Local injections of anesthetics, NSAIDs, and corticosteroids for tendinopathies are empirically used. They are believed to have some cytotoxicity toward tenocytes. The maximal efficacy dosages of local injections should be determined. A commercial 2D microfluidic xCELLigence system had been developed to detect real-time cellular proliferation and their responses to different stimuli and had been used in several biomedical applications. The purpose of this study is to determine if human tenocytes can successfully proliferate inside xCELLigence system and the result has high correlation with conventional cell culture methods in the same condition. First passage of human tenocytes was seeded in xCELLigence and conventional 24-well plates. Ketorolac tromethamine, bupivacaine, methylprednisolone, and betamethasone with different concentrations (100, 50, and 10% diluted of clinical usage) were exposed in both systems. Gene expression of type I collagen, type III collagen, tenascin-C, decorin, and scleraxis were compared between two systems. Human tenocytes could proliferate both in xCELLigence and conventional cell culture systems. Cytotoxicity of each drug revealed dose-dependency when exposed to tenocytes in both systems. Significance was found between groups. All the four drugs had comparable cytotoxicity in their 100% concentration. When 50% concentration was used, betamethasone had a relatively decreased cytotoxicity among them in xCELLigence but not in conventional culture. When 10% concentration was used, betamethasone had the least cytotoxicity. Strong and positive correlation was found between cell index of xCELLigence and result of WST-1 assay (Pearson’s correlation [r] = 0.914). Positive correlation of gene expression between tenocytes in xCELLigence and conventional culture was also observed. Type I collagen: [r] = 0.823; type III collagen: [r] = 0.899; tenascin-C: [r] = 0.917; decorin: [r] = 0.874; and scleraxis: [r] = 0.965. Human tenocytes could proliferate inside xCELLigence system. These responses varied when tenocytes were exposed to different concentrations of ketorolac tromethamine, bupivacaine, methylprednisolone, and betamethasone. The result of cell proliferation and gene expression of tenocytes in both xCELLigence and conventional culture system is strongly correlated. xCELLigence culture system may replace conventional cell culture, which made real-time tenocyte proliferation monitoring possible.

Rotator cuff tears are very common and their incidence increases with age. Shoulder ultrasonography has recently gained popularity in detecting rotator cuff tears because of its efficiency, cost-effectiveness, time-saving, and real-time nature of the procedure. Well-trained orthopedic surgeons may utilize shoulder ultrasonography to diagnose rotator cuff tears. The wait time of patients planned to have shoulder MRI (magnetic resonance imaging) to rule in rotator cuff tears may decrease after orthopedic surgeon start doing shoulder ultrasonography as a screening tool for that. Patients with rotator cuff tears may be detected earlier by ultrasonography and have expedited surgical repair. The efficacy in determination of rotator cuff tears will also increase. Patients were retrospectively reviewed from January 2007 to December 2012. They were divided into 2 groups: Ultrasound (-) group and the Ultrasound (+) group. Age, gender, wait time from outpatient department (OPD) visit to MRI exam, MRI exam to operation (OP), and OPD visit to OP, patient number for MRI exam, and number of patients who finally had rotator cuff repair within two groups were compared. The wait time of OPD visit to OP and MRI to OP in patients who received shoulder ultrasonography was significantly less than that in patients did not receive shoulder ultrasonography screening. Only 23.8% of the patients with a suspected rotator cuff injury undergone arthroscopic rotator cuff repair before ultrasonography was applied as a screening tool. The percentage increased to 53.6% after orthopedic surgeon started using ultrasonography as a screening tool for rotator cuff tears. Office-based shoulder ultrasound examination can reduce the wait time for a shoulder MRI. The efficacy of determination of rotator cuff tears will also increase after the introduction of shoulder ultrasonography.

Tendinopathy is a common painful musculoskeletal disorder treated by injection of analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are believed to have cytotoxicity toward tenocytes. Ascorbic acid is an antioxidant that promotes collagen biosynthesis and prevents free radical formation. It is believed to protect tenocytes from oxidative stress. The optimal concentration of ascorbic acid, especially when used in conjunction with anesthetics and NSAIDs injection, to treat different stages of tendinopathies is unknown. Human tenocytes were isolated from a torn edge of the supraspinatus tendon of a 51-year-old male patient during arthroscopic repair. We monitored real-time changes in human tenocyte proliferation upon exposure to different concentrations of ascorbic acid, bupivacaine, and ketorolac tromethamine using the xCELLigence system. No significant changes in cell index were observed between the control group and tenocytes treated with the 3 concentrations of ascorbic acid. Tenocytes exposed to 0.5% bupivacaine and 30 or 15 mg/mL ketorolac tromethamine revealed significant reduction in tenocytes proliferation. Bupivacaine 0.5% with 250 μg/mL ascorbic acid and 15 mg/mL ketorolac tromethamine with 250 μg/mL ascorbic acid showed the least cytotoxicity against tenocytes. The optimal ascorbic acid concentration required to reduce the cytotoxic effects of bupivacaine and ketorolac tromethamine was demonstrated using this platform.

