J Oral Maxillofac Surg 65:1495-1502, 2007 Bone Engineering of the Rabbit Ulna Ahmed El-Ghannam, PhD,* Larry Cunningham, Jr, DDS, MD,† David Pienkowski, PhD,‡ and Amanda Hart, MS§ Purpose: The purpose of the present preliminary study is to show that a novel 3-dimensional porous silica-calcium phosphate nanocomposite (SCPC) can provide a controlled release of rhBMP-2 and regenerate bone in a load-bearing segmental defect. Materials and Methods: A bone replica of the rabbit ulna was created from SCPC powder using rapid prototyping technology. The ceramic bone replica was coated with rhBMP-2 and then implanted into a 10-mm segmental defect created in a rabbit ulna and fixated with a 1-mm titanium adaptation plate. Bone healing was evaluated using computed tomography (CT) scan, histomorphometry, and biomechanical techniques. The release kinetics of rhBMP-2 and the dissolution kinetics were also determined in vitro. Statistical analysis was performed to compare the biomechanical strength of the grafted bone with the contralateral unoperated ulna. Results: After 4 weeks, CT scans showed that the critical size defect had been replaced by newly formed bone. Torsional testing of the ulna after 12 weeks showed restoration of maximum torque and angle at failure. Histological evaluation showed that the regenerated bone had the morphological characteristics of mature bone. SCPC provided a sustained release profile of an effective dose of rhBMP-2 for 14 days. Conclusions: The SCPC-rhBMP-2 hybrid enhanced bone regeneration in a load-bearing segmental defect in a rabbit ulna. The regenerated bone acquired morphology and mechanical strength typical for natural bone. The enhanced bone formation correlates well with the surface bioactivity and effective release profile of rhBMP-2. The present preliminary study shows the proof of principles that porous, resorbable, bioactive SCPC-rhBMP-2 tissue engineering hybrid can serve as a substitute for autologous bone in load-bearing applications. This is a US government work. There are no restrictions on its use. Published by Elsevier, Inc on behalf of the American Association of Oral and Maxillofacial Surgeons. J Oral Maxillofac Surg 65:1495-1502, 2007 The repair of large segmental bone defects is a chal- lenging problem in orthopedic and maxillofacial sur- geries. Current treatment options include bone graft- ing (auto- or allogenic), vascularized bone grafts, or distraction osteogenesis. However, these techniques often involve multistage surgical procedures, inhibit early limb function, and require several revision pro- cedures to maintain acceptable alignment and achieve osseous healing. An alternative approach in- volves the design of biomaterials with specific osteo- conductive and osteoinductive properties, geometry to provide the correct anatomy, and internal structure conducive to autogenous bone cells invasion and vas- cularization. These characteristics in principle repre- sent the prerequisites for ideal graft integration and subsequent optimal mechanical performance. Bone morphogenetic proteins (BMPs) are biologi- cally active osteoinductive cytokines with significant clinical potential, but the lack of a delivery system enabling full osteoinduction has precluded their wider implementation in clinical therapeutics. Incor- poration of BMP in hydroxyapatite (HA) ceramic, 1-3 HA/collagen, 4 and HA/tricalcium phosphate (TCP) composites 5-7 accelerate bone formation but require a high BMP dose (100 mg) because of their inability to retain BMPs. 8 Other issues that must be considered for the effective application of HA ceramic are the limited resorbability and poor mechanical strength. Moreover, like the collagen composite, there were problems associated with inflammatory and immuno- Received from the University of Kentucky, Lexington, KY. *Associate Professor of Biomedical Engineering, Center for Bio- medical Engineering and Center for Oral Health Research, College of Dentistry. †Associate Professor of Oral and Maxillofacial Surgery, Depart- ment of Oral and Maxillofacial Surgery, College of Dentistry. ‡Associate Professor of Biomechanics, Orthopaedic Biomechan- ics Laboratory, Center for Biomedical Engineering. §Master of Biomedical Engineering, Center for Biomedical Engi- neering. Supported by the Kentucky Science and Engineering Foundation (Grant KSEF-414-RDE-004) and NIH Grant P30-AR46031. Address correspondence and reprint requests to Dr El-Ghannam: Center for Biomedical Engineering, University of Kentucky, Rose Street, Lexington, KY 40506; e-mail: arelgh2@uky.edu This is a US government work. There are no restrictions on its use. Published by Elsevier, Inc on behalf of the American Association of Oral and Maxillo- facial Surgeons. 0278-2391/07/6508-0010$32.00/0 doi:10.1016/j.joms.2006.10.031 1495