Twelve-month outcomes following surgical repair of the Achilles tendon

Fox, Georgia; Gabbe, Belinda; Richardson, Martin; Oppy, Andrew; Page, Richard; Edwards, Elton; Hau, Raphael; Ekegren, Christina L.

doi:10.1016/j.injury.2016.07.013

Cited by 22 publications

(14 citation statements)

References 16 publications

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“…36 Functional impairments identified by calf atrophy, heel-raise power compared with the opposite side, poor walking pattern (gait) and lower levels of physical activity are reported as outcomes of these management strategies. 37 Platelet-rich plasma Although significant advancements in the clinical management of ATR have resulted in some improvements in functional outcomes, 38 there has been little progress made with regard to the restoration of the structural and biomechanical integrity of an injured tendon to its original state. Thus, it is unsurprising that novel therapies are being explored to diminish the degree and duration of morbidity.…”

Section: Management Of Achilles Tendon Rupturementioning

confidence: 99%

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

et al. 2019

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Background Achilles tendon rupture (ATR) has a long healing period, which is challenging for patients and clinicians. Platelet-rich plasma (PRP) is an autologous concentration of platelets thought to improve tendon function recovery. Although preliminary research has indicated positive effects, there is, as yet, no evidence of clinical efficacy from adequately powered robust clinical trials. Objectives The objectives were to determine the clinical efficacy of PRP in patients with acute ATR using an objective mechanical muscle–tendon function measure and patient-reported outcome measures (PROMs), and to determine which PRP components contribute to its mechanism. Design This was a multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo. Two embedded substudies investigated the PRP’s quality and composition and its effects on healing tendon tissues. Setting This trial was set in trauma and orthopaedic surgery departments in 19 NHS hospitals in England and Wales. Participants Adults with acute ATR presenting within 12 days of injury to be treated non-surgically were eligible. Patients with platelet dysfunction or leg functional deficiency were excluded. Interventions Participants were randomised 1 : 1 to the PRP injection group or the placebo group (dry needle in the rupture gap) by central computer-based randomisation using minimisation, stratified by centre and age. Main outcome measures The primary outcome measure was the Limb Symmetry Index (LSI) of work during the heel-rise endurance test at 24 weeks. Secondary outcomes measures, collected at 4, 7, 13 and 24 weeks, were repetitions, maximum heel-rise height, Achilles tendon Total Rupture Score (ATRS), quality of life (as measured using the Short Form questionnaire-12 items version 2), pain and participant goal attainment. Needle biopsies of the affected tendon zone were taken under ultrasound guidance at 6 weeks from 16 participants from one centre. Whole blood was analysed for cell count. PRP was analysed for cell count, platelet activation and growth factor concentration. The primary analysis was intention to treat. Results A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). One participant withdrew after randomisation but before the intervention. At 24 weeks, 201 out of 230 participants (87.4%) completed the primary outcome and 216 out of 230 participants (93.9%) completed the PROMs. The treatment groups had similar participant characteristics. At 24 weeks, there was no difference in work LSI (mean difference –3.872; 95% confidence interval –10.454 to 2.710; p = 0.231), ATRS, pain or goal attainment between PRP- and placebo-injected participants. There were no differences between the groups in any PROM at any time point or in complication rates, including re-rupture and deep-vein thrombosis. There was no correlation between work LSI and platelet activation in PRP, or erythrocyte, leucocyte or platelet counts in whole blood or PRP. Biopsies showed similar cellularity and vascularity between groups. Conclusions This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. Trial registration Current Controlled Trials ISRCTN54992179. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme.

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Section: Management Of Achilles Tendon Rupturementioning

confidence: 99%

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

et al. 2019

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“…This change, coupled with the tissues already hypocellular and hypovascular nature (Liu et al 2011), results in a 'slow' process of healing, particularly when addressing complete ruptures, which often require surgery. Even after 12 months post-injury or surgical intervention, the tissue still lacks the biomechanical and ultrastructural characteristics it had prior to the injury (Fox et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

2019

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There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.

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“…Animals were euthanised 1, 2, 4 and 8 weeks after surgery and healing assessed by morphometry, mechanical testing and histology. www.ecmjournal.org (Chan et al, 1997;Fu et al, 2003;Kashiwagi et al, 2004) in a volume of 10 µL of buffer (see Growth factors); 4) tiered GF group: 100 ng of bFGF were applied during surgery into the tendon defect, as bFGF increases cellularity and it is augmented early during natural tendon healing (Freedman et al, 2014;Heisterbach et al, 2012;Würgler-Hauri et al, 2007). 48 h postoperatively, 100 ng of TGFβ 1 were introduced directly into the tendon gap -marked by the middle skin suture, to facilitate accuracy -by percutaneous injection, to promote an early switch from type III to type I collagen .…”

Section: Animal Modelmentioning

confidence: 99%

“…Tendon ruptures are common sporting injuries (Schepsis et al, 2002), with an increasing incidence (Fox et al, 2016;Ganestam et al, 2016;Huttunen et al, 2014;Jacobsson et al, 2012;Lantto et al, 2015;Mattila et al, 2015;Sheth et al, 2017;Wertz et al, 2013). Treatment options include both conservative and operative approaches.…”

Section: Introductionmentioning

confidence: 99%

“…Tendon healing is promoted and guided by a variety of growth factors (GFs) produced locally that orchestrate the complex biology of tissue healing. Numerous GFs are identified, including connective tissue growth factor (CTGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), bone morphogenetic www.ecmjournal.org proteins (BMPs) and transforming growth factor beta (TGFβ) (Docheva et al, 2015;Evans, 1999;Freedman et al, 2014;Heisterbach et al, 2012;Kaux et al, 2014;Molloy et al, 2003;Müller et al, 2015;Ohba et al, 2012;Sharma and Maffulli, 2006;Würgler-Hauri et al, 2007;Yang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

Majewski

Heisterbach

Jaquiéry

et al. 2018

eCM

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Several growth factors (GFs) are expressed as tendons heal, but it remains unknown whether their combined application enhances the healing process. This matter was addressed by applying a combination of basic fibroblast growth factor (bFGF), bone morphogenetic protein 12 (BMP-12) and transforming growth factor beta 1 (TGFβ1) in a rat Achilles tendon transection model. GFs were applied in one of the three following ways: i) direct application of all three factors at the time of surgery; ii) sequential, tiered percutaneous injection of individual factors immediately after surgery, 48 h and 96 h later; iii) load of all three factors onto a collagen sponge implanted at the time of surgery. After 1, 2, 4 and 8 weeks, healing was assessed based on tendon length and thickness, mechanical strength, stiffness and histology. Best results were achieved when GFs were loaded onto a collagen sponge - with a rapid increase in mechanical strength (load to failure, 71.2 N vs. 7.7 N in controls), consistent tendon length over time (9.9 mm vs. 16.2 mm in controls) and faster tendon remodelling, as measured by histology - followed by tiered injection therapy over 96 h. In conclusion, implantation of a GF-loaded collagen sponge could provide a promising treatment, especially in high-performance athletes and revision cases prone to re-rupture. For conservative treatment, tiered percutaneous GF application could be an option for improving clinical outcome.

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Twelve-month outcomes following surgical repair of the Achilles tendon

Cited by 22 publications

References 16 publications

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

Improved tendon healing using bFGF, BMP-12 and TGFβ1 in a rat model

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