Case report: pulsed radiofrequency surgery combined with platelet-rich plasma injection in the treatment of supraspinatus injury.

RATIONALE: The shoulder joint is the most movable joint of the human body, and the incidence of aseptic inflammation of the muscles and tendons around the shoulder joint and acute and chronic muscle injuries is relatively high. Pulsed radiofrequency neuromodulation technology is gradually being used in shoulder joint diseases. Platelet-rich plasma (PRP) is a high-power platelet plasma solution obtained by centrifugation of autologous blood. Platelet cells contain many growth factors that promote tissue repair. PATIENT CONCERNS: Shoulder soreness, limited movement of the shoulder joint, abduction of the upper limbs, and aggravation of pain during flat lifting. The pain radiates to the deltoid muscle stop and forearm. INTERVENTIONS: In this study, radiofrequency pulses combined with PRP were used to treat supraspinatus muscle injury and explore new methods for the treatment of shoulder joint muscle and tendon injuries represented by supraspinatus muscle injury. DIAGNOSIS: We reported 4 patients with supraspinatus injury who received radiofrequency pulse combined with PRP treatment in our hospital. OUTCOMES: After treatment, the patients were followed up at the first month, the third month, and the sixth month, and the Constant-Murley shoulder score and visual analog scale were used to comprehensively evaluate the postoperative improvement of the patients. There was no significant increase in postoperative pain, the Constant-Murley shoulder Score was significantly increased, the range of movement of the shoulder joint was significantly improved, and there were no postoperative complications. LESSONS: The combined application of the 2 treatments can make full use of the analgesic effect of pulsed radiofrequency technology and the repairing effect of PRP, and can maximize the advantages of the 2 more advanced treatment methods in the field of minimally invasive.

A randomized double blinded placebo controlled study to evaluate motor unit abnormalities after experimentally induced sensitization using capsaicin.

Central sensitization is a condition that represents a cascade of neurological adaptations, resulting in an amplification of nociceptive responses from noxious and non-noxious stimuli. However, whether this abnormality translates into motor output and more specifically, ventral horn abnormalities, needs to be further explored. Twenty healthy participants aged 20-70 were randomly allocated to topical capsaicin or a placebo topical cream which was applied onto their left upper back to induce a transient state of sensitization. Visual analogue scale (VAS) ratings of pain intensity and brush allodynia score (BAS) were used to determine the presence of pain and secondary allodynia. Surface electromyography (sEMG) and intramuscular electromyography (iEMG) were used to record motor unit activity from the upper trapezius and infraspinatus muscles before and twenty minutes after application of capsaicin/placebo. Motor unit recruitment and variability were analyzed in the sEMG and iEMG, respectively. An independent t-test and Kruskal-Wallis H test were performed on the data. The sEMG results demonstrated a shift in the motor unit recruitment pattern in the upper trapezius muscle, while the iEMG showed a change in motor unit variability after application of capsaicin. These results suggest that capsaicin-induced central sensitization may cause changes in ventral horn excitability outside of the targeted spinal cord segment, affecting efferent pathway outputs. This preclinical evidence may provide some explanation for the influence of central sensitization on changes in movement patterns that occur in patients who have pain encouraging of further clinical investigation.Clinical Trials registration number: NCT04361149; date of registration: 24-Apr-2020.

Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg2+/curcumin from injectable self-healing hydrogels.

Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. Methods: In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg2+ and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated in vitro and in vivo. Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. Results: The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg2+ promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. Conclusions: The composite hydrogel mediated sustained in situ release of curcumin and Mg2+ to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.

Chronic Nicotine Exposure Minimally Affects Rat Supraspinatus Tendon Properties and Bone Microstructure.

