M6®, Spinal Kinetics - 6 degree-of-freedom cervical disc prosthesis

[Slackwater]

The M6® clinical trial started as mentioned in the article library posting. The FDA clinical trial is mentioned in the company's press release, but I can't find it on clinicaltrials.gov. The M6 abstract from the Orthopaedic Research Society 2008 Annual Meeting is:<UL TYPE=SQUARE>Quality and Quantity of Motion of the Cervical Spine after Total Disc Replacement Using a Compressible Six-Degree-of-Freedom Prosthesis[/list]The PDF is about 170KB. Below acronyms were oblique on my first reading.<UL TYPE=SQUARE>FE: Flexion-Extension
AR: Axial Rotation
LB: Lateral Bending
ROM: Range-of-Motion

Copyright © 2008 Orthopaedic Research Society

"Discussion: Overall, the data suggest that this 6-DOF TDR provides similar kinematics to the lower cervical spine as compared to the intact spine in FE and AR. The M6 prosthesis maintained the range and quality of motion in FE to intact levels. The AR ROM decreased but was within physiologic norms of healthy subjects. The decrease in LB ROM after implantation was similar to what has been reported for other cervical prostheses, and is likely related to the surgical technique, which retained the uncinate processes and antero-lateral annulus. We also observed a significant decrease in the coupled lateral bending motion for each degree of angular motion in axial rotation. Further studies are needed to discern the effects of compressive preload, uncinatectomy, and the removal of the antero-lateral band of the annulus on the response of the M6 prosthesis in lateral bending. Finally, controlled in vitro comparisons of this compressible, six-degree of freedom disc design with more constrained cervical prostheses designs will provide valuable data in advancing total disc replacement technology."[/list]The M6, by Spinal Kinetics, w/ 6DOF, results are pending more testing, trials, surgical outcome measurements, ... Think the mobile core ADR - TDR devices are 5DOF, don't quote me on this. This post ~might belong/get moved to the article library if the FE, AR numbers are pushed into table format.

Slackwater

[Terry]

This looks like a great disc design. I am eager to see what their design will look like for a lumbar disc replacement. I think that the design is revolutionary and makes perfect sense.

Terry Newton

[FIXITRIGHT]

It does look like a good design. It has a more natural action to it. It doesn't seem to be restricted to 2 axis. Looks like it would have much more shock absorbing ability than some of the others.

[chasswen]

i think theres to many diff mat'l used for the body to reject.
just my 3 cents.
but the design to cool if it acceptable to the body.

[Don]

I think mechanically it looks great, but, I work in a fermentation and biologics plant and can't help but also think that it looks like a potential breeding ground for contaminants. Too many pores and nooks and crannies for critters to hide and grow in. But, medias do not have immune systems, that can actively fight infections. Hopefully they know that this sort of material can stay "clean" in the human body.

[Harrison]

Don, interesting point. Here’s my 2 cents on an issue we’ve not discussed that often within this forum.

Blood flow around a diseased area, or a new device, is not a given. There are many factors that can inhibit blood flow to the spinal tissues, namely, disease. Obviously, surgery creates scar tissue and will change the natural innate anatomy -- especially blood flow -– which may then alter the immune function (see the abstract below).

The spinal discs themselves are avascular (and when healthy) are intact and under slight vacuum. But they still must absorb certain nutrients from proper blood flow. But for some reason, they can be a “spongey magnet” for certain microbes; perhaps because this environment is less active immunologically? Or a “window is opened,” when there’s a compromise to the disc annulus? See this topic with abstracts for more insights into this critical but neglected area of research.

So, back to Don’s point: if the device is “complicated” in terms of design, and Charles’ point of different materials, does that raise the risk factors for infection? Whatever the case, in the next few years, we will be hearing much more about the role of biofilms in the context of infections. The discoveries are unfolding as we discuss these issues…

That said, the M6 looks very slick from a mechanical standpoint. It appears (competitively or comparatively) accurate in terms of its emulation of a biological spinal disc.

