Rabbit Tendon Research Articles

Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy: contralateral effects suggest the involvement of central neuronal mechanisms

ObjectiveTo determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons.DesignFour groups of six New Zealand white rabbits per group...

Tissue engineered intrasynovial tendons: in vivo graft survival and tensile strength

Rabbit flexor tendons can be harvested, acellularized, and used as scaffolds for reseeding of flexor tendon constructs. The purpose of this study was to compare the biomechanical characteristics of seeded and unseeded flexor tendon constructs to autologous grafts in vivo in the rabbit model. The experimental groups were created using acellularized rabbit tendon scaffolds: scaffolds with no cells, and scaffolds re-seeded with either tenocytes or adipoderived stem cells. Autologous flexor tendon grafts were used as controls. All constructs bridged a zone II defect in the rabbit and were explanted at 2, 4, 10, or 20 weeks. These tendons were then tested for ultimate tensile strength (UTS) or processed for histology. The experimental groups exhibited UTS comparable to autologous grafts up to 4 weeks, and were significantly weaker at 10 weeks (p < 0.000–0.024). At 20 weeks, UTS was significantly improved (p = 0.013) in tenocyte-seeded constructs compared with 10 weeks. There was no significant difference in UTS between seeded or unseeded constructs at 2, 4, and 20 weeks. In all groups, there were more cells at the repair ends, and the cells penetrated to the core of the grafts over time. The goal of this technology is the development of tissue engineered tendon grafts for clinical use. This study provides proof of the concept that tissue-engineered flexor tendons—both acellularized and reseeded—can survive and incorporate over time. Further work will focus on bioreactor preconditioning of reseeded constructs to increase ultimate tensile strength.

Metrenperone enhances collagen turnover and remodeling in the early stages of healing of tendon injury in rabbit

This study evaluated the effects of metrenperone on healing of unilateral, collagenase-induced lesions in the Superficial Digital Flexor Tendons (SDFT) of rabbits. After controlled injury of the left SDFT, nine rabbits received daily treatment with metrenperone for 28 days. Another nine were untreated controls; in both groups the contra-lateral tendons served as uninjured controls. Histological and ultrastructural changes, mechanical properties, dry weight, collagen content, and amount of DNA in healing and control tendons were assessed 28 days after injury. Restoration of structural hierarchy was more organized in treated than in untreated tendons while cellularity was greater in the latter. At the ultrastructural level, collagen in treated lesions was predominantly in the form of small-diameter, new fibrils, with few large, old fibrils; in untreated lesions there was a high proportion of large, old fibrils but relatively few small, new ones. The amount of DNA in untreated injuries was much greater than in normal tendons, while in treated lesions it was not significantly different from that of uninjured controls. There were no significant differences in total collagen, stiffness and ultimate strength of injured, treated, and untreated tendons 28 days after injury. Both were significantly weaker than their corresponding contralaterals. The findings suggest that metrenperone had positive effects on collagen turnover, remodelling, and organization during acute inflammation and fibroplasia. Provided that the new fibrils subsequently matured in a normal manner, mechanical characteristics of the organized scar should be better than those of an untreated lesion.

Characterization of differential properties of rabbit tendon stem cells and tenocytes

BackgroundTendons are traditionally thought to consist of tenocytes only, the resident cells of tendons; however, a recent study has demonstrated that human and mouse tendons also contain stem cells, referred to as tendon stem/progenitor cells (TSCs). However, the differential properties of TSCs and tenocytes remain largely undefined. This study aims to characterize the properties of these tendon cells derived from rabbits.MethodsTSCs and tenocytes were isolated from patellar and Achilles tendons of rabbits. The differentiation potential and cell marker expression of the two types of cells were examined using histochemical, immunohistochemical, and qRT-PCR analysis as well as in vivo implantation. In addition, morphology, colony formation, and proliferation of TSCs and tenocytes were also compared.ResultsIt was found that TSCs were able to differentiate into adipocytes, chondrocytes, and osteocytes in vitro, and form tendon-like, cartilage-like, and bone-like tissues in vivo. In contrast, tenocytes had little such differentiation potential. Moreover, TSCs expressed the stem cell markers Oct-4, SSEA-4, and nucleostemin, whereas tenocytes expressed none of these markers. Morphologically, TSCs possessed smaller cell bodies and larger nuclei than ordinary tenocytes and had cobblestone-like morphology in confluent culture whereas tenocytes were highly elongated. TSCs also proliferated more quickly than tenocytes in culture. Additionally, TSCs from patellar tendons formed more numerous and larger colonies and proliferated more rapidly than TSCs from Achilles tendons.ConclusionsTSCs exhibit distinct properties compared to tenocytes, including differences in cell marker expression, proliferative and differentiation potential, and cell morphology in culture. Future research should investigate the mechanobiology of TSCs and explore the possibility of using TSCs to more effectively repair or regenerate injured tendons.

