Tendon‐derived progenitor cells improve healing of collagenase‐induced flexor tendinitis

Tendinitis is a common and a performance‐limiting injury in athletes. This study describes the value of intralesional tendon‐derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase‐induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10⁷ autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI‐labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a “control.” Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI‐labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform‐second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase‐induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162–2171, 2016.     

Effects of platelet‐rich plasma on the quality of repair of mechanically induced core lesions in equine superficial digital flexor tendons: A placebo‐controlled experimental study

Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet‐rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness. A placebo‐controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital Flexor Tendons (SDFT) of both front limbs, one of which was treated with PRP and the other with saline. After 24 weeks, the tendons were harvested for biochemical, biomechanical, and histological evaluations. Collagen, glycosaminoglycan, and DNA content (cellularity) was higher in PRP‐treated tendons (p = 0.039, 0.038, and 0.034, respectively). The repair tissue in the PRP group showed a higher strength at failure (p = 0.021) and Elastic Modulus (p = 0.019). Histologically, PRP‐treated tendons featured better organization of the collagen network (p = 0.031) and signs of increased metabolic activity (p = 0.031). It was concluded that PRP increases metabolic activity and seems to advance maturation of repair tissue over nontreated experimentally induced tendon lesions, which suggests that PRP might be beneficial in the treatment of clinical tendon injuries. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:211–217, 2010     

Effects of corticosteroids and hyaluronic acid on torn rotator cuff tendons in vitro and in rats

Corticosteroids (CS) or hyaluronic acid (HA) is used in subacromial injection for the conservative treatment of rotator cuff tears (RCT); this study addresses the question of how CS and HA affect the tendon tissue and fibroblasts in vitro and in rats. Cell proliferation assays were performed in human tendon fibroblasts from RCT. Rats underwent surgery to create RCT, and the surgical sites were injected with CS or HA. The rotator cuff tendons were subjected to biomechanical testing, microscopic and immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), and ultrastructural analysis. Cell proliferation was significantly decreased with CS in vitro (p < 0.05). Maximal load of CS‐treated tendons was significantly decreased compared with that of HA‐treated tendons (p < 0.05), as well as PCNA⁺ cells at 2 weeks (p < 0.05). Ultrastructural observations of the CS‐treated rats detected apoptosis of tendon fibroblasts 24 h after surgery. Histological and biomechanical data 4 weeks after surgery were not significant among the three groups. Unlike HA, CS caused cell death, and inhibition of the proliferation of tendon fibroblasts, leading to a delay of tendon healing involved and a subsequent decrease of biomechanical strength at the surgical site. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1523–1530, 2015.     

Sodium cromolyn reduces expression of CTGF,ADAMTS1, and TIMP3 and modulates post‐injury patellar tendon morphology

The purpose of this study was to determine whether administration of a mast cell inhibitor (sodium cromolyn, SC) would influence tendon repair and extracellular matrix gene expression following acute injury. CD1 mouse patellar tendons were unilaterally injured and mast cell prevalence was determined. The effect of SC injection on tendon hypercellularity, cross‐sectional area, collagen organization, and expression of extracellular matrix‐related genes was examined. Mast cell prevalence was markedly increased in injured patellar tendons (p = 0.009), especially at 8 weeks post‐injury (p = 0.025). SC injection increased collagen organization compared to uninjected animals at 4 weeks and attenuated the development of tendon hypercellularity and tendon thickening post‐injury. Expression of CTGF, ADAMTS1, and TIMP3 in injured tendon was reduced in the SC group. SC injections moderated the structural alterations of healing tendon in association with downregulation of several genes associated with tendon fibrosis. This work corroborates previous findings pointing to a role of mast cells in tendon repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:678–683, 2011     

Biomechanical and immunohistochemical analysis of high hydrostatic pressure-treated Achilles tendons

