Re-rupture rates after rotator cuff repair remain high because of inadequate biological healing at the tendon-bone interface. Single-growth factor therapies to augment healing at the enthesis have so far yielded inconsistent results. An emerging approach is to combine multiple growth factors over a spatiotemporal distribution that mimics normal healing. We propose a novel combination treatment of insulin-like growth factor 1 (IGF-1), transforming growth factor β1 (TGF-β1) and parathyroid hormone (PTH) incorporated into a controlled-release tyraminated poly-vinyl-alcohol hydrogel to improve healing after rotator cuff repair. We aimed to evaluate this growth factor treatment in a rat chronic rotator cuff tear model. A total of 30 male Sprague-Dawley rats underwent unilateral supraspinatus tenotomy. Delayed rotator cuff repairs were then performed after 3 weeks, to allow tendon degeneration that resembles the human clinical scenario. Animals were randomly assigned to: [1] a control group with repair alone; or [2] a treatment group in which the hydrogel was applied at the repair site. All animals were euthanized 12 weeks after rotator cuff surgery and the explanted shoulders were analyzed for biomechanical strength and histological quality of healing at the repair site. In the treatment group had significantly higher stress at failure (73% improvement, P=0.003) and Young's modulus (56% improvement, P=0.028) compared to the control group. Histological assessment revealed improved healing with significantly higher overall histological scores (10.1 of 15 vs 6.55 of 15, P=0.032), and lower inflammation and vascularity. This novel combination growth factor treatment improved the quality of healing and strength of the repaired enthesis in a chronic rotator cuff tear model. Further optimization and tailoring of the growth factors hydrogel is required prior to consideration for clinical use in the treatment of rotator cuff tears. This novel treatment approach holds promise for improving biological healing of this clinically challenging problem

Common tendon injuries impair healing, leading to debilitation and an increased re-rupture risk. The impact of oxygen-sensing pathways on repair mechanisms, vital in regulating inflammation and fibrosis, remains unclear despite their relevance in tendon pathologies. Recent studies show that pulsed electromagnetic field (PEMF) reduce inflammation in human tendon cells (hTDCs) and in hypoxia-induced inflammation. We investigated the hypoxia's impact (1% and 2% oxygen tension) using magnetic cell sheet constructs (IL-1β-magCSs) primed with IL-1β. IL-1β-magCSs were exposed to low OT (1h, 4h,6h) in a hypoxic chamber. To confirm the role of PEMF (5Hz, 4mT, 50% duty cycle) on hypoxia modulation, IL-1β-magCSs, previously exposed to OT, were 1h-stimulated with PEMF. Our results show a significant increase in HIF- 1a and HIF-2a expression on IL-1β-magCSs after exposure to 2%-OT at all time points, compared to 1%- OT and normoxia. TNFa, IL-6, and IL-8 expression increased after 6 hours of 1%-OT exposure. PEMF stimulation of hypoxic IL-1β-magCSs led to decreased pro-inflammatory genes and increased anti-inflammatory (IL-4,IL-10) expression compared to unstimulated magCSs. IFN-g, TNF-α, and IL-6 release increased after 6 hours, regardless of %-OT, while IL-10 levels tended to rise after PEMF stimulation at 2%-OT. Also, NFkB expression was increased on IL-1β-magCSs exposed to 4 h and 6 h of 2%-OT, suggesting a link between NFkB and the production of pro-inflammatory factors. Moreover, PEMF stimulation showed a significantly decreased NFkB level in IL-1β-magCSs. Overall, low OT enhances expression of hypoxia-associated genes and inflammatory markers in IL-1β-magCSs with the involvement of NFkB. PEMF modulates the response of magCSs, previously conditioned to hypoxia and to inflammatory triggers, favouring expression of anti-inflammatory genes and proteins, supporting PEMF impact in pro-regenerative tendon strategies. Acknowledgements: ERC CoG MagTendon(No.772817), FCT under the Scientific Employment Stimulus-2020.01157.CEECIND. Thanks to Hospital da Prelada for providing tendon tissue samples (Portugal), and TERM. RES Hub (Norte-01-0145-FEDER-022190)

