Towards retrievable vascularized bioartificial pancreas: induction and long-lasting stability of polymeric mesh implant vascularized with the help of acidic and basic fibroblast growth factors and hydrogel coating.
Towards retrievable vascularized bioartificial pancreas: induction and long-lasting stability of polymeric mesh implant vascularized with the help of acidic and basic fibroblast growth factors and hydrogel coating.
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DOI：
10.1089/152091501300209624
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发表时间：
2001
影响因子：
5.4
通讯作者：
A. Prokop;E. Kozlov;S. Nun Non;M. Dikov;G. Sephel;J. Whitsitt;J. Davidson
中科院分区：
文献类型：
--
作者：
A. Prokop;E. Kozlov;S. Nun Non;M. Dikov;G. Sephel;J. Whitsitt;J. Davidson
我们试图改进现有的胰岛同种异体移植方法。目前，在腹膜腔内囊化移植胰岛的成功率的缺乏归因于植入物的不良血管化。厚的纤维化包膜通常包围移植物，限制了存活。我们已经测试了这一假设，即移植材料的新血管形成可以通过添加适当的血管生成因子嵌入聚合物涂层来诱导。将涂覆有亲水性聚合物的生物相容性和不可吸收补片植入大鼠体内，并在1周、6周和12周后收获。通过对血管分布、纤维化和炎症程度的组织学观察来评估植入反应。补片的宏观结构几何形状有利于组织长入补片细丝之间的间隙。在与聚电解质和/或肝素的静电复合物中掺入酸性或碱性FGF的水凝胶涂层提供了血管生成生长因子的持续缓慢释放。抗因子VIII和抗胶原IV型抗体和GSL I-B4凝集素用于测量血管化的程度。从植入物辐射出几百微米的强有力和持久的血管化。血管化的水平应提供足够的营养和氧气扩散到植入的胰岛。根据我们的观察，稳定的血管形成可能需要持续的血管生成信号，以允许永久性植入物结构的形成。
We seek to improve existing methodologies for allogenic grafting of pancreatic islets. The lack of success of encapsulated transplanted islets inside the peritoneal cavity is presently attributed to poor vascularization of the implant. A thick, fibrotic capsule often surrounds the graft, limiting survival. We have tested the hypothesis that neovascularization of the graft material can be induced by the addition of proper angiogenic factors embedded within a polymeric coat. Biocompatible and nonresorbable meshes coated with hydrophilic polymers were implanted in rats and harvested after 1-, 6-, and 12-week intervals. The implant response was assessed by histological observations on the degree of vascularity, fibrosis, and inflammation. Macrostructural geometry of meshes was conducive to tissue ingrowth into the interstitial space between the mesh filaments. Hydrogel coating with incorporated acidic or basic FGF in an electrostatic complex with polyelectrolytes and/or with heparin provided a sustained slow release of the angiogenic growth factor. Anti-factor VIII and anti-collagen type IV antibodies and a GSL I-B4 lectin were used to measure the extent of vascularization. Vigorous and persistent vascularization radiated several hundred microns from the implant. The level of vascularization should provide a sufficient diffusion of nutrients and oxygen to implanted islets. Based on our observations, stable vascularization may require a sustained angiogenic signal to allow for the development of a permanent implant structure.