Allan Wang

Scaffolds for tendon and ligament repair: review of the efficacy of commercial products.

Driven by market demand, many biological and synthetic scaffolds have been developed during the last 15 years. Both positive and negative results have been reported in clinical applications for tendon and ligament repair. To obtain data for this review, multiple electronic databases were used (e.g., Pubmed and ScienceDirect), as well as the US FDA website and the reference lists from clinical trials, review articles and company reports, in order to identify studies relating to the use of these commercial scaffolds for tendon and ligament repair. The commercial names of each scaffold and the keywords ‘tendon’ and ‘ligament’ were used as the search terms. Initially, 378 articles were identified. Of these, 47 were clinical studies and the others were reviews, editorials, commentaries, animal studies or related to applications other than tendons and ligaments. The outcomes were reviewed in 47 reports (six on Restore™, eight on Graftjacket®, four on Zimmer®, one on TissueMend®, five on Gore-Tex®, six on Lars®, 18 on Leeds–Keio® and one study used both Restore and Graftjacket). The advantages, disadvantages and future perspectives regarding the use of commercial scaffolds for tendon and ligament treatment are discussed. Both biological and synthetic scaffolds can cause adverse events such as noninfectious effusion and synovitis, which result in the failure of surgery. Future improvements should focus on both mechanical properties and biocompatibility. Nanoscaffold manufactured using electrospinning technology may provide great improvement in future practice.

Perioperative Exercise Programs Improve Early Return of Ambulatory Function After Total Hip Arthroplasty

Wang AW, Gilbey HJ, Ackland TR: Perioperative exercise programs improve early return of ambulatory function after total hip arthroplasty: A randomized, controlled trial. Am J Phys Med Rehabil 2002;81:801–806. Objective Patients with endstage hip arthritis have poor ambulatory function. The aim of this study was to determine if perioperative exercise programs are well tolerated by these elderly patients and if a customized program can achieve an earlier recovery of normal ambulatory function after total hip arthroplasty. Design Twenty-eight subjects scheduled for total hip arthroplasty were randomized to either the exercise group and received a perioperative customized exercise program or the control group and received the routine perioperative care. Ambulatory function was assessed by measurement of gait parameters during a 25-m walk test, and walking endurance was assessed by a 6-min walk test. Results Exercise group subjects attended 97.3% of scheduled exercise sessions with no training injuries. Exercise group subjects demonstrated greater stride length and gait velocity at 3 wk postsurgery. At 12 and 24 wk postsurgery, gait velocity was greater, and the 6-min walking distance was significantly greater than the control group. Conclusion The study indicates that perioperative customized exercise program are well tolerated in the elderly patient with endstage hip arthritis and are effective in improving the rate of recovery in ambulatory function in the first 6 mo after total hip arthroplasty.

Do Postoperative Platelet-Rich Plasma Injections Accelerate Early Tendon Healing and Functional Recovery After Arthroscopic Supraspinatus Repair? A Randomized Controlled Trial

Background: Tendon-bone healing after rotator cuff repair directly correlates with a successful outcome. Biological therapies that elevate local growth-factor concentrations may potentiate healing after surgery. Purpose: To ascertain whether postoperative and repeated application of platelet-rich plasma (PRP) to the tendon repair site improves early tendon healing and enhances early functional recovery after double-row arthroscopic supraspinatus repair. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 60 patients underwent arthroscopic double-row supraspinatus tendon repair. After randomization, half the patients received 2 ultrasound-guided injections of PRP to the repair site at postoperative days 7 and 14. Early structural healing was assessed with MRI at 16 weeks, and cuff appearances were graded according to the Sugaya classification. Functional scores were recorded with the Oxford Shoulder Score; Quick Disability of the Arm, Shoulder and Hand; visual analog scale for pain; and Short Form–12 quality-of-life score both preoperatively and at postoperative weeks 6, 12, and 16; isokinetic strength and active range of motion were measured at 16 weeks. Results: PRP treatment did not improve early functional recovery, range of motion, or strength or influence pain scores at any time point after arthroscopic supraspinatus repair. There was no difference in structural integrity of the supraspinatus repair on MRI between the PRP group (0% full-thickness retear; 23% partial tear; 77% intact) and the control group (7% full-thickness retear; 23% partial tear; 70% intact) at 16 weeks postoperatively (P = .35). Conclusion: After arthroscopic supraspinatus tendon repair, image-guided PRP treatment on 2 occasions does not improve early tendon-bone healing or functional recovery.

