(1) Background: Arthrofibrosis is a common cause of patient debility and dissatisfaction after total knee arthroplasty (TKA). The diversity of molecular pathways involved in arthrofibrosis disease progression suggest that effective treatments for arthrofibrosis may require a multimodal approach to counter the complex cellular mechanisms that direct disease pathogenesis. In this study, we leveraged RNA-seq data to define genes that are suppressed in arthrofibrosis patients and identified adiponectin (ADIPOQ) as a potential candidate. We hypothesized that signaling pathways activated by ADIPOQ and the cognate receptors ADIPOR1 and ADIPOR2 may prevent fibrosis-related events that contribute to arthrofibrosis. (2) Methods: Therefore, ADIPOR1 and ADIPOR2 were analyzed in a TGFβ1 inducible cell model for human myofibroblastogenesis by both loss- and gain-of-function experiments. (3) Results: Treatment with AdipoRon, which is a small molecule agonist of ADIPOR1 and ADIPOR2, decreased expression of collagens (COL1A1, COL3A1, and COL6A1) and the myofibroblast marker smooth muscle α-actin (ACTA2) at both mRNA and protein levels in basal and TGFβ1-induced cells. (4) Conclusions: Thus, ADIPOR1 and ADIPOR2 represent potential drug targets that may attenuate the pathogenesis of arthrofibrosis by suppressing TGFβ-dependent induction of myofibroblasts. These findings also suggest that AdipoRon therapy may reduce the development of arthrofibrosis by mediating anti-fibrotic effects in joint capsular tissues.

Reconstruction of the abductor mechanism remains a primary challenge with contemporary proximal femoral replacement (PFR) surgery. Previously, techniques such as trochanteric preservation or direct repair to the implant have been described; however, these strategies are limited in their ability to tension the repair and reattach other muscles of the hip girdle. The aim of this study was to evaluate the outcomes of patients undergoing oncologic PFR using a novel technique of mesh augmentation for soft tissue repair. Methods: We reviewed 18 (mean age 64 years; 8 female: 10 male) consecutive patients undergoing PFR with Marlex mesh augmentation between 2018 and 2023 at a single institution. The most common indication was metastatic disease (n = 13). The mean follow-up in the 14 surviving patients was 27 months (range 12–34). Results: All patients were ambulatory at final follow-up. There were no post-operative dislocations, infections, or wound issues. At the final follow-up, the mean total MSTS score was 77%. Conclusion: Mesh augmentation of PFRs allowed for adequate soft tissue tensioning and muscular attachment to the body of the implant. In our series, this technique was durable, with no dislocations and no mesh-related complications. In summary, mesh augmentation of PFRs may be considered during reconstruction for oncologic indications.