Introduction and Objective. In the elderly population, chronic rotator cuff tears are often associated with high re-rupture rates after surgical tendon refixation. Implant materials, especially in combination with additives are supposed to positively influence healing outcome. Furthermore, adequate mechanical properties are crucial. In order to realize degradable implants with high specific surface area, polycaprolactone (PCL) was chosen as basic material and processed by electrospinning to achieve a high surface area for growth factor implementation and subsequent cell attachment. Materials and Methods. PCL (M. n. approx. 80,000 g/mol) was used to generate fibre mats by electrospinning (relative collector velocity 8 m/s; flow rate of 4 ml/h). Mechanical analysis was performed according to EN ISO 527–2:2012 with test specimen 1BA (5 mm in diameter). Maximum force at failure (Fmax) as well as stiffness were evaluated. For preclinical in vivo testing, a coating with CS-g-PCL was performed to increase cellular adhesion and biological integration. Native and TGF-ß3 loaded mats were examined in a chronic rat tendon defect model with dissection of the M. infraspinatus, four week latency and following refixation at the humerus with different PCL-fibre mats (approval Nr. 33.12–42502–04–15/2015). After 8 weeks, rats were finalized and tendon-bone insertions were analyzed biomechanically and via histological methods. Results. Electrospun PCL-fibre mats (n = 6) showed maximum forces of 2.19 ± 0.8 N and a stiffness of 0.38 ± 0.12 N/mm. Native rat infraspinatus tendons showed Fmax values of 28.4 ± 7.2 N and a stiffness of 11.8 ± 4.9 N/mm. After implantation, Fmax of the implant-tendon-regenerate was significantly lower in CS-g-PCL - fibre mat groups compared to native control tendons (mean 52 % of native tendon value). Functionalization with TGF-ß3 led to increased Fmax (78 % of the native tendon value). However, differences were not statistically significant. Histological evaluation revealed no differences between non loaded and TGF-ß3 loaded mats. The implants were strongly disintegrated. Granulation tissue and a high number of foreign body giant cells were present. Conclusions. Although mechanical properties of fabricated mats were low, loading of the fibre mats influenced the biomechanical outcome of refixed tendons, presumably due to their high potential for binding biological active substances like TGF-ß3. However, in ongoing studies these cell reactions, especially regarding polarization of macrophages and foreign body cells need to be characterized. This research project has been supported by the German Research Foundation “Graded Implants FOR 2180 – tendon- and bone junctions” WE 4262/6-2 and parts were published in J Tissue Eng Regen Med. 2020 Jan;14(1):186–197. doi: 10.1002/term.2985

After anterior cruciate ligament (ACL) rupture, reconstructive surgery with a hamstring tendon autograft is often performed. Despite overall good results, ACL re-rupture occurs in up to 10% of the patient population, increasing to 30% of the cases for patients aged under 20 years. This can be related to tissue remodelling in the first months to years after surgery, which compromises the graft's mechanical strength. Resident graft fibroblasts secrete matrix metalloproteinases (MMPs), which break down the collagen I extracellular matrix. After necrosis of these fibroblasts, myofibroblasts repopulate the graft, and deposit more collagen III rather than collagen I. Eventually, the cellular and matrix properties converge towards those of the native ACL, but full restoration of the ACL properties is not achieved. It is unknown how inter-patient differences in tissue remodelling capacity contribute to ACL graft rupture risk. This research measured patient-specific tissue remodelling-related properties of human hamstring tendon-derived cells in an in vitro micro-tissue platform, in order to identify potential biological predictors for graft rupture. Human hamstring tendon-derived cells were obtained from remnant autograft tissue after ACL reconstructions. These cells were seeded in collagen I gels on a micro-tissue platform to assess inter-patient cellular differences in tissue remodelling capacity. Remodelling was induced by removing the outermost micro-posts, and micro-tissue compaction over time was assessed using transmitted light microscopy. Protein expression of tendon marker tenomodulin and myofibroblast marker α-smooth muscle actin (αSMA) were measured using Western blot. Expression and activity of remodelling marker MMP2 were determined using gelatin zymography. Cells were obtained from 12 patients (aged 12–51 years). Patient-specific variations in micro-tissue compaction speed or magnitude were observed. Up to 50-fold differences in αSMA expression were found between patients, although these did not correlate with faster or stronger compaction. Surprisingly, tenomodulin was only detected in samples obtained from two patients. Total MMP2 expression varied between patients, but no large differences in active fractions were found. No correlation of patient age with any of the remodelling-related factors was detected. Remodelling-related biological differences between patient tendon-derived cells could be assessed with the presented micro-tissue platform, and did not correlate with age. This demonstrates the need to compare this biological variation in vitro - especially cells with extreme properties - to clinical outcome. Sample size is currently increased, and patient outcome will be determined. Combined with results obtained from the in vitro platform, this could lead to a predictive tool to identify patients at risk for graft rupture