Cigarette smoking is the largest cause of preventable deaths, and a known risk factor for musculoskeletal issues including rotator cuff tendon tears. Tendon degeneration is believed to be due in part to changes in tendon cell health and collagen structure. Several studies have demonstrated that exposure to nicotine negatively impacts tendon healing, but surprisingly, nicotine exposure was shown to increase rat supraspinatus tendon stiffness. In order to address this seeming contradiction, the objective of this study was to comprehensively investigate the effects of long-term (18 weeks) exposure of nicotine on tendon-to-bone microstructural properties in a rat model. We hypothesized that long term subcutaneous nicotine delivery would lead to diminished tendon mechanical properties, decreased bone microstructure in the humeral head, and altered tendon cell morphology compared to age-matched control rats receiving saline. Results demonstrated a small decrease in tendon size and stiffness, with decreased cell density in the tendon midsubstance. However, no differences were found in the enthesis fibrocartilage or in the underlying subchondral or trabecular bone. In conclusion, our study revealed limited effects of nicotine on the homeostatic condition of the supraspinatus tendon, enthesis, and underlying bone. Future studies are needed to ascertain effects of other components of tobacco products.

Effects of applying platelet-rich plasma during arthroscopic rotator cuff repair: a systematic review and meta-analysis of randomised controlled trials.

Because of its healing properties, platelet-rich plasma (PRP) has been applied to the bone-tendon interface during arthroscopic rotator cuff repair to improve surgical outcomes. However, its effects remain ambiguous. Therefore, we conducted this systematic review and meta-analysis to assess the effects of PRP on retear rate and functional outcomes. Randomised control trials were identified and extracted. Data collection was completed on 15 February 2020. The results are expressed as the risk ratio (RR) for the categorical variables and weighted mean difference for the continuous variables, with 95% confidence intervals (CIs). Analyses were performed using RevMan 5.3 software. Seven randomised controlled trials published from 2013 to 2018, with 541 patients in total, were included. The results revealed a significant decrease in retear rate [RR 0.38, 95% CI (0.22, 0.68), P = 0.0009). Furthermore, a significant improvement was observed regarding short-term Constant score [mean difference = 3.28, 95% CI (1.46, 5.11), P = 0.0004), short-term University of California at Los Angeles activity score [mean difference = 1.60, 95% CI (0.79, 2.42), P = 0.0001], and short-term visual analogue scale score [mean difference = - 0.14, 95% CI (- 0.23, - 0.05), P = 0.002]. This systematic review indicates the efficacy of PRP when applied to the bone-tendon interface during arthroscopic rotator cuff repair.

Calcific tendinosis of rotator cuff with intraosseous extension.

Calcific tendinosis is characterized by macroscopic deposits of hydroxyapatite within the tendon. Commonest location is rotator cuff of shoulder. Cortical erosion with intraosseous migration of calcium deposits is rare complication of this condition. It may be confused with neoplasm or infection, resulting in unnecessary biopsies or interventions. The knowledge of this uncommon complication and its appearance should enable its detection by imaging and lead to specific treatment.

Synergic regenerative effects of polydeoxyribonucleotide and microcurrent on full-thickness rotator cuff healing in a rabbit model.

