Journal of Musculoskeletal Research

Cartilage can redistribute human body’s daily loads and decrease the friction force in the diarthrodial joints. However, it may be injured due to trauma, sports injury, biomechanical imbalance, and genetic disease. Microfracture (MF), osteochondral autograft transplantation (OAT), and autologous chondrocyte implantation (ACI) are the most common treatment procedures in the hospital. Recently, the concept of tissue engineering involving the combination of cells, scaffolds, and bioactive signals has inspired researchers. Our team of researchers synthesized a tri-copolymer from biological polymer by using gelatin, chondroitin-6-sulfate, and hyaluronic acid through cross-linking reaction. Lacuna formation could be seen in the tri-copolymer surrounding the chondrocytes, and some newly formed glycosaminoglycan was found in the engineered cartilage. Considering the dedifferentiation possibility of chondrocyte, bone marrow mesenchymal stem cells (BMSCs) become an ideal cell source for cartilage tissue regeneration, since they can be easily harvested from adult tissue, and be expanded in vitro. In an in-vivo porcine pilot study, the results showed that the defect site could be regenerated by BMSCs/collagen gel, and is formed with fibro/hyaline mixed cartilage tissue after implantation for six months. Several clinical studies using BMSCs for cartilage defect treatment were also conducted recently; clinical outcomes such as IKDC, Lysholm, and Tegner scores improved when the cartilage defects were repaired by several millions of mesenchymal stem cells, and there is no tumor formation after being treated with BMSCs during the 10-year follow-up. Moreover, recently a commercial BMSCs/collagen gel composite for cartilage repair was developed in Taiwan and clinical trial was conducted in 2008; the results showed that there is an improvement in IKDC and MRI scores during the nine-year follow-up. It seems that using an engineered cartilage made from BMSCs/collagen gel for cartilage defect treatment is a promising method.

Osteoarthritis (OA) results from aging joints, injury, and obesity, emerging as an epidemic joint disease in addition to being a significant cause of pain disability. Despite decades of efforts from scientists and physicians, the trend of the global increase in the incidence of OA does not slow down. As there are no effective pharmacotherapies able to reverse the degenerative process, cell-based and biological therapies for OA were invented and developed into a thriving field of regenerative medicine for orthopedics. First, autologous chondrocyte implantation (ACI) has been used to treat osteoarticular defects for over two decades. While ACI has demonstrated its capability to decelerate OA progression, there are still many issues that hamper its therapeutic efficacy. Therefore, researchers and physicians invented innovative biomaterials-assisted cell therapies, advanced surgical techniques for preserving primary chondrocytes’ biological function and avoiding the donor-site mortality. Later, the discovery of mesenchymal stem cells (MSCs) revoluted cell therapies for cartilage repair. MSCs not only provide an alternative cell source with much higher proliferation rates but also have these advantages: no donor-site mortality, non-tumorigenic, and, most importantly, the capability of chondrogenic differentiation. This review paper explores the challenges associated with OA treatments using cell-based therapies and shares our vision for the future development of regenerative medicine for cartilage.

Achilles tendon disorders, including tendinopathy and ruptures, are common among competitive runners. Relatively high complication rates, recurring injuries, and the need to return to sport have led to the use of regenerative medical treatment in tendon disorders in competitive athletes. Biologic therapies, including bone marrow aspirate concentrate (BMAC) injections, have been effective in restoring injured tissue in a limited number of cases. In this case, a collegiate cross country runner with Achilles tendon pain underwent years of failed, non-surgical conservative management. The patient’s MRI demonstrated moderate distal calcaneus tendinosis with high-grade partial thickness tearing of the anterior fibers of the Achilles tendon (50% tear). The patient underwent peritendinous injection of BMAC. Post-procedure MRI demonstrated minimal tendinosis of the distal and lateral margins of the Achilles tendon, and no evidence of Achilles tendon tear. The patient followed a progressive return to running program, ultimately training 40 miles per week with minimal Achilles tendon pain.

