Milk exosome-infused fibrous matrix for treatment of acute wound

J Control Release. 2024 Dec:376:79-93. doi: 10.1016/j.jconrel.2024.09.053. Epub 2024 Oct 9.

Abstract

To provide an advanced therapy for wound recovery, in this study, pasteurized bovine milk-derived exosomes (mEXO) are immobilized onto a polydopamine (PDA)-coated hyaluronic acid (HA)-based electrospun nanofibrous matrix (mEXO@PMAT) via a simple dip-coating method to formulate an mEXO-immobilized mesh as a wound-healing biomaterial. Purified mEXOs (∼82 nm) contain various anti-inflammatory, cell proliferation, and collagen synthesis-related microRNAs (miRNAs), including let-7b, miR-184, and miR-181a, which elicit elevated mRNA expression of keratin5, keratin14, and collagen1 in human keratinocytes (HaCaT) and fibroblasts (HDF). The mEXOs immobilized onto the PDA-coated meshes are gradually released from the meshes over 14 days without burst-out effect. After treatment with HaCaT and HDF, the degree of in vitro cell migration increases significantly in the mEXO@PMAT-treated HaCaT and HDF cells compared to the unmodified or PDA-coated meshes-treated cells. Additionally, the mEXO@PMAT provides significantly faster wound closure in vivo without notable toxicity. Thus, the sustained liberation of bioactive mEXO from the meshes can effectively enhance cell proliferation in vitro and accelerate wound closure in vivo, which could be harnessed mEXO@PMAT as a promising wound-healing biomaterial.

Keywords: Hyaluronic acid; Milk exosomes; Nanofibers; Polydopamines; Wound healing.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / chemistry
  • Cattle
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation* / drug effects
  • Exosomes*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Hyaluronic Acid* / chemistry
  • Indoles / administration & dosage
  • Indoles / chemistry
  • Keratinocytes / drug effects
  • Male
  • MicroRNAs / administration & dosage
  • Milk*
  • Nanofibers / chemistry
  • Polymers / chemistry
  • Wound Healing* / drug effects

Substances

  • Hyaluronic Acid
  • polydopamine
  • Polymers
  • MicroRNAs
  • Indoles
  • Anti-Inflammatory Agents