EFFECT OF BONE MORPHOGENETIC PROTEIN ON TENDON TO BONE HEALING

骨形态发生蛋白对肌腱骨愈合的影响

• 批准号: 6100738
• 负责人: SCOTT RODEO
• 金额: $ 10.7万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6100738
• 关键词: biomechanics; bone morphogenetic proteins; histology; laboratory rabbit; musculoskeletal regeneration; musculoskeletal transplantation; northern blottings; radiography; tendons

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.

具体目标：本研究将探讨一种改善愈合的方法 将肌腱移植物植入关节内骨隧道，这是必需的 在一些重建手术中，例如前十字韧带 (ACL) 膝关节重建。在目标#1中，我们将评估能力 rhBMP-2 rhBMP-12 促进骨中肌腱移植物的愈合 隧道。这些药物的效果将相互比较并 无需 BMP 即可愈合，并且将确定最佳 BMP 剂量。这 目标 #1 中确定的 BMP 类型和剂量最有效 肌腱到骨骼的愈合将在目标 #2 中进一步评估 详细的组织学和生物力学测量。目标 #3 将使用 分子生物学，以进一步了解其机制 肌腱到骨骼的愈合过程。如果发现 rhBMP-2 和/或 rhBMP-12 是有效的，这可能允许使用 BMP 来增强愈合 ACL 重建等手术中的肌腱到骨骼。 研究设计和方法：我们将使用 兔前交叉韧带（ACL）模型的建立 重建，其中将肌腱移植物放入骨隧道中 股骨和胫骨。外源性 rhBMP-12 将应用于肌腱 实验肢体的骨界面，而对照（对侧） 端不会收到 BMP。骨内肌腱移植物的愈合 将使用详细的组织学、射线照相和 比较四肢愈合情况的生物力学测量 位图。组织形态计量学将用于量化骨向内生长 将使用移植物和 Northern 印迹来评估特定的表达 基质蛋白基因。 长期目标：这项工作的目标是进一步推进我们的工作 了解肌腱到骨骼的愈合过程并发展诺埃尔 改善愈合的方法。由于移植物固定在骨上的部位 代表移植后早期最薄弱的区域， 改善移植物固定和愈合的技术的发展 对于改善患者的治疗效果至关重要。