A2A adenosine receptors are involved in the reparative response of tendon cells to pulsed electromagnetic fields.

Tendinopathy is a degenerative disease in which inflammatory mediators have been found to be sometimes present. The interaction between inflammation and matrix remodeling in human tendon cells (TCs) is supported by the secretion of cytokines such as IL-1ß, IL-6 and IL-33. In this context, it has been demonstrated that pulsed electromagnetic fields (PEMFs) were able to reduce inflammation and promote tendon marker synthesis. The aim of this study was to evaluate the anabolic and anti-inflammatory PEMF-mediated response on TCs in an in vitro model of inflammation. Moreover, since PEMFs enhance the anti-inflammatory efficacy of adenosine through the adenosine receptors (ARs), the study also focused on the role of A2AARs. Human TCs were exposed to PEMFs for 48 hours. After stimulation, A2AAR saturation binding experiments were performed. Along with 48 hours PEMF stimulation, TCs were treated with IL-1ß and A2AAR agonist CGS-21680. IL-1Ra, IL-6, IL-8, IL-10, IL-33, VEGF, TGF-ß1, PGE2 release and SCX, COL1A1, COL3A1, ADORA2A expression were quantified. PEMFs exerted A2AAR modulation on TCs and promoted COL3A1 upregulation and IL-33 secretion. In presence of IL-1ß, TCs showed an upregulation of ADORA2A, SCX and COL3A1 expression and an increase of IL-6, IL-8, PGE2 and VEGF secretion. After PEMF and IL-1ß exposure, IL-33 was upregulated, whereas IL-6, PGE2 and ADORA2A were downregulated. These findings demonstrated that A2AARs have a role in the promotion of the TC anabolic/reparative response to PEMFs and to IL-1ß.

Magnetic Stimulation Drives Macrophage Polarization in Cell to-Cell Communication with IL-1ß Primed Tendon Cells.

Inflammation is part of the natural healing response, but it has been simultaneously associated with tendon disorders, as persistent inflammatory events contribute to physiological changes that compromise tendon functions. The cellular interactions within a niche are extremely important for healing. While human tendon cells (hTDCs) are responsible for the maintenance of tendon matrix and turnover, macrophages regulate healing switching their functional phenotype to environmental stimuli. Thus, insights on the hTDCs and macrophages interactions can provide fundamental contributions on tendon repair mechanisms and on the inflammatory inputs in tendon disorders. We explored the crosstalk between macrophages and hTDCs using co-culture approaches in which hTDCs were previously stimulated with IL-1ß. The potential modulatory effect of the pulsed electromagnetic field (PEMF) in macrophage-hTDCs communication was also investigated using the magnetic parameters identified in a previous work. The PEMF influences a macrophage pro-regenerative phenotype and favors the synthesis of anti-inflammatory mediators. These outcomes observed in cell contact co-cultures may be mediated by FAK signaling. The impact of the PEMF overcomes the effect of IL-1ß-treated-hTDCs, supporting PEMF immunomodulatory actions on macrophages. This work highlights the relevance of intercellular communication in tendon healing and the beneficial role of the PEMF in guiding inflammatory responses toward regenerative strategies.

The use of allograft tendons in primary ACL reconstruction.

PURPOSE: Graft choice in primary anterior cruciate ligament (ACL) reconstruction remains controversial. The use of allograft has risen exponentially in recent years with the attraction of absent donor site morbidity, reduced surgical time and reliable graft size. However, the published evidence examining their clinical effectiveness over autograft tendons has been unclear. The aim of this paper is to provide a current review of the clinical evidence available to help guide surgeons through the decision-making process for the use of allografts in primary ACL reconstruction. METHODS: The literature in relation to allograft healing, storage, sterilisation, differences in surgical technique and rehabilitation have been reviewed in addition to recent comparative studies and all clinical systematic reviews and meta-analyses. RESULTS: Early reviews have indicated a higher risk of failure with allografts due to association with irradiation for sterilisation and where rehabilitation programs and post-operative loading may ignore the slower incorporation of allografts. More recent analysis indicates a similar low failure rate for allograft and autograft methods of reconstruction when using non-irradiated allografts that have not undergone chemically processing and where rehabilitation has been slower. However, inferior outcomes with allografts have been reported in young (< 25 years) highly active patients, and also when irradiated or chemically processed grafts are used. CONCLUSION: When considering use of allografts in primary ACL reconstruction, use of irradiation, chemical processing and rehabilitation programs suited to autograft are important negative factors. Allografts, when used for primary ACL reconstruction, should be fresh frozen and non-irradiated. Quantification of the risk of use of allograft in the young requires further evaluation. LEVELS OF EVIDENCE: III.