Chronic rotator cuff tears are a major problem especially in the elderly population. Refixation is associated with high re-rupture rates. Therefore new implants or healing methods are needed. For a control of success biomechanical characteristics of native as well as treated tendons are of particular importance. Currently, tensile tests with static material testing machines are the most common technique for the biomechanical characterization of tendons. Resulting values are the maximum force (Fmax), stiffness and the Young´s modulus. However, no information is given about the allocation of strains over the tendon area. In addition, the determination of Fmax results in tissue destruction thus foreclosing further evaluation like histology. The Digital Image Correlation (DIC) is a contact-free non-destructive optical measuring method which gives information about distribution of strains by tracking the areal shift of an applied speckle pattern. The needed speckle pattern has to have a high contrast, a homogeneous distribution and a good adhesion to the surface. The method is established for the characterization of construction materials [1] to detect e.g. weak points. The present study examined if DIC is applicable for the complementary biomechanical evaluation of the sheep infraspinatus tendon. Fine ground powder extracted from a printer cartridge was chosen as a starting point. Preliminary to the in vitro experiments, the powder was applied on sheets with different methods: brushing, blowing, sieving and stamping. Stamping showed best results and was used for further in vitro tests on cadaveric native tendons (n=5). First, the toner powder was transferred to coarse-grained abrasive paper using a brush and stamped on the tendon surface. Afterwards DIC analysis was performed. For the in vivo tests, the left infraspinatus tendon of two German black-headed Mutton Sheep was detached and then refixed with bone anchors, the right tendon was used as native control (authorization: AZ 33.19-42502-04-17/2739). 12 weeks after surgery the animals were euthanized, the shoulders were explanted and DIC measurement performed. The speckle pattern could be applied adequately on the smooth tendon surfaces of native tendons. All specimens could be analyzed by DIC with sufficient correlation coefficients. The highest displacements were measured in the peripheral areas, whereas the central part of the tendon showed a low displacement. Repaired left tendons showed obvious differences already macroscopically. The tendons were thicker and showed inhomogeneous surfaces. Application of the toner powder by stamping was distinctly more complicated, DIC analysis could not produce sufficient correlation coefficients. In summary, transfer of DIC to native infraspinatus tendons of sheep was successful and can be further transferred to other animal and human tendons. However, irregular surfaces in tendon scar tissues affect the application of an adequate speckle pattern with a stamp technique. Therefore, further modifications are necessary. This research project has been supported by the German Research Foundation “Graded Implants FOR 2180 – tendon- and bone junctions” WE 4262/6-1

Tendon pathologies represent an unresolved clinical challenge where the patients suffer from pain and impaired mobility. One of the most frequently ruptured tendons is the Achilles tendon and primarily seen in recreational and professional athletes. A study from Sweden reported a significant increase in the incidence of Achilles tendon ruptures of 17% in men and 22% in women due to the demographic changes and the higher sportive activity of older adults (Huttunen TT Am J Sports Med 2014). The re-rupture rate is between 2–10%, and the patients suffer from an impairment over a long time accompanied with incapability to work. The healing process results in the formation of a mechanically insufficient scar tissue. A detailed knowledge on the cellular and molecular processes underlying human Achilles tendon healing is necessary to develop new treatment strategies and judge therapeutic success. The analysis of human Achilles tendon samples at different time points post rupture and the comparison to intact and degenerated tendon tissue provides important information on the healing process

