Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea.
Department of Chemical Engineering, Pohang University of Science and Technology, Pohang, 37673, Republic of Korea; Division of Chemical Engineering and Materials Science, Ewha Womans University, Seoul, 03760, Republic of Korea.
Biomaterials. 2021 Nov;278:121171. doi: 10.1016/j.biomaterials.2021.121171. Epub 2021 Oct 1.
Heart failure following myocardial infarction (MI), the primary cause of mortality worldwide, is the consequence of cardiomyocyte death or dysfunction. Clinical efforts involving the delivery of growth factors (GFs) and stem cells with the aim of regenerating cardiomyocytes for the recovery of structural and functional integrity have largely failed to deliver, mainly due to short half-lives and rapid clearance in in vivo environments. In this work, we selected and genetically fused four biofunctional peptides possessing angiogenic potential, originating from extracellular matrix proteins and GFs, to bioengineered mussel adhesive protein (MAP). We found that MAPs fused with vascular endothelial growth factor (VEGF)-derived peptide and fibronectin-derived RGD peptide significantly promoted the proliferation and migration of endothelial cells in vitro. Based on these characteristics, we fabricated advanced double-layered adhesive microneedle bandages (DL-AMNBs) consisting of a biofunctional MAP-based root and a regenerated silk fibroin (SF)-based tip, allowing homogeneous distribution of the regenerative factor via swellable microneedles. Our developed DL-AMNB system clearly demonstrated better preservation of cardiac muscle and regenerative effects on heart remodeling in a rat MI model, which might be attributed to the prolonged retention of therapeutic peptides as well as secure adhesion between the patch and host myocardium by MAP-inherent strong underwater adhesiveness.
心肌梗死后的心力衰竭（MI）是全球主要的死亡原因，是心肌细胞死亡或功能障碍的结果。临床研究致力于通过输送生长因子（GFs）和干细胞来再生心肌细胞，以恢复结构和功能的完整性，但主要由于体内环境中半衰期短和快速清除而未能实现。在这项工作中，我们选择并遗传融合了四种具有血管生成潜力的生物功能肽，这些肽源自细胞外基质蛋白和 GFs，用于生物工程贻贝类黏蛋白（MAP）。我们发现，与血管内皮生长因子（VEGF）衍生的肽和纤连蛋白衍生的 RGD 肽融合的 MAP 显著促进了体外内皮细胞的增殖和迁移。基于这些特性，我们制造了先进的双层粘附微针绷带（DL-AMNB），由基于生物功能的 MAP 的根部和基于再生丝素纤维（SF）的尖端组成，通过可溶胀的微针实现再生因子的均匀分布。我们开发的 DL-AMNB 系统在大鼠 MI 模型中明显表现出更好的心肌保护和心脏重构的再生效果，这可能归因于治疗性肽的延长保留以及 MAP 固有的水下强粘附性确保了补片和宿主心肌之间的牢固粘附。
