Background
Post-arthroscopic glenohumeral chondrolysis (PAGCL) is a rare, but significant complication of arthroscopic shoulder surgery. It refers to the death of glenohumeral chondrocytes, which causes rapid cartilage degeneration and extensive osteoarthritis, often in young patients. This produces devastating consequences for affected patients who experience significant pain and functional impairment, often necessitating salvage surgery. The aetiology of PAGCL is poorly understood; however numerous patient and surgical factors have been implicated [
1]. Patient factors, such as genetics and type of glenohumeral pathology, may contribute towards an increased risk of developing PAGCL, with case reports suggesting that chondrolysis is most prevalent amongst young males with shoulder instability [
2]. Furthermore, a number of surgical factors have been implicated in the pathogenesis of PAGCL, including intraarticular local anaesthetic, iatrogenic articular damage, suture anchors, infection, and the use of intraoperative radiofrequency devices. Some hypothesise that the high tensile suture materials used in arthroscopic surgery may also play a role; however, to date, there are no studies to support this assertion.
A number of different sutures are commonly used in arthroscopic shoulder surgery. Ethibond (Ethicon, Somerville, New Jersey, USA) is composed of polyethylene terepthalate with a polybutilate coating. It has been used for many years in both open and arthroscopic shoulder surgery. In the past two decades, various sutures have been introduced which claim to have higher tensile strength and superior handling characteristics to traditional sutures. Two of these sutures have become widely adopted in arthroscopic shoulder surgery. FibreWire (Arthrex, Naples, Florida, USA) is a polyethylene/polyester cobraid with a silicone coating that was introduced in 2002. Orthocord (Mitek, Raynham, Massachusetts, USA) is composed of a polyethylene fibre braided around a central polydiaxannone core with a 90% caprolactone and 10% glycolide copolymer coating [
3]. In arthroscopic shoulder surgery, these sutures are commonly used in conjunction with suture anchors. The suture is free to move within the anchor eyelet, thereby subjecting the suture material to bending and frictional forces that can lead to suture wear and the formation of particulate debris [
4]. Moreover, shuttling of sutures and use of a knot pusher to lay down arthroscopic knots may lead to similar frictional and abrasive forces on suture material.
Current literature suggests that suture material stimulates a foreign body reaction within synovial tissue, resulting in the recruitment of macrophages and inflammatory cells, which attempt to phagocytose the foreign material. Failure to digest the foreign body results in the formation of multinucleated giant cells which can be identified histologically. In their study in a rabbit model, Carr et al. demonstrated that eight commonly used orthopaedic sutures induce an inflammatory response in soft tissue. However, FibreWire, Ethibond, and Orthocord did not induce a significantly greater inflammatory response than other orthopaedic sutures [
3]. Further studies suggest that wear debris from orthopaedic biomaterials such as ultra-high-molecular-weight polyethylene (UHMWPE)—a common component of contemporary suture materials—induces an inflammatory response, with production of inflammatory cells and inflammatory cytokines IL-1 and TNF α [
5].
As part of a systematic approach to determine the causal pathways of PAGCL, the aim of this study was to determine whether suture material commonly used in arthroscopic shoulder surgery and their wear particles stimulate an inflammatory reaction in synovial tissue. Further, we sought to determine whether this inflammatory response was associated with the production of various matrix metalloproteinases (MMP) that have been implicated in cartilage destruction [
6]. We utilised a murine airpouch model to examine the inflammatory response of a synovial membrane towards commonly used sutures including intact Ethibond, FiberWire, Orthocord, and FiberWire suture wear particles. We chose to study FibreWire wear particles, as Savage et al’s study demonstrated that FibreWire produces significantly more wear debris under abrasion than Ethibond and Orthocord [
4]. The inflammatory response was quantified using both histological and immunohistochemical methods. We hypothesised that all intact suture material would trigger an inflammatory response and MMP production and that suture wear particles would induce a stronger biologic reaction than intact suture.
Discussion
Despite it being a significant cause of morbidity following arthroscopic shoulder surgery, little is known about the aetiology and molecular pathways underlying PAGCL. Hedbom and Hauselmann suggest that chondrolysis is promoted by molecular and biochemical signals received from the inflamed synovial membrane [
11]. Subsequently, an inflammatory response triggered by suture material or its wear debris may play a potential role in the development of PAGCL.
In this study, we examined the biologic response of synovial tissue to commonly used orthopaedic sutures material. A limitation of this study is that only three types of sutures were tested and only Fibrewire was examined in the particle form. These three sutures were chosen as they were felt to reflect the most commonly used sutures in current shoulder surgical practice. However, it is important to note that a similar inflammatory response may be seen with other suture materials not tested in our study. As has been highlighted above, FibreWire wear particles were chosen in light of previous studies demonstrating increased abrasive wear compared with Ethibond and Orthocord [
4]. Ideally, future studies should examine the bioreactivity of wear particles for all sutures being investigated, as sutures with a different material composition may elicit a different host response in particle form.
This study confirmed that Ethibond, FibreWire, and Orthocord sutures stimulate an inflammatory reaction in synovial tissue, as demonstrated by the presence of multinucleated giant cells. In addition, this study demonstrated a significantly increased inflammatory reaction to FibreWire wear particles compared to intact FibreWire. Moreover, the significant increase in MMP production in response to FibreWire wear particles compared to intact FibreWire demonstrated in this study points to a potential aetiological pathway in the development of chondrolysis.