Various arthroscopic techniques using differing graft materials have been described and present a potential alternative to arthroplasty for rotator cuff arthropathy. We describe the short-term outcomes of allograft reconstruction, having evolved of our surgical technique from graft interposition to superior capsule reconstruction (SCR). All patients with an irreparable tear, in the absence of clinical and radiograph evidence of osteoarthritis, who underwent an allograft (Graft Jacket. TM. ) reconstruction with either an arthroscopic interposition or SCR technique within our institution were included. A retrospective case note analysis was performed to ascertain perioperative details including total operating and consumable implant costs. 15 patients were in the interposition group, mean age 66 years (48–77). Mean postoperative follow-up time was 17 months (1.9 −27.8). The mean OSS improved from 30.6 to 35.7 (p<0.05). Additionally, mean pain scores out of 10 improved from 7.7 to 1.5 (p<0.01). Mean satisfaction for the surgery was 7.8 out of 10. Complications included 2 re-ruptures (13.3%), 1 infection (6.7%) and 1 case of no improvement (6.7%). In the SCR group, there were 10 patients, mean age 64.5 (56– 68 years). Half of these patients had previous rotator cuff surgery. Mean postoperative follow-up time was 8.7 months (1.9 – 16.3). The mean OSS improved from 24 to 32.9 (p<0.01). Similarly, pain scores decreased from 7.9 to 3.5 (p<0.01). Mean satisfaction was 7.2. Complications included 1 case of no improvement (10%) resulting in a reverse TSR and 1 re-rupture (10%). A formal, prospective comparison trial is advocated to determine if SCR is superior

There is a growing socio-economic need (i.e. “ageing society”) for effective and reproducible strategies to repair musculoskeletal tissue. In particular, acute tendon injury and chronic tendinopathies remain clinically challenging and novel treatment modalities are urgently needed. Tendons resemble a connective tissue rich in highly organized collagen fibers, displaying a remarkably high tensile strength. However, partly due to the low number of cells and their more or less avascular nature tendons heal relatively slowly. Ultimately, tendon regeneration encompasses the full restoration of the biological, biochemical and biomechanical properties, which are often impaired by endogenous healing cascades. Usually, a connective scar tissue forms at the injury site and the replaced tissue does not function adequately at high strain levels, increasing the chance of re-rupture. Despite significant advancements in tissue regeneration and engineering strategies, the clinical impact for the regeneration of tendon remains limited. For the development of novel methods to repair tendons we need to pin down the molecular and cellular mechanisms amenable to modulate endogenous (or exogenous) cell behaviour towards functional tissue regeneration. By comparing the gene expression profile of Achilles tendon tissue harvested from young-mature and old mice we demonstrate profound changes in the expression of ECM-related proteins and a previously unknown role of Secreted protein acidic and rich in cysteine (Sparc; also known as BM-40 or osteonectin) in tendons. Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties potentially drives adipogenic differentiation of tendon stem and progenitor cells (TDSPCs) and consequently lipid accretion in tendons. Generally, the fate of stem/ progenitor cells is largely determined by stimuli from the stem cell niche. In tendons, we describe a novel cellular barrier, most likely preventing the leakage of blood-borne products into the tendon proper. We propose that this “blood-tendon barrier” is part of the stem cell niche in tendons controlling TDSCP fate, preventing erroneous differentiation. By investigating the developmental programs driving tendon tissue formation and on the other hand the mechanisms contributing to the senescence of tendons, ultimately resulting in decreased quality of tendons in the elderly, novel targets for clinical intervention potentially can be discovered

Achilles tendon (AT) rupture may lead to complaints of heel pain. In forefoot ulcer patients AT lengthening is used to transfer pressure from forefoot to the heel. The primary aim was to investigate if AT was longer or associated with changes in pedobaric measurements, in particular heel pressure, on the injured leg 4–5 years after the injury. Methods. We invited all participants from an RCT (n=56) of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB). 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany), with 5 trials for each foot. Statistics. T-test for limb to limb comparisons and linear regression for correlations was applied. Results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1.8 (1.2–2.3) cm longer on the injured limb (p<0.001). When comparing the ratio of the medial (1–2 ray) to lateral (3–5 ray) forefoot mean peak pressure, we found no difference between the injured and healthy limb (p=0.26). Mean heel peak pressure was not different from the injured to the healthy leg (difference was 3,9 (−1,7 – 9,45) p=0,17). Heel lift-off was delayed in the injured limb by 2% (0.4%–4.4%) of the total roll over process (ROP) (p= 0.02). Achilles tendon length could not be linked to either heels lift-off or mean peak pressure of the heel using linear regression (p 0.27 to 0.78). Conclusion. Conservatively treated Achilles tendon ruptures were approximately 1.8 cm longer. A subtle change in the time of heel rise could be detected on the injured limb, but contrary to our expectations AT length did not correlate to time of heel lift or mean heel peak pressure. This is in contrast to the common practice in diabetics, where the Achilles tendon is elongated to relieve pressure from the forefoot – a mechanism we cannot observe from elongation of the tendon after acute rupture, treated conservatively - though this study is underpowered

