Multifunctional coatings combining bioactive peptides and affinity-based cytokine delivery for enhanced integration of degradable vascular grafts.,Biomaterials Science

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Multifunctional coatings combining bioactive peptides and affinity-based cytokine delivery for enhanced integration of degradable vascular grafts.
Biomaterials Science ( IF 5.8 ) Pub Date : 2020-01-30 , DOI: 10.1039/c9bm01801h
Franziska Clauder ₁ , Franziska D Zitzmann ₂ , Sabrina Friebe ₃ , Stefan G Mayr ₃ , Andrea A Robitzki ₂ , Annette G Beck-Sickinger ₁

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Insufficient endothelialization of cardiovascular devices is a high-risk factor for implant failure. Presentation of extracellular matrix (ECM)-derived coatings is a well-known strategy to improve implant integration. However, the complexity of the system is challenging and strategies for applying multifunctionality are required. Here, we engineered mussel-derived surface-binding peptides equipped with integrin (c[RGDfK]) and proteoglycan binding sites (FHRRIKA) for enhanced endothelialization. Surface-binding properties of the platform containing l-3,4-dihydroxyphenylalanine (DOPA) residues were confirmed for hydrophilized polycaprolactone-co-lactide scaffolds as well as for glass and polystyrene. Further, heparin and the heparin-binding angiogenic factors VEGF, FGF-2 and CXCL12 were immobilized onto the peptide in a modular assembly. Presentation of bioactive peptides greatly enhanced human umbilical vein endothelial cell (HUVEC) adhesion and survival under static and fluidic conditions. In subsequent investigations, peptide-heparin-complexes loaded with CXCL12 or VEGF had an additional increasing effect on cell viability, differentiation and migration. Finally, hemocompatibility of the coatings was ensured. This study demonstrates that coatings combining adhesion peptides, glycosaminoglycans and modulators are a versatile tool to convey ECM-inspired multifunctionality to biomaterials and efficiently promote their integration.

中文翻译：

多功能涂层结合了生物活性肽和基于亲和力的细胞因子传递，可增强可降解血管移植物的整合。

心血管设备的内皮化不足是植入失败的高风险因素。呈现细胞外基质（ECM）衍生的涂层是提高植入物集成度的众所周知的策略。但是，系统的复杂性具有挑战性，并且需要应用多功能性的策略。在这里，我们设计了配有整合素（c [RGDfK]）和蛋白聚糖结合位点（FHRRIKA）的贻贝衍生的表面结合肽，以增强内皮化作用。对于亲水化的聚己内酯-共-乳酸支架以及玻璃和聚苯乙烯，证实了含有1-3,4-二羟基苯丙氨酸（DOPA）残基的平台的表面结合性能。此外，将肝素和结合肝素的血管生成因子VEGF，FGF-2和CXCL12以模块组装形式固定在肽上。生物活性肽的存在大大增强了人脐静脉内皮细胞（HUVEC）的粘附性和在静态和流体条件下的存活率。在随后的研究中，载有CXCL12或VEGF的肽-肝素复合物对细胞活力，分化和迁移具有额外的增加作用。最后，确保了涂层的血液相容性。这项研究表明，结合粘附肽，糖胺聚糖和调节剂的涂料是一种多功能工具，可以将ECM启发的多功能传递给生物材料并有效地促进它们的整合。载有CXCL12或VEGF的多肽-肝素复合物对细胞活力，分化和迁移有额外的增加作用。最后，确保了涂层的血液相容性。这项研究表明，结合粘附肽，糖胺聚糖和调节剂的涂料是一种多功能工具，可以将ECM启发的多功能传递给生物材料并有效地促进它们的整合。载有CXCL12或VEGF的多肽-肝素复合物对细胞活力，分化和迁移有额外的增加作用。最后，确保了涂层的血液相容性。这项研究表明，结合粘附肽，糖胺聚糖和调节剂的涂料是一种多功能工具，可以将ECM启发的多功能传递给生物材料并有效地促进它们的整合。

更新日期：2020-03-19

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