____________________________________________


Relationship between the blood flow in a spinal nerve root and its functional state in patients with lumbar disk hernia

Authors: Shchurova, E.; Khudyaev, A.Source: Human Physiology, Volume 33, Number 1, February 2007 , pp. 69-74(6) Publisher: MAIK Nauka Interperiodica

Capillary blood flow in the spinal roots was studied in 52 patients with lumbar osteochondrosis during discectomy for lumbar disk herniation, before and after decompression. It was determined that the value of the capillary blood flow in the nerve root influenced markedly the severity of the pain syndrome, the threshold of sensitivity to pain in the dermatome involved, and the strength of the indicator group of muscles. It was shown that the level of intact reserves of the spinal nerve root microcirculation influenced the degree of functional restoration after the discectomy.

[Don]

Originally posted by Harrison:

Capillary blood flow in the spinal roots was studied in 52 patients with lumbar osteochondrosis during discectomy for lumbar disk herniation, before and after decompression. It was determined that the value of the capillary blood flow in the nerve root influenced markedly the severity of the pain syndrome, the threshold of sensitivity to pain in the dermatome involved, and the strength of the indicator group of muscles.

So, maybe my backs not that bad, I just have good blood flow and that makes me a wuss?

When I first saw the M6 disc, I thought of the "packed" agitator seals on large fermentors, which are great seals and even better sources of contamination. I hope they work as good as they look.

[Slackwater]

Originally posted by Don:
When I first saw the M6 disc, I thought of the "packed" agitator seals on large fermentors, which are great seals and even better sources of contamination. I hope they work as good as they look.

Agree, lots of small places to store things. Side effects may be as you describe for contamination. The containment of wear particles is an OK objective, I suggest.



My simple analogy has been ADR / TDR might be like Total Hip Arthroplasty (THA); causes for THA revision limiting survivorship may have a relationship to ADR / TDR. The main cause for THA revision has been aseptic loosening. What are the causes of aseptic loosening? I think it's partially wear particles, PolyEthylene (PE) or metal. The THA (Hip) revision rate is measureable because of the decades of use.

Some of the THA revision rate may be/is caused by the use of earlier PE materials. The good news is the PE is upgraded. ADR / TDR Polyethylene particle load decreased a statistically significant amount post-1998. "PE in TDR changed in 1997, from gamma sterilization in air to gamma sterilization in a first generation polymeric barrier package."

THA Survivorship Perspectives:<UL TYPE=SQUARE><LI>THA in Italy has a cumulative survival rate at 7 years of 96.8%, affected by pathology, where the worst conditions are rheumatoid arthritis, femoral neck fracture, and sequelae of coxitis or Paget's disease (2007).
<LI>THA two- to 9-year surviorship of alumina ceramic-on-ceramic THA is 99.3%, without prior surgery (2006).
<LI>THA using Metal-on-Metal Articulation in active patients younger than 50 yrs old, 10-year survivorship with the end point of revision (ie, exchange of at least one prosthetic or bearing component) was 100%, 2008 in France (Level of Evidence: Level IV, therapeutic study)
<LI>2005 Mayo Clinic: Long-term follow-up studies of cemented total hip arthroplasty (THA) are restricted to a few successful designs. The most studied design, the Charnley THA, has demonstrated excellent, though not perfect, survivorship at long-term follow-up in most studies. Patient-related factors including age, gender, and patient diagnosis, affect implant survivorship. (2005)[/list]Hips used to get fused, as most spines are today. It's not that simple though comparing ADR/TDR with THA; improved training, techniques, successful designs and patient related factors will affect ADR / TDR success rates.

ADR / TDR revisions to date are done for causes other than aseptic loosening, I believe. Two references follow below that may relate to containing wear particles:

The first reference below indicates polyethylenes may cause issues not only involving inflammation and bone degradation, but also decreased bone formation.

