findings

- 3D hypoxic exosomes significantly improved COL-III/COL-I ratio during wound healing in mice.
- miR-185-5p targets RhoA/YAP signaling to regulate fibroblasts and collagen balance.
- Exosomes enriched with miR-185-5p maintain collagen type balance both in vivo and in vitro.

## Abstract

Hypertrophic scars have long posed a significant challenge in wound healing, primarily because of an imbalance between Type I (COL‐I) and Type III (COL‐III) collagen caused by excessive fibroblast activation. Existing treatments cannot directly regulate collagen formation to intervene in scar hyperplasia. This study is the first to elucidate the key mechanism through which human umbilical cord‐derived mesenchymal stem cell (hUC‐MSCs) exosomes expressing miR‐185‐5p achieve scarless healing through remodeling of the collagen‐type ratio. In this method, a hypoxic three‐dimensional (3D‐HO) suspension culture system that more closely mimics the in vivo microenvironment was established, and functional exosomes with enhanced physiological activity and higher yields were harvested. In vivo experiments demonstrated that 3D‐HO exosomes significantly improved the COL‐III/COL‐I regeneration ratio during mouse wound healing. Mechanistic studies revealed that the RhoA/YAP signaling axis plays a key regulatory role in the collagen regeneration ratio. Further molecular analysis revealed enrichment of miR‐185‐5p in 3D‐HO exosomes, which directly target RhoA to regulate fibroblasts. Both in vivo and in vitro functional interventions confirmed miR‐185‐5p in maintaining collagen type balance. In summary, this study demonstrates that microenvironment‐enhanced hUC‐MSCs exosomes remodel the composition of different types of collagen via the miR‐185‐5p–RhoA/YAP signaling axis, thereby driving scarless healing.

miR‐185‐5p derived from UC‐MSC exosomes via hypoxic suspension culture promotes scarless wound healing in mice by precisely regulating collagen I/III regeneration. Exosomes derived from UC‐MSCs under a three‐dimensional bioreactor and hypoxic conditions were injected into the skin wounds of mice. B miR‐185‐5p in 3H‐EXOs can decrease the production of RhoA and the expression of YAP while inhibiting the overexpression of COL‐I and thereby increasing the production of COL‐III to promote scarless wound healing.