Abstract Background The incidence of Achilles tendinopathy has risen over the past decades. Insertional Achilles tendinopathy is characterised by tissue degeneration of the Achilles tendon from its insertion in the calcaneus to up to 2 cm proximally. This clinical condition is accompanied by pain, loss of function and diminished exercise tolerance. Numerous conservative treatment modalities are available to participants with insertional Achilles tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, laser therapy, cryotherapy, therapeutic ultrasound, and orthotics. Eccentric exercise and extracorporeal shockwave therapy may reduce pain in participants with non-calcified insertional Achilles tendinopathy. However, no specific treatment is recommended over another due to the low methodological quality of trials. Given the lack of standard or preferred non-surgical treatment and the potential risks of surgical treatment, there is an imminent need to reassess different non-surgical treatments based on the newest evidence. Thus, this systematic review aims to evaluate the clinical effectiveness of the various non-surgical treatments for insertional Achilles tendinopathy. Methods AMED EBSCOhost, CINAHL, EBSCOhost, EMBASE, PEDro, PubMed, Web of Science, and Clinicaltrials.gov were searched from 1992 to 14th October 2022, randomised controlled trials of adults with insertional Achilles tendinopathy investigating non-surgical treatments compared with each other or no treatment, placebo/sham control. Two reviewers independently screened and extracted the data. Random effects of network meta-analysis immediately after treatments were used to report comparative treatment effects. The surface under the cumulative ranking probabilities was calculated to assess the relative ranking of treatments. Results Nine trials (total n = 464 participants) were included. This review recommended the combination of eccentric exercise and soft tissue therapy to manage insertional Achilles tendinopathy. With the highest SUCRA values of 84.8, and the best mean rank of 1.9, Eccentric exercise plus soft tissue treatment ranked as the most effective treatment for short-term pain. Conclusions This is the first NMA of non-surgical treatment focusing on short-term pain control for IAT which eccentric exercise plus soft-tissue therapy was found to be the most effective treatment combination. However, the overall confidence in non-surgical treatments from all included trials was very low. No recommendation of the best treatment option can be made from this review.
Growth factors potentially promote tendon healing. Understanding the right time to administer growth factors and the dosage of growth factors are prerequisites for designing effective cytokine therapy. We investigated the supplementation-time dependence of the effects of platelet-derived growth factor isoform B at various dosages on tendon healing, and the temporal responsiveness of healing tendon toward platelet-derived growth factor. Platelet-derived growth factor isoform B at various dosages (0, 10, 100, or 1000 ng) was delivered into the gap wound of rat patellar tendons via microsyringe injection on Day 3 or Day 7 after injury. Tendon specimens were harvested on Day 14 for measurement of cell proliferation, pyridinoline content, and mechanical properties. We found increased proliferative response only when the growth factor was supplemented on Day 3 after injury, whereas supplementation on Day 7 resulted in greater peak load, cross-sectional area, and pyridinoline content. The ultimate stress did not change. Our findings suggest supplementation of platelet-derived growth factor isoform B at Day 7 benefits the mechanical properties and maturation of healing tendons. We also found platelet-derived growth factor receptor β expressing cells at the remodeling site as much as 6 months after injury, suggesting healing tendon also may be responsive to long-term delivery of platelet-derived growth factor.
Our body systems are comprised of numerous multi-tissue units. For the musculoskeletal system, one of the predominant functional units is comprised of bone, tendon/ligament, and muscle tissues working in tandem to facilitate locomotion. To successfully treat musculoskeletal injuries and diseases, critical consideration and thoughtful integration of clinical, biological, and engineering aspects are necessary to achieve translational bench-to-bedside research. In particular, identifying ideal biomaterial design specifications, understanding prior and recent tissue engineering advances, and judicious application of biomaterial and fabrication technologies will be crucial for addressing current clinical challenges in engineering multi-tissue units. Using rotator cuff tears as an example, insights relevant for engineering a bone-tendon-muscle multi-tissue unit are presented. This review highlights the tissue engineering strategies for musculoskeletal repair and regeneration with implications for other bone-tendon-muscle units, their derivatives, and analogous non-musculoskeletal tissue structures.
Graft healing in anterior cruciate ligament (ACL) reconstruction is often slow and compromised. There are numerous treatment strategies targeting at the biological healing process in ACL reconstruction. Most of these treatments attempt to promote graft incorporation at the tendon to bone interface, although the intra-articular mid substance would be more problematic. As intraoperative injection of vitamin C has been reported to be able to promote tendon healing, we speculate that vitamin C supplementation may also work for graft healing enhancement in ACL reconstruction. The purpose of this study is to formulate a vitamin C-supplemented saline for intraoperative irrigation, in order to promote biological healing in ACL reconstruction. The study hypothesis was tested using 114 rats. During ACL reconstruction, the knee joint of the rats were irrigated with either normal saline, or saline supplemented with 3 mg/mL, 10 mg/mL, or 30 mg/mL vitamin C. Inflammatory response was measured by serum C-reactive protein enzyme-linked immunosorbent assay at Day 1, Day 4, and Day 7 postoperation. Functional recovery was evaluated by gait analysis at preinjury, and Week 4 and Week 6 postoperation. Knee samples were harvested at Week 6 postoperation for anterior–posterior (A–P) knee laxity test and graft pull-out test. Histology was performed at Day 1, Day 4, Day 7, and Day 42 for scoring. Vitamin C supplementation at all doses significantly reduced serum C-reactive protein level as compared to saline control at Day 1 (p = 0.029) postoperation. At 6 weeks postoperation, ACL reconstruction with 3 mg/mL vitamin C irrigation led to a better restoration of A–P knee laxity as compared to saline irrigation (p = 0.032), whereas no positive effect was observed in the groups with 10 mg/mL and 30 mg/mL vitamin C irrigation. Vitamin C irrigation did not affect ultimate load of the graft complex. Histological analysis revealed that at Week 6 postoperation, graft deterioration was significantly reduced in 3 mg/mL and 10 mg/mL vitamin C groups, but no significant difference was observed in graft incorporation among different groups at Day 42 postoperation. Although no significant difference was detected in the gait parameters among experimental groups, increased percentage of rats with asymmetric walking gait (with limb idleness index > 1.3) was found in the groups of 10 mg/mL or 30 mg/mL vitamin C irrigation. The results showed that intraoperative supplementation of low dose (3 mg/mL) vitamin C effectively reduced graft deterioration and improved restoration of A–P knee laxity at 6 weeks postoperation, but higher doses of vitamin C irrigation may have side effects that lead to a higher chance of gait asymmetry. This study reveals the potential use of surgical irrigation saline as a delivery method for bioactive agents to promote healing, which might be a cost-effective and translatable approach for biological modulation for orthopaedic surgeries.