Autologous Tenocyte Injection for the Treatment of Severe, Chronic Resistant Lateral Epicondylitis A Pilot Study

Background: Severe chronic lateral epicondylitis (LE) is associated with degenerative tendon changes, extracellular matrix breakdown, and tendon cell loss. On the basis of positive outcomes from preclinical studies, this study is the first clinical trial of autologous tenocyte injection (ATI) on severe tendinopathy associated with chronic LE. Hypothesis: Autologous tenocyte injection is a safe and effective procedure that enables a reduction in pain and improvement in function in resistant LE. Study Design: Case series; Level of evidence, 4. Methods: Patients with severe refractory LE underwent clinical evaluation and magnetic resonance imaging (MRI) before intervention. A patellar tendon needle biopsy was performed under local anesthetic, and tendon cells were expanded by in vitro culture. Tenocytes used for the injection were characterized by flow cytometry and real-time polymerase chain reaction. Autologous tenocytes were injected into the site of tendinopathy identified at the origin of the extensor carpi radialis brevis tendon under ultrasound guidance on a single occasion. Patients underwent serial clinical evaluations and repeat MRI at 12 months after intervention. Results: A total of 20 consecutive patients were included in the study. Three patients withdrew consent after enrollment and before ATI. No adverse event was reported at either biopsy or injection sites. Furthermore, no infection or excessive fibroblastic reaction was found in any patient at the injection site. Clinical evaluation revealed an improvement in mean visual analog scale scores, for a maximum pain score from 5.94 at the initial assessment to 0.76 at 12 months (P < .001). Mean quick Disabilities of the Arm, Shoulder and Hand (QuickDASH) and grip strength scores also significantly improved over the 12-month follow-up (QuickDASH score, 45.88 [baseline] to 3.84; grip strength, 20.17 kg [baseline] to 37.38 kg; P < .001). With use of a validated MRI scoring system, the grade of tendinopathy at the common extensor origin improved significantly by 12 months (P < .001). One patient elected to proceed to surgery 3 months after ATI following a reinjury at work. Conclusion: In this study, patients with chronic LE who had previously undergone an unsuccessful full course of nonoperative treatment showed significantly improved clinical function and structural repair at the origin of the common extensor tendon after ATI. This novel treatment is encouraging for the treatment of tendinopathy and warrants further evaluation.

In chronic lateral epicondylitis, apoptosis and autophagic cell death occur in the extensor carpi radialis brevis tendon.

HYPOTHESIS Despite its common occurrence, lateral epicondylitis is poorly understood from a cellular and molecular perspective. We hypothesize that apoptosis and autophagic cell death are involved in the development of chronic lateral epicondylitis. MATERIALS AND METHODS In 10 patients undergoing surgery for chronic recalcitrant lateral epicondylitis, tendon samples were taken from the extensor carpi radialis brevis (ECRB) tendon and were processed for hematoxylin and eosin, terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling (TUNEL) assay, and immunostaining. Extracellular matrix structure was graded I to III according to collagen fiber structure and arrangement. Apoptotic rate, autophagic cell death rate, cell density, and type I collagen content were measured and compared between areas with different collagen grade. RESULTS Apoptotic and autophagic cell death occur in the ECRB tendon and varied with the grade of collagen structure. In grade I matrix with relatively less disrupted collagen structure, the apoptosis rate was 23.2% +/- 4.8% and the autophagy cell death rate was 7.6% +/- 2.2%. In grade II matrix with more advanced breakdown of collagen structure, the apoptosis rate increased to 34.4% +/- 4% (P < .05) and the autophagic cell death rate to 13.7% +/- 3% (P < .05). DISCUSSION This study demonstrated that apoptosis and autophagic cell death occur in the ECRB tendon in chronic lateral epicondylitis. The markedly elevated apoptotic rate and autophagic cell death rate in the grade II matrix may be responsible for the decrease in cellularity and further deterioration of collagen quality seen in end-stage grade III matrix, and this eventually compromised the tendons ability to maintain its integrity and resulted in tendon tear. CONCLUSION Both apoptosis and autophagic cell death play an important role in the development of tendon degeneration in chronic lateral epicondylitis.

