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PubMed2000

Studies in flexor tendon wound healing: neutralizing antibody to TGF-beta1 increases postoperative range of motion.

The postoperative outcome of hand flexor tendon repair remains limited by tendon adhesions that prevent normal range of motion. Recent studies using in situ hybridization techniques have implicated transforming growth factor beta-1 (TGF-beta1) in both intrinsic and extrinsic mechanisms of repair. TGF-beta1 is a growth factor that plays multiple roles in wound healing and has also been implicated in the pathogenesis of excessive scar formation. The purpose of this study was to examine the effect of neutralizing antibody to TGF-beta1 in a rabbit zone II flexor tendon wound-healing model. Twenty-two adult New Zealand White rabbits underwent complete transection of the middle digit flexor digitorum profundus tendon in zone II. The tendons were immediately repaired and received intraoperative infiltration of one of the following substances: (1) control phosphate-buffered saline; (2) 50 microg neutralizing antibody to TGF-beta1; (3) 50 microg each of neutralizing antibody to TGF-beta1 and to TGF-beta2. Eight rabbits that had not been operated on underwent analysis for determination of normal flexion range of motion at their proximal and distal interphalangeal joints, using a 1.2-N axial load applied to the flexor digitorum profundus tendon. All rabbits that had been operated on were placed in casts for 8 weeks to allow maximal tendon adhesion and were then killed to determine their flexion range of motion. Statistical analysis was performed using the Student's unpaired t test. When a 1.2-N load was used on rabbit forepaws that had not been operated on, normal combined flexion range of motion at the proximal and distal interphalangeal joints was 93+/-6 degrees. Previous immobilization in casts did not reduce the range of motion in these forepaws (93+/-4 degrees). In the experimental groups, complete transection and repair of the flexor digitorum profundus tendon with infiltration of control phosphate-buffered saline solution resulted in significantly decreased range of motion between the proximal and distal phalanges [15+/-6 degrees (n = 8)]. However, in the tendon repairs infiltrated with neutralizing antibody to TGF-beta1, flexion range of motion increased to 32+/-9 degrees (n = 7; p = 0.002). Interestingly, a combination of neutralizing antibody to TGF-beta1 and that to TGF-beta2 did not improve postoperative range of motion [18+/-4 degrees (n = 7; p = 0.234)]. These data demonstrate that (1) the rabbit flexor tendon repair model is useful for quantifying tendon scar formation on the basis of degrees of flexion between proximal and distal phalanges; (2) intraoperative infiltration of neutralizing antibody to TGF-beta1 improves flexor tendon excursion; and (3) simultaneous infiltration of neutralizing antibody to TGF-beta2 nullifies this effect. Because TGF-beta1 is thought to contribute to the pathogenesis of excessive scar formation, the findings presented here suggest that intraoperative biochemical modulation of TGF-beta1 levels limits flexor tendon adhesion formation.

Animals↗
PubMed2005

The chronic painful Achilles and patellar tendon: research on basic biology and treatment.

The etiology and pathogenesis of chronic tendon pain are unknown. Even though tendon biopsies having shown an absence of inflammatory cell infiltration, anti-inflammatory agents (non-steroidal anti-inflammatory drugs, corticosteroidal injections) are commonly used. We have demonstrated that it is possible to use intratendinous microdialysis to investigate human tendons, and found normal prostaglandin E2 (PGE2) levels in chronic painful tendinosis (Achilles and patellar) tendons. Furthermore, gene technological analyses of biopsies showed no upregulation of pro-inflammatory cytokines. These findings show that there is no PGE2-mediated intratendinous inflammation in the chronic stage of these conditions. The neurotransmitter glutamate (a potent modulator of pain in the central nervous system) was, for the first time, found in human tendons. Microdialysis showed significantly higher glutamate levels in chronic painful tendinosis (Achilles and patellar) tendons, compared with pain-free normal control tendons. The importance of this finding is under evaluation. Treatment is considered to be difficult, and not seldom, surgery is needed. However, recent researches on non-surgical methods have shown promising clinical results. Painful eccentric calf-muscle training has been demonstrated to give good clinical short- and mid-term results on patients with chronic painful mid-portion Achilles tendinosis. Good clinical results were associated with decreased tendon thickness and a structurally more normal tendon with no remaining neovessels. Using ultrasonography (US)+color Doppler (CD), and immunhistochemical analyses of biopsies, we have recently demonstrated a vasculo/neural (Substance-P and Calcitonin Gene-Related Peptide nerves) ingrowth in the chronic painful tendinosis tendon, but not in the pain-free normal tendon. A specially designed treatment, using US- and CD-guided injections of the sclerosing agent Polidocanol, targeting the neovessels outside the tendon, has been shown to cure tendon pain in pilot studies, in a majority of the patients. A recent, randomized, double-blind study verified the importance of injecting the sclerosing substance Polidocanol.