Achilles tendon rupture may lead to significant functional deficits, which mechanisms are poorly understood. The primary aim was to investigate if the Achilles tendon (AT) was longer, muscles weaker or gait changed on the injured leg 4–5 years after the injury. Secondary aim was to compare functional outcomes with patient reported Achilles Tendon Total Rupture Score (ATRS). We invited all participants from an RCT of conservatively treated AT Rupture (ATR) with or without early weight-bearing (early-WB, non-WB), and 12 moths of follow up. Of the original 56, 37 patients participated, 19 from early-WB (1 re-rupture (RR)), and 18 from non-WB (2 RR). Time from injury to follow up was 4,5 years (4,1 to 5,1). AT length was measured using ultrasound with a validated protocol (Barfod K.W. et al.). Heel raise work was measured on a 10 degree inclining platform. The exercise lasted until the patient could not maintain frequency or height of lift. Number and height of lift was measured using reflective markers in a Vicon system, and total work calculated. Foot pressure mapping (FPM) was measured barefoot, using an EMED platform (novel, Germany). Statistics: T-test for limb to limb comparisons and linear regression for ATRS correlations was applied. Including RR in the sample did not impact the results. We found no differences in any of the variables between the early-WB and non-WB groups. Compared to the uninjured limb, the Achilles tendon was an average of 1,8 (1,2–2,3) cm longer on the injured limb, which produced 40% less work. A smaller calf circumference (p < 0.001), larger dorsiflextion (p = 0.001), and Achilles tendon resting angle (p < 0.001) was found for the injured limb. Difference in mean medial forefoot peak pressure was approaching significance (healthy 484 (SD 165) KPa, injured: 439 (SD 160), p = 0.08). Similarly the difference in pressure / time integral of the medial forefoot was approaching significance (Healthy: 129 (SD 35)KPa, injured: 115 (SD 44)KPa, p = 0.08). Duration of contact time of the heel was extended and heel lift off was delayed in the injured limb (p = 0.02 for both). ATRS could not be linked to Achilles tendon length or total work using linear regression. Conservatively treated Achilles tendon ruptures were approximately 1,8 cm longer. The limb was persistently weaker. A subtle change in heel contact duration and time of heel rise could be detected on the injured limb. ATRS does not appear to correlate directly with AT length or loss of total work

Summary. Silver nanoparticles improve the tensile property of the repaired Achilles tendon by modulating the synthesis and deposition of collagen. This makes silver nanoparticles a potential drug for tendon healing process with less undesirable side effect. Introduction. Tendon injury is a common injury that usually takes a long time to fully recover and often lead to problems of joint stiffness and re-rupture due to tissue adhesions and scarring on the repaired tendon respectively. Recently, it has been proven that silver nanoparticles (AgNPs) are capable of regenerating skin tissue with minimal scarring and comparable tensile property to normal skin. Hence, it is hypothesised that AgNPs could also improve the healing in tendon injury as both tissues are predominating with fibroblasts. The objective of this study is to look at the in vitro response of primary tenocytes to AgNPs and to investigate the mechanical and histological outcome in vivo. Methods and Materials. Primary tenocytes were harvested from 4 weeks old Sprague Dawley rat. 1.5×10. 4. cells per cm. 2. were seeded in triplicate for BrdU incorporation assay and Sirius red/ fast green staining to study the proliferation and collagen synthesis respectively. In vivo rat Achilles tendon injury model was used to investigate the effect of AgNPs to tendon regeneration. Briefly, the Achilles tendon was transected at 0.5cm from its insertion. The wound was either treated with 1mM AgNPs every 5 days or left untreated as the control. Skin incision was done without transecting the tendon in the sham group. The tendons were harvested on day 42 post operation. Tensile test and immunohistological staining on 7μm cryosections were performed to assess the mechanical property and biological events in healing respectively. SHG imaging was used to determine the collagen fibre orientation and abundance. Results. In vitro BrdU incorporation and Sirius red fast green assay suggested that AgNPs promoted the proliferation and collagen synthesis of tenocytes between 1 to 20μM and 10 to 20μM respectively. Tensile test on in vivo tissue showed that AgNPs-treated samples had significantly better tensile modulus compared to the untreated ones (p<0.05). SHG imaging suggested a better collagen alignment and density in AgNPs-treated samples. Immunohistochemistry demonstrated that AgNPs suppressed tumor necrosis factor (TNF α) whilst promoted fibromodulin (Fmod) and proliferating cell nucleus antigen (PCNA) expression. Discussion. Collagen is the major component that contributes to the tensile strength of a tendon. Its thickness, abundance and alignment directly affect the strength. In this study, it is found that AgNPs stimulate cell proliferation both in vitro and in vivo which is believed to be the reason of the increase in collagen synthesis. Fmod is an important proteoglycan responsible for collagen fibrillogenesis and TNF α is related to ECM degradation which directly affects collagen integrity. Stimulation of Fmod and alleviation of TNF α therefore promote collagen maturity and integrity which attributes to the improvement in the tensile property of the regenerated tissue. Furthermore, inflammation is known to relate to fibrosis and scarring in healing of many types of tissue. It is therefore postulated that the anti-inflammatory effect of AgNPs is one of the major reasons for this phenomenal healing of tendon. To conclude, this study demonstrates a positive effect of AgNPs to the early events of tendon healing which is important for accelerating the whole healing process and shortening of rehabilitation time