BACKGROUND: Rotator cuff tendon tears (RCTTs) are common adult injuries. We hypothesized that a local injection of polydeoxyribonucleotide (PDRN) and microcurrent therapy (MIC) would be more effective in regenerating a tendon tear than PDRN administration alone. OBJECTIVES: To evaluate the effect of PDRN combined with MIC on the regeneration of RCTTs in a rabbit subscapularis tendon chronic RCTT model. METHODS: Rabbits (n=24) were allocated to 3 groups at 6 weeks after full-thickness RCTT (FTRCTT): 0.2mL normal saline (G1-SAL); 0.2mL PDRN with Sham MIC (G2-PDRN+Sham MIC); and 0.2mL PDRN with MIC (G3-PDRN+MIC). All treatments were performed under ultrasound guidance. PDRN was injected weekly for 4 weeks and sham MIC or MIC was applied daily for 4 weeks after the first PDRN injection. RESULTS: In the G3-PDRN+MIC group, the mean (SD) subscapularis tendon tear size was continuously reduced from 1 week post-treatment to 4 weeks and was significantly decreased as compared with the other 2 groups [6.0 (1.5) vs. G1: 11.5 (1.8) and G2: 9.1 (1.6) mm2; G3 vs. G1, P<0.001; G3 vs. G2, P=0.018]. The gross morphologic mean tendon tear size was significantly smaller in the G3-PDRN+MIC group than G1-SAL and G2-PDRN+ Sham MIC groups [8.8 (3.5) vs. 15.9 (2.3) and 12.4 (1.6) mm2; G3 vs. G1, P<0.001; G3 vs. G2, P=0.03]. Mean values for regenerated collagen type 1 fibers, angiogenesis, and walking parameters were all greater for the G3-PDRN+MIC group than the other 2 groups based on histological examination and motion analysis [collagen type 1, G3: 1.60 (0.80) vs. G1: 0.45 (0.60), G2: 1.10 (0.74), G3 vs. G1, P<0.001; G3 vs. G2, P=0.002] [angiogenesis, G3: 2.44 (0.73) vs. G1: 0.80 (0.82) and G2: 2.06 (0.81), G3 vs. G1, P<0.001; G3 vs. G2, P=0.006] [walking distance, G3: 6391.4 (196.9) vs. G1: 4852.8 (137.3) and G2: 5514.4 (257.3) cm; G3 vs. G1, P<0.001; G3 vs. G2, P<0.001]. CONCLUSIONS: On gross morphologic, histological, and motion analysis, combined PDRN with MIC therapy was more effective than PDRN alone treating a rabbit model of chronic traumatic FTRCTT.

Intra-substance steroid injection for full-thickness supraspinatus tendon rupture.

BACKGROUND: The use of steroid injection for treatment of a full-thickness rotator cuff tear is still controversial. This study aimed to evaluate the effectiveness and safety of this treatment method. METHODS: Twelve patients in Group 1 received an intra-substance injection into rupture area of supraspinatus tendon with Diprospan 1 cc (betamethasone disodium phosphate 2 mg and betamethasone dipropionate 5 mg) and 1% xylocaine 1 cc. Twelve patients in Group 2 received an injection with normal saline 1 cc and 1% xylocaine 1 cc. The rupture size was measured by sonography before the injection, 3 months after the injection, and 6 months after the injection. Shoulder Pain and Disability Index (SPADI) score and Pain Visual Analogue Scale (VAS) score were measured and compared between the two groups before the injection, 1 week after the injection, 3 months after the injection, and 6 months after the injection. RESULTS: Pain and function improved more in Group 1 than in Group 2. The therapeutic effect lasted for at least 6 months in both groups. The size of the supraspinatus tendon rupture was not increased after injection in either group. CONCLUSIONS: Intra-substance injection into rupture area of supraspinatus tendon with steroid and xylocaine is effective to reduce pain and improve function in patients with full-thickness supraspinatus tendon rupture without increasing the size of the rupture. TRIAL REGISTRATION: Current Controlled Trials ChiCTR1900026376, data of registration: 2019/10/05 retrospectively registered.

Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Experimental shoulder pain models do not validly replicate the clinical experience of shoulder pain.

