Intratendinous pressure changes in the Achilles tendon during stretching and eccentric loading: Implications for Achilles tendinopathy.

Mechanical overload is considered the main cause of Achilles tendinopathy. In addition to tensile loads, it is believed that the Achilles tendon may also be exposed to compressive loads. However, data on intratendinous pressures are lacking, and consequently, their role in the pathophysiology of tendinopathy is still under debate. Therefore, we aimed to evaluate the intratendinous pressure changes in the Achilles tendon during stretching and eccentric loading. Twelve pairs of human cadaveric legs were mounted in a testing rig, and a miniature pressure catheter was placed through ultrasound-guided insertion in four different regions of the Achilles tendon: the insertion (superficial and deep layers), mid-portion, and proximal portion. Intratendinous pressure was measured during three simulated loading conditions: a bent-knee calf stretch, a straight-knee calf stretch, and an eccentric heel-drop. It was found that the intratendinous pressure increased exponentially in both the insertion and mid-portion regions of the Achilles tendon during each loading condition (p < 0.001). The highest pressures were consistently found in the deep insertion region (p < 0.001) and during the eccentric heel-drop (p < 0.001). Pressures in the mid-portion were also significantly higher than in the proximal portion (p < 0.001). These observations offer novel insights and support a role for compression in the pathophysiology of Achilles tendinopathy by demonstrating high intratendinous pressures at regions where Achilles tendinopathy typically occurs. To what extent managing intratendinous pressure might be successful in patients with Achilles tendinopathy by, for example, avoiding excessive stretching, modifying exercise therapy, and offering heel lifts requires further investigation.

Comparison of the Effects of Pulsed Electromagnetic Field and Extracorporeal Shockwave Therapy in a Rabbit Model of Experimentally Induced Achilles Tendon Injury.

Achilles tendon injuries are a common cause of complications including adhesions and tendon degeneration. As a result of these complications, the biomechanical properties are lost. Extracorporeal shockwave therapy (ESWT) and pulsed electromagnetic field (PEMF) recover the injured tendon structure; however, detailed studies of changes in tendon biomechanical properties are limited. We hypothesized that PEMF application would improve Achilles tendon biomechanical properties similar to ESWT. The curative effects of a PEMF 4-week application (15 Hz, 1 mT, 260 µs, 1 h/day) and ESWT (3 doses/28 days, 1st dose: 0.12 mJ/mm2 , 15 Hz, 300 impulses; 2nd dose: 0.14 mJ/mm2 , 15 Hz, 500 impulses; 3rd dose: 0.14 mJ/mm2 , 15 Hz, 500 impulses) on rabbits with Achilles tendon injury were investigated in terms of histopathological and biomechanical properties. The clinical feasibility of PEMF application was evaluated by comparing the results of both methods. Fifty New Zealand female rabbits were divided into two groups to be used in either biomechanical or immunohistochemical studies. Each of the two groups was further divided into five groups: C (Control), SH (Sham), TI (tendon injury), TI + ESWT, and TI + PEMF. Biomechanical evaluations revealed that maximum load, toughness, and maximum stress averages of the TI + PEMF group significantly increased (P < 0.05). When immunohistochemical images of the TI + PEMF group were compared with those of the TI group, the amount of fibrous tissue was less, the homogeneity of collagen fibers recovered, and collagen organization was more uniform. We conclude that both ESWT and PEMF are equally efficient for Achilles tendon recovery. PEMF application is effective and can be used in the clinic as a painless alternative treatment method. © 2020 Bioelectromagnetics Society.

Biomechanical properties of the repaired and non-repaired rat supraspinatus tendon in the acute postoperative period.