Achilles Tendon↗
PubMed2006

Surface treatment of flexor tendon autografts with carbodiimide-derivatized hyaluronic Acid. An in vivo canine model.

BACKGROUND: Clinical and experimental studies have demonstrated that restrictive adhesions and poor digital motion are common complications after extrasynovial tendon grafting in an intrasynovial environment. The purpose of this study was to test the hypothesis that surface modification of an extrasynovial tendon with use of a carbodiimide-derivatized hyaluronic acid-gelatin polymer (cd-HA) improves gliding ability and digital function after tendon grafting in a canine model in vivo. METHODS: The peroneus longus tendons from both hindpaws of twenty-four dogs were harvested and transplanted to replace the flexor digitorum profundus tendons in the second and fifth digits of one forepaw. Prior to grafting, one of the peroneus longus tendons was coated with cd-HA, which consists of 1% hyaluronic acid, 10% gelatin, 0.25% 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), and 0.25% N-hydroxysuccinimide (NHS), while the other was immersed in saline solution only. Eight dogs were killed at one, three, and six weeks. Digital normalized work of flexion, tendon gliding resistance, and hyaluronic acid quantification (with the hyaluronic acid-binding-protein staining technique) were the outcome measures. RESULTS: The normalized work of flexion of the tendons treated with cd-HA was significantly lower than that of the saline-solution-treated controls at each time-point (p < 0.05). The gliding resistance of the cd-HA group was significantly lower than that of the saline-solution group at three and six weeks (p < 0.05). The ratio between the intensity of staining of the cd-HA-treated tendons with that of the saline-solution-treated controls was significantly greater at time-0 than at three or six weeks (p < 0.05), but there was no significant difference between time-0 and one-week values. CONCLUSIONS: Treating the surface of an extrasynovial tendon autograft with a carbodiimide-derivatized hyaluronic acid-gelatin polymer decreases digital work of flexion and tendon gliding resistance in this flexor tendon graft model in vivo. CLINICAL RELEVANCE: cd-HA gelatin may provide surgeons with a new and useful method to improve the quality of tendon graft surgery.

Animals↗
PubMed1991

Repair of Achilles tendon ruptures with a polylactic acid implant: assessment with MR imaging.

An investigational tendon repair device composed of a polymer of lactic acid (PLA) is currently undergoing multicenter clinical trials for use in repairing rupture of the Achilles tendon. The advantages of the PLA device include high tensile strength and the induction of a rapid proliferative tissue response resulting in a shorter rehabilitation period than with conventional surgical repair. We reviewed 16 MR examinations performed in 10 patients 3-35 months after repair to characterize the MR appearance. All 16 T1-weighted sagittal images revealed a thickened fusiform tendon with streaks of moderate signal within the tendon corresponding to the PLA device and its surrounding collagenogenic response. The double-echo T2-weighted axial images at the mid tendon level demonstrated progressive changes in the signal pattern of the central portion of the tendon that reflected the maturation of the healing tendon. All tendons repaired with PLA implants were uniformly hypertrophied relative to the contralateral normal side because of the induced proliferative collagenogenic ingrowth. Two follow-up MR examinations were performed in six patients and showed mean reductions in tendon caliber of 24% and 30% at the mid and inferior levels. MR imaging of the Achilles tendon repaired with PLA implants shows a diffusely thickened tendon with streaks of signal within the tendon that distinguish it from tendons repaired by conventional techniques.

