EFFECT OF BONE MORPHOGENETIC PROTEIN ON TENDON TO BONE HEALING

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Specific Aims: This study will examine a method to improve the healing of a tendon graft into an intra-articular bone tunnel, which is required in several reconstructive procedures such as anterior cruciate ligament (ACL) reconstruction in the knee. In aim #1 we will evaluate the ability of rhBMP-2 rhBMP-12 to augment healing of a tendon graft in a bone tunnel. The effect of these agents will be compare to each other and to healing without BMP, and the optimum BMP dose will be determined. The type and dosage of BMP identified in aim #1 as most effective for tendon-to-bone healing will be further evaluated in aim #2 using detailed histological and biomechanical measures. Aim #3 will use molecular biology to gain further insight into the mechanism of the tendon-to-bone healing process. If rhBMP-2 and/or rhBMP-12 are found to be effective, this may allow the use of BMP to augment healing of tendon-to-bone in procedures such as ACL reconstruction. Research Design and Methods: We will accomplish these aims using an established rabbit model of anterior cruciate ligament (ACL) reconstruction in which a tendon graft is placed into bone tunnels in the femur and tibia. Exogenous rhBMP-12 will be applied to the tendon- bone interface in experimental limbs, while the control (contralateral) side will not receive BMP. Healing of the tendon graft in the bone tunnel will be examined using detailed histologic, radiographic, and biomechanical measures to compare healing between limbs with and without BMP. Histomorphometry will be used to quantify bone-ingrowth into the graft and Northern blot will be used evaluate expression of specific matrix protein genes. Long-Term Objective: The objective of this work is to further our understanding of the process of tendon-to-bone healing and develop noel methods for improved healing. Since the site of graft fixation to bone represents the weakest area in the early post transplant period, the development of techniques to improve graft fixation and healing are critical for improving patient outcomes.