Segmental defects in bones often are difficult to manage and require multiple-phase surgery to achieve adequate union and function. Current treatment options including autografts, allografts, and distraction osteogenesis have brought forth successes, yet are still with many limitations. In case of treatment failure, alternative treatment may involve serious consequences such as leg shortening or amputation. To overcome the limitations in these treatment options, we are exploring tissue engineering. Tissue engineering approach uses a biodegradable scaffold to carry biological factors and/or cells to facilitate tissue regeneration. This approach has been successful when scaffold is protected from load bearing. Bone regeneration in scaffolds subjected to loading has been challenging due to the relatively low mechanical properties in scaffolds. In this project, we propose to regenerate bone in large segmental bone defects using a load-bearing, biodegradable carrier carrying demineralized bone matrix (DBM). Unlike traditional porous scaffolds, the degradable carrier can be stabilized by intramedullary pin and participate in load-bearing function in the initial healing phase. After providing biomechanical stability and DBM delivery, the carrier will degrade at a later time. The hypotheses we have for this proposal are: 1. Load-bearing carrier combined with DBM shortens the time required for bone union to take place in rat femoral segmental defects. 2. Load-bearing carrier combined with DBM improves bone formation in rat femoral segmental defects. 3. Load-bearing carrier combined with DBM improves final mechanical properties of the rat femur after segmental defect regeneration. Forty-five Long-Evans rats will be used to test the hypotheses. Biodegradable carriers will be manufactured from poly(caprolacton) trimethacrylate/tricalcium phosphate composites. Low (0.05ml) and high (0.3 ml) dose of putty type DBM (DBX(r), Densply) will be incorporated into the carrier. The carrier will be implanted in a 5 mm segmental defect in rat femurs for 24 weeks. The time for unions to occur will be evaluated with x-ray at week 1, 3, 6, 15 and 24 weeks after implantation. The femurs will be retrieved after 24 weeks of implantation. Five femurs from each group will be evaluated with dual energy X-ray absorptiometry (DXA) for bone mineral content (BMC; g) and with peripheral computed tomography (pQCT) for the bone cross sectionaj area (CSA; mm2), volumetric bone density (vBMD; mg/cm3), and bone mineral content (BMC; mg/cm). The specimens will then be embedded in paraffin, decalcified, sectioned, and stained with McNeals Tetrachrome and Safarin-0 in alternating sections for bone and cartilage. The BMC, CSA, and vBMD of control versus low dose and control versus high dose groups will be compared. Ten femurs from each group will be tested with four-point-bending on a material testing machine for bending strength. The ultimate force (Fu; N), stiffness (S; N/mm) and energy to ultimate force (U; N.mm) will be compared between the control and the DBM treated groups.
| Chu, Tien-Min G; Warden, Stuart J; Turner, Charles H et al. (2007) Segmental bone regeneration using a load-bearing biodegradable carrier of bone morphogenetic protein-2. Biomaterials 28:459-67 |
