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

血管生成对于骨-软骨骨化至关重要。由7个氨基酸残基组成的功能肽SVVYGLR被认为是骨桥蛋白的片段，具有高的血管生成活性。在此，我们假设SVVYGLR肽在骨再生中具有重要作用，并研究其对成骨细胞功能的影响。SVVYGLR对细胞粘附有明显的促进作用，但对细胞增殖和分化无明显影响。SVVYGLR具有高血管生成活性，并且应该可用于促进伤口愈合，随后是骨再生。而且。很少有报道提到用材料递送这种小分子量和大小的肽的方法。因此，我们研究了生物可降解材料（例如聚乳酸、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，以创建最佳SVVYGLR递送材料。采用冷冻干燥法制备聚乳酸-ε-己内酯共聚物多孔结构时，其孔隙率受冷冻速度的控制（这改变了冰晶的生长尺寸）。通过该方法产生的多孔尺寸在10-110 μm范围内变化。空气等离子体辐照聚合物表面增加了亲水性残基的数量，这种方法可用于将溶于水的肽固定在聚合物表面。体内血管生成效果的评价，这种聚合物改性的SVVYGLR显示显着增加新形成的血管的数量。本研究开发了新的修饰方法，将功能肽与生物可降解材料一起应用于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.