Biohybrid Strategies for Decellularized Tissues

University Of Maryland, College Park, College Park MD

Investigators

Abstract

PI: Fisher, John P Proposal Number: 1604742 When 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.