Arthroscopic capsular release allows direct visualization and release of inflamed tissues in refractory frozen shoulder. The reticular neural network in the long head of the biceps tendon (LHBT) and nerve endings of the transverse humeral ligament (THL) might be responsible for shoulder pain. We hypothesized that patients with painful refractory frozen shoulder benefited from pan-capsular release, THL release, and LHBT tenodesis. The LHBT tenodesis decreased the possibility of LHBT instability. The balance of the shoulder joint was maintained after such extensive release. From October 2013 to June 2019, patients with painful refractory frozen shoulder were enrolled consecutively at the same institute. All patients received arthroscopic pan-capsular, THL release, and suprapectoral LHBT tenodesis with a minimum of 2-year follow-up. Preoperative and postoperative shoulder range of motion (ROM), pain visual analog scale (PVAS), subjective shoulder value (SSV), constant score, LHBT score, acromio-humeral distance (AHD), and critical shoulder angle (CSA) were recorded. In total, 35 patients with an average age of 53.1 ± 9 years were enrolled. The average follow-up period was 24 ± 1.5 months. Forward elevation improved from 105.1° ± 17° to 147° ± 12° (p < 0.001), external rotation improved from 24.1° ± 13.3° to 50.9° ± 9.7° (p < 0.001), and internal rotation improved from L3 to T9 (p < 0.001), respectively, at final follow-up. PVAS improved from 7.3 ± 1.1 to 1.8 ± 0.6 (p < 0.001), constant score from 23.4 ± 11 to 80.7 ± 5.2 (p < 0.001), and SSV from 27.7 ± 10.5 to 77.4 ± 3.8, respectively, at follow-up. No differences were found in AHD and CSA after surgery (p = 0.316, and p = 0.895, respectively). Patients with painful refractory frozen shoulder benefited from pan-capsular and THL release. A radiographically balanced shoulder joint was maintained even after such extensive release.

Platelet-rich plasma (PRP) contains bioactive cytokines to enhance tissue healing. The best PRP preparation protocol and timing of the treatment have not been determined yet. To screen the best-fit PRP, a 3-chamber co-culture device was developed. We hypothesized the concentrations of the cytokines from different PRPs in the co-culture plates had a high correlation with those in conventional 24-well culture plates at different time points. The concentrations of the cytokine from PRPs would be correlated with platelet concentrations. The correlation of transforming growth factor beta-1 (TGF-β1) and platelet-derived growth factor AB (PDGF-AB) in both devices were compared at 0, 24, 48, 72, and 96 h from two PRPs as well as that of platelet and cytokines concentrations. The results revealed that there was a moderate to high correlation in TGF-β1 concentrations between the 3-chamber co-culture and conventional culture device until 96 h. The correlation of PDGF-AB concentrations in both devices had moderate to high correlation in the first 24 h, and then it became modestly correlated from 48 to 96 h. A high correlation was found between platelet and TGF-β1 concentration at 96 h. However, they were modestly correlated in other time points. A negative or modest correlation was found between platelet and PDGF-AB concentration in all time points. In conclusion, TGF-β1 and PDGF-AB revealed a time-dependent manner of release at five time points. There is a moderate to high correlation of the TGF-β1 and PDGF-AB concentration in both devices at different time points. However, TGF-β1 and PDGF-AB concentrations are not always proportional to the platelet concentration of the PRPs.

Hamstring tendon is one of the best graft choices for anterior cruciate ligament reconstruction. The upper age limit of reconstruction is not determined because tenocytes from old individuals have less proliferative ability than young ones. Dexamethasone is commonly used to deal with musculoskeletal disorder with dose-dependent cytotoxicity toward tenocytes. Ascorbic acid is essential for tenocytes culture and collagen secretion and can alleviate the cytotoxicity of dexamethasone. In the current study, a microfluidic platform was used to screen the best dexamethasone and ascorbic acid combination treatment for tenocytes from young and old donors because it has been proven to provide a high throughput analysis platform. Comparison of their proliferation under three concentrations of ascorbic acid and dexamethasone was performed. Tenocytes proliferation among young and old donors was also measured when exposed to nine combinations of ascorbic acid and dexamethasone. The result confirmed the differences in cells proliferation when hamstring tenocytes from different ages of donors are exposed to different concentrations of dexamethasone and ascorbic acid. Tenocytes from old donors are not always more susceptible to dexamethasone and ascorbic acid. An optimal dose of ascorbic acid in decreasing the cytotoxic effect of dexamethasone can be screened by a high throughput microfluidic platform.