Maximum load to failure of high dose versus low dose gamma irradiation of anterior cruciate ligament allografts: A meta-analysis.

BACKGROUND: The objective of this study was to systematically evaluate the existing literature to compare the biomechanical effects of low dose and high dose gamma irradiation on commonly used ACL allografts. METHODS: A systematic search was performed in PubMed, Cumulative Index for Nursing and Allied Health Literature (CINAHL), Cochrane Reviews, SCOPUS, and SportDiscus. Nine studies were identified that met the following inclusion criteria: 1) controlled laboratory study, 2) investigation of standard allografts for anterior cruciate ligament reconstruction (ACLR), 3) gamma irradiation (dose reported) and a negative control group, and 4) mechanical loading (results reported). RESULTS: Nine studies met all inclusion and exclusion criteria. There was a dose-dependent relationship between radiation and decreased mechanical tendon integrity. Low dose radiation (<2.5Mrad [Mrad]) showed graft weakening with an average of 4.3% decrease in load to failure (standardized mean difference [SMD], 0.23; 95% CI 0.216, 0.68; p=0.31), whereas high-dose radiation showed a significantly larger (32.4% average) decrease in load to failure (SMD, 1.79; 95% CI 1.194, 2.38; p<0.001). CONCLUSIONS: Gamma irradiation has a negative effect on tendon allograft strength that is dose-dependent, with particularly large effects noted at irradiation doses of ≥2.5Mrad.

In vitro and in vivo assessment of magnetically actuated biomaterials and prospects in tendon healing.

AIM: To expand our understanding on the effect of magnetically actuated biomaterials in stem cells, inflammation and fibrous tissue growth. MATERIALS & METHODS: Magnetic biomaterials were obtained by doping iron oxide particles into starch poly-ϵ-caprolactone (SPCL) to create two formulations, magSPCL-1.8 and 3.6. Stem cell behavior was assessed in vitro and the inflammatory response, subcutaneously in Wistar rats. RESULTS: Metabolic activity and proliferation increased significantly overtime in SPCL and magSPCL-1.8. Electromagnetic fields attenuated the presence of mast cells and macrophages in tissues surrounding SPCL and magSPCL-1.8, between weeks 1 and 9. Macrophage reduction was more pronounced for magSPCL-1.8, which could explain why this material prevented growth of fibrous tissue overtime. CONCLUSION: Magnetically actuated biomaterials have potential to modulate inflammation and the growth of fibrous tissue.

Low-level laser therapy modulates pro-inflammatory cytokines after partial tenotomy.

Tendon injuries give rise to substantial morbidity, and current understanding of the mechanisms involved in tendon injury and repair is limited. This lesion remains a clinical issue because the injury site becomes a region with a high incidence of recurrent rupture and has drawn the attention of researchers. We already demonstrated that low-level laser therapy (LLLT) stimulates the synthesis and organization of collagen I, MMP-9, and MMP-2 and improved the gait recovery of the treated animals. The aim of this study was to evaluate the effects of LLLT in the nitric oxide and cytokines profile during the inflammatory and remodeling phases. Adult male rats were divided into the following groups: G1--intact, G2-- injured, G3--injured + LLLT (4 J/cm(2) continuous), G4--injured + LLLT (4 J/cm(2)-20 Hz--pulsed laser). According to the analysis, the animals were euthanized on different dates (1, 4, 8, or 15 days after injury). ELISA assay of TNF-α, IL-1ß, IL-10, and TGF-ß was performed. Western blotting of isoform of nitric oxide synthase (i-NOS) and nitric oxide dosage experiments was conducted. Our results showed that the pulsed LLLT seems to exert an anti-inflammatory effect over injured tendons, with reduction of the release of proinflammatory cytokines, such as TNF-α and the decrease in the i-NOS activity. Thanks to the pain reduction and the facilitation of movement, there was a stimulation in the TGF-ß and IL-1ß release. In conclusion, we believe that pulsed LLLT worked effectively as a therapy to reestablish the tendon integrity after rupture.