PURPOSE: The rat rotator cuff (RC) model is used to study RC pathology and potential treatment; however, native scar-mediated healing allows the rat RC to recover at 4-6 weeks but little is known about acute healing. This study characterized the properties of the repaired and non-repaired rat RC following surgical detachment. MATERIALS AND METHODS: Forty-eight rats underwent surgical RC detachment and received surgical repair (Repair) or left unrepaired (Defect) to either 12 or 19 days. Healthy controls were obtained from contralateral limbs. Biomechanical properties were assessed using stress relaxation and failure testing and mechanical modeling performed using quasilinear viscoelastic (QLV) and structurally based elastic models. Histology and micro-magnetic resonance imaging were used to qualitatively grade tendon-to-bone healing. RESULTS: Repair and Defect exhibited significantly inferior mechanical properties compared to Healthy at both time points. Repair had significant increases in peak, equilibrium, and ultimate stress, modulus, and stiffness and significant decreases in cross-sectional area, % relaxation, and QLV constant "C" between 12 and 19 days, whereas Defect showed no change. CONCLUSIONS: This study demonstrates acute differences in mechanical properties of the rat supraspinatus tendon in the presence and absence of surgical repair. Understanding the longitudinal recovery of mechanical properties can facilitate more accurate characterization of RC pathology or future treatments.

Load magnitude affects patellar tendon mechanical properties but not collagen or collagen cross-linking after long-term strength training in older adults.

BACKGROUND: Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS: Seventeen women and 19 men, age 62-70 years, were recruited and randomly allocated to 12 months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS: Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+ 21%) than MRT (+ 8%) and CON (+ 7%) (p < 0.05). Tendon stiffness (p < 0.05) and Young's modulus (p = 0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION: Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.

Multiscale mechanical effects of native collagen cross-linking in tendon.

The hierarchical structure of tendon allows for attenuation of mechanical strain down decreasing length scales. While reorganization of collagen fibers accounts for microscale strain attenuation, cross-linking between collagen molecules contributes to deformation mechanisms at the fibrillar and molecular scales. Divalent and trivalent enzymatic cross-links form during the development of collagen fibrils through the enzymatic activity of lysyl oxidase (LOX). By establishing connections between telopeptidyl and triple-helical domains of adjacent molecules within collagen fibrils, these cross-links stiffen the fibrils by resisting intermolecular sliding. Ultimately, greater enzymatic cross-linking leads to less compliant and stronger tendon as a result of stiffer fibrils. In contrast, nonenzymatic cross-links such as glucosepane and pentosidine are not produced during development but slowly accumulate through glycation of collagen. Therefore, these cross-links are only expected to be present in significant quantities in advanced age, where there has been sufficient time for glycation to occur, and in diabetes, where the presence of more free sugar in the extracellular matrix increases the rate of glycation. Unlike enzymatic cross-links, current evidence suggests that nonenzymatic cross-links are at least partially isolated to the surface of collagen fibers. As a result, glycation has been proposed to primarily impact tendon mechanics by altering molecular interactions at the fiber interface, thereby diminishing sliding between fibers. Thus, increased nonenzymatic cross-linking decreases microscale strain attenuation and the viscous response of tendon. In conclusion, enzymatic and nonenzymatic collagen cross-links have demonstrable and distinct effects on the mechanical properties of tendon across different length scales.

Biomechanical properties of the patellar tendon in children with heritable connective tissue disorders.

PURPOSE: Hereditary connective tissue disorders (HCTDs), such as classic Ehlers-Danlos syndrome (cEDS) and Marfan syndrome (MS) share overlapping features like hypermobility and tissue fragility. In clinical practice it remains a challenge to distinguish children and adolescents with HCTD from healthy children. The purpose of this study was to investigate the biomechanical properties of the patellar tendon and joint laxity (Beighton score) in children with HCTDs (n = 7) compared to healthy controls (n = 14). METHODS: The mechanical properties of the patellar tendon were assessed using simultaneous force and ultrasonographic measurements during isometric ramp contractions. Ultrasonography was also used to measure tendon dimensions. The HCTD children were matched with 2 healthy controls with regard to age, body mass index (BMI), sex and physical activity level. RESULTS: The HCTD children had a greater degree of joint laxity (P < 0.01). Although, the patellar tendon dimensions did not differ significantly between the two groups, the HCTD children showed a tendency toward a larger patellar tendon cross-sectional area (CSA) (35%, P = 0.19). Moreover, stiffness did not differ between the two groups, but secant modulus was 27% lower in children with a HCTD (P = 0.05) at common force and 34% lower at maximum force (P = 0.02). CONCLUSIONS: The present study demonstrates for the first time that children with HCTDs have lower material properties (modulus) of their patellar tendon, which may be indicative of general impairment of connective tissue mechanics related to their increased joint laxity.