Programmable mechanical stimulation influences tendon homeostasis in a bioreactor system

Identification of functional programmable mechanical stimulation (PMS) on tendon not only provides the insight of the tendon homeostasis under physical/pathological condition, but also guides a better engineering strategy for tendon regeneration. The aims of the study are to design a bioreactor system with PMS to mimic the in vivo loading conditions, and to define the impact of different cyclic tensile strain on tendon. Rabbit Achilles tendons were loaded in the bioreactor with/without cyclic tensile loading (0.25 Hz for 8 h/day, 0–9% for 6 days). Tendons without loading lost its structure integrity as evidenced by disorientated collagen fiber, increased type III collagen expression, and increased cell apoptosis. Tendons with 3% of cyclic tensile loading had moderate matrix deterioration and elevated expression levels of MMP‐1, 3, and 12, whilst exceeded loading regime of 9% caused massive rupture of collagen bundle. However, 6% of cyclic tensile strain was able to maintain the structural integrity and cellular function. Our data indicated that an optimal PMS is required to maintain the tendon homeostasis and there is only a narrow range of tensile strain that can induce the anabolic action. The clinical impact of this study is that optimized eccentric training program is needed to achieve maximum beneficial effects on chronic tendinopathy management. Biotechnol. Bioeng. 2013; 110: 1495–1507.

The Reliability and Validity of Magnetic Resonance Imaging in the Assessment of Chronic Lateral Epicondylitis

PURPOSE Lateral epicondylitis is a painful condition affecting the proximal enthesis of the extensor carpi radialis brevis tendon. Although magnetic resonance imaging (MRI) has been highlighted as an important diagnostic tool, to our knowledge no previous study has established the observer reliability of MRI for lateral epicondylitis or the relationship between MRI abnormalities of the common extensor origin and the patients clinical assessment. METHODS Twenty-one consecutive subjects with a clinical diagnosis of chronic lateral epicondylitis were assessed. An MRI scoring system was used to grade the degree of tendinosis and length of tendon separation of the common extensor origin from the lateral epicondyle. Three independent musculoskeletal radiologists, who were blinded to patient clinical severity, scored images separately. Each scored the images on 3 separate occasions. Clinical symptoms were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) and Upper Extremity Functional Scale clinical measures. Maximum pain levels were scored on a visual analog scale, and objective assessment was made with grip strength. RESULTS Moderate or severe signal changes consistent with tendinosis were observed in 18 of 21 patients. Significant inter-observer reliability and intra-observer agreement were demonstrated for MRI interpretation of grade of tendinosis and length of tendon separation. Significant negative correlation was found between the length of tendon separation and both the QuickDASH and maximum pain levels. CONCLUSIONS Magnetic resonance imaging is a reliable tool in determining radiological severity of lateral epicondylitis. However, the severity of MRI signal changes does not positively correlate with symptoms. These findings question the validity of MRI in the assessment of lateral epicondylitis.

Autologous tenocyte implantation, a novel treatment for partial-thickness rotator cuff tear and tendinopathy in an elite athlete

Tendinopathy and small partial-thickness tears of the rotator cuff tendon are common presentations in sports medicine. No promising treatment has yet been established. Corticosteroid injections may improve symptoms in the short term but do not primarily treat the tendon pathology. Ultrasound-guided autologous tenocyte implantation (ATI) is a novel bioengineered treatment approach for treating tendinopathy. We report the first clinical case of ATI in a 20-year-old elite gymnast with a rotator cuff tendon injury. The patient presented with 12 months of increasing pain during gymnastics being unable to perform most skills. At 1 year after ATI the patient reported substantial improvement of clinical symptoms. Pretreatment and follow-up MRIs were reported and scored independently by two experienced musculoskeletal radiologists. Tendinopathy was improved and the partial-thickness tear healed on 3 T MRI. The patient was able to return to national-level competition.