We propose using the single-leg squat-and-hold (SLSH) task with kinematic analysis to objectively measure dynamic knee stability after anterior cruciate ligament (ACL) injury. There are three objectives of this study: to compare the knee kinematics of ACL-deficient patients and healthy controls by capturing knee wobbling during the SLSH task, to detect kinematic changes after ACL reconstruction, and to correlate the kinematic variables with self-reported knee function. Twenty-five ACL-deficient participants and 18 healthy matched participants were recruited. The knee kinematics involving both the magnitudes and frequency of motion fluctuation was captured during SLSH by 3D motion analysis system (Vicon). Compared to the limbs of the control participants, the ACL involved limbs exhibited a greater range of flexion-extension (4.33 ± 1.96 vs. 2.73 ± 1.15; p = 0.005) and varus-valgus (2.52 ± 0.99 vs. 1.36 ± 0.42; p < 0.001). It also inhibited higher frequency of flexion-extension (4.87 ± 2.55 vs. 2.68 ± 1.23; p = 0.003) and varus-valgus (3.83 ± 2.59 vs. 1.42 ± 0.55; p < 0.001). The range of flexion-extension (4.50 ± 2.24 vs. 2.90 ± 1.01; p = 0.018), frequency of flexion-extension (4.58 ± 2.53 vs. 3.05 ± 1.80; p = 0.038) and varus-valgus (3.46 ± 2.11 vs. 1.80 ± 1.23; p = 0.022) was reduced after ACL reconstruction. Increased frequency of knee varus-valgus was correlated with lower IKDC score (r = −0.328; p = 0.034). Knee wobbling was more prominent in ACL-deficient patients, which was associated with poor knee function. SLSH task with kinematic analysis appears to be a potential assessment method for monitoring dynamic knee stability after ACL injury.
The OASIS working group was first initiated in 2001, published the new format in March 2004, which was ratified as an official SEMI standard in September 2005. A follow-on initiative expanded the new standard to cover the needs of the mask manufacturing equipment sector with a derived standard called OASIS.MASK (P44) that was released in November 2005 and updated in May 2008. While there are many potential benefits from this improved format over the incumbent GDSII and MEBES standards, the main driver for the development of the OASIS format was the looming data volume explosion from the onward march of processing and design technology. With a demonstrated benefit of roughly 10x over the GDSII format, it was expected that the new OASIS format would be embraced quickly by the semiconductor industry. In reality, the adoption process took significantly longer and is still in progress. The paper analyzes the data volume and adoption trends by manufacturing steps - e.g design, post tapeout flow and mask manufacturing. Survey results on the adoption status are shared and an analysis of the technical, economic, and environmental factors influencing it will be discussed.
Hand flexor tendon injuries are compromised with tendon adhesion. Tendon adhesion forms between flexor tendon and tendon sheath, reduces the range of motion of fingers, and affects their function. Oxidative stress is increased in flexor tendon after injury and might play a role in tendon adhesion formation. Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), a water-soluble analog of vitamin E, is antioxidative. Trolox reduced oxidative stress and the expression of fibrotic cytokines in the bile gut ligation animal model. Vitamin C and Trolox are strong antioxidants, but they might also have prooxidant properties. The prooxidant properties of vitamin C and Trolox are different. In this study, our aim was to determine the effect of Trolox in reducing tendon adhesion formation.Flexor digitorum profundus tendon injury was induced in 54 Kai-Mei Chicken according to a well-established protocol. After wound closure, an injection of 50 μL saline, 10mM Trolox, or 100mM Trolox was administered into the wound area. At 2 weeks or 6 weeks after the surgery, chicken feet were harvested for gliding test, high-resolution ultrasound measurement on a fibrotic area, and histology.At Week 2 after the surgery, Trolox has no effect on the flexion angle and gliding resistance, whereas a significant improvement was observed in the flexion angle and gliding resistance in the Trolox-treated groups at Week 6. However, no dose response was observed. In the ultrasound measurement, there was no significant difference in the fibrotic mass in the Trolox-treated group as compared to the saline group at Week 2. At Week 6, fibrotic mass was significantly reduced in both Trolox-treated groups. From the histological examination, the Trolox-treated groups presented a higher cellularity at Week 2 as compared to the saline group, and reduced fibrosis and adhesion at Week 6.Our results suggest that local administration of Trolox can reduce tendon adhesion, and a higher dose of Trolox did not have negative effects.Trolox solution might be feasible to reduce tendon adhesion via intraoperative injection at the wound area during tendon repair.
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