糖尿病性神经病变是常见的糖尿病并发症，其病变神经周围也存在复杂的血管网络，为了有效地治疗神经病变，微血管疾病也必须解决。目前利用生长因子治疗神经血管疾病仍缺乏好的药物递送系统，且都是应用单一生长因子。我们推测通过生物材料控制局部释放神经生长因子(NGF)和碱性成纤维细胞生长因子(FGF-2)将协同治疗神经病变和微血管损伤，从而开发出新的治疗糖尿病神经病变的方法。课题组前期开发的多聚阳离子PEAD可与肝素竞争结合生长因子，因此我们开发了[PEAD:肝素] 团聚体，结果显示[PEAD:肝素]可通过调整其分子量和电荷数来控释FGF-2或NGF，并保持其生物活性。本项目是在前期基础上通过[PEAD：肝素]控制NGF和FGF-2的释放和活性，进一步优化[PEAD：肝素：(NGF+FGF-2)]药物递送系统，并利用细胞和动物模型评价其对神经血管的再生作用，探讨分子机制，为其潜在的临床应用奠定理论基础。

Diabetic neuropathy is one of the common complications of diabetes, there is strong vascular link in diabetic neuropathy. To effectively treat neuropathy, microvascular diseases also need to be addressed. Most growth factor therapies are limited by the lack of an appropriate delivery system, and almost all focuses on one growth factor alone. Therefore, we postulate that controlled local release of NGF and FGF-2 will synergistically treat neuropathy and the underlying microvascular defect. We expect that the regenerated nerve and vascular tissue will positively reinforce each other and represent a powerful new therapeutic approach to treating diabetic neuropathy. We have previously shown that polycation molecular weight controls the release rate of FGF-2: larger polycations compete more favorably for heparin and increase the growth factor release rate. Our group found the polycations(PEAD) will compete more efficiently for heparin to grwoth factors, so we developed the [PEAD:heparin] and we found the charge density with a fixed molecular weight will lead to NGF and FGF-2 release and keep the bioactivity of growth factor. Based on the strong preliminary data, we expect [PEAD:heparin] to offer appropriate heparin binding and growth factor release. We will optimise the [PEAD：heparin：(NGF+FGF-2)] drug delivery systems, and evaluate the effect and the role in the regeneration of the nerves and blood vessels by cellular and animal models. This project will give a potential clinical applications for diabetic neuropathy.