Department of Medical Biomaterials Engineering, Kangwon National University, Chuncheon 24341, Republic of Korea.
Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
J Control Release. 2024 Dec;376:79-93. doi: 10.1016/j.jconrel.2024.09.053. Epub 2024 Oct 9.
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.
为了提供一种先进的伤口恢复治疗方法,本研究通过简单的浸涂法将巴氏杀菌牛乳衍生的外泌体(mEXO)固定在聚多巴胺(PDA)涂层透明质酸(HA)基电纺纳米纤维基质(mEXO@PMAT)上,从而构建了一种 mEXO 固定化网格作为伤口愈合生物材料。纯化的 mEXO(∼82nm)含有各种具有抗炎、细胞增殖和胶原合成相关的 microRNAs(miRNAs),包括 let-7b、miR-184 和 miR-181a,它们可上调人角质形成细胞(HaCaT)和成纤维细胞(HDF)中角蛋白 5、角蛋白 14 和胶原 1 的 mRNA 表达。固定在 PDA 涂层网格上的 mEXO 在 14 天内无爆发效应的情况下逐渐从网格中释放出来。用 HaCaT 和 HDF 处理后,与未修饰或 PDA 涂层网格处理的细胞相比,mEXO@PMAT 处理的 HaCaT 和 HDF 细胞的体外细胞迁移程度显著增加。此外,mEXO@PMAT 在体内可显著加快伤口闭合,且无明显毒性。因此,从网格中持续释放生物活性 mEXO 可有效增强体外细胞增殖,并加速体内伤口闭合,这使得 mEXO@PMAT 有望成为一种有前途的伤口愈合生物材料。