Achilles tendon elastic properties remain decreased in long term after rupture.

PURPOSE: Rupture of the Achilles tendon results in inferior scar tissue formation. Elastography allows a feasible in vivo investigation of biomechanical properties of the Achilles tendon. The purpose of this study is to investigate the biomechanical properties of healed Achilles tendons in the long term. MATERIALS AND METHODS: Patients who suffered from Achilles tendon rupture were recruited for an elastographic evaluation. Unilateral Achilles tendon ruptures were included and scanned in the mid-substance and calcaneal insertion at least 2 years after rupture using shear wave elastography. Results were compared to patients' contralateral non-injured Achilles tendons and additionally to a healthy population. Descriptive statistics, reliability analysis, and correlation analysis with clinical scores were performed. RESULTS: Forty-one patients were included in the study with a mean follow-up-time of 74 ± 30; [26-138] months after rupture. Significant differences were identified in shear wave elastography in the mid-substance of healed tendons (shear wave velocity 1.2 ±1.5 m/s) compared to both control groups [2.5 ±1.5 m/s (p < 0.01) and 2.8 ±1.6 m/s (p < 0.0001) contralateral and healthy population, respectively]. There was no correlation between the measurements and the clinical outcome. CONCLUSIONS: This study shows that the healed Achilles tendon after rupture has inferior elastic properties even after a long-term healing phase. Differences in elastic properties after rupture mainly originate from the mid-substance of the Achilles tendon, in which most of the ruptures occur. Elastographic results do not correspond with subjective perception. Clinically, sonoelastographical measurements of biomechanical properties can be useful to provide objective insights in tendon recovery.

Real-time sonoelastography as novel follow-up method in Achilles tendon surgery.

PURPOSE: To evaluate the sonoelastographic features of Achilles tendon healing after percutaneous treatment using real-time sonoelastography, a new tool able to quantify deformation in biological tissues. METHODS: Patients with atraumatic Achilles tendon ruptures, treated with a percutaneous technique, were assessed. Sonoelastographic evaluations were performed at the myotendinous junction, tendon body/lesion site and osteotendinous junction, both for the operated and contralateral side, at 40 days, 6 months and 1 year after surgery. Using standard regions of interest, the "strain index" (SI) was calculated as an indicator of tendon elasticity. Clinical outcomes were assessed by the ATRS questionnaire at 6 months and 1 year post-operatively and correlated with sonoelastographic findings. Sixty healthy tendons from 30 volunteers were used to provide a healthy control range. RESULTS: Twenty-five patients were recruited for this study. The SI in treated tendons showed progressive stiffening over time, especially at myotendinous junction and at the site of the sutured lesion, resulting in significantly higher stiffness than both the contralateral tendon and healthy volunteers. Peak thickness of treated tendons occurred at 6 months, with a tendency to reduce at 1 year, while never achieving a normal physiological state. Greatest remodelling was seen at the lesion site. The contralateral tendon showed significant thickening at the myotendinous and osteotendinous junctions. The SI of the contralateral tendon was found to be stiffer than physiological values found in the control group. ATRS score improved significantly between 6 months and 1 year, being negatively correlated with the SI (p < 0.001). CONCLUSION: RTSE showed that operatively treated Achilles tendons become progressively stiffer during follow-up, while the ATRS score improved. From a biomechanical point of view, at 1 year after surgery Achilles tendons did not show a "restitutio ad integrum". Real-time sonoelastography provides more qualitative and quantitative details in the diagnostics and follow-up of Achilles tendon conditions as the post-operative evolution of the repairing tissue. LEVEL OF EVIDENCE: Diagnostic and therapeutic study, Level III.

