Cardiovascular Tissue Engineering


Cardiovascular disease is one of the leading causes of death in the United States and can manifest as the breakdown of functional heart muscle due to an impaired blood supply, heightened cardiovascular pressures resulting from thickened heart muscle and blood vessels, calcification of blood vessels or heart valves and several other etiologies.  Tissue engineering represents one strategy in overcoming poor prognosis as a result of cardiovascular disease. Tissue engineering is the combination of biomaterials, cells and/or bioactive compounds to generate a product with properties that mimic the native tissue.  To date several investigators have used tissue engineering to create biomimetic heart valves, blood vessels and heart muscle patches as a solution to repairing damage to cardiovascular tissues.  The VIRC is helping to lead the way in developing novel biological scaffolds that can be used as biomaterials for cardiovascular tissue engineering.


Xenogeneic Scaffold generation for Heart Valve Tissue Engineering

The ability of residual antigens on decellularized tissue to elicit the immune response upon implantation motivates development of a more rigorous antigen removal (AR) process for xenogeneic scaffold generation. Antigen removal strategies promoting solubilization of hydrophilic proteins (predominantly cytoplasmic) enhance the reduction of hydrophilic antigenicity; however, the diversity of protein antigens within a tissue necessitates development of AR strategies capable of addressing a spectrum of protein antigen solubilities. Methods for promoting solubilization of lipophilic proteins (predominantly membrane) were investigated for their ability to reduce lipophilic antigenicity of BP when applied as a second AR step following hydrophilic AR. Bovine pericardium following AR (BP-AR) was assessed for residual hydrophilic and lipophilic antigenicity, removal of known lipophilic xenoantigens, tensile properties, and extracellular matrix structure and composition. Facilitating hydrophile solubilization followed by lipophile solubilization (using amidosulfobetaine-14 (ASB-14)), in a two-step sequential, differential AR strategy, significantly reduces residual hydrophilic and lipophilic antigenicity of BP-AR beyond that achieved with either one-step hydrophilic AR or decellularization using 1% (w/v) sodium dodecyl sulfate. This work demonstrates the importance of a sequential, differential protein solubilization approach to reduce biomaterial antigenicity in the production of a xenogeneic scaffold for heart valve tissue engineering.

Investigators: Leigh Griffiths


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