The role of macrophages (Mφs) in tendon injury healing is controversy. The aims of this study were to determine whether there is a shift in Mφs polarisation after an acute and chronic tendon injury ​and to assess whether the Mφs polarisation between the partial and complete rupture is different. This systematic review of the scientific literature was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines. PubMed database and Excerpta Medica Database (EMBASE) were used for specific search criteria. Only studies measuring Mφs using specific cell markers in Achilles tendon tissue and rotator cuff tendon tissue were included, respectively. Five Achilles tendon injury studies and four rotator cuff injury studies were included. Expression of the pan Mϕs marker Cluster of Differentiation (CD) 68 was significantly upregulated in acute Achilles tendon ruptures compared to intact tendons, while no significant changes were found in Mφs polarisation markers CD80 (M1 Mφs) and CD206 (M2 Mφs). High levels of CD86 (M1 Mφs) and CD206 were observed in acute partial rupture. Expression of CD68 and CD206 were significantly upregulated in chronic rotator cuff tendinopathy and downregulated as structural failure increases. A low level of CD206 was observed in complete tendon rupture regardless of acute or chronic injury. In spite of the limited number of articles included, findings from this study suggested that the process of inflammation plays an important role in acute Achilles tendon injuries, indicated by the increased expression of CD68+ Mφs. Low levels of CD206+ Mφs were constantly observed in complete Achilles tendon rupture, while high levels of CD80+ Mφs and CD206+ Mφs were observed in partial Achilles tendon rupture, which suggested the potential correlation between M2 Mφs and tendon structure. For chronic rotator cuff injury, CD68+ Mφs and CD206+ Mφs were higher in tendinopathic tissues in comparison to the intact control tissues. Both CD68+ Mφs and CD206+ Mφs has an inverse relation to the structural failure in the torn rotator cuff tendon. After tendon rupture, the time point of biopsy specimen collection is an important factor, which could occur in the acute phase or chronic phase. Collectively, the understanding of the roles in Mφs after tendon injury is inadequate, and more research efforts should be devoted to this direction. This article provided a potential implication on how pan Mφs or M2 Mφs might be associated with ruptured or torn tendon structure. Managing Mφs numbers and phenotypes may lead to possible novel therapeutic approaches to the management of early tendinopathy, early acute tendon rupture, hence, promote healing after restoration surgery.

Tendon healing is a complex process involving inflammation, proliferation, and remodeling, eventually achieving a state of hypocellularity and hypovascularity. Currently, few treatments can satisfactorily restore the structure and function of native tendon. Bioactive glass (BG) has been shown to possess immunomodulatory and angiogenic properties. In this study, we investigated whether an injectable hydrogel fabricated of BG and sodium alginate (SA) could be applied to enhance tenogenesis following suture repair of injured tendon. We demonstrated that BG/SA hydrogel significantly accelerated tenogenesis without inducing heterotopic ossification based on histological analysis. The therapeutic effect could attribute to increased angiogenesis and M1 to M2 phenotypic switch of macrophages within 7 days post‐surgery. Morphological characterization demonstrated that BG/SA hydrogel partially reverted the pathological changes of Achilles tendon, including increased length and cross‐sectional area (CSA). Finally, biomechanical test showed that BG/SA hydrogel significantly improved ultimate load, failure stress, and tensile modulus of the repaired tendon. In conclusion, administration of an injectable BG/SA hydrogel can be a novel and promising therapeutic approach to augment Achilles tendon healing in conjunction with surgical intervention.

As one of the most common genetic conditions, Duchenne muscular dystrophy (DMD) is a fatal disease caused by a recessive mutation resulting in muscle weakness in both voluntary and involuntary muscles and, eventually, in death because of cardiovascular failure. Currently, there is no pharmacologically curative treatment of DMD, but there is evidence supporting that mesenchymal stem cells (MSCs) are a novel solution for treating DMD. This systematic review focused on elucidating the therapeutic efficacy of MSCs on the DMD in vivo model. A key issue of previous studies was the material-choice, naïve MSCs or modified MSCs; modified MSCs are activated by culture methods or genetic modification. In summary, MSCs seem to improve pulmonary and cardiac functions and thereby improve survival regardless of them being naïve or modified. The improved function of distal skeletal muscles was observed only with primed MSCs treatment but not naïve MSCs. While MSCs can provide significant benefits to DMD mouse models, there is little to no data on the results in human patients. Due to the limited number of human studies, the differences in study design, and the insufficient understanding of mechanisms of action, more rigorous comparative trials are needed to elucidate which types of MSCs and modifications have optimal therapeutic potential.