Bone-Prosthesis Junction for Active Tendon Implants: A Biomechanical Comparison of 2 Fixation Techniques.

PURPOSE: To study the biomechanical characteristics (percent stretch, stiffness, and ultimate load) of 2 distal fixation techniques for an active tendon implant used in the reconstruction of flexor tendons. METHODS: We evaluated percent stretch after cyclical loading and at failure, stiffness during load-to-failure, and peak load of 28 bone-prosthesis junctions using cadaveric canine middle phalanges to study 2 fixation techniques: metal cleat and screw versus polyester cords secured with a knot. RESULTS: The knot constructs displayed greater percent stretch during and following cyclical loading between 2 N and 50 N and at peak load. The screw construct showed greater stiffness from 50 N to 150 N during load-to-failure. Both fixation techniques failed at a mean peak load greater than 340 N. CONCLUSIONS: Both fixation techniques for active tendon implants withstood loads seen with passive and active motion in the immediate postoperative period. Knot constructs displayed significant stretch during cyclical and load-to-failure testing, which would need to be compensated for during surgery. The screw constructs showed greater stiffness than the constructs secured with the surgeon's knot, but failure created an intra-articular fracture. CLINICAL RELEVANCE: The results may aid the surgeon in choosing which fixation technique to use, during tensioning of cords, and in permitting active motion following surgery.

Patch-augmented rotator cuff repair: influence of the patch fixation technique on primary biomechanical stability.

INTRODUCTION: There is an ongoing debate about the potential of patch augmentation to improve biomechanical stability and healing associated with rotator cuff repair. The biomechanical properties of three different patch-augmented rotator cuff repair techniques were assessed in vitro and compared with a standard repair. Dermal collagen patch augmentation may increase the primary stability and strength of the repaired tendon in vitro, depending on the technique used for patch application. METHODS AND MATERIALS: Forty cadaveric sheep shoulders with dissected infraspinatus tendons were randomized into four groups (n = 10/group) for tendon repair using a knotless double-row suture anchor technique. A xenologous dermal extracellular matrix patch was used for augmentation in the three test groups using an "integrated", "cover", or "hybrid" technique. Tendons were preconditioned, cyclically loaded from 10 to 30 N at 1 Hz, and then loaded monotonically to failure. Biomechanical properties and the mode of failure were evaluated. RESULTS: Patch augmentation significantly increased the maximum load at failure by 61 % in the "cover" technique test group (225.8 N) and 51 % in the "hybrid" technique test group (211.4 N) compared with the non-augmented control group (140.2 N) (P ≤ 0.015). For the test group with "integrated" patch augmentation, the load at failure was 28 % lower (101.6 N) compared with the control group (P = 0.043). There was no significant difference in initial and linear stiffness among the four experimental groups. The most common mode of failure was tendon pullout. No anchor dislocation, patch disruption or knot breakage was observed. CONCLUSION: Additional patch augmentation with a collagen patch influences the biomechanical properties of a rotator cuff repair in a cadaveric sheep model. Primary repair stability can be significantly improved depending on the augmentation technique.

Clinical outcomes and structural integrity rate of arthroscopic augmented rotator cuff repairs using extracellular porcine matrix patch.

Background: Structural failure rate in rotator cuff repairs is still high. The purpose of the study is to assess the structural integrity of a series of augmented rotator cuff repairs with porcine matrix patch and report the functional outcomes. Methods: Between 2014 and 2017, 44 consecutive patients underwent arthroscopic double-row repair of medium to massive rotator cuff tears with extracellular porcine dermal matrix augmentation. At one-year follow-up, magnetic resonance imaging scan was performed to assess the integrity of the repair. Oxford Shoulder Score (OSS), Constant Score (CS) and Visual Analogue Scale pain score, together with range of motion were used to assess patients. Results: Patients mean age was 68 (53-82); mean follow-up was 17.2 (12-24) months. On magnetic resonance imaging scans, seven rotator cuff repair failures (15.9%) were observed: tear size was an independent predictor of re-rupture at one-year follow-up. Clinical scores showed a statistically significant improvement at three months and until final follow-up (p< 0.001). No complications occurred. Conclusion: Observed structural failure rate of 15.9% is lower than those reported in the literature for standard rotator cuff repair of medium to massive tears in similar cohorts to ours. Extracellular matrix augmentation for rotator cuff repair was shown to be a safe and reliable support to the repairs and patients recovered good shoulder function.Level of Evidence: Level IV.

