Modification of functional peptide SVVYGLR and its application for bone tissue regeneration

血管生成对骨软骨成骨至关重要。功能肽SVVYGLR由7个氨基酸残基组成，被发现具有高血管生成活性，被称为骨桥蛋白片段。本研究假设SVVYGLR肽对骨再生具有重要作用，并研究其对成骨细胞功能的影响。SVVYGLR对细胞附着有明显的高影响，但对细胞增殖和细胞分化没有明显的影响。SVVYGLR具有较高的血管生成活性，可用于促进伤口愈合和骨再生。此外。很少有报道提到用材料递送如此小分子量和大小的肽的方法。因此，我们研究了生物降解材料（如聚乳酸、聚乳酸/ε-己内酯共聚物）的最佳改性方法和孔隙率控制方法，以制备最佳的SVVYGLR传递材料。采用冷冻干燥法制备多孔结构时，通过冻结速度（改变冰晶生长尺寸）控制聚乳酸-己内酯共聚物的孔隙度。该方法制备的孔尺寸范围为10 ~ 110 μm。空气等离子体照射这些聚合物表面，增加了亲水性残基的数量，该方法可用于在聚合物表面固定溶解在水中的肽。经SVVYGLR修饰的聚合物在体内血管生成效果评价显示，其新生血管数量明显增加。在这项研究中，我们开发了新的修饰方法，将功能肽与生物可降解材料结合使用，促进伤口愈合，包括骨再生。

Angiogenesis is crucial for osteo-chondral ossification. Functional peptide SVVYGLR composed of 7 amino acids residues and found as high angiogenic activity is known as a fragment of osteopontin. Here, we hypothesized that SVVYGLR peptide have an important role for bone regeneration, and investigated its effect on osteoblast function. SVVYGLR showed significantly high effect on cell attachment, however, the peptide did not indicate cell proliferation and cell differentiation effect. SVVYGLR has a high angiogenic activity and should be useful for promoting wound healing followed by bone regeneration. Moreover. there are few reports, in which mention the method for delivering such a small molecular weight and size peptide with materials. So, we investigated the optimal modification method and porosity control method for biodegradable material (e.g. poly lactic acid, poly lactic acid/ε-caprolactone co-polymaer) for creating optimal SVVYGLR delivery material. The porosity of poly lactic acidε-caprolactone co-polymaer is controlled by freezing speed (this changes growing size of ice crystals), when the porous structure is fabricated by freeze drying method. The porous size created by this method varied in a range of 10-110 μm. Air plasma irradiation to the surface of these polymers increased the number of hydrophilic residues, and this method was useful for immobilizing peptide dissolved in water on polymer surface. In vivo evaluation of angiogenic effect of this polymer modified by SVVYGLR showed significantly increased the number of newly formed vessels. In this study, we developed new modification methods for applying functional peptide with biodegradable materials for promoting wound healing including bone regeneration.