Supplying oxygen and nutrients to implanted cells or tissues is an important factor that improves their survivability and function in regenerative medicine. Various efforts have been made to develop angiogenic materials by incorporating and releasing growth factors such as vascular endothelial growth factor (VEGF). However, these exogenous growth factors have a short half-life under physiological conditions. We therefore designed a novel angiogenic microparticle (C12-MP) comprising Alaska pollock-derived gelatin (ApGltn) modified with a dodecyl group (C12-ApGltn) to stimulate endogenous VEGF secretion. The C12-MP suspension formed an injectable hydrogel, the rheological properties and enzymatic degradation of which were evaluated. RAW264 cells, mouse macrophage-like cells, cultured with C12-MPs, secreted significantly more VEGF than the original ApGltn MPs. Based on laser Doppler perfusion imaging, the C12-MP hydrogel clearly induced increased blood perfusion in a subcutaneous mouse model compared with the original ApGltn microparticle (Org-MP) or phosphate-buffered saline controls. Histological studies revealed that the areas of nuclear factor (NF)-κB, CD31, and myeloperoxidase staining showed a greater increase at the site injected with C12-MPs than at the site injected with the original ApGltn microparticles or phosphate-buffered saline. The C12-MP hydrogel is a promising angiogenic material for constructing vascular beds for cell transplantation by promoting endogenous VEGF secretion without additional growth factors.

向植入的细胞或组织供应氧气和营养是提高其在再生医学中的生存能力和功能的重要因素。通过掺入和释放生长因子例如血管内皮生长因子（VEGF），已经做出了各种努力来开发血管生成材料。但是，这些外源性生长因子在生理条件下的半衰期很短。因此，我们设计了一种新颖的血管生成微粒（C12-MP），其中包括经十二烷基（C12-ApGltn）修饰以刺激内源性VEGF分泌的阿拉斯加波洛克派生明胶（ApGltn）。C12-MP悬浮液形成可注射的水凝胶，评估其流变性和酶促降解。用C12-MPs培养的RAW264细胞，小鼠巨噬细胞样细胞，分泌的VEGF比原始ApGltn MP明显多。基于激光多普勒灌注成像，与原始ApGltn微粒（Org-MP）或磷酸盐缓冲盐水对照组相比，C12-MP水凝胶明显诱导了皮下小鼠模型中血液灌注的增加。组织学研究表明，与注射原始ApGltn微粒或磷酸盐缓冲盐水的部位相比，注射C12-MPs的部位的核因子（NF）-κB，CD31和髓过氧化物酶染色的面积显示出更大的增加。C12-MP水凝胶是一种有前途的血管生成材料，可通过促进内源性VEGF分泌而无需其他生长因子来构建用于细胞移植的血管床。与原始ApGltn微粒（Org-MP）或磷酸盐缓冲盐水对照组相比，C12-MP水凝胶在皮下小鼠模型中明显诱导了增加的血液灌注。组织学研究表明，与注射原始ApGltn微粒或磷酸盐缓冲盐水的部位相比，注射C12-MPs的部位的核因子（NF）-κB，CD31和髓过氧化物酶染色的面积显示出更大的增加。C12-MP水凝胶是一种有前途的血管生成材料，可通过促进内源性VEGF分泌而无需其他生长因子来构建用于细胞移植的血管床。与原始的ApGltn微粒（Org-MP）或磷酸盐缓冲盐水对照组相比，C12-MP水凝胶明显诱导了皮下小鼠模型中的血液灌注增加。组织学研究表明，与注射原始ApGltn微粒或磷酸盐缓冲盐水的部位相比，注射C12-MPs的部位的核因子（NF）-κB，CD31和髓过氧化物酶染色的面积显示出更大的增加。C12-MP水凝胶是一种有希望的血管生成材料，可通过促进内源性VEGF分泌而无需其他生长因子来构建用于细胞移植的血管床。髓过氧化物酶染色显示，在注射C12-MPs的部位比注射原始ApGltn微粒或磷酸盐缓冲液的部位增加更多。C12-MP水凝胶是一种有前途的血管生成材料，可通过促进内源性VEGF分泌而无需其他生长因子来构建用于细胞移植的血管床。髓过氧化物酶染色显示，注射C12-MPs的部位比注射原始ApGltn微粒或磷酸盐缓冲液的部位增加更多。C12-MP水凝胶是一种有前途的血管生成材料，可通过促进内源性VEGF分泌而无需其他生长因子来构建用于细胞移植的血管床。