Achilles Tendon↗
PubMedDate not supplied

Biology of tendon injury: healing, modeling and remodeling.

Tendon disorders are frequent, and are responsible for much morbidity both in sport and the workplace. Although the presence of degenerative changes does not always lead to symptoms, pre-existing degeneration has been implicated as a risk factor for acute tendon rupture. The term tendinopathy is a generic descriptor of the clinical conditions in and around tendons arising from overuse. The terms "tendinosis" and "tendinitis/tendonitis" should only be used after histopathological examination. Disordered healing is seen in tendinopathy, and inflammation is not typically seen. In acute injuries, the process of tendon healing is an indivisible process that can be categorized into three overlapping phases for descriptive purposes. Tendon healing can occur intrinsically, via proliferation of epitenon and endotenon tenocytes, or extrinsically, by invasion of cells from the surrounding sheath and synovium. Despite remodeling, the biochemical and mechanical properties of healed tendon tissue never match those of intact tendon. Tendon injuries account for considerable morbidity, and often prove disabling for several months, despite what is considered appropriate management. Chronic problems caused by overuse of tendons probably account for 30% of all running-related injuries, and the prevalence of elbow tendinopathy in tennis players can be as high as 40%. The basic cell biology of tendons is still not fully understood, and the management of tendon injury poses a considerable challenge for clinicians. This article describes the structure of tendons, and reviews the pathophysiology of tendon injury and healing.

Animals↗
PubMed1991

Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients.

We evaluated specimens obtained from the biopsy of spontaneously ruptured tendons in 891 patients who were treated between 1968 and 1989. The specimens, which were removed at the time of repair, included 397 Achilles tendons, 302 biceps brachii tendons, forty extensor pollicis longus tendons, eighty-two quadriceps tendons and patellar ligaments, and seventy other tendons. Age and sex-matched control specimens, from 445 tendons taken at the time of death from the cadavera of previously healthy individuals who died accidentally, also were obtained and evaluated. The histopathological analyses of the specimens included light and polarized light microscopy and scanning and transmission electron microscopy. A healthy structure was not seen in any spontaneously ruptured tendon, but two-thirds of the control tendons were structurally healthy (p less than 0.001). There were characteristic histopathological patterns in the spontaneously ruptured tendons. Most (97 per cent) of the pathological changes were degenerative; they included hypoxic degenerative tendinopathy, mucoid degeneration, tendolipomatosis, and calcifying tendinopathy, either alone or in combination. These changes were also found in 34 per cent of the control tendons, but significantly less frequently (p less than 0.001). In the other twenty-six ruptured tendons (3 per cent), the pathological change was an intratendinous foreign body, rheumatoid tendinitis, a xanthoma, a tumor, or a tumor-like lesion such as an intratendinous ganglion. The findings clearly indicate that, at least in an urban population, degenerative changes are common in the tendons of people who are older than thirty-five years and that these changes are associated with spontaneous rupture.

Achilles Tendon↗
PubMed1985

Suture materials and suture techniques used in tendon repair.

Immediately after a tendon repair, the tendon contributes nothing to the strength of repair. During that time, the suture itself and suture technique are the sole contributors to the strength of repair. Although stainless steel is the strongest material that can be used at the time of repair, it has serious disadvantages. It is difficult to work with and makes a bulky knot. Conversely, all absorbable sutures become too weak too soon to be of value. At this time, nonabsorbable, synthetic fibers that are relatively strong, such as Supramid or prolene, are the most desirable materials available. Regarding suture techniques, the lateral trap and end-weave techniques produce the strongest repairs; however, the end-weave technique can only be used with tendon grafts and the lateral trap, though it can be used for end-to-end primary repairs. It is too bulky for use in the fingers and hand but is ideal for the forearm and wrist. In the hand and fingers, the strongest repair techniques available are the Bunnell, Kessler, and Mason-Allen; however, the Bunnell stitch is more strangulating to the microcirculation of the tendon than the latter two stitches; thus, it contributes to tendomalacia and gap formation. The simplest and least traumatic suture technique, though weakest at first, will allow tendon healing to proceed more rapidly. If such a repair is protected from tension by splinting the wrist and metacarpophalangeal joints in flexion during healing (while allowing controlled passive motion of the finger joints), there will be a rapid increase in tensile strength of the tendon juncture with minimal gap formation, as the repaired hand is progressively stressed up until about 90 days postrepair. At that point, strength plateaus and maximum stress can be applied to the repaired tendon. Somewhere between three and six weeks post-tendon repair, the suture material and technique become secondary to tendon healing as the primary provider of tensile strength to the tendon wound. The less traumatic suture techniques facilitate closure of the tendon sheath, which not only acts as a mechanical barrier to the ingrowth of extrasheath adhesion, which produces fibroblasts, but also re-establishes the continuity of the synovial fluid system, which is a major source of nutrition to the tendon. The healing tendon then can be thought of as a delicate structure, one not to be overmanipulated, traumatized, strangulated, or stretched.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