Background and aims People with shoulder pain often present with abnormal shoulder muscle function. It is not known whether shoulder pain causes or is the result of muscle dysfunction. If pain leads to muscle dysfunction, therapeutic interventions that produce shoulder pain may be contraindicated. Experimentally induced nociception can be used to investigate a causal relationship between shoulder pain and muscle dysfunction. However, the validity of current experimental shoulder pain protocols has not been established. The aim of this study was to determine whether current experimental shoulder pain protocols validly replicate the clinical experience of shoulder pain with respect to pain distribution, quality and behaviour. Methods Nine pain free participants received two injections of hypertonic saline, one into the subacromial space and one into supraspinatus, in random order, at least 1 week apart. Investigators blind to the injection site assessed pain distribution, pain response to clinical tests which provoke shoulder pain and pain quality assessed using the McGill Pain Questionnaire. Results Following hypertonic saline injection into both the subacromial space and supraspinatus: pain was most commonly reported in the deltoid region and did not extend beyond the elbow; the most common response to clinical tests which provoke shoulder pain was a decrease in pain; and the highest rating of pain quality was in the sensory domain with very few responses in the affective domain. Conclusions Experimental shoulder pain induced by injection of hypertonic saline into either the subacromial space or supraspinatus produced a pain distribution similar to that observed in clinical shoulder pain, but neither experimental pain protocol could reproduce the increases in pain intensity following shoulder provocation tests or the emotional distress commonly observed in people with clinical shoulder pain. Implications Pain induced by local shoulder nociception produced by hypertonic saline injection into shoulder structures has significant limitations as a model of clinical shoulder pain. While it is perhaps unsurprising that short duration, chemically-induced experimental pain does not replicate the quality of the clinical experience of shoulder pain, the validity of experimental shoulder pain models which produce the opposite response to provocation testing to clinical shoulder pain must be questioned.

N-acetylcysteine reduces glutamate-induced cytotoxicity to fibroblasts of rat supraspinatus tendons.

Purpose: Neuronal theory regarding rotator cuff degeneration has developed from the findings that glutamate, an amino acid and an excitatory neurotransmitter, is present in increased concentrations in tendon tissues with tendinopathy and that glutamate induces cell death in fibroblasts of origin in rat supraspinatus tendon. The purpose of the current study was to determine whether N-acetylcysteine (NAC) has cytoprotective effects against glutamate-induced fibroblast death. Materials and Methods: Primary cultured fibroblasts were obtained from rat supraspinatus tendons. Varying concentrations of glutamate (0.5, 1, 5, and 10 mM) and of NAC (0.5, 1, 2, and 5 mM) were used for evaluation of cytotoxicity. Cell viability, cell cycles, types of cell death, intracellular ROS production, expressions of caspase-3/7, and Ca2+ influx were evaluated. Results: Glutamate significantly induced cell death, apoptosis, and Ca2+ influx and significantly increased caspase-3/7 activity and intracellular ROS production (p < 0.001). NAC significantly reduced the glutamate-induced cell death, apoptosis, Ca2+ influx, caspase-3/7 activity, and intracellular ROS production (p < 0.001). Conclusions: The glutamate-induced cytotoxic effects can be reduced by NAC, an antioxidant, through the reduction of intracellular oxidative stress and/or Ca2+ influx.

Intra-articular treatment with corticosteroids increases apoptosis in human rotator cuff tears.

PURPOSE: The aim of this study is to evaluate in vivo the level of apoptosis in human rotator cuff tears and the relationship it might have with tendon degeneration. METHODS: Rotator cuff biopsies from 19 male and female patients, ages between 38 and 68 years, with and without previous corticosteroid infiltrations were collected via arthroscopy. Biopsies from seven patients with healthy rotator cuffs were used as a control group. An in situ terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed to detect the level of apoptosis, which was expressed as a percentage of apoptotic cells (PAC). RESULTS: PAC in patients with corticosteroid infiltrations was 76.97 ± 16.99 in all tendon rupture zones, in non-infiltrated patients was 35.89 ± 22.96, whereas in control patients was 14.48 ± 8.15. Likewise, the tendency of PAC reveals that apoptosis in control and non-infiltrated groups was different and dispersed in all tear zones; while in corticosteroid treated patients, the tendency was similar in all rupture sites. CONCLUSIONS: This investigation leads us to conclude that the administration of corticosteroid is associated with a higher amount of apoptosis at the insertion site of the rotator cuff (rupture edge).

The effect of autologous platelet rich plasma on tenocytes of the human rotator cuff.

