Development of a biomimetic composite scaffold to promote vascular network growth

开发仿生复合支架以促进血管网络生长

• 批准号: 8316267
• 负责人: David A Rubenstein
• 金额: $ 22.25万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8316267
• 关键词: Acetates; Address; Angiogenic Factor; Autologous; Behavior; Biochemistry; Biocompatible; Biocompatible Materials; Biological; Biological Assay; Biomimetics; Blood Vessels; Caliber; Cell Culture Techniques; Cells; Chemicals; Chronic; Complex; Cues; Data; Development; Diffusion; E-Selectin; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Excision; Extracellular Matrix; Fiber; Fibroblast Growth Factor; Flow Cytometry; Goals; Growth; Growth Factor; Hydrophobicity; In Vitro; Knowledge; Legal patent; Life; Mechanics; Methods; Mission; Modeling; Monitor; Mus; Nutrient; Organ; Porosity; Property; Public Health; Research; Solutions; Source; Stimulus; Surface; System; Techniques; Testing; Thick; Time; Tissue Engineering; Tissues; Vascular System; Work; Wound Healing; angiogenesis; base; cadherin 5; chemical property; design; in vivo; innovation; insight; intercellular cell adhesion molecule; mimetics; nanoindentation; novel; novel strategies; physical property; scaffold; shear stress; success; vascular tissue engineering; wasting

DESCRIPTION (provided by applicant): The development of novel biomimetic scaffolds that promote and direct new vascular network growth is a critical hurdle for the success of tissue engineering and for a rapid solution for chronic wound healing. Traditionally, biomimetic scaffolds only match the extracellular matrix (ECM) fiber diameter, but our preliminary results suggest that scaffolds that mimic the mechanical, chemical and topographical properties of the vascular ECM promote new vascular network growth faster than traditional scaffolds. The long-term goal of this project is too successful fabricate biomimetic scaffolds that promote vascular network growth. The objective of this proposal is to fabricate novel composite biomimetic coaxial electrospun scaffolds and to test the propensity of these scaffolds to promote new vascular growth in an in vitro, ex vivo and in vivo angiogenesis model. Here our base scaffolds will be our established partially mimetic electrospun scaffolds and we will tailor the remaining physical properties to match the ECM. The central hypothesis of this proposal is that electrospun scaffolds that mimic multiple physical properties of the vascular ECM will support new vessel growth better than scaffolds that do not mimic the vascular ECM properties. Our rationale is that by designing a scaffold that facilitates functional vascular network growth, vascular tissue can be incorporated into tissue engineered products or can be used to facilitate wound healing. The success of either of these applications, would significantly transform the fields of vascular tissue engineering, tissue engineering and wound healing. This proposal is especially relevant to the NIH's mission that pertains to the pursuit of fundamental knowledge about the behavior of systems and the application of that knowledge to extend healthy life. Guided by our preliminary data, the hypothesis of this proposal will be tested by pursing three specific aims: 1) To fabricate vascular ECM mimicking scaffolds, 2) To investigate the in vitro and ex vivo new vascular network growth throughout ECM mimicking scaffolds, and 3) To examine in vivo angiogenesis throughout ECM mimicking scaffolds using a murine wound healing model. Electrospinning will be used to fabricate complex composite biomimetic coaxial scaffolds. Scaffold physical properties will be investigated with nanoindentation, TEM, SEM and goniometry. Endothelial cell activation will be investigated with flow cytometry and ELISA directed towards E-selectin, VE-cadherin, ICAM, etc., in cell culture, in a bioassay chamber optimized to monitor new angiogenesis from an autologous cell source and in a murine model. The proposed work is innovative because we have developed a new coaxial electrospinning technique that is tailored to enhance the mechanical properties of formed scaffolds. Also, we use a pro-angiogenic bioassay chamber that was developed by this group. This research will have a positive impact on tissue engineering/wound healing research and is significant because we will develop a technique to fabricate new vascular networks within a biocompatible biomimetic scaffold. We have put together a research team that has the expertise and drive to successfully address this important question.

描述（由申请人提供）：促进和直接直接新血管网络生长的新型仿生支架的发展是组织工程成功的关键障碍，并为快速的慢性伤口愈合解决方案而言。传统上，仿生支架仅与细胞外基质（ECM）纤维直径相匹配，但是我们的初步结果表明，模仿血管ECM的机械，化学和地形特性的支架可促进新血管网络的生长速度，而不是传统脚手架。该项目的长期目标是太成功地制造了仿生脚手架，以促进血管网络的增长。该提案的目的是制造新型的复合仿生同轴电孔支架，并在体外，体内和体内血管生成模型中测试这些支架的倾向以促进新的血管生长。在这里，我们的基本支架将是我们建立的部分模拟电纺支架，我们将定制其余的物理特性以匹配ECM。该提议的中心假设是，模仿血管ECM的多个物理特性的电纺支架比不模仿血管ECM特性的支架更好地支持新容器的生长。我们的理由是，通过设计促进功能性血管网络生长的脚手架，可以将血管组织纳入组织工程产品中，或可用于促进伤口愈合。这两种应用的成功都将显着改变血管组织工程，组织工程和伤口愈合的领域。该提议与NIH的使命尤其重要，该使命与追求有关系统行为的基本知识以及该知识延长健康生活的基本知识有关。 Guided by our preliminary data, the hypothesis of this proposal will be tested by pursing three specific aims: 1) To fabricate vascular ECM mimicking scaffolds, 2) To investigate the in vitro and ex vivo new vascular network growth throughout ECM mimicking scaffolds, and 3) To examine in vivo angiogenesis throughout ECM mimicking scaffolds using a murine wound healing model.静电纺丝将用于制造复杂的复合仿生同轴支架。脚手架物理特性将通过纳米凹陷，TEM，SEM和性腺法进行研究。在细胞培养物中，将使用针对E-选择素，VE-钙粘蛋白，ICAM等的流式细胞仪和ELISA研究内皮细胞活化，该细胞活化在细胞培养中，在细胞培养物中，在生物测定室中优化，可从自体细胞源和鼠模型中监测新的血管生成。拟议的工作具有创新性，因为我们开发了一种新的同轴静电纺丝技术，该技术的定制是为了增强形成的支架的机械性能。另外，我们使用该组开发的促血管生物生物测定室。这项研究将对组织工程/伤口愈合研究产生积极影响，并且很重要，因为我们将开发一种在生物相容性仿生型支架内制造新的血管网络的技术。我们组建了一个研究团队，该研究团队具有专业知识，并能够成功解决这个重要问题。