Background. High re-rupture rates following repairs of rotator cuff tears (RCTs) have resulted in the increased use of repair grafts to act as temporary scaffolds to support tendon healing. It has been estimated that thousands of extracellular matrix repair grafts are used annually to augment surgical repair of rotator cuff tears. The only mechanical assessment of the suitability of these grafts for rotator cuff repair has been made using tensile testing only, and compared grafts to canine infraspinatus. As the shoulder and rotator cuff tendons are exposed to shearing as well as uniaxial loading, we compared the response of repair grafts and human rotator cuff tendons to shearing mechanical stress. We used a novel technique to study material deformation, dynamic shear analysis (DSA). Methods. The shear properties of four RCT repair grafts were measured (Restore, GraftJacket, Zimmer Collagen Repair and SportsMesh). 3mm-sized biopsy samples were taken and subjected to DSA using oscillatory deformation under compression to calculate the storage modulus (G') as an indicator of mechanical integrity. To assess how well the repair grafts were matched to normal rotator cuff tendons, the storage modulus was calculated for 18 human rotator cuff specimens which were obtained from patients aged between 22 and 89 years (mean age 58.8 years, with 9 males and 9 females). Control human rotator cuff tendons were obtained from the edge of tendons during hemiarthoplasties and stabilisations. A 1-way ANOVA of all of the groups was performed to compare shear properties between the different commercially available repair grafts and human rotator cuff tendons to see if they were different. Specific comparison between the different repair grafts and normal rotator cuff tendons was done using a Dunn's multiple comparison test. Results. We report a significant difference in the shear moduli of all four rotator cuff repair grafts (P<0.0001, 1 way ANOVA, Kruskall-Wallis test). 2 of the grafts, Zimmer Collagen Repair and SportMesh, were not significantly different when compared to rotator cuff tendons and were found to have comparable shear mechanical properties (P > 0.05, Dunn's multiple comparison test). The other repair grafts, GraftJacket and Restore, had a significantly lower storage modulus when compared to human rotator cuff tendons. Conclusions. With increasing numbers of repairs of rotator cuff tears, and augmentation of these repairs, there is a need to understand the mechanical and biological properties of the both repair grafts and the tendons they are designed to augment. At present there is no clear definition of the ideal mechanobiological properties of rotator cuff repair patches. Current rotator cuff repair grafts display a wide variation in their shear mechanical properties, and how closely they are matched to the mechanical properties of human rotator cuff tendons. It is hoped that this study may help to guide surgeons in deciding on the most appropriate rotator cuff tendon repair graft