[Experimental study on the effects of tension-reduced early mobilization on extensor tendon healing].

Numerous clinical and experimental studies have been reported on early postoperative mobilization after flexor tendon repair. However, there have been only a few experimental studies reported on extensor tendon repair. In 1989, Ishiguro reported the usefulness of tension-reduced early mobilization in clinical cases of extensor tendon ruptures. The purpose of this experimental study was to examine the in vivo effect of tension-reduced early mobilization on extensor tendon healing in chicken. An experiment was performed on the extensor tendons of 218 chickens in an attempt to examine the effects of tension-reduced early mobilization on tendon healing and adhesion. The extensor tendon of the fourth toe was cut and the distal stump of the tendon was transferred to the extensor tendon of the third toe. Postoperatively two protocols were employed. In the immobilization group, a cast was applied for three weeks. In the early-mobilization group, immediate active motion of the digits was allowed. A tension-reduced position was maintained by taping the fourth toe to the dorsum of the third. The findings from the early mobilization group and from the immobilization group were as follows: 1. Macroscopically, sutures at the repair site of the early-mobilized tendon were not evident after three weeks because of fibrous connective tissue growth. Despite this abundant connective tissue, tendon gliding was observed to be smooth. Between the suture site and the gliding floor, loose connective tissue, similar to normal paratenon, was observed. Histology confirmed this observation. 2. The tensile strength required to extend the MP joint was significantly lower for the early-mobilization group than for the immobilization group, suggesting minimal adhesion between the sutured tendon and the gliding floor in the early-mobilization group. 3. No significant difference in tensile strength among the various tendon repair techniques employed was observed at the suture site.

Animals↗
PubMed2001

Development of the shields for tendon injury repair using polyvinyl alcohol--hydrogel ( PVA-H).

In recent years, marked advances have been made in repair techniques for tendon injury, but the treatment of finger flexor tendon injury is still one of the most difficult and important problems in the orthopedic field. The main problem in tendon repair is adhesion between the tendon and surrounding tissue. To prevent this adhesion and achieve tendon union, we developed adhesion preventive shields for tendon repair using polyvinyl alcohol hydrogel ( PVA-H) with 90% water content, and carried out an implant experiment using the deep flexor tendon of the third toe of domestic fowl. Injured tendons shielded with PVA-H showed union at about 3 weeks after the operation without adhesion to the surrounding tissue and good function such as gliding and range of motion. Neither breakage of the PVA-H shield itself nor infection, nor degeneration in the surrounding tissue were observed. These results confirmed that the tendon itself has repair ability, and the tendon is regenerated by synovial nutrition through PVA-H. High water content PVA-H may have clinically potential and be applicable to adhesion-preventive shields for tendon repair. However, re-rupture was observed, probably due to accidental tendon injury at an early period after the operation. In some cases, tendon immobilization methods to prevent re-rupture might be necessary.

Animals↗
PubMed1988

Cell populations of tendon: a simplified method for isolation of synovial cells and internal fibroblasts: confirmation of origin and biologic properties.

