Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.

Osteoarthritis (OA) is the most common form of arthritis globally and a major cause of pain, physical disability, and loss of economic productivity, with currently no causal treatment available. This review article focuses on current research on OA biomarkers and the potential for using biomarkers in future clinical practice and clinical trials of investigational drugs. We discuss how biomarkers, specifically soluble ones, have a long path to go before reaching clinical standards of care. We also discuss how biomarkers can help in phenotyping and subtyping to achieve enhanced stratification and move toward better-designed clinical trials. We also describe how biomarkers can be used for molecular endotyping and for determining the clinical outcomes of investigational cell-based therapies. Biomarkers have the potential to be developed as surrogate end points in clinical trials and help private-public consortia and the biotechnology and pharmaceutical industries develop more effective and targeted personalized treatments and enhance clinical care for patients with OA.

Knee osteoarthritis, the most prevalent degenerative joint disorder worldwide, is driven by chronic low‐grade inflammation and subsequent cartilage degradation. Clinical data on the role of the Hoffa or infrapatellar fat pad in knee osteoarthritis are, however, scarce. The infrapatellar fat pad is a richly innervated intracapsular, extrasynovial adipose tissue, and an abundant source of adipokines and proinflammatory and catabolic cytokines, which may contribute to chronic synovial inflammation, cartilage destruction, and subchondral bone remodeling during knee osteoarthritis. How the infrapatellar fat pad interacts with neighboring tissues is poorly understood. Here, we review available literature with regard to the infrapatellar fat pad's interactions with cartilage, synovium, bone, menisci, ligaments, and nervous tissue during the development and progression of knee osteoarthritis. Signaling cascades are described with a focus on immune cell populations, pro‐ and anti‐inflammatory cytokines, adipokines, mesenchymal stromal cells, and molecules derived from conditioned media from the infrapatellar fat pad. Understanding the complex interplay between the infrapatellar fat pad and its neighboring articular tissues may help to better understand and treat the multifactorial pathogenesis of osteoarthritis.

Various therapeutic strategies that aim to influence clinical outcome after severe skeletal muscle trauma have been considered. One such method, the local transplantation of stem cells, has been shown to improve tissue regeneration. The number of cells required for successful regeneration, however, remains unclear. The aim of this study was therefore to examine the correlation between the number of transplanted bone marrow–derived mesenchymal stem cells (MSCs) and the resulting muscle function. One week after inducing an open crush trauma in 34 female Sprague Dawley rats, increasing quantities of autologous MSCs (0.1 × 10⁶, 1 × 10⁶, 2.5 × 10⁶, and 10 × 10⁶ cells) or saline solution (control group) were transplanted into the left soleus muscle of the rat hind limb. At 4 weeks posttrauma, the outcome was assessed by measuring muscle contraction forces following an indirect fast twitch and tetanic stimulation. A logarithmic dose–response relationship was observed for both maximum twitch and tetanic contraction forces (R² = 0.9 for fast twitch [p = 0.004]; R² = 0.87 [p = 0.002] for tetanic contraction). The transplantation of 10 × 10⁶ cells resulted in the most pronounced improvement of muscle force. MSC therapy represents a promising new tool for the treatment of skeletal muscle trauma that shows potential for aiding in the prevention of severe functional deficiencies. The logarithmic dose–response relationship demonstrates the association between the number of transplanted cells and the resulting muscle forces, as well as the amount of MSCs required for promoting muscular regeneration.

Two-stage exchange arthroplasty is still the preferred treatment choice for chronic PJI. However, the results remain unpredictable. We analyzed the treatment success of patients with an infected hip prosthesis, who were treated according to a standardized algorithm with a multidisciplinary team approach and evaluated with a strict definition of failure. In this single-center prospective cohort study, all hip PJI episodes from March 2013 to May 2015 were included. Treatment failure was assessed according to the Delphi-based consensus definition. The Kaplan-Meier survival method was used to estimate the probability of infection-free survival. Patients were dichotomized into two groups depending on the number of previous septic revisions, duration of prosthesis-free interval, positive culture with difficult-to-treat microorganisms, microbiology at explantation, and microbiology at reimplantation. Eighty-four patients with hip PJI were the subject of this study. The most common isolated microorganisms were coagulase-negative staphylococci (CNS) followed by Staphylococcus aureus and Propionibacterium. Almost half of the study cohort (46%) had at least one previous septic revision before admission. The Kaplan-Meier estimated infection-free survival after 3 years was 89.3% (95% CI, 80% to 94%) with 30 patients at risk. The mean follow-up was 33.1 months (range, 24–48 months) with successful treatment of PJI. There were no statistical differences in infect eradication rate among the dichotomized groups. High infect eradication rates were achieved in a challenging cohort using a standardized two-stage exchange supported by a multidisciplinary approach.