Background Reconstruction of bone defects caused by malignant tumors is carried out in different ways. At present, tumor-bearing bone segments are devitalized mainly by extracorporeal irradiation or autoclaving, but both methods have substantial disadvantages. In this regard, high hydrostatic pressure (HHP) treatment of the bone is a new, advancing technology that has been used in preclinical testing to inactivate normal cells and tumor cells without altering the biomechanical properties of the bone. The aim of this study was to examine the biomechanical and immunohistochemical properties of tendons after exposure to HHP and to evaluate whether preservation of the bony attachment of tendons and ligaments is possible. Methods For this, 19 paired Achilles tendons were harvested from both hindlimbs of 4-month-old pigs. After preparation, the cross-sectional area of each tendon was determined by magnetic resonance imaging (MRI). For each animal, one of the two tendons was taken at random and exposed to a pressure of 300 MPa (n = 9) or 600 MPa (n = 10). Results The contralateral tendon served as an untreated control. The biomechanical properties of the tendons remained unchanged with respect to the tested parameters: Young's modulus (MPa) and tensile strength (MPa). This finding is in line with immunohistochemical labeling results, as no difference in the labeling pattern of collagen I and versican was observed when comparing the HHP group (at 600 MPa) to the untreated control group. Conclusions We anticipate that during orthopedic surgery HHP can serve as a novel, promising methodical approach to inactivate Achilles tendon and bone cells without altering the biomechanical properties of the tendons. This should allow one to preserve the attachment of tendon and ligaments to the devitalized bone and to facilitate functional reconstruction.     

Injury response of geriatric mouse patellar tendons

Injury adversely impacts the structure and mechanical properties of a tendon, thus causing pain and disability. Previously, we demonstrated that patellar tendons in mature (P150) and aged (P300) mice do not recover original functionality, even 6 weeks after injury, and that uninjured geriatric tendons (P570) are functionally inferior to uninjured mature tendons. In this study, we hypothesized that the repair response in injured geriatric mice would be further compromised, thus undermining patellar tendon function post‐injury. Patellar tendons from wild‐type mice were injured at 540 days. At 3 and 6 weeks post‐surgery, structural, mechanical, and biochemical analyses were performed and compared to uninjured controls. Mechanical properties of geriatric tendons failed to improve after injury. When compared to mature and aged tendons post‐injury, it was determined that at no age was there a suitable repair response. In previous studies, we were able to associate the absence of SLRPs with phenotypic changes both early and late in repair. Here we found that SLRPs were significantly decreased after injury, thus offering a possible explanation for why geriatric tendons were unable to mount an adequate repair response. Thus, we conclude that regardless of age after maturity, tendon healing ultimately results in a substandard outcome. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1256–1263, 2016.     

Cumulative effects of hypercholesterolemia on tendon biomechanics in a mouse model

High cholesterol represents a significant healthcare problem. Clinical studies have linked hypercholesterolemia to Achilles tendon xanthomas and rotator cuff tears, and research in other systems indicates detrimental effects of high cholesterol; however, understanding of its impact on tendon properties and healing is limited. We hypothesized that tendons from aging hypercholesterolemic (APOE) mice would exhibit inferior baseline and healing mechanical properties compared to controls, while younger, but mature mice would be no different. Surprisingly, tensile testing of patellar tendons from 14‐week‐old APOE mice receiving a unilateral full‐thickness central defect resulted in normalized (injured:sham) cross‐sectional areas closer to baseline (p = 0.02) compared to controls. Uninjured data from 10‐month‐old APOE mice showed a decrease in elastic modulus (p = 0.02), indicating a detrimental effect of hypercholesterolemia on tendon properties in this model. These results could benefit patients through knowledge that high cholesterol could increase the likelihood of tendon tears. Furthermore, knowledge that tendon tears are indicative of high cholesterol could provide orthopedic clinicians with an additional preventive treatment opportunity for patients with undiagnosed hypercholesterolemia. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:380–383, 2011     

Tissue reactions of adenoviral, adeno-associated viral, and liposome-plasmid vectors in tendons and comparison with early-stage healing responses of injured flexor tendons

PURPOSE: Delivery of growth factor genes that may substantially increase the healing rate of injured digital flexor tendons is a new application of gene therapy. Adenoviral, adeno-associated viral (AAV), and liposome-plasmid vectors have been used to deliver genes to tendons, but the tendon reactions to these vectors--particularly in contrast to the healing responses in the injured tendons--were unknown. This study was designed to compare the tissue reactions of the earlier-mentioned vectors in tendons with the healing responses of injured flexor tendons. METHODS: Forty-two flexor digitorum profundus tendons of 6 New Zealand white rabbits were used. Eighteen tendons were divided into 3 groups of 6 each and injected with different vectors: adenoviral vector, AAV2-luciferase vector, or pCMV-beta vector with liposome. Another 12 tendons were cut and repaired. At 3, 7, and 14 days, the tendons were harvested and stained with hematoxylin and eosin. Normal flexor tendons were harvested as controls. RESULTS: The tissue reactions of the liposome-plasmid vector in tendons were the most prominent among the 3 vectors tested. The adenoviral vector elicited a moderate degree of tissue reaction. The AAV2 vector caused remarkable reactions in epitenon but almost no reactions in endotenon. Early-stage tissue reactions were more robust in the injured tendons. Compared with early-stage inflammatory and healing responses, the reactions elicited by these vectors were less severe. CONCLUSIONS: The 3 gene delivery systems tested elicit less severe tissue reactions in flexor tendons compared with early-stage inflammatory changes in injured tendons. Adenoviral and AAV vectors elicit less severe tissue reactions than liposome-plasmid vectors. The AAV2 vector appears to cause almost no reaction in endotenon. In terms of tissue reactions, the adenoviral and AAV2 vectors, in particular AAV2, are suitable gene delivery systems for future gene transfer to the tendon in vivo.     