Extracorporeal Shock Wave Treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs).

Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury.

Focal Adhesion Kinase Signaling Mediated the Enhancement of Osteogenesis of Human Mesenchymal Stem Cells Induced by Extracorporeal Shockwave.

Extracorporeal shockwave (ESW) has been shown of great potential in promoting the osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but it is unknown whether this osteogenic promotion effect can also be achieved in other MSCs (i.e., tendon-derived stem cells (TDSCs) and adipose-derived stem cells (ADSCs)). In the current study, we aimed not only to compare the osteogenic effects of BMSCs induced by ESW to those of TDSCs and ADSCs; but also to investigate the underlying mechanisms. We show here that ESW (0.16 mj/mm(2)) significantly promoted the osteogenic differentiation in all the tested types of MSCs, accompanied with the downregulation of miR-138, but the activation of FAK, ERK1/2, and RUNX2. The enhancement of osteogenesis in these MSCs was consistently abolished when the cells were pretreated with one of the following conditions: overexpression of miR-138, FAK knockdown using specific siRNA, and U0126, implying that all of these elements are indispensable for mediating the effect of ESW. Moreover, our study provides converging genetic and molecular evidence that the miR-138-FAK-ERK1/2-RUNX2 machinery can be generally activated in ESW-preconditioned MSCs, suggesting that ESW may be a promising therapeutic strategy for the enhancement of osteogenesis of MSCs, regardless of their origins.

Effect of a novel sterilization method on biomechanical properties of soft tissue allografts.

PURPOSE: Evaluate allograft tissue commonly used in soft tissue reconstruction to determine whether stiffness and strength were significantly altered after grafts were treated with different sterilization methods. Unprocessed, irradiated, and grafts treated with supercritical CO2 were compared. METHODS: Thirty-eight anterior or posterior tibialis tendons were obtained from a tissue bank (Allograft Innovations, Gainesville, FL). Group I was unprocessed, group II was sterilized with gamma irradiation (20-28 kGy), and group III was sterilized with supercritical CO2. The grafts were pretensioned to 89 N for 300 s. Specimens were then loaded from 50 to 300 N at 0.5 Hz for 250 cycles before being loaded to failure at 50 mm/min. Dependent variables were compared between sterilization groups with one-way ANOVA (P < 0.05) and equivalence trial. RESULTS: There was no significant difference in load to failure or failure stress among groups I, II, and III. Group III resulted in 27-36 % lower stiffness than group I and II. This difference was significant at 1, 10, 50, 100, and 250 cycles. There was no significant difference in stiffness between group I and group II. CONCLUSION: The two sterilization methods tested in this study do not affect allograft strength. The supercritical CO2 sterilization method resulted in significantly lower stiffness than unprocessed and irradiated allografts. However, the stiffness and strength of all groups tested were greater than that of published values of the native intact anterior cruciate ligament (ACL). This study provides previously unpublished mechanical test data on a new sterilization technique that will assist surgeons to decide which allograft to use in ACL reconstruction surgery. LEVEL OF EVIDENCE: III.

Effects of gamma irradiation on collagen damage and remodeling.

PURPOSE: To evaluate the dose-time dependences of structural changes occurring in collagen within 24 hours to three months after gamma-irradiation at doses from 2-40 Gy in vivo. MATERIALS AND METHODS: Rat's tail tendon was chosen as in vivo model, with its highly ordered collagen structure allowing the changes to be interpreted unambiguously. Macromolecular level (I) was investigated by differential scanning calorimetry (DSC); fibers and bundles level (II) by laser scanning microscopy (LSM), and bulk tissue microstructural level (III) by cross-polarization optical coherence tomography (CP-OCT). RESULTS: For (I), the formation of molecular cross-links and breaks appeared to be a principal mechanism of collagen remodeling, with the cross-links number dependent on radiation dose. Changes on level (II) involved primary, secondary and tertiary bundles splitting in a day and a week after irradiation. Bulk collagen microstructure (III) demonstrated early widening of the interference fringes on CP-OCT images observed to occur in the tendon as result of this splitting. At all three levels, the observed collagen changes demonstrated complete remodeling within ∼ a month following irradiation. CONCLUSION: The time course and dose dependencies of the observed collagen changes at different levels of its hierarchy further contribute to elucidating the role of connective tissue in the radiotherapy process.

