OTA 2006 Posters

Scientific Poster #96 Basic Science

· · Tricalcium Phosphate Putty as an Osteogenic Protein-1 (OP-1/BMP-7) Carrier
Donna L. Wheeler, PhD1 (*); G. Elizabeth Pluhar, DVM, PhD2 (*);
A. Simon Turner, DVM3 (*); Allen R. Pierce, BA4 (e-Stryker Biotech);
1Charles River Laboratories, Southbridge, Massachusetts, USA;
2University of Minnesota, Minnesota, Minnesota, USA;
3Colorado State University, Fort Collins, Colorado, USA;
4Stryker Biotech

Purpose: OP-1 (bone morphogenetic protein-7 [BMP-7]) is usually delivered to skeletal defects via a particulate collagen carrier. A "putty-like" carrier containing ceramic particles would allow the surgeon to mold the implant and fill osseous defects while also providing an osteoconductive scaffold for osseous regeneration. The study objective was to evaluate bone regeneration of a critical-sized (5-cm) ovine tibial diaphyseal defect when grafted with tricalcium phosphate (TCP) within a natural polymer binder combined with OP-1.

Methods: 20 mature ewes had unilateral 5-cm tibial middiaphyseal defects created and stabilized with an 8-mm interlocking nail. The defects were either left empty (N, negative control) or filled with 4.2 cc of TCP combined with a carboxymethylcellulose binder (CMC) and OP-1 at 4 doses (A = 0.0 mg, B = 1.15 mg, C = 2.3 mg, or D = 3.45 mg). Healing was monitored with monthly radiographs until necropsy at 3 months. Tibiae were evaluated histomorphometrically. One-way ANOVA was used to determine significant differences between groups (a = 0.05).

Results: Incidence of radiographic callus bridging increased with OP-1 dose (N = 0/4, A = 1/4, B = 3/4, C = 4/4, D = 4/4). Histomorphometrically, higher doses of OP-1 had greater callus area (P = 0.0064), more complete bone bridging across the defect (P = 0.0001) and a trend toward greater resorption of the graft material (P = 0.089).

Conclusion/Significance: The healing properties of the osteoconductive TCP material were potentiated by the addition of an osteoinductive agent (OP-1). As OP-1 dose increased, the variability in the histomorphometric parameters decreased, indicating consistent complete bony bridging of the defect and concurrent graft resorption. The percent bone within the callus was increased from 30% to more than 50% when the osteoinductive agent OP-1 was added to the osteoconductive TCP + CMC mixture. The use of the natural polymer (CMC) did not cause adverse tissue reaction and improved handling and delivery of the TCP particles. Clinically, this synthetic biomaterial carrier provides a convenient and effective way to deliver an osteoconductive scaffold with or without an osteoinductive protein to skeletal defects resulting from trauma.

If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.
· The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an "off label" use). · · FDA information not available at time of printing.