Decellularized xenogeneic tissues as a novel biomaterial

Akio Kishida, Tokyo Medical and Dental University

Natural tissue, especially autologous tissue is one of ideal materials for tissue regeneration. Decellularized tissue could be assumed as a second choice because the structure and the mechanical properties are well maintained. Decellularized human tissues (allogeneic tissues), for instance, heart valve, blood vessel, and corium, have already been developed and applied clinically. Nowadays, decellularized porcine tissues (xenogeneic tissues) are also investigated because of their enough supply. Several technologies have been developed to fabricate such as artificial valves, blood vessels and dermis. Decellularization techniques are classified by the chemicals used, such as acid or alkaline treatment, detergent treatment, or enzymatic digestion, and the physical methods used, such as snap freezing and mechanical agitation. Among these, detergent treatment is the most widely used. Decellularization of biological tissues by detergent treatment has the advantage of being easy to use, but its drawbacks include long treatment time, alteration of mechanical properties, and residual toxicity. Researchers have developed specific treatment recipes to overcome each of these problems. As another candidate for a new decellularization treatment, we have reported our work on the high-hydrostatic pressure (HHP) method. As the tissue set in the pressurizing chamber is treated uniformly, the effect of the high-hydrostatic pressurization does not depend on the size of tissue. Furthermore, HHP treatments are reported to have the ability of the extinction of bacillus and the inactivation of virus. So, the HHP treatment is also expected as the sterilization method. The unique characteristics of the HHP method are the destruction of cell membranes, uniform treatment, and short treatment time. Subsequent washing of the treated tissue can produce a decellularized tissue that does not adopt any chemical agents. We are investigating efficient processes of decellularization and re-cellularization of biological tissues to have biological scaffolds keeping intact structure and biomechanical properties. The presentation will focus particularly on the immunological reaction to the decellularized porcine blood vessel and cornea using the HHP technique. Determining the optimal conditions for obtaining biologic scaffold with undamaged extracellular matrices (ECM) and high decellularization was one of the goals of our research, because such decellularized tissues show the ideal biocompatibility. Our recent studies on tissue engineering using HHP decellularized tissue will be presented.