Biologically Enhanced Healing of Autograft ACL Reconstruction.

自体移植 ACL 重建的生物增强愈合。

• 批准号: 8020913
• 负责人: Braden C Fleming
• 金额: $ 35.77万
• 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: 2009-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8020913
• 关键词: Address; Adolescent; Animal Model; Animals; Anterior Cruciate Ligament; Arthritis; Articular ligaments; Autologous; Autologous Transplantation; Blood Platelets; Cartilage; Cell Therapy; Cells; Cellularity; Clinical; Clinical Research; Data; Degenerative polyarthritis; Economics; Evaluation; Failure; Family suidae; Foundations; Growth Factor; Healed; Health; Histology; Hydrogels; India ink stain; Injury; Investigation; Joint Laxity; Joints; Knee; Knee joint; Life; Ligaments; Magnetic Resonance Imaging; Maps; Mechanics; Methods; Modeling; Operative Surgical Procedures; Outcome; Outcome Measure; Patients; Performance; Permeability; Platelet Count measurement; Postoperative Period; Property; Quality of life; Rehabilitation therapy; Research; Risk; Risk Factors; Role; Techniques; Tendon structure; Time; anterior cruciate ligament healing; anterior cruciate ligament reconstruction; anterior cruciate ligament rupture; articular cartilage; bone; cytokine; graft healing; healing; improved; injured; ligament injury; premature; primary outcome; public health relevance; reconstruction; response; secondary outcome; standard of care; success; translational study; young adult

DESCRIPTION (provided by applicant): The objective of this study is to improve the functional performance of an anterior cruciate ligament reconstruction (ACLR) by using a platelet hydrogel to enhance the early biologic incorporation of the graft. The current "standard of care" for an anterior cruciate ligament (ACL) tear is ACLR using autograft tendon. Despite short-term success of ACLR, temporal increases in joint laxity occur after surgery, which may place the knee at risk for subsequent damage and early arthritis. Thus, techniques to enhance graft healing to reduce early laxity, protect the joint, and preserve articular cartilage would provide better long-term outcome for the ACL injured patient. A platelet hydrogel was recently developed by the 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, and thus we hypothesize they will improve graft healing as well. A method has been developed to contain the platelets around the graft using a hydrogel. Aim 1 is to define the effects of platelet concentration (5X vs 3X vs 0X) on the structural properties (failure load/linear stiffness) and histology (cellularity/vascularity) of the ACL graft after 12 weeks of healing when the graft is treated with the hydrogel at the time of surgery. Aim 2 is to delineate the effects of the platelet hydrogel on knee joint laxity and the articular cartilage material properties after 12 weeks of healing. A translational model, which has been developed by this research team to study intra-articular ACL healing, will be used. The primary outcomes to address the study hypotheses will be the structural properties of the graft, graft histology, knee joint laxity and cartilage mechanics. Secondary outcome variables include the material properties of the graft, MRI assessments of vascularity and graft properties, meniscal status, and articular cartilage integrity via India ink staining and histology. If successful, these data will provide the foundation for a long-term translational study, and then subsequent clinical studies to further delineate the role of autologous platelets 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 autologous platelets to improve the functional healing of an ACL autograft (as evidenced by the faster return of graft strength and a reduction in knee laxity) could reduce rehabilitation time and promote a more stable knee, which in turn could reduce the risk of premature osteoarthritis for 200,000 ACLR patients annually. The results of this study will also stimulate entirely 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 which 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血小胶凝胶来增强移植物的早期生物掺入，以提高前交叉韧带重建（ACLR）的功能性能。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，这可能会使膝盖有可能随后损伤和早期关节炎的风险。因此，增强移植物愈合以减少早期松弛，保护关节并保存关节软骨的技术将为ACL受伤的患者提供更好的长期结局。研究小组最近开发了一个血小凝胶，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，因此我们假设它们也可以改善移植物的愈合。已经开发了一种方法，可以使用水凝胶在移植物周围包含血小板。目的1是定义血小板浓度（5x vs 3x vs 0x）对ACL疗法12周后ACL移植物的结构特性（失败载荷/线性刚度）和组织学特性（细胞/血管）的影响。 AIM 2是描绘血小凝胶对膝关节松弛的影响和关节软骨材料在愈合12周后的影响。将使用该研究团队开发的一种转化模型来研究关节内ACL愈合。解决研究假设的主要结果将是移植物，膝关节学，膝关节松弛和软骨力学的结构特性。次要结果变量包括通过印度通过印度墨水染色和组织学的关节软骨状态和关节软骨的完整性，对血管和移植特性的MRI评估，MRI评估的材料特性。如果成功，这些数据将为长期翻译研究提供基础，然后随后进行临床研究，以进一步描述自体血小板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。 公共卫生相关性：使用自体血小板来改善ACL自体移植的功能愈合（如移植力量的更快恢复和减轻膝盖松弛的速度所证明）可以减少康复时间，并促进更稳定的膝盖，这又可以减少200,000万名ACLR患者的早产骨性炎的风险。这项研究的结果还将刺激针对关节内愈合的基于细胞的疗法的全新研究领域，并可能导致从单个生长因子使用单个生长因子向使用细胞的使用范式转移，这些细胞可以随时间推移将多种生长因子和细胞因子作为辅助内愈合提供多种生长因子和细胞因子。