The second reference below describes tissues surrounding a prosthetic joint include the fibrous pseudomembrane and joint capsule surrounding an arthroplasty, mostly related to Total Hip Arthroplasty (THA) and Total Knee Arthroplasty (TKA). Wear particles (metal or polyethylene) are somewhat trapped by the joint capsule. THA, TKA aseptic loosening is measurable & the most common cause of arthroplasty failure, this affects survivorship.


============================

#1<UL TYPE=SQUARE>(C) 2008 Copyright Orthopaedic Research Society, 2008 Annual Mtg
Ultrahigh Molecular Weight Polyethylene Wear Debris Inhibits Osteoblastic Differentiation of Bone Marrow Osteoprogenitors and MC3T3-E1 Preosteoblasts In Vitro
Richard Chiu, Ting Ma, Robert L. Smith, Stuart B. Goodman
Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, CA

Introduction: Osteolysis and prosthetic loosening may result from the biological effects of polyethylene wear debris. Polyethylene particles not only trigger inflammation and bone degradation, but also inhibit bone formation through the suppression of osteoblast function. However, whether polyethylene particles also inhibit osteoprogenitor differentiation is unknown. In this study, we examined the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on the ability of primary murine bone marrow osteoprogenitors and MC3T3-E1 cells, a murine osteoprogenitor cell-line, to differentiate into osteoblasts in vitro.

...
Discussion: This study has shown that UHMWPE particles inhibit the differentiation of primary bone marrow osteoprogenitors and MC3T3-E1 preosteoblasts in a dose-dependent fashion, with complete suppression of osteogenesis occuring at particle doses ≥ 0.150% v/v. Previous studies have shown that polymethylmethacrylate (PMMA) particles inhibit the differentiation of osteoprogenitors in heterogeneous bone marrow cell cultures, which contain hematopoietic cells and precursors that may influence the response of osteoprogenitor cells to particles [2]. This study confirms that the inhibitory effects of PMMA particles on the differentiation of osteoprogenitors in heterogeneous marrow stromal cell cultures are also observed with polyethylene wear debris. This study also confirms that these inhibitory effects can be reproduced in pure osteoprogenitor populations such as the MC3T3-E1 cell-line. The mechanism of polyethylene particle-induced implant loosening may therefore involve not only inflammation and bone degradation, but also decreased bone formation by osteoblasts due to the inhibition of osteoprogenitor differentiation.[/list]===================================

#2<UL TYPE=SQUARE>(c) 2007 Copyright Orhtopaedic Research Society, 6th Combined Meeting, Orthopaedic Research Societies, October 20-24, 2007
Peri-Implant Osteolysis
Australian and New Zealand Orthopaedic Research Society and the Orthopaedic Research Society (USA)

PERI-IMPLANT PATHOLOGY OF REVISION ARTHROPLASTY
NA Athanasou Department of Pathology, Nuffield Department of Orthopaedic Surgery, University of Oxford, Nuffield Orthopaedic Centre, Oxford, OX3 7LD

Peri-implant tissues surrounding a failed prosthetic joint include the fibrous pseudomembrane and joint capsule surrounding an arthroplasty. These tissues often contain numerous polymeric and metallic biomaterial wear particles derived from the implant components (1,2,3). Acrylic cement, composed of polymethylmethacrylate (PMMA), is dissolved in processing and appears as an empty space surrounded by foreign body macrophages and giant cells; PMMA particles vary considerably in size but are often large; if the PMMA contains radio-opaque markers, such as barium or zirconium, these appear as weakly birefringent granules within the PMMA spaces. Ultra-high-molecular weight polyethylene (UHMWP) wear particles are usually submicron in size. Millions of these particles are phagocytosed by plump macrophages, which often have a glassy or granular cytoplasm. Larger flakes of UHMWP, measuring up to several hundred micrometers in size, may also be noted and are commonly surrounded by macrophages and giant cells. Metals used in prosthetic implants include low-carbon stainless steel, cobalt-based alloys and titanium alloys. If metal wear is extensive, this may result in gross black discolouration of the peri-implant tissues. The metal particles are usually small and found either within macrophages or in aggregates in extra cellular connective tissue. Metal components may undergo corrosion, resulting in the release of metal ions into soft tissues and the bloodstream. Ceramic wear particles are granular and non-birefringent; they are usually submicron in size and lie in small aggregates either within macrophages or in extra cellular connective tissue. These particles do not usually produce a pronounced foreign body macrophage response unless debris from other material is also present.