BACKGROUND: Platelet rich plasma (PRP) is widely used in rotator cuff repairs but its effect on the healing process is unclear. Several cell culture studies on the effect of allogenic PRP have reported promising results but are not transferable to clinical practice. The aim of the present study is to assess the possible effect of autologous PRP on rotator cuff tendon cells. The amount of growth factors involved with tendon-bone healing (PDGF-AB, IGF-1, TGF-ß1, BMP-7 and -12) is quantified. METHODS: Rotator cuff tissue samples were obtained from (n = 24) patients grouped by age (>/< 65 years) and sex into four groups and cells were isolated and characterized. Later, autologous PRP preparations were obtained and the effect was analyzed by means of cell proliferation, collagen I synthesis and expression of collagen I and III. Furthermore, the PRPs were quantified for growth factor content by means of platelet-derived growth factor (PDGF-AB), insulin-like growth factor (IGF-1), transforming growth factor (TGF-ß1), as well as bone morphogenetic protein (BMP) -7 and - 12. RESULTS: Cell proliferation and absolute synthesis of collagen I were positively affected by PRP exposure compared to controls (p < 0.05), but expression and relative synthesis of collagen I (normalized to cell proliferation) were significantly reduced. PRP contained high amounts of IGF-1 and lower levels of TGF-ß1 and PDGF-AB. The amounts of BMP-7 and -12 were below the detection limits. CONCLUSIONS: PRP is a source of growth factors such involved with tendon-bone healing. PRP had an anabolic effect on the human rotator cuff tenocytes of the same individual in vitro by means of cell proliferation and absolute, but not relative collagen I synthesis. These results encourage further studies on clinical outcomes with more comparable standards in terms of preparation and application methods. LEVEL OF EVIDENCE: Controlled laboratory study.

Doxycycline improves cage activity, but not exercised, supraspinatus tendon and muscle in a rat model.

The objective of this study was to investigate the effects of doxycycline, a broad-spectrum MMP inhibitor, on cage activity and exercised supraspinatus tendon and muscle using a Sprague-Dawley rat model of non-injurious exercise. Because exercise may alter muscle and tendon MMP activity and matrix turnover, we hypothesized that doxycycline would abolish the beneficial adaptations found with exercise but have no effect on cage activity muscle and tendon properties. Rats were divided into acute or chronic exercise (EX) or cage activity (CA) groups, and half of the rats received doxycycline orally. Animals in acute EX groups were euthanized 24 h after a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill and were euthanized at 2 or 8 week time points. Assays included supraspinatus tendon mechanics and histology and muscle fiber morphologic and type analysis. Doxycycline improved tendon mechanical properties and collagen organization in chronic cage activity groups, which was not consistently evident in exercised groups. Combined with exercise, doxycycline decreased average muscle fiber cross-sectional area. Results of this study suggest that administration of doxycycline at pharmaceutical doses induces beneficial supraspinatus tendon adaptations without negatively affecting the muscle in cage activity animals, supporting the use of doxycycline to combat degenerative processes associated with underuse; however, when combined with exercise, doxycycline does not consistently produce the same beneficial adaptations in rat supraspinatus tendons and reduces muscle fiber cross-sectional area, suggesting that doxycycline is not advantageous when combined with activity.

The effects of hyperlipidemia on rotator cuff diseases: a systematic review.

BACKGROUND: Rotator cuff disease is a common condition that causes shoulder pain and functional disability. Recent studies suggested that hyperlipidemia might be associated with the development of rotator cuff disease. The objective of this study was to explore the relationship of hyperlipidemia and rotator cuff diseases. METHODS: A computerized search using relevant search terms was performed in the PubMed, EMBASE, and Cochrane Library databases, as well as a manual search of reference and citation lists of the included studies. Searches were limited to studies that explored the association of hyperlipidemia and rotator cuff diseases. RESULTS: Sixteen studies were included in this systematic review. Ten of sixteen included studies suggested an association between dyslipidemia and rotator cuff diseases, while the other six studies did not find an association. Two studies demonstrated there were an association between statins and reduced risk of developing rotator cuff diseases or decreased incidence of revision after rotator cuff repair. CONCLUSION: The current study suggested that there was an association between hyperlipidemia and rotator cuff diseases. Furthermore, current evidence suggested that use of statins could decrease the risk of developing rotator cuff diseases and the incidence of revision after rotator cuff repair. Future high-quality studies are highly needed to confirm these findings.

