Pence Jacquelyn C, Clancy Kathryn B H, Harley Brendan A C
Department of Chemical Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Department of Anthropology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
Biotechnol Bioeng. 2015 Oct;112(10):2185-94. doi: 10.1002/bit.25622. Epub 2015 Jul 22.
Nutrient transport remains a major limitation in the design of biomaterials. One approach to overcome this constraint is to incorporate features to induce angiogenesis-mediated microvasculature formation. Angiogenesis requires a temporal presentation of both pro- and anti-angiogenic factors to achieve stable vasculature, leading to increasingly complex biomaterial design scheme. The endometrium, the lining of the uterus and site of embryo implantation, exemplifies a non-pathological model of rapid growth, shedding, and re-growth of dense vascular networks regulated by the dynamic actions of estradiol and progesterone. In this study, we examined the individual and combined response of endometrial epithelial cells and human umbilical vein endothelial cells to exogenous estradiol within a three-dimensional collagen scaffold. While endothelial cells did not respond to exogenous estradiol, estradiol directly stimulated endometrial epithelial cell transduction pathways and resulted in dose-dependent increases in endogenous VEGF production. Co-culture experiments using conditioned media demonstrated estradiol stimulation of endometrial epithelial cells can induce functional changes in endothelial cells within the collagen biomaterial. We also report the effect of direct endometrial epithelial and endothelial co-culture as well as covalent immobilization of estradiol within the collagen biomaterial. These efforts establish the suitability of an endometrial-inspired model for promoting pro-angiogenic events within regenerative medicine applications. These results also suggest the potential for developing biomaterial-based models of the endometrium.
营养物质运输仍然是生物材料设计中的一个主要限制因素。克服这一限制的一种方法是引入一些特征来诱导血管生成介导的微血管形成。血管生成需要同时适时呈现促血管生成和抗血管生成因子，以实现稳定的脉管系统，这导致生物材料设计方案日益复杂。子宫内膜是子宫的内衬和胚胎着床的部位，它是由雌二醇和孕酮的动态作用调节的致密血管网络快速生长、脱落和重新生长的非病理性模型。在本研究中，我们在三维胶原支架内研究了子宫内膜上皮细胞和人脐静脉内皮细胞对外源雌二醇的单独及联合反应。虽然内皮细胞对外源雌二醇没有反应，但雌二醇直接刺激子宫内膜上皮细胞转导途径，并导致内源性VEGF产生呈剂量依赖性增加。使用条件培养基进行的共培养实验表明，雌二醇刺激子宫内膜上皮细胞可诱导胶原生物材料内内皮细胞的功能变化。我们还报告了直接的子宫内膜上皮细胞与内皮细胞共培养以及雌二醇在胶原生物材料内的共价固定化的效果。这些工作确立了一种受子宫内膜启发的模型在促进再生医学应用中的促血管生成事件方面的适用性。这些结果还表明了开发基于生物材料的子宫内膜模型的潜力。
