EFFECT OF BONE MORPHOGENETIC PROTEIN ON TENDON TO BONE HEALING

具体目的：本研究将研究一种方法，以改善愈合 肌腱移植到关节内骨隧道，这是必要的 在几种重建手术中 (ACL)膝盖的重建。在目标#1中，我们将评估 rhBMP-2和rhBMP-12以增强骨中肌腱移植物的愈合 隧道这些试剂的效果将相互比较， 在没有BMP的情况下愈合，并且将确定最佳BMP剂量。的 在目标#1中确定的BMP的类型和剂量对于 肌腱-骨愈合将在目标#2中使用 详细的组织学和生物力学测量。目标#3将使用 分子生物学，以进一步了解的机制， 肌腱到骨的愈合过程如果发现rhBMP-2和/或rhBMP-12 有效，这可能允许使用BMP来增强 在ACL重建等手术中， 研究设计和方法：我们将使用 建立兔前交叉韧带（ACL）模型 将肌腱移植物置入骨隧道的重建术， 股骨和胫骨将外源性rhBMP-12应用于肌腱- 骨界面在实验肢体，而对照（对侧） 方将不会收到BMP。肌腱移植物在骨中的愈合 将使用详细的组织学、放射学和 生物力学测量比较有和没有肢体之间的愈合 BMP。将使用组织形态测定法定量骨长入 移植物和北方印迹将用于评估特异性 基质蛋白基因。 长期目标：这项工作的目标是进一步促进我们的 了解肌腱-骨愈合的过程并开发诺埃尔 改善愈合的方法。由于移植物固定在骨上的部位 代表移植后早期最弱的区域， 提高移植物固定和愈合的技术的发展是 对于改善患者预后至关重要。

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.