Sex-based Muscular Adaptations, Capillary dysfunction and functional decline impact Knee-related psychosocial outcomes after acute knee injury (SMACK)

摘要 在前交叉韧带（ACL）重建后，女性的结果更差;然而， 骨骼肌生物学和功能优先在男性中进行研究。这些观察结果表明 在促进肌肉功能恢复的生物学机制中存在性别差异。 这项提案中有趣的试点数据显示，股四头肌的恢复优先受损， 与男性相比，ACL重建后女性的功能和心理社会恢复减少。 这项建议旨在测试新的假设，即在ACL损伤后，女性的经历被夸大了。 肌肉细胞和分子缺陷，阻碍其恢复力量，导致明显的缺陷 在步态力学和心理社会恢复方面比男性差。通过识别 细胞和分子基础的性别差异，随后的临床试验可以测试性别特异性 改善ACL损伤后女性结局的方法。我们将在目标1中定义分子、细胞 前交叉韧带损伤和重建后股四头肌的形态学性别差异。在目标2中 确定性别对ACL重建后膝关节功能的影响。最后，目标3将确定 ACL术后女性和男性之间心理社会恢复的时间和程度差异 重建这项工作的结果将对临床实践指南产生直接影响， 确定关键的治疗目标，以推动后续的循证临床试验， 改善女性康复成果。

Abstract Following an Anterior Cruciate Ligament (ACL) reconstruction, females have worse outcomes; however, skeletal muscle biology and function have preferentially been studied in males. These observations suggest that there are sex-based differences in the biological mechanisms contributing to recovery of muscle function. Intriguing pilot data in this proposal show preferential impairment in the recovery of quadriceps muscle and function and diminished psychosocial recovery in females as compared to males following ACL reconstruction. This proposal seeks to test the novel hypothesis that following an ACL injury, females experience exaggerated muscle cellular and molecular deficits, hindering their recovery of strength, resulting in pronounced deficiencies in gait mechanics and disproportionally worse psychosocial recovery compared to males. By identifying the cellular and molecular foundation of sex-based differences, subsequent clinical trials can test sex specific approaches to improve outcomes for women after ACL injury. We will in Aim 1 define the molecular, cellular and morphological sex-based differences in quadriceps muscle after ACL injury and reconstruction. In Aim 2 determine the effect of sex on knee function after an ACL reconstruction. Lastly, in Aim 3 will determine the timing and magnitude of psychosocial recovery differences between females and males following an ACL reconstruction. Results from this work will exert an immediate impact on clinical practice guidelines, as well as identify critical therapeutic targets needed to propel subsequent evidence-based clinical trials designed to improve rehabilitative outcomes for females.