Biohybrid Strategies for Decellularized Tissues

主要研究者：Fisher，John P提案编号：1604742在更换故障或患病组织时，心血管外科医生通常使用含有天然组织成分的生物材料，例如脱细胞心包，其可用作植入物的细胞外基质（ECM）。为了保持机械性能，组织的一种常见处理是通过化学固定，例如浸泡在戊二醛（GA）中。 然而，GA处理通常导致植入物的有害钙化。该提案的目标是通过用新型可生物降解聚合物涂层（聚（富马酸丙二醇酯）或PPF）涂覆ECM来消除对GA处理的需要，所述新型可生物降解聚合物涂层将提供具有许多期望性质的增强基底。 机械性能和降解时间是可调的。 通过在PPF中嵌入生长洗脱微粒可以增强局部生物活性。 因此，所得的混合材料将表现出减少的钙化和来自宿主的免疫应答，并且抵抗快速降解，同时促进天然组织向内生长。这种新型材料的成功开发将显著改善可用的材料选择，并彻底改变许多心血管修复手术的预期。教育的影响是通过一个新的生物材料和生物织物（B B）研讨会的发展，其目标是介绍与工程和科学背景的本科生到一个涉及生物材料和生物织物的多样化的研究环境。这个为期三年的项目的目标是开发新的混合材料，以创建一个故障或病变组织的替代品。心血管外科手术中使用的许多基于组织的假体采用戊二醛（GA）处理的心包。硅藻土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。本研究检验了以下假设：通过用合成聚合物聚富马酸丙二醇酯（PPF）的物理涂层处理心包细胞外基质（ECM），所得混合材料不仅在植入时表现出钙化和免疫反应减少，而且将提供适合于组织受控再生和维持的平台。 本研究还将检验以下假设：通过添加生长因子洗脱聚（乳酸-乙醇酸共聚物）（PLGA）微粒，可增强平台的生物学和活性。将确定两种组分（PPF和ECM）的理想组成，以获得贴片模型的适当机械性能和降解，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。将在大鼠皮下模型中评价PPF增强ECM和3DP PPF增强ECM的性能。将评估混合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。 该项目的更广泛影响包括开发一类新的混合生物材料，以及阐明再生医学中的新策略和技术。所提出的混合材料将提供一种基质，促进天然细胞向内生长和新ECM的沉积。具有降低的免疫活性和随后的钙化率的新型材料将显著改善可用的材料选择，并彻底改变许多心血管修复手术的期望。教育的影响是通过一个新的生物材料和生物织物（B B）研讨会，其目的是介绍与工程和科学背景的本科生，涉及生物材料和生物织物的多样化的研究环境的发展。

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.