Abstract
Loss of large bone segments due to fracture resulting from trauma or tumor removal is a common clinical problem. The goal of this study was to evaluate the use of scaffolds containing testosterone, bone morphogenetic protein-2 (BMP-2), or a combination of both for treatment of critical-size segmental bone defects in mice. A 2.5-mm wide osteotomy was created on the left femur of wildtype and androgen receptor knockout (ARKO) mice. Testosterone, BMP-2, or both were delivered locally using a scaffold that bridged the fracture. Results of X-ray imaging showed that in both wildtype and ARKO mice, BMP-2 treatment induced callus formation within 14 days after initiation of the treatment. Testosterone treatment also induced callus formation within 14 days in wildtype but not in ARKO mice. Micro-computed tomography and histological examinations revealed that testosterone treatment caused similar degrees of callus formation as BMP-2 treatment in wildtype mice, but had no such effect in ARKO mice, suggesting that the androgen receptor is required for testosterone to initiate fracture healing. These results demonstrate that testosterone is as effective as BMP-2 in promoting the healing of critical-size segmental defects and that combination therapy with testosterone and BMP-2 is superior to single therapy. Results of this study may provide a foundation to develop a cost effective and efficient therapeutic modality for treatment of bone fractures with segmental defects.
Highlights
Bone fracture is a common and serious medical problem
The use of bone morphogenetic protein-2 (BMP-2) loaded scaffold to stabilize the fracture and to initiate bone regeneration has been shown to be an effective treatment for segmental defects [6]
We found that treating the fracture with a scaffold containing bone morphogenetic proteins (BMPs)-2 resulted in callus formation 14 days after initiation of the treatment, whereas no callus was formed if the fracture was treated with a scaffold containing no BMP-2 or testosterone during the entire period (35 days) of the study (Fig. 1, 2)
Summary
Bone fracture is a common and serious medical problem. Fractures may occur in any bone due to high force impact and are much more prevalent in individuals with osteoporosis, bone cancer, or osteogenesis imperfecta. Segmental defects are very difficult to manage, as multiple phases of surgery are usually required to achieve an adequate union and to regain the function of bone. Current treatment options such as autografts, allografts, and distraction osteogenesis have yielded some successes [1,2,3], serious consequences such as leg shortening or amputation may result if the treatment fails. To overcome these limitations, tissue engineering by delivering therapeutic substances such as bone morphogenetic proteins (BMPs) to the segmental defect to facilitate bone regeneration has been attempted [4,5,6]
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