Scleraxis expression is coordinately regulated in a murine model of patellar tendon injury

This study investigated the expression of Scleraxis in a murine model of patellar tendon injury in which the central third of the patellar tendon was unilaterally injured. The presence of tendon pathology was assessed using dual photon microscopy, conventional histology and microCT. Tendon pathology was also quantified noninvasively over a 12‐week period using high‐frequency ultrasound and laser Doppler flowmetry. Gene expression (Scx, Tnmd, and Col1a1) was determined at defined end‐points (1, 4, 8, and 12 weeks) using qPCR on RNA from individual patellar tendons on injured and uninjured sides. There was significant development of tendon pathology as gauged by ultrasound and laser Doppler over 12 weeks. Injured tendons demonstrated significant histological and microCT evidence of pathological change, and disorganized collagen with reduced density. The expression of Scx and Col1a1 was unchanged at 1 week, significantly upregulated at 4 and 8 weeks, and had returned to baseline by 12 weeks. Tnmd expression was unchanged at 1 week, and significantly increased at 4, 8, and 12 weeks. Patellar tendon injury was associated with marked increases in the expression of Scx, Tnmd, and Col1a1. Our data suggest new roles for Scleraxis in coordinating the response to injury in the pathogenesis of tendon disorders. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:289–296, 2011     

Auto‐crosslinked hyaluronic acid gel accelerates healing of rabbit flexor tendons in vivo

This study's purpose was to assess the in vivo effect of auto‐crosslinked hyaluronic acid (HA) gel, a natural HA derivative with increased viscosity and tissue residence time, on adhesions and healing of injured and surgically repaired rabbit digital flexor tendons. The second and third right deep digital flexor tendons from 48 rabbits (n = 96 tendons) were cut and repaired with a modified Kessler and running peripheral suture. Animals were randomized to two groups, receiving either HA gel or saline injected around both freshly repaired tendons. After 2, 3, 6, and 12 weeks, six rabbits in each group were euthanized. Tendon pull‐out force and breaking strength were measured as a value for adhesion formation and tendon healing, respectively. A histological assessment of adhesions and healing was related to the mechanical results. A significantly faster increase in breaking strength was found in HA gel‐treated compared to saline‐treated tendons; this coincided with a significantly accelerated tissue repair response after injury. No significant difference in adhesion formation was found between the two groups at any time. Our results indicate a significant acceleration of in vivo healing of tendons treated with HA gel. Adhesion formation was unaffected. These results could have important clinical value in promoting rehabilitation after tendon injury. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:408–415, 2009     

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.     

Experimental treatment of tendon injury with heparin

The effect of heparin on the progress of healing in the injured tendon was examined after a standard injury had been created in the Achilles tendons of New Zealand White rabbits. Half of the rabbits were then treated by the intratendinous injection of heparin. The diameters of the injured right hind and the uninjured left hind Achilles tendon and overlying skin were measured using vernier calipers before injury and at one month after injury. At this time histological analysis was carried out on all Achilles tendons and tendon dry weight, collagen concentration and DNA concentration were measured. Orientation of collagen fibres was more pronounced in treated than untreated tendons while cellularity and blood vessel density were less pronounced. Analysis by Students t-test demonstrated a statistically significant difference between treated and untreated tendons in terms of leg diameter (p less than 0.005), dry weight (p less than 0.01) and DNA concentration (p less than 0.01).     

