Biologically Enhanced Healing of Autograft ACL Reconstruction

自体 ACL 重建的生物促进愈合

• 批准号: 7807720
• 负责人: Braden C Fleming
• 金额: $ 149.18万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-28 至 2013-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7807720
• 关键词: Adolescent; Aftercare; Animal Model; Animals; Anterior; Anterior Cruciate Ligament; Articular ligaments; Autologous; Autologous Transplantation; Blood Platelets; Cartilage; Cell Therapy; Cells; Clinical; Clinical Research; Collagen; Contralateral; Control Groups; Data; Degenerative Disorder; Degenerative polyarthritis; Development; Economics; Evaluation; Foundations; Funding; Grant; Growth Factor; Healed; Health; Injury; Joint Laxity; Joints; Knee; Life; Ligaments; Mechanics; Methods; Miniature Swine; Modeling; Operative Surgical Procedures; Outcome; Outcome Measure; Parents; Patients; Performance; Porifera; Property; Quality of life; Rehabilitation therapy; Research; Risk; Risk Factors; Role; Stress; Synovial Fluid; Synovial Membrane; Techniques; Tendon structure; Time; Tissue Engineering; Work; anterior cruciate ligament healing; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; articular cartilage; base; cytokine; follow-up; graft healing; healing; improved; injured; injury and repair; ligament injury; premature; prevent; public health relevance; reconstruction; response; scaffold; secondary outcome; standard care; standard of care; success; young adult

DESCRIPTION (provided by applicant): The objective of this study is to improve the functional healing of an anterior curiae ligament reconstruction (ACLR) by using a collagen-platelet composite to enhance the biologic incorporation of the graft. The current "standard of care" for an anterior cruciate ligament (ACL) tear is ACLR using an autograft tendon. Despite short-term success of ACLR, increases in joint laxity occur after surgery, which may place the knee at risk for subsequent damage and early osteoarthritis (OA). Thus, techniques to enhance graft healing which reduce laxity, protect the joint, and preserve articular cartilage would provide better long-term outcome for the ACL injured patient. A collagen-platelet composite was recently developed by this research team to enhance the healing response of the ACLR graft. Platelets are known to release various growth factors and cytokines that stimulate intra-articular ligament healing. We hypothesized that they will improve graft healing as well. We have developed a method to contain the platelets around the graft using a collagen sponge. In the work funded by the parent R01, we have found significant improvements in both graft performance (300% increases in modulus and 250% improvement in yield stress) as well as significant reductions in knee laxity after 15 weeks of healing. Due to the relatively short follow-up evaluation (15 weeks), we have been unable to detect whether these improvements will significantly impact cartilage health after an ACL reconstruction. In this competitive revision, we propose to include two longer-term groups of animals (ACL reconstruction with collagen-platelet composite vs traditional ACL reconstruction) with survivals of 6 and 12 months. These groups will expand our original proposal and provide information as to whether the collagen-platelet composite, which significantly improves graft quality and knee laxity in the short-term, will continue in the long term and prevent the development of premature osteoarthritis. If successful, these data will provide the foundation for subsequent clinical studies to further delineate the role of biologic scaffolds in improving graft healing and promoting long- term joint stability and articular cartilage health, thus reducing OA after ACLR. PUBLIC HEALTH RELEVANCE: The use of a collagen scaffold with autologous platelets (a collagen-platelet composite) to improve the functional healing of an anterior cruciate ligament (ACL) autograft could decrease rehabilitation time, promote a more stable knee and significantly reduce the risk of premature osteoarthritis for 250,000 ACL reconstructed patients in the US annually. We are hopeful that the results of this study will inspire new fields of inquiry into cell-based therapies for intra-articular healing, and may result in a paradigm shift from use of a single growth factor toward the use of cells that can deliver multiple growth factors and cytokines over time as adjuncts to intra-articular healing.

描述（由申请人提供）：这项研究的目的是通过使用胶原蛋白血小板复合材料来改善前羊皮韧带重建（ACLR）的功能愈合，以增强移植物的生物掺入。前交叉韧带（ACL）撕裂的当前“护理标准”是使用自体肌腱的ACLR。尽管ACLR短期成功，但手术后的关节松弛性会增加，这可能会使膝盖处于随后损害和早期骨关节炎（OA）的风险。因此，增强移植物愈合的技术可减少松弛，保护关节并保存关节软骨，为ACL受伤的患者提供更好的长期结局。该研究团队最近开发了胶原蛋白血域复合材料，以增强ACLR移植物的愈合反应。已知血小板会释放刺激关节内韧带愈合的各种生长因子和细胞因子。我们假设它们也将改善移植物愈合。我们已经开发了一种使用胶原蛋白海绵在移植物周围容纳血小板的方法。在父母R01资助的工作中，我们发现，在愈合15周后，膝关节胁迫的移植性能均显着改善（模量增加了300％和屈服应力提高250％），膝盖松弛大大降低。由于随访评估相对较短（15周），我们无法检测到这些改进是否会在ACL重建后显着影响软骨健康。在这项竞争性修订中，我们建议包括两个长期的动物组（ACL重建具有胶原蛋白 - 植物 - 植物复合材料与传统的ACL重建），生存期为6个月和12个月。这些群体将扩大我们的原始建议，并提供有关在短期内显着改善移植物质量和膝盖松弛的胶原蛋白 - 情绪复合材料的信息，并将在长期内持续下去并阻止过早骨关节炎的发展。如果成功，这些数据将为后续临床研究提供基础，以进一步描述生物脚手架在改善移植物愈合和促进长期关节稳定性和关节软骨健康方面的作用，从而减少ACLR后的OA。 PUBLIC HEALTH RELEVANCE: The use of a collagen scaffold with autologous platelets (a collagen-platelet composite) to improve the functional healing of an anterior cruciate ligament (ACL) autograft could decrease rehabilitation time, promote a more stable knee and significantly reduce the risk of premature osteoarthritis for 250,000 ACL reconstructed patients in the US annually.我们希望这项研究的结果将激发对基于细胞内愈合的细胞疗法的调查领域的新领域，并可能导致从使用单个生长因子到使用细胞的使用范式转变，这些细胞可以随着时间的推移提供多个生长因子和细胞因子，而随着时间的流逝，作为辅助性辅助性。