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Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons.

ABSTRACT: Tendon rupture can occur at any age and is commonly treated nonoperatively, yet can result in persisting symptoms. Thus, a need exists to improve nonoperative treatments of injured tendons. Photobiomodulation (PBM) therapy has shown promise in the clinic and is hypothesized to stimulate mitochondrial-related metabolism and improve healing. However, the effect of PBM therapy on mitochondrial function during tendon maturation and healing are unknown, and its effect on tendon structure and function remain unclear. In this study, near-infrared light (980:810 nm blend, 2.5 J/cm² ) was applied at low (30 mW/cm² ) or high (300 mW/cm² ) irradiance to unilateral Achilles tendons of CD-1 mice during postnatal growth (maturation) as well as adult mice with bilateral Achilles tenotomy (healing). The chronic effect of PBM therapy on tendon structure and function was determined using histology and mechanics, and the acute effect of PBM therapy on mitochondrial-related gene expression was assessed. During maturation and healing, collagen alignment, cell number, and nuclear shape were unaffected by chronic PBM therapy. We found a sex-dependent effect of PBM therapy during healing on mechanical outcomes (eg, increased stiffness and Young's modulus for PBM-treated females, and increased strain at ultimate stress for PBM-treated males). Mitochondria-related gene expression was marginally influenced by PBM therapy for both maturation and healing studies. This study was the first to implement PBM therapy during both growth and healing of the murine tendon. PBM therapy resulted in marginal and sex-dependent effects on the murine tendon. Clinical significance: PBM may be beneficial for tendon healing because functional remodeling improves without adverse effects.

SUBMITTER: Locke RC

PROVIDER: S-EPMC8637462 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Achilles tendon ruptures affect 15 of 100,000 women and 55 of 100,000 men each year. Controversy continues to exist regarding optimal treatment and rehabilitation protocols. The objective of this study was to investigate the temporal effects of surgical repair and immobilization or activity on Achilles tendon healing and limb function after complete transection in rodents.Injured tendons were repaired (n = 64) or left nonrepaired (n = 64). The animals in both cohorts were further randomized into groups immobilized in plantar flexion for 1, 3, or 6 weeks that later resumed cage and treadmill activity for 5, 3, or 0 weeks, respectively (n = 36 for each regimen), which were euthanized at 6 weeks after injury, or into groups immobilized for 1 week and then euthanized (n = 20).At 6 weeks after injury, the groups that had 1 week of immobilization and 5 weeks of activity had increased range of motion and decreased ankle joint toe stiffness compared with the groups that had 3 weeks of immobilization and 3 weeks of activity. The groups with 6 weeks of immobilization and no activity period had decreased tendon cross-sectional area but increased tendon echogenicity and collagen alignment. Surgical treatment dramatically decreased fatigue cycles to failure in repaired tendons from groups with 1 week of immobilization and 5 weeks of activity. Normalized comparisons between 1-week and 6-week postinjury data demonstrated that changes in tendon healing properties (area, alignment, and echogenicity) were maximized by 1 week of immobilization and 5 weeks of activity, compared with 6 weeks of immobilization and no activity period.This study builds on an earlier study of Achilles tendon fatigue mechanics and functional outcomes during early healing by examining the temporal effects of different immobilization and/or activity regimens after initial postinjury immobilization.This study demonstrates how the temporal postinjury healing response of rodent Achilles tendons depends on both surgical treatment and the timing of immobilization/activity timing. The different pattern of healing and qualities of repaired and nonrepaired tendons suggest that two very different healing processes may occur, depending on the chosen immobilization/activity regimen.

Project description:BackgroundTendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β. It is thought that the metabolic changes play a role in tendon healing after injury.HypothesisGlucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair.Study designControlled laboratory study.MethodsThe authors used the tendon injury model involving a complete incision of the Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model.ResultsSignificant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons.ConclusionThe findings indicate that injured tendons acutely increase glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing.Clinical relevanceChanging metabolism in injured tendons may be a therapeutic target for tendon repair.

Project description:ObjectivesUltrasound often corroborates clinical diagnosis of Achilles tendinopathy (AT). Traditional measures assess macromorphological features or use qualitative grading scales, primarily focused within the free tendon. Shear wave imaging can non-invasively quantify tendon elasticity, yet it is unknown if proximal structures are affected by tendon pathology. The purpose of the study was to determine the characteristics of both traditional sonographic measures and regional shear wave speed (SWS) between limbs in patients with AT.MethodsTwenty patients with chronic AT were recruited. Traditional sonographic measures of tendon structure were measured. Regional SWS was collected in a resting ankle position along the entire length of the tendon bilaterally. SWS measures were extracted and interpolated across evenly distributed points corresponding to the free tendon (FT), soleus aponeurosis (SA), and gastrocnemius aponeurosis (GA). Comparisons were made between limbs in both traditional sonographic measures and regional SWS.ResultsSymptomatic tendons were thicker (10.2 (1.9) vs. 6.8 (1.8) mm; p < 0.001) and had more hyperemia (p = 0.001) and hypoechogenicity (p = 0.002) than the contralateral tendon. Regional SWS in the FT was lower in the symptomatic limb compared to the contralateral limb (11.53 [10.99, 12.07] vs. 10.97 [10.43, 11.51]; p = 0.03). No differences between limbs were found for the SA (p = 0.13) or GA (p = 0.99).ConclusionsLower SWS was only observed in the FT in AT patients, indicating that alterations in tendon elasticity associated with AT were localized to the FT and did not involve the proximal passive tendon structures.Key points• Baseline characteristics of a pilot sample of 20 subjects suffering from chronic Achilles tendinopathy showed differences in conventional sonographic measures of tendon thickness, qualitatively assessed hypoechogenicity, hyperemia, and quantitative measures of shear wave speed. • Regional shear wave speeds were lower in the free tendon but not in the proximal regions of the soleus or gastrocnemius aponeuroses in Achilles tendinopathy patients. • Using shear wave imaging to estimate tendon stiffness may prove beneficial for clinical validation studies to address important topics such as return to activity and the effectiveness of rehabilitation protocols.

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Photobiomodulation does not influence maturation and mildly improves functional healing of mouse achilles tendons.

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