EFFECT OF BONE MORPHOGENETIC PROTEIN ON TENDON TO BONE HEALING

具体目标：这项研究将研究一种改善伤口愈合的方法 将肌腱移植到关节内骨隧道中，这是必需的 在几个重建程序中，如前十字韧带 (前交叉韧带)膝关节重建。在目标1中，我们将评估 重组人骨形态发生蛋白-2、重组人骨形态发生蛋白-12促进肌腱移植骨愈合 隧道。这些药剂效果将相互比较，并 在没有BMP的情况下愈合，BMP的最佳剂量将被确定。这个 目标1中确定的最有效的骨形态发生蛋白类型和剂量 在Aim#2中，将进一步评估肌腱到骨骼的愈合情况 详细的组织学和生物力学测量。AIM#3将使用 分子生物学进一步深入了解糖尿病的发病机制 肌腱到骨骼的愈合过程。如果发现重组人骨形态发生蛋白-2和/或重组骨形态发生蛋白-12 是有效的，这可能允许使用骨形态发生蛋白来促进愈合 在前交叉韧带重建等手术中进行肌腱到骨骼的移植。 研究设计和方法：我们将使用一种 兔前交叉韧带模型的建立 将肌腱移植物置入骨隧道的重建 股骨和胫骨。外源性rhBMP-12将应用于肌腱- 实验肢体的骨界面上，而对照(对侧) 一端不会收到BMP。骨内肌腱移植物的愈合 隧道将使用详细的组织学、放射学和 肢体有无愈合的生物力学指标比较 BMP。组织形态计量学将用于量化骨向内的生长。 移植物和Northern印迹将用于评估特异性的表达 基质蛋白基因。 长期目标：这项工作的目标是推动我们的 对肌腱-骨愈合过程的理解和发展 改善愈合的方法。因为植骨固定的部位 代表了移植后早期最薄弱的领域， 改善移植物固定和愈合的技术的发展是 对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.