Tendons transmit the force of muscle contraction to bone to effect limb movement. Special structural and biological properties of tendon have developed to facilitate force transmission. The tendon has a complex organization of cells surrounding the collagen bundles inside tendon as well as at the tendon surface. Internal cells may act to maintain the bulk of the collagen in tendon. External cells in the epitenon may provide lubrication for tendon gliding. To develop better understanding of these processes and the roles the cell populations play, we isolated cells from the surface and interior of tendon and studied them in vitro. Flexor tendons from 8-week-old white Leghorn chickens were separated into two distinct cell populations: the outer synovial cells and the fibroblasts more internal in tendon. These cell populations were discernible by their locations in the intact tendon, determined by sequential enzymatic and physical release from their substrata. Initially, some cells eluted in Hanks' salt solution (HSS) (population 1); then synovial cells were released after a 2-min treatment with 0.5% collagenase (population 2). Next, a population of synovial cells was released in high yield by treatment with 0.25% trypsin (step III, population 3). Step III, population 3 cells were used as synovial cells (SCs). Next, a population of SCs and fibroblasts were released by scraping with a rubber policeman (population 4). Subsequently, fibroblasts were released after incubation with 0.5% collagenase (population 5). A more direct procedure (procedure 2) to isolate the synovial and internal tendon cells involved treatment in 0.5% collagenase followed by sedimentation at 900 g. Cells that sedimented were largely fibroblasts, whereas the cells that remained at the top of the tube were largely SCs. Cells designated as SCs, isolated by procedure 2, most likely contained surface cells from epitenon and internal interfascicular cells from endotenon and paratenon. Surface tendon cells separated by sequential enzymatic and physical release from their substrata (by procedure 1) had all the following characteristics: distinct subpopulations of cells based on morphology; presence of cytoplasmic, lipid-containing vesicles; decreased sensitivity to trypsin; and reduced generation time as compared with that of internal fibroblasts. Conversely, the internal fibroblasts (IFs) appeared to represent a more uniform population based on morphological characteristics.

Animals↗
PubMed1993

Effects of solvent preservation with or without gamma irradiation on the material properties of canine tendon allografts.

We studied the effects of solvent preservation with and without gamma irradiation on the material properties and morphology of canine tendons. Twenty-four paired tendons were harvested from both hind limbs of eight dogs. The tendons from the right legs were divided into three treatment groups of eight tendons each. In the first group, the tendons were subjected to solvent preservation for sterilization and drying (solvent group). In the second group, the tendons were treated in the same manner and then were sterilized by gamma irradiation (solvent/gamma group). The same treatments were applied to the tendons in the third group but in reverse order (gamma/solvent group). Tendons from the contralateral left legs were frozen immediately for use as controls for each corresponding treatment group. Histologically, the tendons treated with solvent, with or without gamma irradiation, had a more prominent wavy pattern in the collagen fibers than the control tendons. Mechanically, the tangent moduli for the solvent, solvent/gamma, and gamma/solvent groups were 58, 53, and 99%, respectively, of each contralateral control. The respective tensile strengths were 85, 39, and 86% of that of the contralateral control. The tendons in the solvent/gamma group underwent the most severe changes in material properties; the tendons in the gamma/solvent group changed the least. This suggests that gamma irradiation followed by solvent drying is the procedure of choice for the preservation of tendon allografts.

Animals↗
PubMed1996

Lesions of the Achilles tendon. A sonographic, biomechanical and histological study.

Thirty-four Achilles tendons were explanted post-mortem. The explanation took place less than 24 h after death. The tendons were examined by means of ultrasonography and after explanation assessed histologically and biomechanically. In the sonograms 19 changes in echogenicity were noted. Changes in form with an increase in the diameter of the tendon of up to 10 mm (compared with the contralateral side) were found in 6 tendons. The changes in echogenicity and form were found most frequently 2-4 cm from the insertion of the tendon at the os calcis. At a speed of 5 mm/min, the average force needed until rupture occurred was calculated as 27.6 N/mm2. The tear was located on average 29.7 mm from the bony insertion of the tendon at the calcaneus. Histologically, necroses could be found most frequently in all regions of the tendon, followed by scars and fissures. When there were differences of more than 25% in tensile strength between the right and left sides, there was a histological change in the weaker tendon at the site of the tear. Sonographic changes in form pointed to histological lesions in this region. Changes in the echogenicity led to the detection of degenerative changes of the tendon, but they have to be analysed carefully, as they are prone to artefacts. There was not statistically relevant correlation either with regard to tensile strength or to the site of the rupture for sonographically proven changes in the area of the rupture. However, when there was a sonographically abnormal finding in the course of a tendon, the tendon tore at an earlier point than those exhibiting no abnormality. Sonography proved to be a useful method in the detection of degenerative lesions of tendons. A direct influence on the biomechanics of the tendon could not be found.