Biomechanical Comparison of Krackow Repair and Percutaneous Achilles Repair System for Achilles Tendon Rupture Fixation: A Cadaveric and Finite Element Analysis Study.

Background: Open and percutaneous repair surgeries are widely used for the Achilles tendon rupture. However, prior biomechanic studies of these 2 approaches have mixed conclusions; therefore, we designed a cadaver and finite element (FE) model biomechanical study to compare the mechanical differences between the percutaneous Achilles repair system (PARS) and Krackow open repair under tensile load and rotation. Methods: Sixteen Achilles tendons were extracted from fresh-frozen cadaver ankles and the calcaneums were fixed in mortar. A force control dynamic tensile mechanical test was performed at 1 Hz with 30- and 100-N cyclic loads. Initial intact baseline testing was followed by an incision on all Achilles tendons, 4 cm from the calcaneus insertion, which were then repaired using the PARS (n = 8) or Krackow (n = 8) method. Recorded force-displacement values were used to calculate mechanical parameters, and statistical significance of differences was determined by unpaired (between repair techniques) and paired (intact vs repaired) t tests. Material properties of the Achilles tendon in the FE model were modified and a 10-Nm flexion was simulated for intact and surgical groups. Results: No differences were found between intact tendons assigned to PARS or Krackow repairs in Young's modulus (P = .582) and stiffness (P = .323). Pre- and postoperative Young's modulus was significantly decreased for both groups (Intact 230.60±100.76 MPa vs PARS 142.44±37.37 MPa, P < .012; Intact 207.46±81.12 MPa vs Krackow109.43±27.63 MPa, P < .002). Stiffness decreased significantly after surgery for both groups (Intact 25.33±10.89 N/mm vs PARS 6.51±1.68 N/mm, P < .003; Intact 20.30±8.65 N/mm vs Krackow 5.97±1.30 N/mm, P < .003). PARS ultimate tensile strength was significantly higher than the Krackow (PARS 280.29±47.32 N vs Krackow 196.97±54.28 N, P < .003) but not significantly different in the ultimate tensile strain. PARS had a significantly lower postoperative gap compared to Krackow (PARS 9.75±5.87 mm vs Krackow 25.19±7.72 mm, P < .001). FE analysis predicted an increased talocalcaneal contact pressure, maximum principal stress, and rotation in the Krackow vs PARS models, respectively. Conclusion: Biomechanical parameters observed in this study through mechanical testing and FE analysis favor the selection of PARS over the Krackow repair based on better strength, higher failure force, and lower gap generation.Clinical Relevance: The study has analyzed two Achilles tendon repair methods using cadaver and numerical estimation and may help clinicians gain insight into selection of tendon repair approaches to generate better clinical outcomes.

Measurements of Tendon Movement Within the Bicipital Groove After Suprapectoral Intra-articular Biceps Tenodesis in a Cadaveric Model.