A Poly(lactic-co-glycolic acid) Knitted Scaffold for Tendon Tissue Engineering: An In Vitro and In Vivo Study

We have designed a composite scaffold for potential use in tendon or ligament tissue engineering. The composite scaffold was made of a cellularized alginate gel that encapsulated a knitted structure. Our hypothesis was that the alginate would act as a cell carrier and deliver cells to the injury site while the knitted structure would provide mechanical strength to the composite construct. The mechanical behaviour and the degradation profile of the poly(lactic-co-glycolic acid) knitted scaffolds were evaluated. We found that our scaffolds had an elastic modulus of 750 MPa and that they lost their physical integrity within 7 weeks of in vitro incubation. Autologous rabbit mesenchymal stem cell seeded composite scaffolds were implanted in a 1-cm-long defect created in the rabbit tendon, and the biomechanical properties and the morphology of the regenerated tissues were evaluated after 13 weeks. The regenerated tendons presented higher normalized elastic modulus of (60%) when compared with naturally healed tendons (40%). The histological study showed a higher cell density and vascularization in the regenerated tendons.

O ultra-som terapêutico não aumentou as propriedades mecânicas de tendões flexores após reparo

OBJETIVO: Estudo experimental idealizado para investigar as propriedades mecânicas de tendões flexores profundos de coelhos submetidos à tenotomia seguida de tenorrafia e aplicação precoce de ultra-som terapêutico com diferentes intensidades, em comparação com tendões submetidos somente à tenorrafia. MATERIAL E MÉTODOS: Quarenta e quatro coelhos foram divididos em quatro grupos experimentais de acordo com a aplicação do ultra-som. Todos foram submetidos a uma secção do tendão flexor profundo na zona 2 e imobilizados com uma órtese mantida durante todo o experimento. O grupo A recebeu tratamento ultra-sônico com uma intensidade de 1,4 W/cm², o grupo B com 0,6 W/cm², ambos no modo contínuo, o grupo C com 0,6 W/cm² SATA, no modo pulsado à 50% e o grupo D não recebeu tratamento ultra-sônico algum. A frequência ultra-sônica empregada foi de 1 MHz. Após a eutanásia os tendões foram dissecados e submetidos ao ensaio mecânico de tração e análise histológica qualitativa. As propriedades mecânicas avaliadas foram: força máxima, deformação na força máxima e rigidez. RESULTADO: Não houve diferença estatisticamente significante entre os grupos experimentais. CONCLUSÃO: O ultra-som terapêutico não melhorou as propriedades mecânicas dos tendões flexores após reparo.

Effects of antisense transforming growth factor-β1 gene transfer on the biological activities of ten-don sheath fibroblasts

Objective To investigate the biological activity changes of rabbit tendon sheath fibro-blasts transfected by antisense TGF-β1 gene so as to provide a novel approach to prevention of postopera-tive tendon adhesion. Methods Tendon sheath fibroblasts were isolated from the New Zealand white rabbits and transfected by antisense TGF-β1 gene with Lipofectin. RT-PCR was used to measure mRNA expressions of collagen Ⅰ, collagen Ⅲ and TGF-β1 expressing and Western blot to measure protein ex-pression of collagen Ⅰ in tendon sheath fibroblasts. Results RT-PCR displayed marked decrease of mRNA expressions of collagen Ⅰ, collagen Ⅲ and TGF-β1 in tendon sheath fibroblasts transfected with antisense TGF-β1 gene, with statistical difference compared with untransfected group or blank transfected group (P<0.01). Western blot showed marked decrease of expression of collagen Ⅰ protein in tendon sheath fibroblasts transfected with antisense TGF-β1 gene, with statistical difference compared with un-transfected group or blank transfected group (P<0.01). Conclusions Tendon sheath fibroblasts can successfully transfect antisense transforming growth factor-β1 gene, decrease production of collagen Ⅰ,collagen Ⅲ and TGF-β1 that are factors for tendon adhesion and may play a certain role in prevention of tendon adhesion after tendon injuries. Key words: Tendon injuries; Oligoribonucleotides,antisense; Transforming growth factor beta; Collagen