Effect of phototherapy with light-emitting diodes (890 nm) on tendon repair: an experimental model in sheep.

The effect of phototherapy with 890-nm light-emitting diodes (LEDs) on the healing of experimentally induced tendinitis in sheep was evaluated in this study. Partial tenotomies measuring 0.2 cm wide × 0.5 cm long were performed on the second third of the superficial digital flexor tendons of 10 healthy sheep. The animals were divided into two groups: "treated" (TG), treated with LEDs at the aforementioned wavelength, and "control" (CG), a control group treated with a placebo. Kinesiotherapy, which consisted of 5-min walks on grassy ground, was performed on both groups. B-mode and power Doppler ultrasonographies (US) were performed to evaluate the tendon healing process during the first 14 days after surgery and on the 21st and 28th postoperative days. Biopsies were performed on day 28 for the histopathological assessment of neovascularisation and the pattern of the tendon fibres. The absence of lameness and a significant improvement (p < 0.05) in the sensitivity to pain during palpation were observed in the treated group. Furthermore, a significant reduction in oedema and an increased number of vessels (p < 0.05) were observed in this group with the B-mode and power Doppler US, respectively. No significant difference in the evolution of the lesion was found. There was a histological difference (p < 0.05) in neovascularisation in the treated group. Phototherapy with 890-nm light-emitting diodes decreases the inflammatory process.

Evaluation of porcine xenograft in collateral ligament reconstruction in beagle dogs.

This study evaluated the effectiveness of irradiated porcine tendon xenografts for lateral collateral ligament (LCL) reconstruction. Twenty healthy adult beagle dogs underwent LCL reconstruction using irradiated porcine tendons treated with poly-gamma-glutamic acid. Serological and histological assessments were performed to evaluate host immunological response at 3 and 12 months after surgery. The healing and functional integrity of the LCL reconstructions were assessed by mechanical testing and gait analysis. Histological assessment of the porcine xenografts showed gradual host cellular infiltration and graft collagen remodeling during the healing process. Porcine xenografts showed angiogenesis and no signs of inflammatory reaction. Additionally, biomechanical and gait evaluations supported graft functional integration with no differences between normal and porcine xenograft reconstruction at 12 months after surgery. Irradiated porcine xenografts showed greater cellular responses and healing properties in short- and long-term evaluations. Irradiated porcine tendons appear to be useful as xenografts for the reconstruction of damaged ligaments.

Soft-tissue allografts terminally sterilized with an electron beam are biomechanically equivalent to aseptic, nonsterilized tendons.

BACKGROUND: Allograft safety is contingent on effective sterilization. However, current sterilization methods have been associated with decreased biomechanical strength and higher failure rates of soft-tissue allografts. In this study, electron beam (e-beam) sterilization was explored as an alternative sterilization method to preserve biomechanical integrity. We hypothesized that e-beam sterilization would not significantly alter the biomechanical properties of tendon allograft compared with aseptic, nonsterilized controls and gamma-irradiated grafts. METHODS: Separate sets of forty fresh-frozen tibialis tendon allografts (four from each of ten donors) and forty bisected bone-patellar tendon-bone (BTB) allografts (four from each of ten donors) were randomly assigned to four study groups. One group received a 17.1 to 21.0-kGy gamma radiation dose; two other groups were sterilized with an e-beam at either a high (17.1 to 21.0-kGy) or low (9.2 to 12.2-kGy) dose. A fourth group served as nonsterilized controls. Each graft was cyclically loaded to 200 N of tension for 2000 cycles at a frequency of 2 Hz, allowed to relax for five minutes, and then tested in tension until failure at a 100%/sec strain rate. One-way analysis of variance testing was used to identify significant differences. RESULTS: Tibialis tendons sterilized with both e-beam treatments and with gamma irradiation exhibited values for cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus that were not significantly different from those of nonsterilized controls. BTB allografts sterilized with the high e-beam dose and with gamma irradiation were not significantly different in cyclic tendon elongation, maximum load, maximum displacement, stiffness, maximum stress, maximum strain, and elastic modulus from nonsterilized controls. BTB allografts sterilized with the e-beam at the lower dose were significantly less stiff than nonsterilized controls (p = 0.014) but did not differ from controls in any other properties. The difference in stiffness likely resulted from variations in tendon size rather than the treatments, as the elastic moduli of the groups were similar. CONCLUSIONS: The biomechanical properties of tibialis and BTB allografts sterilized with use of an e-beam at a dose range of 17.1 to 21.0 kGy were not different from those of aseptic, nonsterilized controls or gamma-irradiated allografts. CLINICAL RELEVANCE: E-beam sterilization can be a viable method to produce safe and biomechanically uncompromised soft-tissue allografts.