BACKGROUND: Lesions of the long head of the biceps can be successfully treated with biceps tenotomy or tenodesis when surgical management is elected. The advantage of a tenodesis is that it prevents the potential development of a cosmetic deformity or cramping muscle pain. Proponents of a subpectoral tenodesis believe that "groove pain" may remain a problem after suprapectoral tenodesis as a result of persistent motion of the tendon within the bicipital groove. PURPOSE/HYPOTHESIS: To evaluate the motion of the biceps tendon within the bicipital groove before and after a suprapectoral intra-articular tenodesis. The hypothesis was that there would be minimal to no motion of the biceps tendon within the bicipital groove after tenodesis. STUDY DESIGN: Controlled laboratory study. METHODS: Six fresh-frozen cadaveric arms were dissected to expose the long head of the biceps tendon as well as the bicipital groove. Inclinometers and fiducials (optical markers) were used to measure the motions of the scapula, forearm, and biceps tendon through a full range of shoulder and elbow motions. A suprapectoral biceps tenodesis was then performed, and the motions were repeated. The motion of the biceps tendon was quantified as a function of scapular or forearm motion in each plane, both before and after the tenodesis. RESULTS: There was minimal motion of the native biceps tendon during elbow flexion and extension but significant motion during all planes of scapular motion before tenodesis, with the most motion occurring during shoulder flexion-extension (20.73 ± 8.21 mm). The motion of the biceps tendon after tenodesis was significantly reduced during every plane of scapular motion compared with the native state (P < .01 in all planes of motion), with a maximum motion of only 1.57 mm. CONCLUSION: There was a statistically significant reduction in motion of the biceps tendon in all planes of scapular motion after the intra-articular biceps tenodesis. The motion of the biceps tendon within the bicipital groove was essentially eliminated after the suprapectoral biceps tenodesis. CLINICAL RELEVANCE: This arthroscopic suprapectoral tenodesis technique can significantly reduce motion of the biceps tendon within the groove in this cadaveric study, possibly reducing the likelihood of groove pain in the clinical setting.

Mechanical properties of the different rotator cuff tendons in the rat are similarly and adversely affected by age.

Rotator cuff tendon tears and tendinopathies are common injuries affecting a large portion of the population and can result in pain and joint dysfunction. Incidence of rotator cuff tears significantly increases with advancing age, and up to 90% of these tears involve the supraspinatus. Previous literature has shown that aging can lead to inferior mechanics, altered composition, and changes in structural properties of the supraspinatus. However, there is little known about changes in supraspinatus mechanical properties in context of other rotator cuff tendons. Alterations in tendon mechanical properties may indicate damage and an increased risk of rupture, and thus, the purpose of this study was to use a rat model to define age-related alterations in rotator cuff tendon mechanics to determine why the supraspinatus is more susceptible to tears due to aging than the infraspinatus, subscapularis, and teres minor. Fatigue, viscoelastic, and quasi-static properties were evaluated in juvenile, adult, aged, and geriatric rats. Aging ubiquitously and adversely affected all rotator cuff tendons tested, particularly leading to increased stiffness, decreased stress relaxation, and decreased fatigue secant and tangent moduli in geriatric animals, suggesting a common intrinsic mechanism due to aging in all rotator cuff tendons. This study demonstrates that aging has a significant effect on rotator cuff tendon mechanical properties, though the supraspinatus was not preferentially affected. Thus, we are unable to attribute the aging-associated increase in supraspinatus tears to its mechanical response alone.

An adhesion G protein-coupled receptor is required in cartilaginous and dense connective tissues to maintain spine alignment.

Adolescent idiopathic scoliosis (AIS) is the most common spine disorder affecting children worldwide, yet little is known about the pathogenesis of this disorder. Here, we demonstrate that genetic regulation of structural components of the axial skeleton, the intervertebral discs, and dense connective tissues (i.e., ligaments and tendons) is essential for the maintenance of spinal alignment. We show that the adhesion G protein-coupled receptor ADGRG6, previously implicated in human AIS association studies, is required in these tissues to maintain typical spine alignment in mice. Furthermore, we show that ADGRG6 regulates biomechanical properties of tendon and stimulates CREB signaling governing gene expression in cartilaginous tissues of the spine. Treatment with a cAMP agonist could mirror aspects of receptor function in culture, thus defining core pathways for regulating these axial cartilaginous and connective tissues. As ADGRG6 is a key gene involved in human AIS, these findings open up novel therapeutic opportunities for human scoliosis.

