Exploiting glycation to stiffen and strengthen tissue equivalents for tissue engineering

Glycation, the nonenzymatic crosslinking of proteins by reducing sugars, is known to cause stiffening of soft tissues over a lifetime, particularly in diabetics. We show here that glycation due to elevated glucose and ribose concentrations in cell culture medium can be exploited in a matter of a few weeks of incubation to stiffen and strengthen tissue equivalents and to increase their resistance to collagenolytic degradation, all without loss of cell viability. Glycated tissue equivalents did not elicit inflammation or induce calcification upon subcutaneous implantation; rather, they were permissive to host integration and remodeling. Thus a pathological process might be used in a targeted way in tissue engineering to fabricate tissue equivalents with the required mechanical properties and desired resorption rate upon implantation.