Bioresorbable Vascular Grafts

The concept of spontaneous in vivo organ regeneration over or within a transient synthetic scaffold opens new avenues to organ replacement. The reconstruction of a functional arterial conduit through natural repair processes linked to the progressive disappearance of a fully resorbable vascular prosthesis presents several challenges: a degradable fabric must be manufactured. It must maintain its physical integrity until the deposition of proteins of biological origin, coupled with cellular ingrowth and tissue organization, provides the mechanical properties needed for a pressurized conduit. Since evaluation of vascular grafts in large laboratory animals is a complex and expensive undertaking, screening of candidate materials in vitro, in small animals and in less demanding locations would facilitate the lengthy development of prostheses of clinical interest. Polymers derived from a-hydroxy acids of the Krebs-cycle series degrade primarily through hydrolysis. Thus one may expect that the rate of depolymerization of the material and degradation of a fabric to be the same in vitro and in vivo, independent of animal species, and of site of implantation. This is only partly true: the mass loss of implants located subcutaneously in the mouse is faster than that of controls immersed in buffered saline at body temperature, even if the molecular weight decay is the same. Subcutaneous implants in the mouse often show slower initial degradation than in a homologous location in the dog. Subcutaneous implants in the dog do not degrade as fast as arterial graft implants. Techniques to assess these differences include measurements of molecular weight by gel permeation chromatography, morphometric measurements of fibril size in the strands of polymer yarns, quantitative assessment of nuclear density of the cell population within a bioresorbable fabric or in the tissue capsule around a polymer implant, and optical characterization of polymer fabric and of its components in the case of blends. The role of mechanical conditions such as stirring, cyclical stress and hydrostatic water flux, and the importance of cell-mediated phenomena such as phagocytosis in the disappearance of bioresorbable polymers, need to be investigated.