The findings of the current study are consistent with those of Carr et al., who also demonstrated an increased number of multinucleated giant cells in response to eight commonly used orthopaedic suture materials implanted into the dorsal fascia of a rabbit [
3]. However, Carr et al.’s study tested only intact suture material rather than suture wear debris. In addition, the tests were conducted in the dorsal fascia of the rabbit, which does not recreate the synovial tissue that is produced by using a murine airpouch model. Accordingly, the results of the present study may more accurately reflect the biologic response to suture material specifically in synovial spaces such as joints and bursae.
The augmented inflammatory response to wear particles from polymers commonly used in orthopaedic surgery has been previously demonstrated in a murine airpouch by Wooley et al. [
5]. This study found that particles of UHMWPE, polymethylmethacrylate, cobalt-chrome, and titanium alloy elicited a significant increase in the number of inflammatory cells and inflammatory cytokines (IL-1, TNFα) when implanted into a murine airpouch. The present study confirms that wear particles from FibreWire suture produce histological evidence of an inflammatory reaction. Moreover, this inflammatory response is significantly greater than that produced in response to intact FibreWire suture, as demonstrated by a statistically significant increase in the number of multinucleated giant cells. To our knowledge, the present study is the first to demonstrate this finding.
In this study, we examined the activity of several MMP subtypes: MMP-1 (collagenase 1), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B), and MMP-13 (collagenase 3). Evidence suggests several of these MMP subtypes can mediate the destruction of articular cartilage by initiating proteolysis of the extracellular matrix proteins that regulate the biomechanical responses of articular cartilage [
6,
12,
13]. Each MMP subtype has been associated with a particular role in chondrolysis. MMP-1 is significantly increased in chondrolysis and has been shown to break down cartilage extra-cellular matrix by cleaving type II collagen. MMP-2 and MMP-9 degrade denatured type II collagen that was initially cleaved by activated MMP-1 [
6]. They also degrade aggrecan, a large proteoglycan critical for cartilage structure and mechanical properties. MMP-3 has been shown to degrade cartilage proteoglycans as well as the link protein which stabilises the non-covalent interactions between aggrecan and hyaluronan. MMP-13 can degrade both type II collagen and aggrecan. The present study used immunohistochemical methods to quantify the activity of these matrix metalloproteinase subtypes in the intact FibreWire and FibreWire particles groups at 4 weeks post-implantation. There was significantly greater production of MMP-1, MMP-2, MMP-9, and MMP-13 in the FibreWire particles group compared to the intact FibreWire group. A twofold increase was also noted for MMP-3 in the particles group. Although the
p value of 0.058 approached significance, it is possible that a larger sample size may have been required to detect a statistically significant difference. Our findings support the notion that several MMP subtypes are produced as a result of the increased immune response to FibreWire wear particles. We hypothesise that this is likely due to the fact that the smaller particles associated with wear debris offer more surface area for macrophage attachment and initiation of the inflammatory response. Previous studies have demonstrated that suture material can increase MMP production in tendon [
14]. However, as far as we are aware, this is the first study to demonstrate an increase in MMP expression in synovial tissue exposed to both intact suture and wear particles. This finding gives insight into a possible molecular mechanism by which suture material may contribute to the development of chondrolysis.
In our study, we did not attempt to quantify the expression of proinflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumour necrosis factor α (TNFα). A previous study by Lock et al. demonstrated that FibreWire significantly increased expression of TNFα in vitro compared to controls, but not other pro-inflammatory cytokines including IL-1α, IL-1β, or IL-8 [
15]. There is a substantial amount of experimental and clinical evidence that these pro-inflammatory cytokines are crucial in mediating inflammation and cartilage destruction in human osteoarthritis by upregulating the gene expression and synthesis of MMP subtypes [
16‐
18]. It is probable that this cascade of events is involved in PAGCL.
Our study has a number of limitations. The use of a murine subcutaneous airpouch to investigate the bioreactivity of different surgical materials in synovial tissue is a well-established, valid model [
19,
20]. However, it is unknown whether the results are completely translatable to humans, and this may therefore limit the study’s application to the clinical situation of PAGCL. Secondly, we studied the inflammatory response at two time points. The first time point of 1 week was chosen to investigate the initial reaction to foreign material, while the 4-week time point was considered adequate to mimic a more chronic setting. In the clinical setting, however, most patients who develop PAGCL will present with symptoms approximately 3 months following arthroscopy [
2]. Therefore, future studies would benefit from investigating the inflammatory response for a more prolonged period. Finally, as discussed above, future studies should examine the bioreactivity of all sutures commonly used in arthroscopic shoulder surgery and their wear particles.
These findings have significant clinical implications for orthopaedic surgeons. Firstly, this study highlights the importance of avoiding damage to suture material during arthroscopic procedures. Surgeons should be vigilant about monitoring for frayed or excess suture material intraoperatively, use sharp instruments when cutting sutures, and use a knot pusher judiciously due to its propensity to cause suture abrasion. Moreover, these findings have implications for surgical technique and suture anchor design, with Bardana et al’s study demonstrating that suture abrasion is significantly reduced when sutures are manipulated in line with the anchor’s eyelet, with minimal rotation or angulation [
21]. In addition, concerns over suture wear debris may make the use of knotless suture anchor systems preferable, by negating the movement of suture material through an eyelet and avoiding knot tying with a knot pusher, thereby minimising abrasion.