Low-frequency pulsed electromagnetic fields significantly improve time of closure and proliferation of human tendon fibroblasts.

BACKGROUND: The promotion of the healing process following musculoskeletal injuries comprises growth factor signalling, migration, proliferation and apoptosis of cells. If these processes could be modulated, the healing of tendon tissue may be markedly enhanced. Here, we report the use of the Somagen™ device, which is certified for medical use according to European laws. It generates low-frequency pulsed electromagnetic fields that trigger effects of a nature that are yet to be determined. METHODS: A 1.5-cm wide, linear scrape was introduced into patellar tendon fibroblast cultures (N = 5 donors). Treatment was carried out every second day. The regimen was applied three times in total with 30 minutes comprising pulsed electromagnetic field packages with two fundamental frequencies (10 minutes of 33 Hz, 20 minutes of 7.8 Hz). Control cells remained untreated. All samples were analyzed for gap closure time, proliferation and apoptosis one week after induction of the scrape wound. RESULTS: The mean time for bridging the gap in the nontreated cells was 5.05 ± 0.33 days, and in treated cells, it took 3.35 ± 0.38 days (P <0.001). For cell cultures with scrape wounds, a mean value for BrdU incorporation of OD = 0.70 ± 0.16 was found. Whereas low-frequency pulsed electromagnetic fields treated samples showed OD = 1.58 ± 0.24 (P <0.001). However, the percentage of apoptotic cells did not differ between the two groups. CONCLUSIONS: Our data demonstrate that low-frequency pulsed electromagnetic fields emitted by the Somagen™ device influences the in vitro wound healing of patellar tendon fibroblasts and, therefore, possibly increases wound healing potential.

Fractionation of 50kGy electron beam irradiation: effects on biomechanics of human flexor digitorum superficialis tendons treated with ascorbate.

The electron beam (Ebeam) irradiation has begun to be considered as an efficient alternative to gamma irradiation in the sterilization of allografts in the reconstruction of anterior cruciate ligament. The purpose of this study was to evaluate the biomechanical properties of human tendons after exposure to electron beam and free radical scavenger ascorbate. Forty human flexor digitorum superficialis tendons were prepared from five fresh cadavers and divided randomly into four groups: A, fresh (0kGy); B, 50kGy Ebeam irradiation; C, fractionated 50kGy Ebeam irradiation; D, fractionated 50kGy Ebeam on ascorbate-treated tendons. The fractionation of 50kGy was achieved by repeated irradiation of 2.5kGy for 20 repetitions. Biomechanical properties were analyzed during load-to-failure testing. The fresh tendons were found to be significant different in ultimate load, ultimate elongation relative to tendons in group B. Statistical differences were found between group B and C in ultimate load. No differences were detected between group A and C in all the parameters. Compare tendons in group C and D, significant differences were found in ultimate load and ultimate stress. It is recommended that fractionated 50kGy electron beam irradiation and free radical scavenger ascorbate should be applied in the sterilization of allografts tendons.

Sterilization of tendon allografts: a method to improve strength and stability after exposure to 50 kGy gamma radiation.