Changes in the expression of matrix extracellular genes and TGFB family members in rotator cuff tears

Lack of synthesis of extracellular matrix compounds may contribute to degeneration of the tendons. Thus, we aimed to evaluate the expression of extracellular matrix and TGFB family members in ruptured and non‐ruptured tendons of the rotator cuff, as well as the effect of clinical factors on gene expression in tendon samples, and the relationship between histological findings and altered gene expression. Injured and non‐injured supraspinatus tendon samples and subscapular non‐injured tendon samples were collected from 38 patients with rotator cuff tears. Non‐injured supraspinatus tendons were obtained from eight controls. Specimens were used for histological evaluation, quantification of collagen fibers, and mRNA and protein expression analyses. Increased COL1A1, COL1A2, COL3A1, COL5A1, FN1, TNC, and TGFBR1 mRNA expression was observed in the tear samples (p < 0.05). Duration of symptoms was correlated with the levels of collagen type I/III fibers (p = 0.032; ρ = 0.0447) and FN1 immunostaining (p = 0.031; ρ = 0.417). Smoking was associated with increased frequency of microcysts, myxoid degeneration, and COL5A1, FN1, TNC, and TGFB1 mRNA expression (p < 0.05). FN1 immunostaining was correlated with the number of years of smoking (p = 0.048; ρ = 0.384). Lower levels of collagen type I/III fibers were detected in samples with fissures (0 = 0.046). High frequency of microcysts was associated with increased COL5A1, FN1, and TNC expression (p < 0.05, for all comparisons). Neovascularization was associated with reduced FN1 (p = 0.035) and TGFBR1 expression (p = 0.034). Our findings show differential expression of matrix extracellular genes and TGFB family members in the degeneration process involved in rotator cuff tears. These molecular alterations are influenced by clinical factors. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2542–2553, 2018.

     

Effect of in vitro stress‐deprivation and cyclic loading on the length of tendon cell cilia in situ

To determine the effect of loading conditions on the length of primary cilia in tendon cells in situ, freshly harvested rat tail tendons were stress‐deprived (SD) for up to 72 h, cyclically loaded at 3% strain at 0.17 Hz for 24 h, or SD for 24 h followed by cyclic loading (CL) for 24 h. Tendon sections were stained for tubulin, and cilia measured microscopically. In fresh control tendons, cilia length ranged from 0.6 to 2.0 µm with a mean length of 1.1 µm. Following SD, cilia demonstrated an increase (p < 0.001) in overall length at 24 h when compared to controls. Cilia length did not increase with time of SD (p = 0.329). Cilia in cyclically loaded tendons were shorter (p < 0.001) compared to all SD time periods, but were not different from 0 time controls (p = 0.472). CL for 24 h decreased cilia length in 24 h SD tendons (p < 0.001) to levels similar to those of fresh controls (p = 0.274). The results of this study demonstrate that SD resulted in an immediate and significant increase in the length of primary cilia of tendon cells, which can be reversed by cyclic tensile loading. This suggests that, as in other tissues, cilia length in tendon cells is affected by mechanical signaling from the extracellular matrix. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:582–587, 2011     

The effects of intratendinous and retrocalcaneal intrabursal injections of corticosteroid on the biomechanical properties of rabbit Achilles tendons

BACKGROUND: The use of corticosteroid injections in the treatment of retrocalcaneal bursitis is controversial. We assessed the effects of corticosteroid injections, both within the tendon substance and into the retrocalcaneal bursa, on the biomechanical properties of rabbit Achilles tendons. The systemic effects of bilateral corticosteroid injections were also studied. METHODS: The rabbits were divided into three treatment groups. The rabbits in Group I received injections of corticosteroid into the Achilles tendon on the left side and injections of normal saline solution into the Achilles tendon on the right, those in Group II received injections of corticosteroid into the retrocalcaneal bursa on the left side and injections of saline solution into the Achilles tendon on the right, and those in Group III received injections of corticosteroid into the Achilles tendon on the left side and injections of corticosteroid into the retrocalcaneal bursa on the right. These injections were given weekly for three weeks. At four weeks after the final injection, the tendons were harvested and were tested biomechanically to determine failure load, midsubstance strain and total strain, modulus of elasticity, failure stress, and total energy absorbed. The site of failure was also documented. The groups were compared according to the location of the injections, the type of injection (steroid or saline solution), and the total systemic load of steroid. RESULTS: Specimens from limbs that had received intratendinous injections of corticosteroid showed significantly decreased failure stress compared with those from limbs that had received intratendinous injections of saline solution (p = 0.008). Specimens from limbs that had received intrabursal injections of corticosteroid demonstrated significantly decreased failure stress (p = 0.05), significantly decreased total energy absorbed (p = 0.017), and significantly increased total strain (p = 0.049) compared with specimens from limbs that had received intratendinous injections of saline solution. Specimens from limbs that had received intratendinous injections of corticosteroid were biomechanically equivalent to specimens from limbs that had received intrabursal injections of corticosteroid. Specimens from rabbits that had received bilateral injections of corticosteroid demonstrated significantly decreased failure load (p = 0.011), modulus of elasticity (p = 0.015), failure stress (p = 0.03), and total energy absorbed (p = 0.015) compared with those from rabbits that had received unilateral injections of steroid. CONCLUSIONS: Local injections of corticosteroid, both within the tendon substance and into the retrocalcaneal bursa, adversely affected the biomechanical properties of rabbit Achilles tendons. Additionally, tendons from rabbits that had received bilateral injections of corticosteroid demonstrated an additive adverse effect, with significantly worse biomechanical properties compared with tendons from rabbits that had received unilateral injections of corticosteroid.     

