Soft tissue trauma of skeletal muscle is one of the most common side effects in surgery. Muscle injuries are not only caused by accident-related injuries but can also be of an iatrogenic nature as they occur during surgical interventions when the anatomical region of interest is exposed. If the extent of trauma surpasses the intrinsic regenerative capacities, signs of fatty degeneration and formation of fibrotic scar tissue can occur, and, consequentially, muscle function deteriorates or is diminished. Despite research efforts to investigate the physiological healing cascade following trauma, our understanding of the early onset of healing and how it potentially determines success or failure is still only fragmentary. This review focuses on the initial physiological pathways following skeletal muscle trauma in comparison to bone and tendon trauma and what conclusions can be drawn from new scientific insights for the development of novel therapeutic strategies. Strategies to support regeneration of muscle tissue after injury are scarce, even though muscle trauma has a high incidence. Based on tissue specific differences, possible clinical treatment options such as local immune-modulatory and cell therapeutic approaches are suggested that aim to support the endogenous regenerative potential of injured muscle tissues.

Background: With increasing life expectancy, the demand for knee replacement is continuously rising. Despite the use of antibiotic prophylaxis and improved aseptic surgical techniques, periprosthetic joint infection (PJI) still occurs in 1% to 5% of patients after primary arthroplasty. An open question is the influence of PJI and resulting surgical procedures on the occurrence of long-term complications such as aseptic loosening. Patients needing multiple revision surgeries are especially at risk for decreases in bone mass and damage to the medullary cavity. Thus, we theorized that prior surgeries on the affected knee increase the risk of aseptic loosening in patients with PJI.Methods: We retrospectively analyzed the cases of 100 patients who underwent total knee replacement exchange surgery as a result of PJI. In addition to clinical, paraclinical, and radiographic examination, we assessed comorbidities and the number of prior surgeries.Results: Prosthetic survival was drastically decreased after PJI-related revision arthroplasty: during the first 7.3 years after reimplantation, 22% and 16% of all patients had aseptic loosening and recurrent PJI, respectively. The prevalence of aseptic loosening was 27.8% for female and 15.2% for male patients. A significant association between increasing patients’ American Society of Anesthesiologists (ASA) classification and prosthetic failure rates was found, as was a strong correlation between number of prior surgeries and aseptic looseningConclusions: In this study, we found notable rates of aseptic loosening and recurrent PJI following PJI-related revision arthroplasty. The difference in the rate of aseptic loosening among male and female patients supports theories of the role of bone metabolism in the development of aseptic loosening. The economic and clinical burdens of prosthetic failure make it paramount to gain a better understanding of bone metabolism in PJI. Additional research should address the need to optimize treatment strategies to increase prosthetic survival.Level of Evidence: TherapeuticLevel IV. See Instructions for Authors for a complete description of levels of evidence.

Osteoarthritis (OA) is a joint disease featuring cartilage breakdown and chronic pain. Although age and joint trauma are prominently associated with OA occurrence, the trigger and signaling pathways propagating their pathogenic aspects are ill defined. Following long-term catabolic activity and traumatic cartilage breakdown, debris accumulates and can trigger Toll-like receptors (TLRs). Here we show that TLR2 stimulation suppressed the expression of matrix proteins and induced an inflammatory phenotype in human chondrocytes. Further, TLR2 stimulation impaired chondrocyte mitochondrial function, resulting in severely reduced adenosine triphosphate (ATP) production. RNA-sequencing analysis revealed that TLR2 stimulation upregulated nitric oxide synthase 2 ( NOS2 ) expression and downregulated mitochondria function-associated genes. NOS inhibition partially restored the expression of these genes, and rescued mitochondrial function and ATP production. Correspondingly, Nos2 ^−/− mice were protected from age-related OA development. Taken together, the TLR2–NOS axis promotes human chondrocyte dysfunction and murine OA development, and targeted interventions may provide therapeutic and preventive approaches in OA.