Achilles Tendon↗
PubMed2001

Tendon involvement in rheumatoid arthritis of the wrist: MRI findings.

OBJECTIVE: To evaluate the distribution and extent of wrist tendon alterations in patients with active rheumatoid arthritis (RA) using magnetic resonance imaging (MRI). DESIGN AND PATIENTS: Forty-three clinically active RA patients with an illness duration of less than 4 years and no clinical evidence of tendons tears were enrolled in the study. There were 10 men and 33 women, with an average age of 52 years (range 33-63 years). MRI of both wrists, with one exception, was performed at 1.0 T using T1- and T2-weighted sequences (slice thickness 3 mm). Twelve healthy subjects (8 women, 4 men; mean age 31 years) were also evaluated as a control group. Two radiologists reviewed each of four schematic anatomical regions (volar, dorsal, ulnar, radial) for the degree of tendon and tendon sheath alterations using two progressive scales. RESULTS: In the control group all tendons had homogeneous low signal intensity on all sequences. A small amount of fluid was found in six subjects but the diameter was always less than 1 mm. In the patient group minimal fluid (< 2 mm) was found in 35 (41%) wrists, grade 2 fluid (< 2 > 5 mm) in 26 (31%) and grade 3 fluid (> 5 mm) in 24 (28%). Fifty-nine (69%) of the grade 1 changes were in the volar compartment but grade 2 involvement was evenly distributed. Grade 3 changes were most common in the dorsal compartment and combined grade 2 and 3 in the dorsal and ulnar compartments were 32 (38%) and 25 (30%) compared with 16 (18%) and 17 (20%) respectively in the volar and radial compartments. The tendons were normal (grade 0) in 47 (46%) wrists. A maximum tendon signal change (grade 1) was demonstrated in 28 wrists (32%). When associated with other individual tendons grades this grade was demonstrated in the dorsal compartment in 30 (35%) wrists, in the volar compartment in 12 (14%), in the radial compartment in 17 (20%) and in the ulnar compartment in 26 (30%). A partial tear (grade 2) was detected in 7 (8%) wrists, all involving the dorsal and ulnar compartments; five underwent surgical repair and one proved to have a complete rupture of extensor digitorum. Three (3%) had a grade 3 complete tendon tear: all of these were in extensor tendons. Surgical repair was successful in one case but two ruptured again within 3 months. CONCLUSIONS: Low grades of peritendinous effusion were more common in the volar compartment whereas moderate and high degrees of tendon sheath fluid collection and/or pannus and signs of tendonitis were more frequent in the dorsal and ulnar tendon sheaths.

Arthritis, Rheumatoid↗
PubMed2005

Macrophages accumulate in the early phase of tendon-bone healing.

A scar tissue interface forms rather than a normal ligament insertion site following attachment of a tendon graft to bone. The specific cell types that initiate the process of tendon-to-bone healing are unknown. We hypothesized that inflammatory cell accumulation following tendon-to-bone repair results in this scar interface. We used a rodent model to examine the temporal and spatial pattern of accumulation of hematopoietic lineage cells in the early phase of tendon-to-bone healing. Thirty-six Lewis rats underwent anterior cruciate ligament (ACL) reconstruction in the left knee using a flexor digitorum longus tendon graft. Six animals were sacrificed at 4, 7, 11, 14, 21, and 28 days after surgery. Serial sections were analyzed for proliferating cells (PCNA), recruited macrophages (ED1), resident macrophages (ED2), neutrophils, T-lymphocytes (CD3), mast cells, immature progenitor cells/pericytes (expressing the NG2 cell-surface chondroitin sulfate proteoglycan), and newly-formed blood vessels (Factor VIII). Neutrophils, ED1(+) and ED2(+) macrophages accumulated sequentially in the healing tendon graft, with progressive cell ingrowth from the interface towards the inner tendon. Neutrophils and ED1(+) cells were seen in the tendon-bone interface at 4 days after surgery, while ED2(+) macrophages were not identified until 11 days. These cells progressively repopulated the tendon graft. NG2-positive progenitor cells were found along the edge of the bone tunnel in the interface, but these cells did not invade the tendon. Occasional T-lymphocytes and mast cells were seen in the tendon-bone interface. There was no proliferation of intrinsic tendon cells, indicating that the tendon does not directly contribute to healing. We hypothesize that cytokines produced by infiltrating macrophages are likely to contribute to the formation of a fibrous scar tissue interface rather than a normal insertion site.