A new clamping technique for biomechanical testing of tendons in small animals. aprobst@uni-muenster.de.

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n = 15). When tested by the new clamping technique, 17 tendons ruptured intratendinously at a mean tensile force of 8.4 +/- 1.1 N. Three Achilles tendons (17%) tore at the site of paper fixation and had to be excluded from investigation. Data from 73% of the measurements fixed by gluing had to be excluded because slippage of the proximal tendon fibers and contamination of the tendon with glue occurred. All the conventionally clamped tendons ruptured at the site of fixation at a mean tensile force of 6.1 +/- 2.3 N (p < .05). This was 30% lower than with the new clamping technique. Thus, the newly developed clamping technique enables investigators to obtain more valid biomechanical studies of the murine Achilles tendon.     

Multidimensional ultrasound imaging of the wrist: Changes of shape and displacement of the median nerve and tendons in carpal tunnel syndrome

Dynamics of structures within the carpal tunnel may alter in carpal tunnel syndrome (CTS) due to fibrotic changes and increased carpal tunnel pressure. Ultrasound can visualize these potential changes, making ultrasound potentially an accurate diagnostic tool. To study this, we imaged the carpal tunnel of 113 patients and 42 controls. CTS severity was classified according to validated clinical and nerve conduction study (NCS) classifications. Transversal and longitudinal displacement and shape (changes) were calculated for the median nerve, tendons and surrounding tissue. To predict diagnostic value binary logistic regression modeling was applied. Reduced longitudinal nerve displacement (p≤ 0.019), increased nerve cross‐sectional area (p≤ 0.006) and perimeter (p≤ 0.007), and a trend of relatively changed tendon displacements were seen in patients. Changes were more convincing when CTS was classified as more severe. Binary logistic modeling to diagnose CTS using ultrasound showed a sensitivity of 70–71% and specificity of 80–84%. In conclusion, CTS patients have altered dynamics of structures within the carpal tunnel. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1332–1340, 2015.     

Smad8/BMP2‐engineered mesenchymal stem cells induce accelerated recovery of the biomechanical properties of the achilles tendon

Tendon tissue regeneration is an important goal for orthopedic medicine. We hypothesized that implantation of Smad8/BMP2‐engineered MSCs in a full‐thickness defect of the Achilles tendon (AT) would induce regeneration of tissue with improved biomechanical properties. A 2 mm defect was created in the distal region of murine ATs. The injured tendons were then sutured together or given implants of genetically engineered MSCs (GE group), non‐engineered MSCs (CH3 group), or fibrin gel containing no cells (FG group). Three weeks later the mice were killed, and their healing tendons were excised and processed for histological or biomechanical analysis. A biomechanical analysis showed that tendons that received implants of genetically engineered MSCs had the highest effective stiffness (>70% greater than natural healing, p < 0.001) and elastic modulus. There were no significant differences in either ultimate load or maximum stress among the treatment groups. Histological analysis revealed a tendon‐like structure with elongated cells mainly in the GE group. ATs that had been implanted with Smad8/BMP2‐engineered stem cells displayed a better material distribution and functional recovery than control groups. While additional study is required to determine long‐term effects of GE MSCs on tendon healing, we conclude that genetically engineered MSCs may be a promising therapeutic tool for accelerating short‐term functional recovery in the treatment of tendon injuries. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1932–1939, 2012     

A New Clamping Technique for Biomechanical Testing of Tendons in Small Animals

When biomechanical properties of tendons are studied, the technique of clamping the tendons in the testing machine presents a methodological challenge, especially when murine tendons are examined. These short tendons tend to rupture at the transition line to the fixation, leading to false interpretations. Therefore a new clamping technique for investigation of healthy murine Achilles tendons (n = 50) was developed, in which the intramuscular tendon fibers were fixed between two paper strips and the calcaneus was wedged into a conical slot in a wooden block and then mounted in the testing machine (n = 20). This technique was compared with the conventional clamping technique that fixes both ends of the tendon by clamps (n = 15) and an earlier described method that used glue or plastic cement for the fixation of the intramuscular tendon fibers and calcaneus in the testing machine (n