Biologically Enhanced Healing of Autograft ACL Reconstruction.

描述(申请人提供)：这项研究的目的是通过使用血小板水凝胶来促进移植物的早期生物融合来改善前交叉韧带重建术(ACLR)的功能表现。目前治疗前十字韧带(ACL)撕裂的“标准护理”是使用自体肌腱移植的ACLR。尽管ACLR在短期内取得了成功，但术后关节松弛的暂时性增加，可能会使膝关节面临后续损伤和早期关节炎的风险。因此，加强植骨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前交叉韧带损伤患者提供更好的长期结果。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来刺激关节内韧带的愈合，因此我们推测它们也会促进移植物的愈合。已经开发出一种使用水凝胶来控制移植物周围的血小板的方法。目的1确定在手术时使用水凝胶处理的前交叉韧带移植物在愈合12周后，血小板浓度(5X比3X比0X)对移植物的结构特性(失效载荷/线刚性)和组织学(细胞/血管)的影响。目的2探讨血小板水凝胶对膝关节松弛程度的影响，以及愈合12周后关节软骨材料性能的变化。将使用由该研究小组开发的用于研究关节内前交叉韧带愈合的转换模型。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，以及通过印度墨汁染色和组织学检查关节软骨的完整性。如果成功，这些数据将为长期转化性研究以及随后的临床研究提供基础，以进一步阐明自体血小板在改善移植物愈合、促进长期关节稳定和关节软骨健康方面的作用，从而减少ACLR后的骨关节炎。 公共卫生相关性：使用自体血小板改善自体前交叉韧带移植物的功能愈合(移植物强度恢复更快，膝关节松弛减少)可以缩短康复时间，促进膝关节更稳定，这反过来又可以降低每年20万ACLR患者过早患骨性关节炎的风险。这项研究的结果还将刺激以细胞为基础的治疗关节内愈合的全新领域的探索，并可能导致从使用单一生长因子到使用能够随着时间的推移提供多种生长因子和细胞因子的细胞作为关节内愈合的辅助细胞的范式转变。

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.