Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study

Camenzind, Roland S.; Tondelli, Timo; Götschi, Tobias; Holenstein, Claude N.; Snedeker, Jess G.

doi:10.1007/s11999.0000000000000247

Cited by 11 publications

(18 citation statements)

References 46 publications

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“…In later stages of tendon degeneration, microtears and degradation can result in collagen distortion with areas of mucoid or fatty degeneration in tendon tissue. 3 Genipin is a chemical agent, which was shown to induce collagen cross-linking in previous in vitro studies, 3,25,45 serving as a general model of collagen cross-linking and biophysical effects associated with decreased porosity and decreased mobility of water within the tissue. The effect of tendon treatment with genipin was visible by a slight blueish coloring of the tendons and confirmed by confocal microscopy serving as the reference standard for increased cross-linking.…”

Section: Discussionmentioning

confidence: 99%

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties

et al. 2019

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The aim of this study was to quantitatively assess changes in collagen structure using MR T1-and T2*-mapping in a novel controlled ex vivo tendon model setup. MATERIALS AND METHODS Twenty-four cadaveric bovine flexor tendons underwent MRI at 3 T before and after chemical modifications, representing mechanical degeneration and augmentation. Collagen degradation (COL), augmenting collagen fiber cross-linking (CXL), and a control (phosphate-buffered saline [PBS]) were examined in experimental groups, using histopathology as standard of reference. Variable echo-time and variable-flip angle gradient-echo sequences were used for T2*-and T1-mapping, respectively. Standard T1-and T2-weighted spin-echo sequences were acquired for visual assessment of tendon texture. Tendons were assessed subsequently for their biomechanical properties and compared with quantitative MRI analysis. RESULTS T1-and T2*-mapping was feasible and repeatable for untreated (mean, 545 milliseconds, 2.0 milliseconds) and treated tendons. Mean T1 and T2* values of COL, CXL, and PBS tendons were 1459, 934, and 1017 milliseconds, and 5.5, 3.6, and 2.5 milliseconds, respectively. T2* values were significantly different between enzymatically degraded tendons, cross-linked tendons, and controls, and were significantly correlated with mechanical tendon properties (r =-0.74, P < 0.01). T1 values and visual assessment could not differentiate CXL from PBS tendons. Photo-spectroscopy showed increased autofluorescence of cross-linked tendons, whereas histopathology verified degenerative lesions of enzymatically degraded tendons. CONCLUSIONS T2*-mapping has the potential to detect and quantify subtle changes in tendon collagen structure not visible on conventional clinical MRI. Tendon T2* values might serve as a biomarker for biochemical alterations associated with tendon pathology.

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Section: Discussionmentioning

confidence: 99%

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties

et al. 2019

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“…The testing machine was equipped with custom-made parts for sample fixation. 8,9 For isolated device testing, the loading suture was looped around a steel pin with a diameter of 6 mm, and the cortical button was placed behind a steel plate ( Figure 2). For tendon-device testing, a clamp was mounted onto the load cell to hold the tendon graft in place.…”

Section: Testing Setupmentioning

confidence: 99%

Biomechanical Evaluation of a Novel Loop Retention Mechanism for Cortical Graft Fixation in ACL Reconstruction

Götschi

Rosenberg

et al. 2020

Orthopaedic Journal of Sports Medicine

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Background: Implant fixation by means of a cortical fixation device (CFD) has become a routine procedure in anterior cruciate ligament reconstruction. There is no clear consensus whether adjustable-length CFDs are more susceptible to loop lengthening when compared with pretied fixed-length CFDs.Purpose: To assess biomechanical performance measures of 3 types of CFDs when subjected to various loading protocols.Study Design: Controlled laboratory study.Methods: Three types of CFDs underwent biomechanical testing: 1 fixed length and 2 adjustable length. One of the adjustablelength devices is based on the so-called finger trap mechanism, and the other is based on a modified sling lock mechanism. A device-only test of 5000 cycles (n ¼ 8 per group) and a tendon-device test of 1000 cycles (n ¼ 8 per group) with lower and upper force limits of 50 and 250 N, respectively, were applied, followed by ramp-to-failure testing. Adjustable-length devices then underwent further cyclic testing with complete loop unloading (n ¼ 5 per group) at each cycle, as well as fatigue testing (n ¼ 3 per group) over a total of 1 million cycles. Derived mechanical parameters were compared among the devices for statistical significance using Kruskal-Wallis analysis of variance followed by post hoc Mann-Whitney U testing with Bonferroni correction.Results: All CFDs showed elongation <2 mm after 5000 cycles when tested in an isolated manner and withstood ultimate tensile forces in excess of estimated peak in vivo forces. In both device-only and tendon-device tests, differences in cyclic performance were found among the devices, favoring adjustable-length fixation devices over the fixed-length device. Completely unloading the suspension loops, however, led to excessive loop lengthening of the finger trap device, whereas the modified sling lock device remained stable throughout the test. The fixed-length device displayed superior ultimate strength over both adjustable-length devices. Both adjustable-length devices showed adequate fatigue behavior during high-cyclic testing.Conclusion: All tested devices successfully prevented critical construct elongation when tested with constant tension and withstood ultimate loads in excess of estimated in vivo forces during the rehabilitation phase. The finger trap device gradually lengthened excessively when completely unloaded during cyclic testing.Clinical Relevance: Critical loop lengthening may occur if adjustable-length devices based on the finger trap mechanism are repeatedly unloaded in situ.