Intrinsic Tendon Regeneration After Application of Purified Exosome Product: An In Vivo Study.

BACKGROUND: Tendons are primarily acellular, limiting their intrinsic regenerative capabilities. This limited regenerative potential contributes to delayed healing, rupture, and adhesion formation after tendon injury. PURPOSE: To determine if a tendon's intrinsic regenerative potential could be improved after the application of a purified exosome product (PEP) when loaded onto a collagen scaffold. STUDY DESIGN: Controlled laboratory study. METHODS: An in vivo rabbit Achilles tendon model was used and consisted of 3 groups: (1) Achilles tenotomy with suture repair, (2) Achilles tenotomy with suture repair and collagen scaffold, and (3) Achilles tenotomy with suture repair and collagen scaffold loaded with PEP at 1 × 1012 exosomes/mL. Each group consisted of 15 rabbits for a total of 45 specimens. Mechanical and histologic analyses were performed at both 3 and 6 weeks. RESULTS: The load to failure and ultimate tensile stress were found to be similar across all groups (P ≥ .15). The tendon cross-sectional area was significantly smaller for tendons treated with PEP compared with the control groups at 6 weeks, which was primarily related to an absence of external adhesions (P = .04). Histologic analysis confirmed these findings, demonstrating significantly lower adhesion grade both macroscopically (P = .0006) and microscopically (P = .0062) when tendons were treated with PEP. Immunohistochemical staining showed a greater intensity for type 1 collagen for PEP-treated tendons compared with collagen-only or control tendons. CONCLUSION: Mechanical and histologic results suggested that healing in the PEP-treated group favored intrinsic healing (absence of adhesions) while control animals and animals treated with collagen only healed primarily via extrinsic scar formation. Despite a smaller cross-sectional area, treated tendons had the same ultimate tensile stress. This pilot investigation shows promise for PEP as a means of effectively treating tendon injuries and enhancing intrinsic healing. CLINICAL RELEVANCE: The production of a cell-free, off-the-shelf product that can promote tendon regeneration would provide a viable solution for physicians and patients to enhance tendon healing and decrease adhesions as well as shorten the time required to return to work or sports.

Elastic and surgeon friendly electrospun tubes delivering PDGF-BB positively impact tendon rupture healing in a rabbit Achilles tendon model.

A major problem after tendon laceration is the low mechanical strength of the repaired tissue. One viable strategy for improving the functional and biomechanical properties of ruptured and repaired tendons is the delivery of growth factors at the injury site. Here, bioactive and reversibly expandable double-layered emulsion and coaxially electrospun tubes made from biodegradable DegraPol® (DP) (polyester urethane), delivering platelet-derived growth factor BB (PDGF-BB), are explored as implants to improve tendon healing in a rabbit Achilles tendon full laceration model. In vitro studies showed that both emulsion and coaxially electrospun scaffolds allow sustained delivery of bioactive PDGF-BB with similar release kinetics (150-190 pg PDGF-BB/mg of DP scaffold) over a period of 30 days. In vivo assessment after three weeks showed that PDGF-BB delivery through the bioactive DP tubes increased the tensile strength of the treated tendons 2-fold without additional pro-fibrotic effects, i.e., cell hyperproliferation or increase in α-smooth muscle actin expression at the wound site. While no major differences in ECM composition at the wound site were observed for ± PDGF-BB treated samples, collagen I and III were upregulated and fibronectin was downregulated compared to native tendons. In areas away from the wound, increased fibronectin expression was observed qualitatively in regions with lower collagen I and III expression. Both types of bioactive DP tubes provided surgeon-friendly and stable implants to deliver bioactive molecules and positively affected the strength of the repaired tendons after 3 weeks, thus presenting promising bioactive implants for clinical applications in the tendon repair field.

Collagen XI regulates the acquisition of collagen fibril structure, organization and functional properties in tendon.