Animals↗
PubMed2003

Effects of stress deprivation on mechanical properties of the in situ frozen-thawed semitendinosus tendon in rabbits.

OBJECTIVE: To clarify the effect of complete stress deprivation on the mechanical properties of the in situ frozen-thawed semitendinosus tendon, an idealized autograft model. DESIGN: Ninety-six rabbits were divided into three groups. In the frozen group (n=36), we applied the freeze-thaw treatment to the semitendinosus tendon to necrotize fibroblasts in the tendon. In the frozen and stress-shielded group (n=30), after we applied the same freeze-thaw treatment to the tendon, we completely released the tendon from stress. In the sham group (n=30), a sham operation was applied. In each group, 6 rabbits were sacrificed at 0 (only in the frozen group), 1, 2, 3, 6 and 12 weeks after surgery. BACKGROUND: Previous studies have not clarified remodeling of the semitendinosus autograft in ligament reconstruction or its idealized model. METHODS: The tendon was frozen with liquid nitrogen. The tendon was released from stress with the originally developed technique using a polyester tape. In each period, 5 out of the 6 rabbits were evaluated with tensile testing, and the remaining rabbit was histologically observed. RESULTS: Complete stress shielding significantly increased the cross-sectional area of the frozen-thawed tendon at 1 and 2 weeks, while it significantly inhibited the increase of the area due to the freeze-thaw treatment at 3 and 6 weeks. Complete stress shielding significantly reduced material properties of the frozen-thawed tendon after 2 weeks. CONCLUSIONS: The frozen-thawed semitendinosus tendon has unique remodeling characteristics under a stress-shielded condition, which were not the same as those of the frozen-thawed patellar tendon. RELEVANCE: Remodeling of the semitendinosus tendon autograft under stress-shielded conditions may be different from that of the patellar tendon autograft.

Animals↗
PubMed1998

The effects of proximal load on the excursion of autogenous flexor tendon grafts.

To determine the relationship between the intrinsic properties of tendon and tendon excursion in 2 types of autogenous tendon grafts, hindpaw intrasynovial and extrasynovial tendons were transferred to the lateral and medial forepaws of adult mongrel dogs (16 experimental and 16 control tendons). After each digit was marked with radiopaque markers, it was placed in a specialized jig, and weights of 25 g, 100 g, or 200 g were applied to the flexor tendons. Specialized radiographs were obtained with the digit in flexion and extension. Tendon excursion and joint rotation were calculated. There were no statistically significant differences between experimental groups for tendon excursion or for joint angular rotation (p > .05). For intrasynovial tendon grafts, the angular rotation per millimeter tendon excursion was 10.9 degrees +/- 2.4 degrees/mm, 9.4 degrees +/- 1.2 degrees/mm, and 9.0 degrees +/- 1.4 degrees/mm with 25-g, 100-g, and 200-g loads, respectively. Comparisons between experimental groups revealed that a statistically significant difference could not be determined (p > .05). With varying proximal loads, both intrasynovial and extrasynovial grafts showed similar amounts of tendon excursion. Variations in proximal load did not significantly influence the amount of excursion within the range of loads tested. Based on these data, it appears that the difference in repair potential for these 2 types of tendon grafts is not related to a differential in the amount of tendon graft excursion following transfer to the synovial space.