Mechanobiological response of tendon stem cells: Implications of tendon homeostasis and pathogenesis of tendinopathy

Tendons are constantly subjected to mechanical loading in vivo. Recently, stem cells were identified in human, mouse, and rabbit tendons, but the mechanobiological responses of tendon stem cells (TSCs) are still undefined. Using an in vitro system capable of mimicking in vivo loading conditions, it was determined that mechanical stretching increased TSC proliferation in a stretching magnitude-dependent manner. Moreover, low mechanical stretching at 4% ("clamp-to-clamp" engineering strain) promoted differentiation of TSCs into tenocytes, whereas large stretching at 8% induced differentiation of some TSCs into adipogenic, chondrogenic, and osteogenic lineages, as indicated by upregulated expression of marker genes for adipocytes, chondrocytes, and osteocytes. Thus, low mechanical stretching may be beneficial to tendons by enabling differentiation of TSCs into tenocytes to maintain tendon homeostasis. However, large mechanical loading may be detrimental, as it directs differentiation of TSCs into non-tenocytes in tendons, thus resulting in lipid accumulation, mucoid formation, and tissue calcification, which are typical features of tendinopathy at later stages.

Comparison of Loop-Tendon Versus End-Weave Methods for Tendon Transfer or Grafting in Rabbits

The loop-tendon method for the stabilization of tendon transfers or grafts has been demonstrated previously to have greater initial tensile strength than that of the end-weave method. To our knowledge, a comparison of the mechanical strengths of these methods over the early postoperative period has not been made. The purpose of this study was to compare the mechanical strengths of loop-tendon and end-weave methods of repair during the early postoperative period in rabbit hind limb tendons. In bilateral hind limbs of 30 New Zealand white rabbits of an average weight of 3.5 kg, a distally cut gastrocnemius Achilles' tendon and a proximally cut flexor digitorum superficialis tendon were connected to each other by using the loop-tendon method with 5 stitches in one limb and a 1-pass end-weave method in the contralateral limb. Postoperatively, all rabbits were immobilized by a short-leg cylinder cast. Six rabbits were killed at each of the following time points: immediately after surgery (baseline) and at 1, 2, 3, and 4 weeks postoperatively. Repaired tendons were harvested and were loaded to failure in a tensile load-testing machine to record the ultimate strength and to calculate the absorbed energy. Ultimate tensile loads were significantly higher in the loop-tendon method group than in the end-weave group from baseline to 3 weeks postoperatively, but there was no difference at 4 weeks postoperatively. During the postoperative period, the ultimate tensile load and absorbed energy decreased over the first 2 weeks postoperatively and then increased to reach baseline strengths at 3 weeks postoperatively in both groups. The loop-tendon method provided greater strength than that of the end-weave method during the early postoperative period in rabbit tendons. The loop-tendon method may provide greater surgical repair strength during the early postoperative rehabilitation period than the end-weave method.

Development of a new model for rotator cuff pathology: the rabbit subscapularis muscle

Background and purpose The New Zealand white rabbit subscapularis tendon passes under a bony arch to insert on the lesser tubercle of the humerus in a manner analogous to the supraspinatus tendon in humans. We assessed whether this unique anatomy may provide a new animal model of the shoulder to improve our understanding of rotator cuff pathology.Methods The dimensions of the rotator cuff insertions (subscapularis, supraspinatus, and infraspinatus) were measured on 10 fresh frozen cadaveric New Zealand white rabbit shoulders. Mechanical testing was performed on 8 fresh frozen subscapularis insertions (4 matched pairs). Video analysis of the gait cycle was performed on 2 live animals.Results The origins, insertions, and innervations of the rabbit rotator cuff musculature are analogous to those in humans. However, the rabbit acromion is a rudimentary structure with only the infraspinatus and teres minor muscles passing beneath. Furthermore, at the point where the infraspinatus passes under the arch, it is muscular rather than tendinous. The anterior aspect of the glenohumeral joint contains an additional bony tunnel with its boundaries being the tuberculum supraglenoidale laterally, the coracoideus process superiorly, the tuberculum infraglenoidale inferiorly, and the coracobrachialis muscle medially. The origin of the rabbit subscapularis muscle resides on the anterior scapula. The subscapularis tendon then traverses this bony tunnel prior to its insertion on the lesser tubercle of the humerus. Video analysis and anatomic dissections confirmed excursion of the subscapularis tendon within this bony tunnel throughout the gait cycle. The subscapularis footprint on the proximal humerus measured 6.8 mm (SD 0.29) × 2.5 mm (SD 0.17). Mechanical testing of the subscapularis tendon showed the stiffness to range from 57 to 117 N/mm (SD 23). Ultimate yield ranged from 88 to 215 N (SD 518). The elastic modulus of the rabbit tendon was 56 MPa. 6 of the 8 subscapularis tendons failed at the tendon mid-substance; the other 2 failed at the bony insertion.Interpretation The unique anatomic architecture and the mechanical characteristics of the rabbit subscapularis muscle provide an opportunity to improve our understanding of rotator cuff pathology.

