ACELLULAR MATRIX - A BIOMATERIALS APPROACH FOR CORONARY-ARTERY BYPASSAND HEART-VALVE REPLACEMENT

We have developed a multistep detergent-enzymatic extraction process ( involving hypotonic and hypertonic solutions, the detergents octyl-phe noxy-polyethoxyethanol and sodium dodecyl sulfate, as well as DNAse an d RNAse) which, while inhibiting autolysis, removes all cells from tis sues and, with them, cellular antigens together with lipids and more s oluble glycosaminoglycans. What remains is acellular matrix with the s tructural proteins well conserved and normally arranged. Canine arteri es extracted to acellular matrix were implanted as coronary artery byp ass allografts in a canine model, without the use of cardiopulmonary b ypass, and compared with autogenous saphenous veins. Of nine pilot ace llular matrix implants, four were patent, as compared with four of sev en saphenous vein grafts. All occlusions in both graft types occurred acutely soon after implantation, with almost all patent grafts followe d up for 6 months. The acellular matrix allografts showed no inflammat ion and only minimal cellular repopulation. This model needs further d evelopment, but appears promising for preclinical evaluation. Canine a ortic and pulmonic valves extracted to acellular matrix using a modifi cation of our extraction process, eliminating the detergent sodium dod ecyl sulfate, were implanted heterotopically as allografts in the left main pulmonary artery in dogs, a location chosen to avoid the need fo r cardiopulmonary bypass. At 1 month, two-dimensional echocardiography of six implants showed leaflet motion and 3- to 5-mm Hg transvalvular gradients. Explant histology of four valves at 1 month showed no infl ammation, cellular repopulation at the base of the valve, and partial endothelialization. Although much remains to be done, the acellular ma trix process has the potential to produce a coronary artery bypass gra ft with performance similar to that of autogenous saphenous vein and a bioprosthetic heart valve with performance similar to cryopreserved h omografts, both from an abundant supply of nonhuman tissues.