自体组织诱导型DM-PCL/UBM盆底修复材料的构建及功能研究

Excellular matrix（ECM）is a kind of material with good biocompatibility, and without erosion, is promising the ideal pelvic floor repair material, but the long time effect is poor, the key reason is that the material degradation rate is more rapid than tissue inductive regeneration in vivo. Therefore, the research key issue is trying to extend the material degradation period and enhance the tissue inductive capacity. Our preliminary study has found that porcine urinary bladder matrix(UBM) is the kind of ECM very suit for femal pelvic floor environment, and the Laminin/Nidogen molecular is the key cause for stem cell chemotaxis and smooth muscle differentiation, and have modified the material surface with dopamine molecular to improve the biological activity. Combined with the latest research: combine the UBM with PCL, the compound material degradation period was extended obviously and the biological activity increased remarkably. In this study we planned to construct a self tissue inductive pelvic repair material with long degradation period, and covalent bonded Laminin/Nidogen and VEGF molecular by dopamine surface modification to continue playing activation, in order to give this material the ability of adult stem cell induction, proliferation and smooth muscle differentiation, consequently would reach an ideal valid pelvic tissue replacement, and give a new idea for pelvic repair material development that clinical needed.

脱细胞基质（ECM）生物相容性好，无侵蚀性，有望成为理想的盆底修复材料，但远期效果欠佳，究其原因是ECM在体内的降解快于诱导组织再生。因此设法延长ECM的降解周期和增强其诱导组织再生能力成为研究的关键。我们前期研究发现猪脱细胞膀胱基质（UBM）是非常适合女性盆底环境的ECM材料，其中的Laminin/Nidogen分子是诱导干细胞趋化及平滑肌分化的关键因素；并成功利用多巴胺表面修饰对材料进行了生物活性改良。结合最新研究：UBM复合PCL后，可以有效延长材料的降解周期和提高其生物活性。本研究拟构建延长降解周期的自体组织诱导型盆底修复材料，通过在PCL/UBM表面进行多巴胺修饰共价结合Laminin/Nidogen和VEGF分子并持续发挥活性，使材料具备诱导成体干细胞趋化、增殖及平滑肌分化能力，从而达到理想的盆底有效组织替代，为临床亟需的女性盆底修复材料的研发开辟一条全新的思路。

猪脱细胞膀胱基质（Urinary bladder matrix，UBM）是一种天然高分子材料， 具有人工合成高分子材料所不具备的与组织高度相似的超微结构和三维结构，且其生物相容性良好，是非常适合女性盆底环境的脱细胞基质材料。为了满足其在体内持久替代的需求，本研究通过不断摸索与改进，1）建立了基于丙酮法法的长降解周期 PCL/UBM盆底修复材料制备方法；2）通过多巴胺分子表面修饰技术将 Laminin/Nidogen，VEGF 等生长因子共价结合到 PCL/ UBM 复合材料上，构建自体组织诱导型盆底修复材料（ SI-PCL/UBM）；3）通过体内外实验，对SI-PCL/UBM的理化特性，特别是力学性能、体外降解特性、生物相容性进行了系统的比较分析，并就其对间充质干细胞的黏附、增殖和诱导分化，以及体内植入反应进行研究。结果表明SI-PCL/UBM具有良好的理化特性和生物学特性，是盆底等高应力部位组织修复潜在的理想材料，为临床亟需的女性盆底修复材料的研发开辟一条全新的思路。