Variation of diameter distribution, number density, and area fraction of fibrils within five areas of the rabbit patellar tendon

The purpose of this investigation is to show microstructural information at various regions within the rabbit patellar tendon. The properties of the rabbit patellar tendon are well documented mechanically, but detailed information at the microscopic level is not available. Increasing attention has been directed to soft tissue microscopy as the demand for development of biologically inspired materials increases. Microstructural examination of the tendon fibrils is performed to provide further insight into understanding of the structure to function relations within the rabbit patellar tendon. Limited studies on rabbit patellar tendon collagen fibrils at the microscopic level have been computed. Furthermore, evaluation of structure-function relations in multiple regions of any given specimen of a particular tissue type has not been conducted. In this study the number density, area fraction, and diameter distribution of collagen fibrils have been determined. Overall, this examination showed considerable variation within each section of the tendon. Correlating these structural results with mechanical tests of the tendon portions in the various regions could provide additional information on the mechanics of the rabbit tendon as well as insight into development of artificial tissue constructs.

IN VITRO TRANSPLANTATION OF GENETICALLY MODIFIED CELLS TO THE TENDON SURFACE.

The objective of this paper was to study in vitro transfection of tendon cells and adherence of transfected cells to different tendon surfaces. Achilles tendon fibroblasts from 2-month-old New Zealand white rabbits were cultured to confluence, after which the cells were transfected by an adenovirus carrying either the β-galactosidase reporter gene or the green fluorescent protein (GFP) gene at multiplicities of infection (MOIs) of 50, 100, or 500. Two days later, the cells were transplanted onto the surfaces of rabbit Achilles, peroneus brevis, flexor profundus, and extensor longus tendons. The tendons were assessed by X-gal staining after 9 days, and by GFP fluorescence at 7, 14, and 21 days. Twenty percent to 50% of the treated cells stained for β-galactosidase at an MOI of 500. The GFP-labeled cells showed nearly 100% fluorescence at an MOI of 50. No positive cells were visible in the control group. The β-galactosidase and GFP-expressing cells remained viable for as long as 3 weeks. It is possible to introduce foreign genes into rabbit tendon cells, transplant the cells onto tendon surfaces, and maintain viability of the cell/tendon construct for several weeks.

Radiofrequency Microtenotomy for Epicondylitis: Five-Year Follow-Up and Proposed Mechanism of Action (SS-65)

Radiofrequency Microtenotomy for Epicondylitis: Five-Year Follow-Up and Proposed Mechanism of Action (SS-65)

The Effect of Local Corticosteroid or Ketorolac Exposure on Histologic and Biomechanical Properties of Rabbit Tendon and Cartilage

