REPAIR OF CRITICAL SIZE RAT CALVARIAL DEFECTS USING EXTRACELLULAR-MATRIX PROTEIN GELS

In this study the authors examined the capacity of gels of reconstitut ed basement membrane, laminin, and type I collagen to mediate repair o f critical size defects in rat calvaria. Although autografts are widel y used to repair bone defects caused by trauma or surgical treatment o f congenital malformations, neoplasms, and infections, an adequate qua ntity of graft is not always available. Allogenic bone is readily avai lable, but its use is associated with an increased incidence of nonuni on, fatigue fracture, and rejection. Biologically active, purified com ponents of basement membranes, which have been shown to promote osteog enic differentiation and angiogenesis in vitro and type I collagen (th e major constituent of bone extracellular matrix) can be formed into n ative isotonic space-filling gels. In this study critical size calvari al defects were created in retired male Sprague-Dawley rats. Thirty-si x animals were divided into seven groups. Group 1 (control) received n o treatment for the defects. Group 2 animals were implanted with methy lcellulose. Groups 3, 4, 5, and 6 were implanted with gels of type I c ollagen, reconstituted basement membrane, or laminin, respectively. Th e last group of three animals (Group 7) was implanted with 100 mu g of type I collagen gels (identical to Group 3) and sacrificed at 20 week s following a single CT scan to determine if complete healing could be obtained with this method given sufficient time. Except for rats in t he type I collagen group that was evaluated by multiple computerized t omography (CT) scans biweekly from 2 to 12 weeks, bone repair was eval uated using CT at 12 weeks. Healing was quantified using three-dimensi onal reconstruction of CT. Following the final CT scan in each experim ental group, animals were sacrificed, and a sample of tissues was eval uated by conventional histology. Animals treated with type I collagen gels showed 87.5% repair of the area of the defects at 12 weeks and 92 .5% repair by 20 weeks. Increasing the gel volume 1.5 x accelerated co mplete repair to 3 months. Murine-reconstituted basement membrane and laminin gels induced 55.5% and 46.3% repair, respectively, at 3 months . In untreated control animals 7% repair of the area of the defects sh owed at 3 months. Histological analysis confirmed new bone formation i n partial and completely healed defects. Bioengineered native collagen gels may have wide applicability for bone repair as an alternative bo ne