Both acute and chronic tendon injuries are disabling sports medicine problems with no effective treatment at present. Sustained oxidative stress has been suggested as the major factor contributing to fibrosis and adhesion after acute tendon injury as well as pathological changes of degenerative tendinopathy. Numerous in vitro and in vivo studies have shown that the inhibition of oxidative stress can promote the tenogenic differentiation of tendon stem/progenitor cells, reduce tissue fibrosis and augment tendon repair. This review aims to systematically review the literature and summarize the clinical and pre-clinical evidence about the potential relationship of oxidative stress and tendon disorders. The literature in PubMed was searched using appropriate keywords. A total of 81 original pre-clinical and clinical articles directly related to the effects of oxidative stress and the activators or inhibitors of oxidative stress on the tendon were reviewed and included in this review article. The potential sources and mechanisms of oxidative stress in these debilitating tendon disorders is summarized. The anti-oxidative therapies that have been examined in the clinical and pre-clinical settings to reduce tendon fibrosis and adhesion or promote healing in tendinopathy are reviewed. The future research direction is also discussed.

Anterior cruciate ligament reconstruction (ACLR) is a commonly performed procedure in Orthopaedic sports medicine. With advances in surgical techniques providing better positioning and fixation of the graft, subsequent graft failure to certain extent should be accounted by poor graft healing. Although different biological modulations for enhancement of graft healing have been tried in different clinical and animal studies, complete graft incorporation into bone tunnels and the “ligamentization” of the intra-articular part have not been fully achieved yet. Based on the understanding of graft healing process and its failure mechanism, the purpose of this review is to combine both the known basic science & clinical evidence, to provide a much clearer picture of the obstacle encountered in graft healing, so as to facilitate researchers on subsequent work on the enhancement of ACL graft healing.

When and where to apply the biological modulations is effective to promote healing in the anterior cruciate ligament (ACL) reconstruction remains unclear. To perform a systematic review of preclinical animal studies on biological modulation in anterior cruciate ligament reconstruction (ACLR) concerning the time and site of delivery. Systematic review of controlled laboratory studies. PubMed, Ovid, and Scopus were searched until December 2020 using a combination of keywords and their synonym to retrieve all animal studies about biological modulation in ACLR. Studies that assessed mechanical strength after ACLR and compared with negative control were included. The methodological quality of animal studies was evaluated. 33 studies were included in this review and the majority reported mechanical strength improvement. 79 ​% of studies applied the biological modulations intra-operatively with different delivery systems used. For 21 ​% of post-operative delivery studies, intermittent delivery was tried. 21 of the included studies directly applied the biological modulations in the bone tunnels, 5 studies applied intra-articularly while 7 studies applied both in the bone tunnels and intra-articular part. Biological modulations applied intra-operatively and those applied in both parts showed better mechanical strength increase. A shift of the failure mode of pull-out from the bone tunnel in the early healing phase, to mid-substance rupture in the later phase was observed in most studies. The improvement of the mechanical strength depends on how the biological modulations (delivery phase, delivery site, delivery form) are applied. The intra-operative delivery showed an overall higher mechanical strength increase and bone tunnel only delivery or intra-articular and bone tunnel both delivery are preferred than intra-articular only delivery. In addition, intra-articular and bone tunnel both delivery can have better mechanical strength increase for a long follow-up time. Thus, intra-operative application with a carrier to control release rate in both parts should be recommended. Further studies are needed to achieve a better healing outcome and more attention should be given to the intra-articular remodeling of the graft along with the tendon bone healing to increase the final mechanical strength. Here, a systematic review of preclinical evidence of the time, site and the method the biological modulations being applied for ACLR to improve the graft healing would be performed. After reviewing the available studies, a choice of when and where to apply the biological modulations can achieve better mechanical strength after ACLR can be obtained. It provides evidence for both researchers and clinicians to decide when and where to apply the biological modulations can achieve their best effectiveness for ACLR before implementing. Promoting graft healing with targeted time and targeted site may reduce the risk of graft failure, safeguard return to sport.

Current rat model of rotator cuff (RC) tear could not mimic the suture anchor (SA) repair technique in the clinical practice. We designed a novel SA for RC repair of rats to establish a clinically relevant animal model. Small suture anchors that fit the rat shoulder were assembled. 60 rats were assigned to the transosseous (TO) repair group or SA repair group (n = 30/group). Micro-computed tomography (Micro-CT) scanning, biomechanical test and histological analysis were implemented at 2, 4, and 8-week post-repair. The failure load and stiffness in the SA group were significantly higher than those of TO group at 4-week post-repair. Micro-computed tomography analysis showed the bone mineral density and trabecular thickness of the SA group were significantly lower than those of TO group. The SA group showed a better insertion continuity at 4-week post-repair compared to TO group. No significant difference in gait parameters was found between groups. Therefore, SA repair is applicable for the rat model of RC tears. The SA repair achieved superior RC tendon healing, but more extensive initial bone damage compared to TO repair, while the shoulder function was comparable. This model could replicate the current repair technique in the clinical situation and be considered for future preclinical studies on healing enhancement for RC tears. Statement of Clinical Significance: With high clinical relevance, this model may facilitate the translation from an animal study into clinical trials.