Evidence for the Durability of Autologous Tenocyte Injection for Treatment of Chronic Resistant Lateral Epicondylitis Mean 4.5-Year Clinical Follow-up

Background: Chronic lateral epicondylitis (LE) induces cell apoptosis and autophagy, which lead to the reduction of tendon-derived cells in the torn tendon. Our previous study has shown that ultrasound-guided autologous tenocyte injection (ATI) to the torn tendon in patients with chronic resistant LE significantly improves pain, function, and structural repair at 1 year. This report is the continued assessment of the clinical outcomes of these patients at mean 4.5-year follow-up. Hypothesis: Improvements in LE clinical function and structural repair after ATI will be maintained at mean 4.5-year follow-up. Study Design: Case series; Level of evidence, 4. Methods: Patients with severe refractory LE underwent clinical evaluation and MRI before intervention. A patellar tendon needle biopsy was performed under local anesthetic, and tendon cells were expanded by in vitro culture. Autologous tenocytes were injected into the central tendinopathy identified at the common extensor tendon origin under ultrasound guidance on a single occasion. Patients underwent serial clinical evaluations for up to 5 years after ATI, including the visual analog scale (VAS) for pain, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), Upper Extremity Functional Scale (UEFS), and grip strength. Post-ATI MRI scanning was performed at 1 year and final follow-up. Results: A total of 16 patients (9 male, 7 female), aged between 37 and 63 years, were included in the study. The mean duration of symptoms before study recruitment was 29.24 months (range, 6-240 months). One patient elected to proceed to surgery 3 months after ATI due to reinjury at work, and 1 patient died of prostate cancer with metastases during the follow-up period. The mean final follow-up time for the remaining 15 patients was 4.51 years (range, 3.08-5.17 years). No complications were observed at the patellar tendon biopsy site for any patient. No adverse events, infection, or excessive fibroblastic reactions were observed in any patient at the injection site. Clinical evaluation revealed significant (P < .001) improvement in mean VAS pain score from 5.73 at initial assessment to 1.21 (78% improvement) at final follow-up. Mean QuickDASH, UEFS, and grip strength scores also significantly (P < .001) improved from initial assessment to final follow-up (from 45.88 to 6.61 [84%], from 31.73 to 9.20 [64%], and from 19.85 to 46.60 [208%], respectively). There was no difference in mean QuickDASH and UEFS scores at 1 year and final follow-up (P > .05); however, grip strength continued to improve (P < .001). A validated MRI scoring system indicated that the mean grade of tendinopathy at the common extensor origin improved significantly (P < .001) from initial assessment (4.31) to 1 year (2.88) and was maintained (P > .05) at final follow-up (2.87). At final follow-up, 93% of patients were either highly satisfied or satisfied with their ATI treatment. Conclusion: ATI significantly improved clinical function and MRI tendinopathy scores for up to 5 years in patients with chronic resistant LE who had previously undergone unsuccessful nonsurgical treatment. This study provides evidence for the midterm durability of ATI for treatment of LE tendinopathy.

Radiographic and histologic analysis of cemented double tapered femoral stems

The macroscopic, radiographic, and histologic features of the prosthesis-cement and cement-bone interfaces and adjacent bone were studied in 21 cemented hemiarthroplasties in sheep that had lived until sacrifice at 9 months. The features were compared with those immediately after implantation of the stem in the contralateral femur. The femoral stem was a double taper that was either polished collarless, matte collarless, or matte collared. There was no prosthesis to cement debonding or cement to bone radiolucent line immediately after implantation, and there was excellent interdigitation at the cement-bone interface. After 9 months there was no evidence of prosthesis to cement debonding and no stem with definite loosening. At 9 months after implantation there was evidence of bone remodeling with new bone filling what were presumed to be gaps at the cement-bone interface from immediately after implantation. Radiolucent lines at the cement-bone interface were found to represent trabeculation of the cortical bone rather than the presence of a complete fibrous interface, which was not seen. There was no difference between stem types. Sheep have been shown to be useful in a model of cemented hip arthroplasty and, although no differences were seen between stem types at 9 months after implantation, long term differences cannot be excluded.