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

摘要 在前十字韧带(ACL)重建后，女性的结果更差；然而， 骨骼肌的生物学和功能在男性中得到了优先研究。这些观察结果表明 在促进肌肉功能恢复的生物机制上存在性别差异。 这项建议中耐人寻味的试点数据显示，股四头肌恢复和 与男性相比，女性前交叉韧带重建后的功能和心理社会恢复较差。 这项建议旨在测试这一新的假设，即在前交叉韧带损伤后，女性经历夸大 肌肉细胞和分子缺陷，阻碍他们恢复力量，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得不成比例。通过识别 性别差异的细胞和分子基础，随后的临床试验可以测试性别特异性 改善女性前交叉韧带损伤后预后的方法。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形态的性别差异。在AIM 2 确定前交叉韧带重建术后性别对膝关节功能的影响。最后，在目标3中将决定 前交叉韧带术后男女心理社会康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以及 确定推动后续循证临床试验所需的关键治疗目标，旨在 改善女性的康复效果。

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.