Effects of carbodiimide crosslinking and load environment on the remodeling of collagen scaffolds

Tissue engineering aims to develop clinical prostheses that are ultimately replaced by a functional, cell-produced matrix. For this goal to be achieved, the material must not only perform all the critical functions of the lost tissue immediately upon implantation, but also be replaced with new tissue at such a rate that tissue integrity is maintained. In the present study, prostheses formed from reconstituted collagen fibers were crosslinked to various levels with a carbodiimide; the same implant material was shown to be perceived in a variety of ways by its host. Variously crosslinked constructs were implanted in rats. Lightly crosslinked collagen fabrics implanted in abdominal wall defects remodeled into a fascia-like material within 90 days, in contrast to heavily crosslinked fabrics that were still persistent at this time point with little new tissue ingrowth and a marked foreign body reaction. However, the remodeling response was found to be site dependent, as heavily crosslinked collagen scaffolds implanted as anterior cruciate ligament (ACL) replacements in a dog model were adequately replaced by functional neoligamentous structures within 12 weeks.