Aseptic loosening is the most common cause of arthroplasty failure. It is usually associated with late implant failure, occurring several years after the implant has been in place. Both mechanical and biological factors contribute to the pathogenesis of aseptic loosening. Release of wear particles results in a heavy foreign body macrophage response to these particles. These macrophages produce numerous cytokines, notably necrosis tumour necrosis factor, interleukin-1 and interleukin-6, all of which promote osteoclast formation and resorption activity. Fibroblasts in the pseudomembrane produce macrophage-colony stimulating factor and the receptor activator for nuclear factor κB ligand both of which are required for osteoclast differentiation of wear particle-associated macrophages. The importance of macrophage involvement in aseptic loosening is particularly evident in cases of aggressive granulomatosis where there is early failure of the prosthesis (4); in these cases, extensive osteolysis around the implant is associated with a heavy macrophage response to prolific wear particle generation.

Histologically, the pseudomembrane in aseptic loosening is often thick and composed of collagenous connective tissue in which there are focal areas of necrosis or tissue degeneration (1,2,3). A heavy macrophage and giant cell response to wear particles is commonly found. There may be abundant amorphous tissue composed of a mixture of particulate wear debris and necrotic collagen. Focal areas of dystrophic calcification, scattered fragments of eroded bone, areas of fibrocartilaginous metaplasia and focal haemosiderin deposits may also be noted. In some cases there may also be deposits of pyrophosphate crystals and amyloid. The pseudomembrane like bone does not contain lymphatic vessels so particles found in lymph nodes draining arthroplasty tissues are derived from the pseudocapsule (which does contain lymphatics). In some cases of aseptic loosening granulomatous pseudotumours may form around the loose prosthetic implant. These lesions are characterised by large collections of macrophages and foreign body giant cells in response to wear particles. These granulomatous pseudotumours may present as a bone tumour or as a soft tissue mass.[/list]Bryan Cervical disc has what appears to be a flexible (?polyurethane?) seal around it also, like the M6® from SpinalKinetics. Doing word look-up to translate some of these articles, Slackwater

[Harrison]

Wow, this is a load to share with the community. It is very difficult to compare studies in wear between hips and spine for many reasons. I'll chime back in soon, but I asked a hip arthroplasty patient to take a looksey at this. I consider him to well-versed in this area.

Also, don't forget the role that contaminants/pathogens/bugs play in both disease and failures. This HUGE factor is usually not accounted for in terms of study designs, so this risk factor is sometimes ignored and therefore not examined. Please see this previous topic for reference:

ADR Complications & Hip Arthroplasty Failures
http://adrsupport.org/eve/forums/a/t...1/m/5251007792

Slack, thx for your research and TLC. It helps many!

[Slackwater]

Originally posted by Harrison:
It is very difficult to compare studies in wear between hips and spine for many reasons.

Agree.

I like simple answers. I didn't find that the primary reason for THA revisions over several decades will apply to ADR / TDR as the primary reason for a revision. ADR / TDR issues might be in technique, placement, kinematics, facet forces as a result of one of the proceeding items, ... so far ...

The above was more sharing data with Don and thinking about a reason to encapsulate the wear particles on the M6 or Bryan cervical disc replacements. Theken is encapsulated, so is ... brain fade. Where's the coffee?