Haptide-coated collagen sponge as a bioactive matrix for tissue regeneration.

Abstract

We previously described a new class of conserved, cell adhesive (haptotactic) peptides, termed Haptides, based on sequences first identified in fibrinogen. Here, we describe a new biomaterial, Haptide-coated Collagen, in which the carbodiimide reagent, EDC, was used to covalently couple a Haptide (preC gamma), equivalent to the carboxy terminus of the fibrinogen gamma chain, to a cross-linked sponge composed of bovine collagen type I. The dose response of Haptide bound to collagen on cell attachment response reached a plateau at a concentration of 5-10 mg Haptide/g collagen. The Haptized-collagen was more stable to 1N NaOH, with a degradation half-time (T(1/2)) of 1.7 h, compared to 0.9 h for untreated control. Haptized collagen discs could be loaded with approximately 30% more human dermal fibroblasts or bovine aortic endothelial cells than unmodified collagen discs (p < 0.001). After a proliferation phase, Haptized collagen discs contained approximately 45% more fibroblasts than non-Haptized discs (p < 0.01). Histological analysis following sub-dermal implantation in rats indicated that at day 8, Haptized collagen sponge was less degraded than unmodified collagen sponge, attracted more endogenous fibroblasts with newly deposited collagen, and provoked less inflammatory or other adverse reactions. These results suggest potential clinical applications for Haptized collagen sponge for tissue regeneration, soft tissue augmentation, skin repair, and wound healing.