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（由申请方提供）：本研究的目的是通过使用血小板水凝胶增强移植物的早期生物结合来改善前交叉韧带重建（ACLR）的功能性能。目前，前交叉韧带（ACL）撕裂的“标准治疗”是使用自体肌腱的ACLR。尽管ACLR短期成功，但术后关节松弛暂时增加，这可能使膝关节处于后续损伤和早期关节炎的风险中。因此，加强移植物愈合以减少早期松弛、保护关节和保存关节软骨的技术将为ACL损伤患者提供更好的长期结局。研究团队最近开发了一种血小板水凝胶，以增强ACLR移植物的愈合反应。众所周知，血小板释放各种生长因子和细胞因子，刺激关节内韧带愈合，因此我们假设它们也会改善移植物愈合。已经开发了一种方法，使用水凝胶将血小板包裹在移植物周围。目的1是确定在手术时使用水凝胶处理移植物时，血小板浓度（5X vs 3X vs 0X）对愈合12周后ACL移植物的结构特性（失效载荷/线性刚度）和组织学（细胞结构/血管分布）的影响。目的2是描述血小板水凝胶在愈合12周后对膝关节松弛和关节软骨材料性质的影响。将使用该研究团队开发的平移模型来研究关节内ACL愈合。解决研究假设的主要结局将是移植物的结构特性、移植物组织学、膝关节松弛和软骨力学。次要结果变量包括移植物的材料特性、血管分布和移植物特性的MRI评估、关节状态和通过印度墨水染色和组织学的关节软骨完整性。如果成功，这些数据将为长期转化研究提供基础，然后进行后续临床研究，以进一步阐明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自体移植物的功能愈合（如移植物强度更快恢复和膝关节松弛减少所证明的）可以缩短康复时间并促进膝关节更稳定，这反过来又可以降低每年20万例ACLR患者过早患骨关节炎的风险。这项研究的结果还将刺激对关节内愈合的基于细胞的疗法进行全新的研究领域，并可能导致从使用单一生长因子向使用细胞的范式转变，这些细胞可以随着时间的推移提供多种生长因子和细胞因子作为关节内愈合的促进剂。