Animals↗
PubMed2002

Matrix metalloproteinase activities and their relationship with collagen remodelling in tendon pathology.

Our aim was to correlate the activity of matrix metalloproteinases (MMPs) with denaturation and the turnover of collagen in normal and pathological human tendons. MMPs were extracted from ruptured supraspinatus tendons (n=10), macroscopically normal ("control") supraspinatus tendons (n=29) and normal short head of biceps brachii tendons (n=24). Enzyme activity was measured using fluorogenic substrates selective for MMP-1, MMP-3 and enzymes with gelatinolytic activity (MMP-2, MMP-9 and MMP-13). Collagen denaturation was determined by alpha-chymotrypsin digestion. Protein turnover was determined by measuring the percentage of D-aspartic acid (% D-Asp). Zymography was conducted to identity specific gelatinases. MMP-1 activity was higher in ruptured supraspinatus compared to control supraspinatus and normal biceps brachii tendons (70.9, 26.4 and 11.5 fmol/mg tendon, respectively; P<0.001). Gelatinolytic and MMP-3 activities were lower in normal biceps brachii and ruptured supraspinatus compared to control supraspinatus (gelatinase: 0.18, 0.23 and 0.82 RFU/s/mg tendon respectively; P<0.001; MMP-3: 9.0, 8.6 and 55 fmol/mg tendon, respectively; P<0.001). Most gelatinase activity was shown to be MMP-2 by zymography. Denatured collagen was increased in ruptured supraspinatus compared to control supraspinatus (20.4% and 9.9%, respectively; P<0.001). The % D-Asp content increased linearly with age in normal biceps brachii but not in control supraspinatus and was significantly lower in ruptured supraspinatus compared to age-matched control tendons (0.33 and 1.09% D-Asp, respectively; P<0.01). We conclude that the short head of biceps brachii tendons show little protein turnover, whereas control supraspinatus tendons show relatively high turnover mediated by the activity of MMP-2, MMP-3 and MMP-1. This activity is thought to represent a repair or maintenance function that may be associated with an underlying degenerative process caused by a history of repeated injury and/or mechanical strain. After tendon rupture, there was increased activity of MMP-1, reduced activity of MMP-2 and MMP-3, increased turnover and further deterioration in the quality of the collagen network. Tendon degeneration is shown to be an active, cell-mediated process that may result from a failure to regulate specific MMP activities in response to repeated injury or mechanical strain.

Adolescent↗
PubMed1998

Characterization of collagens and proteoglycans at the insertion of the human Achilles tendon.

This study provides a unique correlation between a molecular biological and biochemical analysis of the extracellular matrix (ECM) macromolecules in one half of 28 human Achilles tendons with an immunohistochemical study of the other. Both the insertion site and the mid-tendon were studied. The insertion (enthesis) is characterized by three distinctive fibrocartilages, two in the tendon (enthesial and sesamoid) and one on the heel bone (periosteal). Thus, its structure contrasts markedly with the fibrous character of the mid-tendon. RT-PCR analyses were performed on RNA extracted from mid-tendon and from the tendon fibrocartilages to investigate transcription of collagens and proteoglycans. Western blotting was also used to identify and characterize these macromolecules, and immunohistochemistry to localize their distribution. The results demonstrate striking differences in the ECM between the mid-tendon and its insertion. Types I, III, V and VI collagens, decorin, biglycan, fibromodulin and lumican were found in both the mid-tendon and the fibrocartilages, although their precise distribution often differed with site. mRNA for type II collagen was constantly present in the fibrocartilages, but it was only found in the mid-tendon of one specimen. The patterns of distribution for versican and aggrecan mRNA were complimentary - versican mRNA was present in the mid-tendon and absent from the fibrocartilages, while aggrecan mRNA was present in the fibrocartilages and absent from the mid-tendon. The range and distribution of ECM molecules detected in the Achilles tendon reflect the differing forces acting on it - the mid-tendon largely transmits tension and is characterized by molecules typical of fibrous tissues, but the fibrocartilages must also resist compression and thus contain, in addition, molecules typical of cartilage.

Achilles Tendon↗