Biocompatibility of NDGA-polymerized collagen fibers. II. Attachment, proliferation, and migration of tendon fibroblasts in vitro.

The material properties of collagen fibers polymerized with nordihydroguaiaretic acid (NDGA) are equivalent to native tendon, suggesting that NDGA crosslinking may provide a viable approach to stabilizing collagenous materials for use in repairing ruptured, lacerated, or surgically transected fibrous tissues, such as tendons and ligaments (Koob & Hernandez, Biomaterials, in press). The present study evaluated the biocompatibility of these fibers with cultured bovine tendon fibroblasts. Fibroblast attachment, migration, and proliferation on NDGA-crosslinked materials were compared to those on prepolymerized type I tendon collagen constructs as well as on tissue-culture-treated plastic. Fibroblast attachment on NDGA-crosslinked collagen fibrils was equivalent to attachment on plates coated with collagen alone. Over a period of 8 days in culture, attached fibroblasts proliferated on NDGA-crosslinked collagen at a rate identical to that of fibroblasts attached to native collagen. In order for the biomaterial effectively to bridge gaps in fibrous tissues, fibroblasts must be able to migrate and replicate on the bridging fiber. Control and crosslinked fibers were inserted in calf tendon explants, with a portion of the fiber extending out of the sectioned end of the tendon. Explants were cultured for 9 weeks, and the number of cells was measured at weekly intervals. Cells appeared on the fibers after 1 week of culture. By 2 weeks, cells had colonized the entire fiber. The number of cells continued to increase throughout the 9 weeks in culture, forming a layer several cells thick. Histologic analysis indicated that the fibroblasts populating the fibers appeared to originate in the epitenon. There was no difference in the rate of fibroblast migration and replication, nor in the ultimate number of colonizing cells, between control collagen fibers and NDGA-crosslinked fibers. NDGA-crosslinked fibers may provide a means of bridging gaps in ruptured, lacerated, or surgically transected tendons by providing a mechanically competent scaffold on which tendon fibroblasts can migrate, attach, and proliferate.