Tendonitis, tenosynovitis, and the arthritides are clinical problems commonly encountered in daily orthopaedic practice. Systemic anti-inflammatories, physical therapy, and local corticosteroid injections all are used as nonoperative treatments of these conditions. Systemic anti-inflammatory agents and local corticosteroid agents, however, can be associated with adverse effects that render them intolerable to some patients. As a preliminary study assessing the feasibility of local injection of nonsteroidal anti-inflammatory medication, the histological and biomechanical effects of local exposure of rabbit cartilage and tendon to injectable steroidal (corticosteroid) and injectable nonsteroidal anti-inflammatory agents (ketorolac tromethamine, KT) were determined. Thirty rabbits underwent bilateral knee joint, patellar tendon, and Achilles tendon injections with either normal saline, corticosteroid, or KT. Mechanical and histologic evaluation of the tissues was performed at 6 and 15 weeks after injection. Gross tendon adhesions were observed in more corticosteroid-treated specimens than those exposed to normal saline or KT. Microscopic evaluation of tendons revealed no significant differences among the three groups. Mild cartilage degenerative changes were noted across all groups. Evidence of cartilage necrosis was noted for the corticosteroid-treated group only. Tendons exposed to corticosteroid or KT demonstrated increased load and energy to failure, but exhibited no difference in material stiffness or strain. The use of an injectable nonsteroidal anti-inflammatory agent may be safe and even pose less threat to local tissues after intra-articular and peri-tendinous administration.

Histology and Ultrastructure of the Developing Superficial Digital Flexor Tendon in Rabbits

This study was designed to investigate the developmental changes in the superficial digital flexor tendon (SDFT) of the white New Zealand rabbit, from 5 to 7 days pre-natal to 112 days post-natal (PN), at histological and ultrastructural levels. The tendons changed from being highly cellular with 13079 +/- 2538 cell/mm(2) and little directional organization to a longitudinally oriented, predominantly connective tissue structure with relatively few, mature tenocytes (2384 +/- 365 cell/mm(2)). Fibrillogenesis was seen in isolated vacuoles of fibroblast cytoplasm during fetal life as well as after birth, but less frequently with increasing age. At the ultrastructural level, there was a progressive increase in the mean diameter of collagen fibrils with age throughout the population, until PN day 28. A bimodal distribution of collagen fibril size was first observed on PN day 56 while at day 112, the fibrils were fully differentiated and showed a multimodal size distribution. The development of elastic fibres preceded that of collagen fibres and accompanied progressively more marked sinusoidal crimping in collagen fibres on PN days 7 and 14. The tendons of older animals became less tightly crimped. The cells of the epi- and endotenon were less mature and relatively undifferentiated compared with the cells in the body of the tendon of the same age, which might explain their ability to initiate healing of tendon injuries in older animals. In conclusion, extensive changes were observed in tendons during growth and maturation, with diameters of collagen fibrils, tissue orientation and cellularity being the parameters affected, probably due largely to increased physical activity.

The Use of Radiofrequency For the Treatment of Chronic Tendinosis (SS-74)

The purpose of this study was to evaluate the histological and biochemical changes in the aged rabbit tendon compared to a sham control after radiofrequency stimulation as well as to understand the potential mechanism of healing. This model demonstrates similar properties to those in human tendinosis. 18 New Zealand white rabbits aged 4-6 years were used in this study. Bipolar radiofrequency stimulation with a Topaz™ (ArthroCare Corporation, Sunnyvale, California) wand was used on half the tendons with the remaining tendons serving as the sham control. Sacrifice was performed at 9, 30 and 90 days after surgery. Histologic assessment of RF-treated tendons showed mild crimping at 9 days, mature crimping at 30 and 90 days with hypercellularity and dense collagen bundles when compared to the sham control which showed no crimping and very loosely packed collagen bundles. In analyzing molecular gene expression, statistical trends were obtained at 9 days for an increase in VEGF, av, IGF-1 and bFGF in the RF-treated tendons. The lack of an appropriate animal model for tendinosis makes evaluation of this modality of therapy difficult. The aged rabbit tendon has histologic and biochemical characteristics similar to what we understand is present in human tendinosis. This was the first attempt to evaluate both histological and biological effects of RF treatment using the animal model. Dramatic changes in collagen remodeling were demonstrated histologically by restoration of the crimping pattern as well as upregulation of angiogenic and mitogenic markers at 9 days.

