Biohybrid Strategies for Decellularized Tissues

脱细胞组织的生物杂交策略

• 批准号: 1604742
• 负责人: John Fisher
• 金额: $ 30.74万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1604742&HistoricalAwards=false
• 关键词: Biohybrid; Strategies; Decellularized; Tissues

PI: Fisher, John PProposal Number: 1604742When replacing malfunctioning or diseased tissues, cardiovascular surgeons often use biomaterials that contain a natural tissue component such as decellularized pericardium, which serves as an extracellular matrix (ECM) for the implant. To preserve mechanical properties, one common treatment of the tissue is through chemical fixation, such as soaking in glutaraldehyde (GA). However, GA treatment often leads to detrimental calcification of the implant. The goal of this proposal is to eliminate the need for GA treatment by coating the ECM with a novel biodegradable polymer coating (poly(propylene fumarate) or PPF) that will provide a reinforced substrate with many desirable properties. Mechanical properties and degradation times are tunable. Local bioactivity can be enhanced by embedding growth eluting microparticles in the PPF. Thus, the resulting hybrid material will exhibit diminished calcification and immune response from the host and be resistant to rapid degradation while at the same time encouraging native tissue ingrowth. Successful development of this novel material would significantly improve the material options available and revolutionize expectations for many cardiovascular repair operations. Educational Impact is advanced through the development of a new Biomaterials and Biofabrication (B&B) Workshop whose objective is to introduce undergraduates with engineering and science backgrounds to a diverse research environment involving biomaterials and biofabrication.The goal of this three year project is to develop novel hybrid materials to create a replacement for malfunctioning or diseased tissues. Many of the tissue based prosthetics used in cardiovascular surgery employ glutaraldehyde (GA)-treated pericardium. Pericardium possesses advantageous mechanical properties, but GA treatment invariably results in detrimental calcification of the implant. This study tests the hypothesis that by treating pericardium extracellular matrix (ECM) with a physical coating of the synthetic polymer poly(propylene fumarate) (PPF), the resulting hybrid materials will not only exhibit diminished calcification and immune response upon implantation, but will provide a platform suitable for controlled regrowth and maintenance of the tissue. The study will additionally test the hypothesis that the biologic and activity of the platform may be enhanced through the addition of growth factor eluting poly(lactic-co-glycolic acid) (PLGA) microparticles. The ideal composition of both components (PPF and ECM) to obtain appropriate mechanical properties and degradation for a patch model will be determined and a 3D printing resin based on these formulations will be used to investigate the in vitro response to a random organization of the ECM. The performance of PPF-reinforced ECM and 3DP PPF-reinforced ECM will be evaluated in a rat subcutaneous model. The hybrid materials will be assessed for cellular ingrowth, newly produced proteins and signaling factors, as well as possible calcium deposits. The Broader Impacts of the project include the development of a new class of hybrid biomaterials and the elucidation of new strategies and technologies within regenerative medicine. The proposed hybrid material will provide a substrate that encourages native cellular ingrowth and deposition of new ECM. A novel material with a decreased immune activity and subsequent calcification rate would significantly improve the material options available and revolutionize expectations for many cardiovascular repair operations. Educational Impact is advanced through the development of a new Biomaterials and Biofabrication (B&B) Workshop whose objective is to introduce undergraduates with engineering and science backgrounds to a diverse research environment involving biomaterials and biofabrication.

PI：Fisher，John Pproposal编号：1604742当更换故障或患病的组织时，心血管外科医生经常使用含有天然组织成分的生物材料，例如脱毛的心包，例如作为植入物的细胞外基质（ECM）。为了保留机械性能，组织的一种常见治疗方法是通过化学固定，例如浸泡在戊二醛（GA）中。 但是，GA处理通常会导致植入物的有害钙化。该提案的目的是通过将ECM涂上新型可生物降解的聚合物涂层（聚（富马酸丙烯酸丙二烷）或PPF）来消除GA处理的需求，该聚合物涂层（聚（Polylene fumarate）或PPF）将提供具有许多理想特性的增强底物。 机械性能和降解时间是可调的。 可以通过将生长嵌入PPF中的微粒来增强局部生物活性。 因此，所得的杂化材料将表现出宿主的钙化和免疫反应降低，并具有抗性快速降解，同时又鼓励天然组织生长。这种新颖材料的成功开发将显着改善可用的材料选择，并彻底改变许多心血管修复操作的期望。通过开发新的生物材料和生物制造（B＆B）讲习班，其目标是将具有工程和科学背景的本科生引入涉及生物材料和生物制造的多样化的研究环境。该三年三年项目的目的是开发新型混合材料以创造出无数次替代或失调的材料。心血管手术中使用的许多基于组织的假肢采用戊二醛（GA）处理的心包。心包具有有利的机械性能，但GA处理总是导致植入物的有害钙化。这项研究检验了以下假设：通过对合成聚合物聚（PPF）（PPF）（PPF）的物理涂层治疗心包外细胞外基质（ECM），所得的杂化材料不仅会在植入后表现出降低的钙化和免疫反应，而且会在植入后进行免疫，而且会提供适合对组织和维护的平台进行控制和维护的组织。 该研究将进一步检验以下假设：通过添加生长因子洗脱聚（乳酸 - 乙醇酸）（PLGA）微粒，可以增强平台的生物学和活性。将确定两个组件（PPF和ECM）获得适当的机械性能和降解模型的理想组成，并将使用基于这些配方的3D打印树脂来研究对ECM随机组织的体外反应。 PPF增强的ECM和3DP PPF增强ECM的性能将在大鼠皮下模型中进行评估。将评估杂种材料的细胞向内生长，新产生的蛋白质和信号因子以及可能的钙沉积物。 该项目的更广泛影响包括开发新的混合生物材料以及在再生医学中阐明新策略和技术。提出的杂种材料将提供一种底物，以鼓励新ECM的天然细胞向内生长和沉积。一种具有降低免疫活性和随后钙化速率的新型材料将显着改善可用的材料选项，并彻底改变人们对许多心血管修复操作的期望。通过开发新的生物材料和生物制造（B＆B）讲习班，其目标是将工程和科学背景的大学生引入涉及生物材料和生物生物制造的多样化研究环境，从而提高了教育影响。