Collagen XI is a fibril-forming collagen that regulates collagen fibrillogenesis. Collagen XI is normally associated with collagen II-containing tissues such as cartilage, but it also is expressed broadly during development in collagen I-containing tissues, including tendons. The goals of this study are to define the roles of collagen XI in regulation of tendon fibrillar structure and the relationship to function. A conditional Col11a1-null mouse model was created to permit the spatial and temporal manipulation of Col11a1 expression. We hypothesize that collagen XI functions to regulate fibril assembly, organization and, therefore, tendon function. Previous work using cho mice with ablated Col11a1 alleles supported roles for collagen XI in tendon fibril assembly. Homozygous cho/cho mice have a perinatal lethal phenotype that limited the studies. To circumvent this, a conditional Col11a1flox/flox mouse model was created where exon 3 was flanked with loxP sites. Breeding with Scleraxis-Cre (Scx-Cre) mice yielded a tendon-specific Col11a1-null mouse line, Col11a1Δten/Δten. Col11a1flox/flox mice had no phenotype compared to wild type C57BL/6 mice and other control mice, e.g., Col11a1flox/flox and Scx-Cre. Col11a1flox/flox mice expressed Col11a1 mRNA at levels comparable to wild type and Scx-Cre mice. In contrast, in Col11a1Δten/Δten mice, Col11a1 mRNA expression decreased to baseline in flexor digitorum longus tendons (FDL). Collagen XI protein expression was absent in Col11a1Δten/Δten FDLs, and at ~50% in Col11a1+/Δten compared to controls. Phenotypically, Col11a1Δten/Δten mice had significantly decreased body weights (p < 0.001), grip strengths (p < 0.001), and with age developed gait impairment becoming hypomobile. In the absence of Col11a1, the tendon collagen fibrillar matrix was abnormal when analyzed using transmission electron microscopy. Reducing Col11a1 and, therefore collagen XI content, resulted in abnormal fibril structure, loss of normal fibril diameter control with a significant shift to small diameters and disrupted parallel alignment of fibrils. These alterations in matrix structure were observed in developing (day 4), maturing (day 30) and mature (day 60) mice. Altering the time of knockdown using inducible I-Col11a1-/- mice indicated that the primary regulatory foci for collagen XI was in development. In mature Col11a1Δten/Δten FDLs a significant decrease in the biomechanical properties was observed. The decrease in maximum stress and modulus suggest that fundamental differences in the material properties in the absence of Col11a1 expression underlie the mechanical deficiencies. These data demonstrate an essential role for collagen XI in regulation of tendon fibril assembly and organization occurring primarily during development.

Irradiation at 11 kGy conserves the biomechanical properties of fascia lata better than irradiation at 25 kGy.

The objective of this study was to determine the biomechanical properties of the fascia lata and the effects of three preservation methods: freezing, cryopreservation with dimethylsulfoxide solution and lyophilization; and to compare the effects of low-dose (11 kGy) and normal-dose (25 kGy) gamma-ray sterilization versus no irradiation. 248 samples from 14 fasciae latae were collected. Freezing samples were frozen at -80 °C. Cryopreservation with dimethylsulfoxide solution samples were frozen with 10 cl dimethylsulfoxide solution at -80 °C. Lyophilization samples were frozen at -22 °C and lyophilized. Each preservation group were then randomly divided into 3 irradiation groups. The cryopreservation with dimethylsulfoxide solution samples had significantly worse results in all 3 irradiation conditions. Young's modulus was lower for the freezing samples (p < 0.001) and lyophilization samples groups (p < 0.001). Tear deformation was lower for the freezing samples (p = 0.001) and lyophilization samples groups (p = 0.003), as was stress at break (p < 0.001 and p < 0.001). Taking all preservation methods together, samples irradiated at 25 kGy had worse results than the 0 kGy and 11 kGy groups in terms of Young's modulus (p = 0.007 and p = 0.13) and of stress at break (p = 0.006 and p = 0.06). The biomechanical properties of fascia lata allografts were significantly worse under dimethylsulfoxide cryopreservation. The deleterious effects of irradiation were dose-dependent.