Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.

Tendon-bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC-EVs and the underlying mechanisms of their effects on promoting tendon-bone healing. At last, we discuss the present challenges and future research directions.

Anterior Tibial Subluxation of Lateral Compartment Is Associated With High-Grade Rotatory Instability for Acute But Not Chronic Anterior Cruciate Ligament Injuries: An Magnetic Resonance Imaging Case-Control Study.

PURPOSE: To investigate whether anterior tibial subluxation obtained from magnetic resonance imaging (MRI) could be a predictor of high-grade rotatory instability for anterior cruciate ligament (ACL) injuries, including acute and chronic cases. METHODS: From September 2016 to August 2018, we retrospectively investigated 163 patients with ACL injuries who subsequently underwent primary ACL reconstruction. Among them, 30 patients with high-grade rotatory instability (grade II/III pivot shift) were included in the high-grade group, and their age and sex were matched 1:2 to low-grade cases (3 months) phases. RESULTS: The high-grade group had a larger anterior tibial subluxation of lateral compartment (8.1 mm vs 5.9 mm; P =.004) than the low-grade group, whereas no significant difference was found in anterior tibial subluxation of medial compartment (P > .05). Moreover, high-grade anterior tibial subluxation of lateral compartment (≥6 mm) was found to be an independent predictor (odds ratio, 12.992; P = .011) associated with concomitant meniscal tears after ACL injuries. Anterior tibial subluxation of lateral compartment demonstrated statistical significance between the two groups when comparing subgroups within 3 months but not beyond 3 months. CONCLUSION: In ACL-injured patients, high-grade anterior tibial subluxation of lateral compartment (≥6 mm) could be a unique predictor of high-grade knee rotatory instability for acute but not chronic injuries. Prolonged time from injury to surgery and lateral meniscus tears were risk factors for high-grade rotatory laxity in chronic patients. LEVEL OF EVIDENCE: Level III, retrospective prognostic trial.

Magnetic Soft Catheter Robot System for Minimally Invasive Treatments of Articular Cartilage Defects.

Articular cartilage defects are among the most common orthopedic diseases, which seriously affect patients' health and daily activities, without prompt treatment. The repair biocarrier-based treatment has shown great promise. Total joint injection and open surgery are two main methods to deliver functional repair biocarriers into the knee joint. However, the exhibited drawbacks of these methods hinder their utility. The repair effect of total joint injection is unstable due to the low targeting rate of the repair biocarriers, whereas open surgery causes serious trauma to patients, thereby prolonging the postoperative healing time. In this study, we develop a magnetic soft catheter robot (MSCR) system to perform precise in situ repair of articular cartilage defects with minimal incision. The MSCR processes a size of millimeters, allowing it to enter the joint cavity through a tiny skin incision to reduce postoperative trauma. Meanwhile, a hybrid control strategy combining neural network and visual servo is applied to sequentially complete the coarse and fine positioning of the MSCR on the cartilage defect sites. After reaching the target, the photosensitive hydrogel is injected and anchored into the defect sites through the MSCR, ultimately completing the in situ cartilage repair. The in vitro and ex vivo experiments were conducted on a 3D printed human femur model and an isolated porcine femur, respectively, to demonstrate the potential of our system for the articular cartilage repair.