Impact of Collagen Crosslinking on Dislocated Human Shoulder Capsules—Effect on Structural and Mechanical Properties

Abstract

Classical treatments of shoulder instability are associated with recurrence. To determine whether the modification of the capsule properties may be an alternative procedure, the effect of crosslinking treatment on the structure and mechanical properties of diseased human shoulder capsules was investigated. Joint capsules harvested from patients during shoulder surgery (n = 5) were treated or not with UV and/or riboflavin (0.1%, 1.0% and 2.5%). The structure and the mechanical properties of the capsules were determined by atomic force microscopy. The effect of treatments on cell death was investigated. Collagen fibrils were well-aligned and adjacent to each other with a D-periodicity of 66.9 ± 3.2 nm and a diameter of 71.8 ± 15.4 nm in control untreated capsules. No effect of treatments was observed on the organization of the collagen fibrils nor on their intrinsic characteristics, including D-periodicity or their mean diameter. The treatments also did not induce cell death. In contrast, UV + 2.5% riboflavin induced capsule stiffness, as revealed by the increased Young’s modulus values (p < 0.0001 for each patient). Our results showed that the crosslinking procedure changed the biomechanics of diseased capsules, while keeping their structural organisation unchanged at the single fibril level. The UV/riboflavin crosslinking procedure may be a promising way to preserve the functions of collagen-based tissues and tune their elasticity for clinically relevant treatments.

Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients

“…4 ), which supports that MXD targets Plod2 -mediated Pyd cross-linking by limiting the availability of LH2b, either by direct biochemical interference with hydroxylation of lysine residues [ 26 ] or direct suppression of Plod2 transcription [ 12 , 13 , 34 ]. Notably, MXD lowered but did not abrogate Plod2 or Pyd, which are still required to preserve the mechanical integrity of the joint capsule [ 10 ] and vascular structures [ 8 , 47 ]. To that end, strategies to modulate Pyd must be carefully designed and the potential for MXD analogs to directly suppress transcriptional regulators of Plod2 -mediated LH2b expression needs further investigation concurrent with addressing study limitations.…”

Comprehensive Review of Multidirectional Instability of the Shoulder

“…Chemical agents, including glutaraldehyde, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide, genipin, and riboflavin, have all demonstrated improved collagen cross-linking in vitro. 34 Physical treatments, including use of ionizing radiation, ultraviolet light, and dehydrothermal methods, have also showed promising results in preliminary studies, although concerns exist regarding collagen denaturation as a result of irradiation or heat. 34,35 Enzymatic treatment may provide a more targeted approach, with increased in vitro fibroblast collagen deposition and collagen cross-linking detected through the use of lysyl oxidase with bone morphogenetic protein 1 (BMP-1).…”

“…34 Physical treatments, including use of ionizing radiation, ultraviolet light, and dehydrothermal methods, have also showed promising results in preliminary studies, although concerns exist regarding collagen denaturation as a result of irradiation or heat. 34,35 Enzymatic treatment may provide a more targeted approach, with increased in vitro fibroblast collagen deposition and collagen cross-linking detected through the use of lysyl oxidase with bone morphogenetic protein 1 (BMP-1). 33,36 Future preclinical and clinical studies are required to further investigate the in vivo effects of these potential treatment options including the concern that no additional unintended damage occurs to the collagen present in articular cartilage.…”

“…Likely an adaptive response to recurrent instability episodes, increased collagen cross-linking has been associated with higher tissue tensile strength, and regulation of genes involved in collagen cross-linking has been implicated in shoulder instability. [32][33][34] As such, collagen crosslinking modifications may provide an opportunity for therapeutic interventions. Chemical agents, including glutaraldehyde, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide, genipin, and riboflavin, have all demonstrated improved collagen cross-linking in vitro.…”

Exogenous Crosslinking of Tendons as a Strategy for Mechanical Augmentation and Repair: A Narrative Review

“…They have shown 29 that the photocrosslinking of IVD led to reduced annular delamination, increase of the peel strength, and a significant increase of Young’s modulus. In another study, 30 the subject was the shoulder’s glenohumeral joint capsule; its laxity is one of the main lesions leading to shoulder instability. Human capsular specimens (~1 mm 3 each) were harvested during shoulder surgery, and exposed to UV-A (365 nm) for 30 minutes after incubation in riboflavin.…”