Biologically Enhanced Healing of Autograft ACL Reconstruction.

描述（由申请人提供）：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）的功能表现。目前治疗前交叉韧带（ACL）撕裂的“标准护理”是使用自体肌腱移植的ACLR。尽管ACLR短期成功，但术后关节松弛的时间增加，这可能使膝关节面临后续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、保护关节和保留关节软骨的技术将为ACL损伤患者提供更好的长期预后。研究小组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，血小板可以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可以促进移植物愈合。一种利用水凝胶将血小板包裹在移植物周围的方法已经被开发出来。目的1是确定血小板浓度（5X vs 3X vs 0X）在手术时用水凝胶处理ACL移植物12周愈合后对移植物结构特性（失效载荷/线性刚度）和组织学（细胞性/血管性）的影响。目的2是描述血小板水凝胶在愈合12周后对膝关节松弛度和关节软骨材料性能的影响。该研究小组开发的用于研究关节内ACL愈合的翻译模型将被使用。解决研究假设的主要结果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，血管和移植物特性的MRI评估，半月板状态，以及通过墨水染色和组织学检查的关节软骨完整性。如果成功，这些数据将为长期的转化研究和随后的临床研究提供基础，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。

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.