Leigh G. Griffiths, VetMB, MRCVS, PhD, DSAS (Soft Tissue), DipACVIM (Cardiology)
“Xenogeneic Scaffolds in Tissue Engineering: Is the Decellularization Paradigm Flawed?”
In principle xenogeneic biomaterials represent an ideal scaffold for cardiovascular tissue engineering due to their complex matrix architecture and composition. However, following implantation un-fixed xenogeneic biomaterials are subject to an aggressive immune-mediated rejection response. The NHLBI xenotransplantation working group highlighted the significance of this response by identifying biomaterial xenoantigenicity as the critical hurdle to expanding the use of xenogeneic organs and tissues in clinical practice. Consequently, any attempt to use an un-fixed xenogeneic biomaterial as a scaffold for tissue engineering must address the issue of biomaterial xenoantigenicity prior to implantation in an immunocompetent recipient.
Removal of xenoantigens is the stated goal in development of xenogeneic biomaterials as scaffolds for tissue engineering applications. Initial attempts at scaffold production focused on cell removal, confirmed by light microscopy (decellularization). The decellularization paradigm makes two critical assumptions: 1)enoantigens are solely associated with cellular components of the tissue, and 2) removal of cells on light microscopy would equate to xenoantigen removal. Our group has recently challenged both of the assumptions implicit in the decellularization approach by demonstrating that non-cellular xenoantigens are present in the candidate biomaterial (BP) and that assessment of cellularity under light microscopy is prone to both under-and over-estimation of actual antigen removal efficiency. The realization that decellularization is an inadequate outcome measure for prediction of immunogenicity of un-fixed xenogeneic biomaterials has led to renewed focus on antigen removal in the development of xenogeneic scaffolds for tissue engineering applications.
This presentation will discuss the new paradigm of antigen removal in production of xenogeneic scaffolds for tissue engineering applications. Our group has developed an antigen removal approach which exploits the principles of differential solubility to facilitate stepwise removal of xenoantigens from candidate xenogeneic biomaterials. Our approach results in a significant reduction in residual antigenicity of the biomaterial compared to previously reported decellularization methods, while also maintaining superior biomaterial mechanical properties, matrix structure, composition and compatibility with recellularization.
When: 11/17/11 4:00 PM
Where: 1005 GBSF