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“…The viscoelastic behavior on the other hand was strongly affected by GP as assessed by the relative stress relaxation crosslinking and is in agreement with existing literature. [25,45,46].…”

Section: Effects Of Intratendinous Genipin Injections: Mechanical Augmentioning

confidence: 99%

“…[24] Incubation of animal tendon explants in 20 mM GPsolution improved suture retention strength by 30% after 24 hours [25] and successfully mitigated propagation of partial tendon tears [26]. In an ex-vivo model for tendon rupture repair, GP-coated sutures showed an increased suture retention strength by localized tissue strengthening when compared to uncoated sutures [27]. To date, the potential of GP in the repair of degenerative tendon lesions is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Assessing the effects of intratendinous genipin injections: Mechanical augmentation and spatial distribution in an ex vivo degenerative tendon model

et al. 2020

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BackgroundTendinopathy is a common musculoskeletal disorder and current treatment options show limited success. Genipin is an effective collagen crosslinker with low cytotoxicity and a promising therapeutic strategy for stabilizing an intratendinous lesion. PurposeThis study examined the mechanical effect and delivery of intratendinous genipin injection in healthy and degenerated tendons. Study design Controlled laboratory study MethodsBovine superficial digital flexor tendons were randomized into four groups: Healthy control (N = 25), healthy genipin (N = 25), degenerated control (N = 45) and degenerated genipin (N = 45). Degeneration was induced by Collagenase D injection. After 24h, degenerated tendons were subsequently injected with either 0.2ml of 80mM genipin or buffer only. 24h posttreatment, samples were cyclically loaded for 500 cycles and then ramp loaded to failure. Fluorescence and absorption assays were performed to analyze genipin crosslink distribution and estimate tissue concentration after injection. ResultsCompared to controls, genipin treatment increased ultimate force by 19% in degenerated tendons (median control 530 N vs. 633 N; p = 0.0078). No significant differences in mechanical properties were observed in healthy tendons, while degenerated tendons showed a significant difference in ultimate stress (+23%, p = 0.049), stiffness (+27%, p = 0.037), work to PLOS ONE PLOS ONE | https://doi.failure (+42%, p = 0.009), and relative stress relaxation (-11%, p < 0.001) after genipin injection. Fluorescence and absorption were significantly higher in genipin treated tendons compared to control groups. A higher degree of crosslinking (+45%, p < 0.001) and a more localized distribution were observed in the treated healthy compared to degenerated tendons, with higher genipin tissue concentrations in healthy (7.9 mM) than in degenerated tissue (2.3 mM). ConclusionUsing an ex-vivo tendinopathy model, intratendinous genipin injections recovered mechanical strength to the level of healthy tendons. Measured by genipin tissue distribution, injection is an effective method for local delivery. Clinical relevanceThis study provides a proof of concept for the use of intratendinous genipin injection in the treatment of tendinopathy. The results demonstrate that a degenerated tendon can be mechanically augmented by a clinically viable method of local genipin delivery. This warrants further in vivo studies towards the development of a clinically applicable treatment based on genipin. PLOS ONEEffects of intratendinous genipin injections: Mechanical augmentation and spatial distribution PLOS ONE | https://doi.org/10.

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Can Genipin-coated Sutures Deliver a Collagen Crosslinking Agent to Improve Suture Pullout in Degenerated Tendon? An Ex Vivo Animal Study

Abstract: A genipin-coated suture represents a potential delivery vehicle for exogenous crosslink agents to augment suture retention properties. In vivo animal studies are the next logical step to assess safety and efficacy of the approach.

Cited by 11 publications

References 46 publications

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties

T1- and T2*-Mapping for Assessment of Tendon Tissue Biophysical Properties

Biomechanical Evaluation of a Novel Loop Retention Mechanism for Cortical Graft Fixation in ACL Reconstruction

Assessing the effects of intratendinous genipin injections: Mechanical augmentation and spatial distribution in an ex vivo degenerative tendon model

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