Improved understanding of the biomechanics and biology of rotator cuff tendons (RCT) may help reduce high re-rupture rates following repairs, particularly amongst larger tears. This study aims to use novel methods for quantitatively determining differences in the mechanical and thermal properties of intact healthy RCTs compared to torn ‘diseased’ tendons. A common problem in the mechanical testing of small tendon samples is that stress risers at the clamp-tendon interface can obscure measurements. As the shoulder is subject to shear, tension and compression, we developed a novel solution using Dynamic Shear Analysis (DSA), a form of rheology which studies material deformation. As collagen is the main component of RCT, the structure and mechanical properties may be affected by collagen conformational changes. Both dermis and rat tail tendon with increased collagen cross-linking exhibit stronger mechanical properties. Thermal changes detected by differential scanning calorimetry (DSC) can help to quantify collagen structural differences in torn RCT, and has been previously used to study muscle, cartilage and vertebral discs. There were 79 tears (mean age 65.2 years), which were classified according to the size of the tear as small, medium, large and massive. Two separate 3mm-sized biopsy samples were taken and subjected to DSA using oscillatory deformation under compression. The storage modulus (G') was calculated and used as an indicator of mechanical integrity. 18 control tendon specimens were obtained from patients aged between 22-89 years (mean age 58.8 years) during shoulder hemiarthroplasties and stabilisations. Additionally 7 normal, 7 small and 7 massive frozen specimens were thermally characterized. 3 samples per patient were heated between 20-80oC in hermetically sealed vessels. Useful thermal parameters were measured such as the melting temperature (TM) which apparently represents breaking of the amide-amide bonds and protein chains mobility, the denaturation temperature (TD) which supposedly corresponds to proteins falling out of solution and the denaturation enthalpy (ΔH) which reflects the relative amount of triple helical structure. Healthy tendons had a significantly higher modulus than torn tendons, indicating that torn tendons are mechanically weaker than normal tendons (p = 0.032). Normal tendons had significantly higher mean shear modulus than tendons with small and massive tears (p<0.01). Overall there was a negative correlation between moduli and severity of tendon tear (r = −0.698, p=0.189). The moduli did not significantly correlate with age, sex, hand dominance, or length of preservation in formalin. Massive RCT tears had significantly higher TM and TD when compared to normal RCT (p < 0.05), unlike small RCT tears. No significant difference was detected between the denaturation enthalpy of the different RCT groups. This case control study has demonstrated that normal RCTs have a significantly higher modulus than torn tendons, indicating that torn tendons have less mechanical integrity. Our study further demonstrated a trend between increasing tear size and decreasing mechanical integrity. This study has also demonstrated differences in some of the thermal properties of normal and torn RCTs. These are likely due to collagen structural changes. A decrease in the denaturation temperature of torn tendons, suggests that the material is intrinsically less stable. Torn tendons with reduced storage modulus and collagen integrity may be less able to withstand mechanical loads following repair. This pilot study provides some preliminary insight into the mechanisms that may contribute to, or represent adaptations to high rates of failure of RCT repairs

Objectives

All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors.

Objectives

This study aimed to evaluate the histological and mechanical features of tendon healing in a rabbit model with second-harmonic-generation (SHG) imaging and tensile testing.

This protocol describes a pragmatic multicentre randomised controlled trial (RCT) to assess the clinical and cost effectiveness of arthroscopic and open surgery in the management of rotator cuff tears. This trial began in 2007 and was modified in 2010, with the removal of a non-operative arm due to high rates of early crossover to surgery.

Cite this article: Bone Joint Res 2014;3:155–60.

The aim of this study was to investigate the occurrence of tissue hypoxia and apoptosis at different stages of tendinopathy and tears of the rotator cuff.

We studied tissue from 24 patients with eight graded stages of either impingement (mild, moderate and severe) or tears of the rotator cuff (partial, small, medium, large and massive) and three controls. Biopsies were analysed using three immunohistochemical techniques, namely antibodies against HIF-1α (a transcription factor produced in a hypoxic environment), BNip3 (a HIF-1α regulated pro-apoptotic protein) and TUNEL (detecting DNA fragmentation in apoptosis).

The HIF-1α expression was greatest in mild impingement and in partial, small, medium and large tears. BNip3 expression increased significantly in partial, small, medium and large tears but was reduced in massive tears. Apoptosis was increased in small, medium, large and massive tears but not in partial tears.

These findings reveal evidence of hypoxic damage throughout the spectrum of pathology of the rotator cuff which may contribute to loss of cells by apoptosis. This provides a novel insight into the causes of degeneration of the rotator cuff and highlights possible options for treatment.