Effect of repetition rate on the formation of microtears in tendon in an in vivo cyclical loading model

We reported previously the formation of microtears in an in vivo loaded Flexor Digitorum Profundus (FDP) rabbit tendon with a repetition rate of 60 repetitions per minute and a peak force of 15% of maximum peak tetanic force for 80 cumulative hours. Tear area as a percent of tendon area, tear density (tears/mm(2)), and mean tear size (microm(2)) were higher in tendons from the loaded limb compared to the unloaded control limb. The purpose of the present study was to compare those results to results obtained with a repetition rate of 10 while maintaining the same peak force and force-time integral (n = 8). Due to a strain gradient between the inner and outer sides of the FDP tendon, microtears were quantified in four regions, two regions each along the inner and outer sides of the tendon. The tear area as a percent of total tendon area and the mean tear size were significantly greater in the loaded limb compared to the unloaded limb (p < 0.03). However, the effects were less than those observed at 60 repetitions/min. The higher repetition loading pattern resulted in an increase in tear measures in all four regions, while the lower rate produced changes only in the outer regions of the tendon. This finding may establish where the initial sites of damage occur in tendons that insert into bone in a similar arrangement as the FDP. The results suggest that repetition rate or number of loading cycles is associated with increased tendon microtears or fragility in a dose-response pattern.

In Vitro System for Applying Cyclic Loads to Connective Tissues Under Displacement or Force Control

Overuse is thought to be the primary cause of chronic tendon injuries, in which forceful or repetitive loading results in an accumulation of micro-tears leading to a maladaptive repair response. In vitro organ culture models provide a useful method for examining how specific loading patterns affect the cellular response to load which may explain the early mechanisms of tissue injury associated with tendinopathies and ligament injuries. We designed a novel tissue loading system which employs closed-loop force feedback, capable of loading six tissue samples independently under force or displacement control. The system was capable of applying loads up to 40 N at rates of 100 N s(-1) and frequencies of 2 Hz, well above loads and rates measured in rabbit tendons in vivo. Loading parameters such as amplitude, rate, and frequency can be controlled while biomechanical factors such as creep, force relaxation, tangent modulus and Young's modulus can be assessed. The system can be used to examine the relationship between each loading parameter and biomechanical factors of connective tissues maintained in culture which may provide useful information regarding the etiology of overuse injuries.

The impact of polyglycolide membrane on a tendon after surgical rejoining. A histological and histomorphometric analysis in rabbits

Tissue response to self-reinforced polyglycolide (SR-PGA) membranes surrounding rejoined rabbit tendons was compared with tissue response to nonenveloped rejoined tendons, with special focus on scar formation and SR-PGA membrane biodegradation process. Both hind legs of 20 skeletally mature rabbits were operated on by transecting the plantaris longus tendons and rejoining the ends with sutures. The right side seams were enveloped with bioabsorbable SR-PGA membranes, while the left sides served as noncovered controls. The follow-up times were 3, 6, 12, and 24 weeks. Scar formation and tissue response to membranes were studied by histological and histomorphometric analysis. Tendon regeneration was most active at 3 weeks. Capillary formation was more prominent in specimens with shorter follow-up times. Membrane degradation induced an inflammatory reaction observed at all follow-up time points. Under polarizing microscopy, birefringent SR-PGA material was seen to vanish almost completely by 24 weeks. SR-PGA membranes had no specific effect on scar formation and there were no differences in the reunion process of the transected tendon ends between the SR-PGA membrane groups and the controls. Inflammatory cells in the SR-PGA membrane groups reflected a tissue reaction to the membrane. When placed in soft tissues, SR-PGA membranes degraded almost completely within 24 weeks.

The Effect of Repetition Rate on the Formation of Microtears in Tendon in an In Vivo Cyclical Loading Animal Model

Previously (17), we reported the formation of microtears in an in vivo loaded FDP rabbit tendon with a repetition rate of 60 repetitions per minute and a peak force of 15% of maximum (Po). Pathophysiological changes were observed. The tear area as a percent of tendon area, tear density (tears/mm2) and mean tear size (μm2) were higher in tendons from the loaded limb compared to the unloaded limb. The purpose of the present study was to compare those results to results obtained with a lower repetition rate of 10 (per minute) while maintaining the same peak force and work (equal force-time integral) (n=8). Due to regional properties of the tendon, a strain gradient between the inner and outer sides of the FDP tendon exists. Therefore, microtears were quantified in four regions, two regions each along the inner and outer sides of the tendon. The tear area as a percent of total tendon area and the mean tear size were significantly greater in the loaded limb compared to the unloaded limb (p &lt; 0.03). However, the effects were less than those observed at 60 repetitions/min. The high repetition rate loading pattern resulted in an increase in tear measures in all four regions, while the lower rate produced changes only in the outer regions of the tendon. This finding may establish where the initial sites of damage occur in tendons that insert into bone in a similar arrangement as the FDP. The results also suggest that repetition rate is associated with tendon damage in a dose-response pattern.