Terminal sterilization of tendon allografts with high dose gamma irradiation has deleterious effects on tendon mechanical properties and stability after implantation. Our goal is to minimize these effects with radio protective methods. We previously showed that radio protection via combined crosslinking and free radical scavenging maintained initial mechanical properties of tendon allografts after irradiation at 50 kGy. This study further evaluates the tissue response and simulated mechanical degradation of tendons processed with radio protective treatment, which involves crosslinking in 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide followed by soaking in an ascorbate/riboflavin-5-phosphate solution. Control untreated and treated tendons were irradiated at 50 kGy and implanted in New Zealand White rabbit knees within the joint capsule for four and 8 weeks. Tendons were also exposed to cyclic loading to 20 N at one cycle per 12 s in a collagenase solution for 150 cycles, followed by tension to failure. Control irradiated tendons displayed increased degradation in vivo, and failed prematurely during cyclic processing at an average of 25 cycles. In contrast, radio protected irradiated tendons displayed greater stability following implantation over 8 weeks, and possessed strength at 59 % of native tendons and modulus equivalent to that of native tendons after cyclic loading in collagenase. These results suggest that radio protective treatment improves the strength and the stability of tendon allografts.

The effects of low-intensity pulsed ultrasound on tendon-bone healing in a transosseous-equivalent sheep rotator cuff model.

PURPOSE: The purpose of this study was to examine the effects Low-intensity Pulsed Ultrasound has on initial tendon-bone healing in a clinically relevant extra-articular transosseous-equivalent ovine rotator cuff model. METHODS: Eight skeletally mature wethers, randomly allocated to either control group (n = 4) or treatment group (n = 4), underwent rotator cuff surgery following injury to the infraspinatus tendon. All animals were killed 28 days post surgery to allow examination of early effects of Low-intensity Pulsed Ultrasound treatment. RESULTS: General improvement in histological appearance of tendon-bone integration was noted in the treatment group. Newly formed woven bone with increased osteoblast activity along the bone surface was evident. A continuum was observed between the tendon and bone in an interdigitated fashion with Sharpey's fibres noted in the treatment group. Low-intensity Pulsed Ultrasound treatment also increased bone mineral density at the tendon-bone interface (p < 0.01), while immunohistochemistry results revealed an increase in the protein expression patterns of VEGF (p = 0.038), RUNX2 (p = 0.02) and Smad4 (p = 0.05). CONCLUSIONS: The results of this study indicate that Low-intensity Pulsed Ultrasound may aid in the initial phase of tendon-bone healing process in patients who have undergone rotator cuff repair. This treatment may also be beneficial following other types of reconstructive surgeries involving the tendon-bone interface.

Low-level laser irradiation stimulates tenocyte migration with up-regulation of dynamin II expression.

Low-level laser therapy (LLLT) is commonly used to treat sports-related tendinopathy or tendon injury. Tendon healing requires tenocyte migration to the repair site, followed by proliferation and synthesis of the extracellular matrix. This study was designed to determine the effect of laser on tenocyte migration. Furthermore, the correlation between this effect and expression of dynamin 2, a positive regulator of cell motility, was also investigated. Tenocytes intrinsic to rat Achilles tendon were treated with low-level laser (660 nm with energy density at 1.0, 1.5, and 2.0 J/cm(2)). Tenocyte migration was evaluated by an in vitro wound healing model and by transwell filter migration assay. The messenger RNA (mRNA) and protein expressions of dynamin 2 were determined by reverse transcription/real-time polymerase chain reaction (real-time PCR) and Western blot analysis respectively. Immunofluorescence staining was used to evaluate the dynamin 2 expression in tenocytes. Tenocytes with or without laser irradiation was treated with dynasore, a dynamin competitor and then underwent transwell filter migration assay. In vitro wound model revealed that more tenocytes with laser irradiation migrated across the wound border to the cell-free zone. Transwell filter migration assay confirmed that tenocyte migration was enhanced dose-dependently by laser. Real-time PCR and Western-blot analysis demonstrated that mRNA and protein expressions of dynamin 2 were up-regulated by laser irradiation dose-dependently. Confocal microscopy showed that laser enhanced the expression of dynamin 2 in cytoplasm of tenocytes. The stimulation effect of laser on tenocytes migration was suppressed by dynasore. In conclusion, low-level laser irradiation stimulates tenocyte migration in a process that is mediated by up-regulation of dynamin 2, which can be suppressed by dynasore.

Use of controlled low dose gamma irradiation to sterilize allograft tendons for ACL reconstruction: biomechanical and clinical perspective.

As reviewed here, numerous biomechanical and clinical studies support the use of controlled, low temperature irradiation of allograft tendons, to provide both excellent clinical results and medical-device grade sterile allografts with minimal risk of disease transmission.