Center for Engineering in Medicine and Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Shriners Hospitals for Children-Boston, Boston, MA, 02114, USA.
Adv Healthc Mater. 2022 Jul;11(13):e2102795. doi: 10.1002/adhm.202102795. Epub 2022 Apr 28.
Elastin-like peptides (ELPs) are a versatile platform for tissue engineering and drug delivery. Here, micelle forming ELP chains are genetically fused to three therapeutic molecules, keratinocyte growth factor (KGF), stromal cell-derived growth factor 1 (SDF1), and cathelicidin (LL37), to be used in wound healing. Chronic wounds represent a growing problem worldwide. A combinatorial therapy approach targeting different aspects of wound healing would be beneficial, providing a controlled and sustained release of active molecules, while simultaneously protecting these therapeutics from the surrounding harsh wound environment. The results of this study demonstrate that the conjugation of the growth factors KGF and SDF1 and the antimicrobial peptide LL37 to ELPs does not affect the micelle structure and that all three therapeutic moieties retain their bioactivity in vitro. Importantly, when the combination of these micelle ELP nanoparticles are applied to wounds in diabetic mice, over 90 % wound closure is observed, which is significantly higher than when the therapeutics are applied in their naked forms. The application of the nanoparticles designed here is the first report of targeting different aspect of wound healing synergistically.
弹性蛋白样肽 (ELPs) 是组织工程和药物输送的多功能平台。在这里，胶束形成的 ELP 链通过基因融合到三种治疗分子上，即角质细胞生长因子 (KGF)、基质细胞衍生生长因子 1 (SDF1) 和抗菌肽 (LL37)，用于伤口愈合。慢性伤口是一个在全球范围内日益严重的问题。针对伤口愈合不同方面的组合治疗方法将是有益的，它可以提供活性分子的控制和持续释放，同时保护这些治疗剂免受周围恶劣的伤口环境的影响。这项研究的结果表明，将生长因子 KGF 和 SDF1 以及抗菌肽 LL37 与 ELP 缀合不会影响胶束结构，并且所有三种治疗部分在体外都保持其生物活性。重要的是，当将这些胶束 ELP 纳米颗粒组合应用于糖尿病小鼠的伤口时，观察到超过 90%的伤口闭合，这明显高于将治疗剂以其裸露形式应用时的情况。这里设计的纳米颗粒的应用是协同靶向伤口愈合不同方面的首次报道。
