Anterior cruciate ligament (ACL) rupture is a common injury in young athletes. To restore knee stability and function, patients often undergo ACL reconstruction (ACLR). Historically, there has been a focus in this population on the epidemiology of ACL injury, the technical aspects of ACL reconstruction, and post-operative functional outcomes. Although increasingly recognized as an important aspect in recovery, there remains limited literature examining the psychological aspects of post-operative rehabilitation and return to play following youth ACL reconstruction. Despite technical surgical successes and well-designed rehabilitation programs, many athletes never reach their preinjury athletic performance level and some may never return to their primary sport. This suggests that other factors may influence recovery, and indeed this has been documented in the adult literature. In addition to restoration of functional strength and stability, psychological and social factors play an important role in the recovery and overall outcome of ACL injuries in the pediatric population. Factors such as psychological readiness to return-to-play (RTP), motivation, mood disturbance, locus of control, recovery expectations, fear of reinjury, and self-esteem are correlated to the RTP potential of the young athlete. A better understanding of these concepts may help to maximize young patients’ outcomes after ACL reconstruction. The purpose of this article is to perform a narrative review of the current literature addressing psychosocial factors associated with recovery after ACL injury and subsequent reconstruction in young athletes. Our goal is to provide a resource for clinicians treating youth ACL injuries to help identify patients with maladaptive psychological responses after injury and encourage a multidisciplinary approach when treating young athletes with an ACL rupture.

Fibroadipogenic progenitors (FAPs) maintain healthy skeletal muscle in homeostasis but drive muscle degeneration in chronic injuries by promoting adipogenesis and fibrosis. To uncover how these stem cells switch from a pro-regenerative to pro-degenerative role we perform single-cell mRNA sequencing of human FAPs from healthy and injured human muscles across a spectrum of injury, focusing on rotator cuff tears. We identify multiple subpopulations with progenitor, adipogenic, or fibrogenic gene signatures. We utilize full spectrum flow cytometry to identify distinct FAP subpopulations based on highly multiplexed protein expression. Injury severity increases adipogenic commitment of FAP subpopulations and is driven by the downregulation of DLK1. Treatment of FAPs both in vitro and in vivo with DLK1 reduces adipogenesis and fatty infiltration, suggesting that during injury, reduced DLK1 within a subpopulation of FAPs may drive degeneration. This work highlights how stem cells perform varied functions depending on tissue context, by dynamically regulating subpopulation fate commitment, which can be targeted improve patient outcomes after injury.

Background: Sex-based disparities remain a major challenge in musculoskeletal medicine. Women and men experience different anterior cruciate ligament (ACL) injury rates and severity, but the causes remain unclear. We hypothesized that cellular differences in human progenitor cells contribute to the higher ACL tear risk observed in females. Methods: ACL samples were collected from 4 male and 5 female patients undergoing ACL reconstruction surgery. Live cells were collected through flow cytometry and sent for single-cell RNA sequencing. Significantly greater expression in either sex relative to the other was defined as a >25% increase in expression level (log ₂ fold change > 0.32) and p < 0.05). Subpopulation characterization was performed with immunofluorescence on tissue sections. Results: We discovered sex-based differences in all of the native cell types within the ACL. In particular, fibroblast progenitor-like (TPPP3+) cells from female patients expressed genes associated with dysregulation and degradation of collagen more highly than progenitor cells from male patients. Conclusions: These results highlight a ligament progenitor population with a sex-dependent gene expression profile. This work suggests that sex-based differences in stem cell populations may drive differential injury rates and outcomes between male and female patients with musculoskeletal injuries. Clinical Relevance: The differential gene expression among TPPP3+ progenitor-like cells provides a possible target population for studying ligamentous injury and regeneration. Differential expression of collagen and extracellular matrix-related genes provides evidence of specific genes that could be therapeutically targeted to strengthen the ACL and reduce the risk of rupture, particularly in female athletes.

Muscle fibrosis is a key pathological feature of Duchenne muscular dystrophy (DMD) and is closely associated with disease progression. Fibroadipogenic progenitors (FAPs) are major contributors to fibrosis, yet the precise mechanisms remain unclear. To investigate FAP dynamics and lineage specification, we generated dual-reporter mice (PRURD2) by crossing D2.B10-Dmdmdx/J (D2-mdx) mice with FAP and brown/beige adipose tissue (BAT) reporter lines. Corresponding control mice (PRURDBA) were established on the DBA/2J background. At 12 months, heart, diaphragm, and tibialis anterior (TA) muscles were collected for histological analysis. FAPs were isolated via FACS and subjected to single-cell RNA sequencing. PRURD2 mice exhibited increased fibrosis across all muscles compared to controls ( p < 0.01) and a significant rise in PDGFRα-GFP + FAPs ( p < 0.05). UMAP clustering identified 11 distinct FAP subpopulations, with the fibrosis-associated CD55 cluster enriched in PRURD2 mice. Pseudotime analysis showed lineage progression from progenitor clusters toward the fibrogenic CD55 cluster. CellChat analysis indicated increased interactions in PRURD2 mice involving fibrosis-related pathways like COLLAGEN, TGF-β, WNT, NOTCH, and ANGPTL. Additionally, fibrosis-related signaling pathways such as THY1, TWEAK, EPHA, EPHB, and SEMA6 showed increased interactions among FAP clusters in PRURD2 mice. Differential gene expression analysis revealed top upregulated genes including Cxcl13, Cxcl3, Ly6d, Klk1, Fgf23, Serpinb2, Mmp13, Ccl17 , Postn , and Adam12 . PRURD2 mice develop severe fibrosis in skeletal and cardiac muscle, driven by FAP-induced signaling pathways and genes. This model is valuable for understanding muscle fibrosis in DMD and developing anti-fibrotic therapies.

Background: Anterior cruciate ligament (ACL) injuries are one of the most common knee injuries in pediatric patients in the United States. The patient's primary spoken language may affect outcomes after ACL reconstruction (ACLR). Purpose/Hypothesis: The purpose of this study was to identify differences in ACLR outcomes between patients whose primary, preferred spoken language was either English or Spanish. It was hypothesized that there would be a difference in retear rates between patients preferring English versus Spanish. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective cohort study was performed on pediatric and adolescent patients who underwent ACLR at a single institution. Patients were divided into 2 cohorts based on their preferred spoken language: English or Spanish. All patients underwent either hamstring tendon or bone–patellar tendon–bone autograft ACLR performed by the same surgeon with the same postoperative rehabilitation protocols. Linear regression, chi-square tests, and multivariate logistic regression were used to determine if outcomes, graft tear, revision surgery, and contralateral injury differed between groups. Results: A total of 68 patients were identified: 33 patients whose preferred language was English and 35 patients whose preferred language was Spanish. The overall mean age of the patients was 16.4 ± 1.4 years (range, 13.2-20.5 years), and the mean follow-up time was 3.26 ± 1.98 years (range, 0.53-8.13 years). Patients who preferred Spanish were more likely than those who preferred English to experience graft tears requiring revision surgery after ACLR ( P = .02; odds ratio [OR] = 5.81; adjusted OR = 1.94), at a tear rate of 14.3%. Conclusion: Patients who preferred to speak Spanish experienced higher graft tear rates when compared with patients who preferred speaking English, even after adjusting for sex, sport played, graft type, type of insurance, and time to surgery.