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Electrospun tube reduces adhesion in rabbit Achilles tendon 12 weeks post-surgery without PAR-2 overexpression.

ABSTRACT: One great challenge in surgical tendon repair is the minimization of peritendinous adhesions. An electrospun tube can serve as a physical barrier around a conventionally sutured tendon. Six New Zealand White rabbits had one Achilles tendon fully transsected and sutured by a 4-strand suture. Another six rabbits had the same treatment, but with the additional electrospun DegraPol tube set around the sutured tendon. The adhesion formation to the surrounding tissue was investigated 12 weeks post-operation. Moreover, inflammation-related protease-activated receptor-2 (PAR-2) protein expression was assessed. Finally, rabbit Achilles tenocyte cultures were exposed to platelet-derived growth factor-BB (PDGF-BB), which mimicks the tendon healing environment, where PAR-2 gene expression was assessed as well as immunofluorescent staining intensity for F-actin and α-tubulin, respectively. At 12 weeks post-operation, the partially degraded DegraPol tube exhibited significantly lower adhesion formation (- 20%). PAR-2 protein expression was similar for time points 3 and 6 weeks, but increased at 12 weeks post-operation. In vitro cell culture experiments showed a significantly higher PAR-2 gene expression on day 3 after exposure to PDGF-BB, but not on day 7. The cytoskeleton of the tenocytes changed upon PDGF-BB stimulation, with signs of reorganization, and significantly decreased F-actin intensity. An electrospun DegraPol tube significantly reduces adhesion up to twelve weeks post-operation. At this time point, the tube is partially degraded, and a slight PAR-2 increase was detected in the DP treated tendons, which might however arise from particles of degrading DegraPol that were stained dark brown. PAR-2 gene expression in rabbit tenocytes reveals sensitivity at around day 10 after injury.

SUBMITTER: Burgisser GM

PROVIDER: S-EPMC8639666 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAssuming that the mechanisms inducing adaptation in healthy tendons yield similar responses in tendinopathic tendons, we hypothesized that a high-loading exercise protocol that increases tendon stiffness and cross-sectional area in male healthy Achilles tendons may also induce comparable beneficial adaptations in male tendinopathic Achilles tendons in addition to improving pain and function.ObjectivesWe investigated the effectiveness of high-loading exercise in Achilles tendinopathy in terms of inducing mechanical (tendon stiffness, maximum strain), material (Young's modulus), morphological (tendon cross-sectional area (CSA)), maximum voluntary isometric plantar flexor strength (MVC) as well as clinical adaptations (Victorian Institute of Sports Assessment-Achilles (VISA-A) score and pain (numerical rating scale (NRS))) as the primary outcomes. As secondary outcomes, drop (DJ) and counter-movement jump (CMJ) height and intratendinous vascularity were assessed.MethodsWe conducted a controlled clinical trial with a 3-month intervention phase. Eligibility criteria were assessed by researchers and medical doctors. Inclusion criteria were male sex, aged between 20 and 55 years, chronic Achilles tendinopathy confirmed by a medical doctor via ultrasound-assisted assessment, and a severity level of less than 80 points on the VISA-A score. Thirty-nine patients were assigned by sequential allocation to one of three parallel arms: a high-loading intervention (training at ~ 90% of the MVC) (n = 15), eccentric exercise (according to the Alfredson protocol) as the standard therapy (n = 15) and passive therapy (n = 14). Parameters were assessed pre- and-post-intervention. Data analysis was blinded.ResultsPrimary outcomes: Plantar flexor MVC, tendon stiffness, mean CSA and maximum tendon strain improved only in the high-loading intervention group by 7.2 ± 9.9% (p = 0.045), 20.1 ± 20.5% (p = 0.049), 8.98 ± 5.8% (p < 0.001) and -12.4 ± 10.3% (p = 0.001), respectively. Stiffness decreased in the passive therapy group (-7.7 ± 21.2%; p = 0.042). There was no change in Young's modulus in either group (p > 0.05). The VISA-A score increased in all groups on average by 19.8 ± 15.3 points (p < 0.001), while pain (NRS) dropped by -0.55 ± 0.9 points (p < 0.001).Secondary outcomesCMJ height decreased for all groups (-0.63 ± 4.07 cm; p = 0.005). There was no change in DJ height and vascularity (p > 0.05) in either group.ConclusionDespite an overall clinical improvement, it was exclusively the high-loading intervention that induced significant mechanical and morphological adaptations of the plantar flexor muscle-tendon unit. This might contribute to protecting the tendon from strain-induced injury. Thus, we recommend the high-loading intervention as an effective (alternative) therapeutic protocol in Achilles tendinopathy rehabilitation management in males.Clinical trials registration numberNCT02732782.

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Electrospun tube reduces adhesion in rabbit Achilles tendon 12 weeks post-surgery without PAR-2 overexpression.

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