Osteoarthritis (OA) is a degenerative joint disease that may cause joint inflammation, stiffness, and pain. Current therapy for OA involves symptomatic treatment, mainly pain management. Therefore, it does not repair degenerated cartilage or attenuate joint inflammation. Because articular cartilage cannot heal or regenerate these tissues, tissue regeneration remains one of the most important objectives of new and potential OA therapeutics. The main features of adult mesenchymal stem cells (MSCs) are simple acquisition from adult tissues, rapid proliferation in vitro, immunomodulation in vivo, and lasting existence in the host, which are beneficial for OA treatment. In the past 15 years, adult MSCs, including bone marrow-, adipose-, and synovial membrane-derived MSCs, and their secretome have been successfully used in different animal (preclinical) models or in genetic manipulation for regenerating degenerated cartilage, reducing inflammation, or relieving pain. Furthermore, the implantation of adult MSCs showed pain reduction, anti-inflammation, and cartilage protection or healing in early-phase clinical trials. Adult MSCs are the most extensively explored as potential regenerative medicine for OA because of their efficacy in chondrocyte differentiation and their immunomodulatory properties. In this review paper, we highlighted current knowledge and future perspectives regarding preclinical tests, clinical application, and MSC-based/related products for curing OA.

Bone fractures are one of the most common orthopedic cases, yet strategies to resolve excessive inflammation and non-unions still lack satisfactory treatment methods owing to the complex fracture microenvironment, as well as the interactions between the plethora of cell types involved. Fracture is a highly inflammatory process which involves the recruitment of various immune cells which in turn release various cytokines and growth factors to perpetuate inflammation and eventually healing resolution. Osteoimmunology is an interdisciplinary field investigating the extensive interactions between the immune system and skeletal system. Mesenchymal stem cells (MSCs) are resident in almost every adult tissue and are responsible for initiating reparative cascades in the event of injury. A key aspect of MSCs is their role as trophic mediators, secreting a milieu of signaling as well as immunomodulatory cytokines that play important roles in tissue regeneration. This paracrine signaling polarizes macrophages into their anti-inflammatory M2 phenotype, activates osteoblasts, inhibits osteoclasts, as well as suppresses conventional T cell proliferation and promotes regulatory T cell (Treg) proliferation. MSCs have been shown to resolve inflammation whilst also supporting osteogenesis; for these reasons, they are considered promising candidates for cellular therapies to treat musculoskeletal pathologies. Through pretreatment and genetic modifications, MSCs can be predisposed to release specific molecules that can modulate the microenvironment and regulate the activity of the immune system towards enhancing bone repair. By understanding the cross-talk between MSCs and the immune system in bone physiology, more targeted therapies directed towards specific cells and discrete signaling molecules become possible that may allow for expedited healing and improved standard of care in orthopedics. In this review, we discuss the interplay between immune cells and MSCs and the potential ways to harness this cross-talk to improve regenerative medicine strategies.

Distal radius fractures with concomitant ipsilateral elbow dislocation are a rare injury pattern. Only a few cases of a distal radius fracture with ipsilateral elbow dislocation have been reported. We discuss the case of a 46-year-old gentleman presenting with posteromedial elbow dislocation with an ipsilateral closed extra-articular fracture of the distal radius. Plain radiographs showed a right posterior-medial elbow dislocation and ipsilateral distal radius fracture. CT scans of the elbow showed impaction fractures of the coronoid and trochlea, suggesting a concomitant posteromedial varus elbow dislocation injury. CT scans of the wrist showed the presence of a comminuted, extra-articular distal radius fracture. Surgical fixation of the distal radius was performed, as well as repair of the right elbow lateral capsule-ligamentous complex with suture anchors. Proper recognition of the posteromedial varus instability type injury to the elbow, as in this case is important, should be addressed. If VPMRI is missed, it can lead to ulno-humeral osteoarthritis of the elbow joint.