Polydeoxyribonucleotide injection in the patients with partial-thickness tear of supraspinatus tendon: a prospective and pilot study using ultrasound.

OBJECTIVE: Polydeoxyribonucleotide as adenosine receptor (A2A) agonist has been used in plastic surgery and dermatology related to its regenerative property. The aim of this pilot study is to evaluate the safety and efficacy of polydeoxynucleotide injection in patients with rotator cuff tears by a variety of outcomes including pain, disability, physical performance test, and ultrasonography (US). METHODS: Seventeen patients (9 men, 8 women, age: 57.9 ± 9.1) with partial-thickness tear of supraspinatus tendon were evaluated in a prospective, open-label, and pre-and-post study. Seventeen patients underwent 3 times intra-lesional polydeoxynucleotide injection under ultrasound (US) guidance on weeks 0, 2 and 4. The safety and efficacy were assessed on weeks 0, 6 and 12. Main outcome measures included shoulder pain on Visual Analogue Scale (VAS) and DASH (disabilities of arm, hand, shoulder) score, range of motion in shoulder, shoulder strength and tear volume (cm3) by US. Adverse events were monitored. (CRIS: https://www.cris.nih.go.kr , KCT0000767). RESULTS: Active shoulder pain on VAS reduced from 5.53 to 3.53 (P = 0.016), and acting pain, one of DASH questionnaires, reduced from 3.35 to 2.00 (P < 0.001). However, resting shoulder pain on VAS and total DASH scores were not significantly different. Forward flexion and internal rotation in range of motion improved significantly (from 169.41 to 178.13 degrees [P = 0.004] and from 83.53 to 88.75 degrees [P = 0.014], respectively). The volume of torn lesion decreased during the study period, however it was not significant. There were no significant adverse events leading to hospitalization. CONCLUSIONS: Minimally invasive procedure through polydeoxynucleotide injection into torn area of supraspinatus tendon on US could be candidate for the safe and effective treatment on shoulder pain and limited range of motion in patients with rotator cuff tear.

Growth factor delivery strategies for rotator cuff repair and regeneration.

The high incidence of degenerative tears and prevalence of retears (20-95%) after surgical repair makes rotator cuff injuries a significant health problem. This high retear rate is attributed to the failure of the repaired tissue to regenerate the native tendon-to-bone insertion (enthesis). Biological augmentation of surgical repair such as autografts, allografts, and xenografts are confounded by donor site morbidity, immunogenicity, and disease transmission, respectively. In contrast, these risks may be alleviated via growth factor therapy, which can actively influence the healing environment to promote functional repair. Several challenges have to be overcome before growth factor delivery can translate into clinical practice such as the selection of optimal growth factor(s) or combination, identification of the most efficient stage and duration of delivery, and the design considerations for the delivery device. Emerging insight into the injury-repair microenvironment and our understanding of growth factor mechanisms in healing are informing the design of advanced delivery scaffolds to effectively treat rotator cuff tears. Here, we review potential growth factor candidates, design parameters and material selection for growth factor delivery, innovative and dynamic delivery scaffolds, and novel therapeutic targets from tendon and developmental biology for the structural and functional healing of rotator cuff repair.

Effects of Platelet-Rich Plasma and Indomethacin on Biomechanics of Rotator Cuff Repair.

We conducted a study to determine if platelet-rich plasma (PRP) enhances the strength of rotator cuff repair (RCR) and if concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) affects PRP efficacy. We also wanted to determine the optimal centrifugation protocol for making PRP from rats. This study used 48 rats, 14 in a centrifugation protocol and 34 in an operative protocol. Six syngeneic rats from the operative group were used as PRP blood donors; the other 28 operative rats underwent bilateral RCRs. The Autologous Conditioned Plasma system (Arthrex) was used to prepare leukocyte-poor PRP. One shoulder was randomized to an intratendinous PRP injection, and the other received normal saline. Each rat was also randomly placed on a postoperative diet, either a regular diet or an indomethacin-enhanced diet. After rats were euthanized at 3 weeks, specimens were dissected to isolate the supraspinatus tendon at its humeral attachment, which was subjected to biomechanical testing. PRP prepared with a protocol of 5 minutes × 1300 revolutions per minute had the highest platelet index. Mean (SD) energy to failure was significantly higher (P = .03) in tendons treated with PRP, 11.7 (7.3) N-mm, than in tendons treated with saline, 8.7 (4.6) N-mm. Both groups (PRP, saline) showed no significant differences between tendons treated with NSAIDs and those not treated with NSAIDs. Intraoperative application of PRP enhances energy to failure after RCR in rats. There were no differences in biomechanical strength with NSAID use and no interactions between PRP and NSAID use.

Poly-N-Acetyl Glucosamine (sNAG) Enhances Early Rotator Cuff Tendon Healing in a Rat Model.

Rotator cuff injuries frequently require surgical repairs which have a high failure rate. Biological augmentation has been utilized in an attempt to improve tendon repair. Poly-N-acetyl glucosamine (sNAG) polymer containing nanofibers has been shown to increase the rate for healing of venous leg ulcers. The purpose of this study was to investigate the healing and analgesic properties of sNAG in a rat rotator cuff injury and repair model. 144 adult male Sprague-Dawley rats underwent a transection and repair of their left supraspinatus tendons. Half of the animals received a sNAG membrane on the tendon-to-bone insertion site. Animals were further subdivided, receiving 1 or 3 days of analgesics. Animals were sacrificed 2, 4, or 8 weeks post-injury. Animals sacrificed at 4 and 8 weeks underwent longitudinal in vivo ambulatory assessment. Histological properties were assessed at 2, 4, and 8 weeks, and mechanical properties at 4 and 8 weeks. In the presence of analgesics, tendons receiving the sNAG polymer had significantly increased max load and max stress at 4 weeks, but not at 8 weeks. Ambulatory improvements were observed at 14 days in stride length and speed. Therefore, sNAG improves tendon-to-bone healing in a rat rotator cuff detachment and repair model.

Atelocollagen Enhances the Healing of Rotator Cuff Tendon in Rabbit Model.

BACKGROUND: Failure of rotator cuff healing is a common complication despite the rapid development of surgical repair techniques for the torn rotator cuff. PURPOSE: To verify the effect of atelocollagen on tendon-to-bone healing in the rabbit supraspinatus tendon compared with conventional cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A tear of the supraspinatus tendon was created and repaired in 46 New Zealand White rabbits. They were then randomly allocated into 2 groups (23 rabbits per group; 15 for histological and 8 for biomechanical test). In the experimental group, patch-type atelocollagen was implanted between bone and tendon during repair; in the control group, the torn tendon was repaired without atelocollagen. Each opposite shoulder served as a sham (tendon was exposed only). Histological evaluation was performed at 4, 8, and 12 weeks. Biomechanical tensile strength was tested 12 weeks after surgery. RESULTS: Histological evaluation scores of the experimental group (4.0 ± 1.0) were significantly superior to those of the control group (7.7 ± 2.7) at 12 weeks ( P = .005). The load to failure was significantly higher in the experimental group (51.4 ± 3.9 N) than in the control group (36.4 ± 5.9 N) ( P = .001). CONCLUSION: Histological and biomechanical studies demonstrated better results in the experimental group using atelocollagen in a rabbit model of the supraspinatus tendon tear. CLINICAL RELEVANCE: Atelocollagen patch could be used in the cuff repair site to enhance healing.