Degenerative disc disease is a painful, disabling condition. In the 1960s, total disc replacement (TDR) was conceived as an alternative treatment to spinal fusion and the resulting complications. Now, after two decades of clinical use in Europe, and FDA approval in the US, the outcomes of TDR and implant design can be assessed. A fundamental objective of device retrieval research is to understand successful implants and assess failures through explant analysis. Failure mechanisms of TDRs may be design-related and/or result from material degradation. Potential mechanisms of device failure come from studies on total joint replacements (TJR). Many TJR failures are due to component degradation, wear debris generation and the stimulation of an inflammatory response. In contrast to TJRs, little is known about in vivo degradation or the contribution of wear debris to biologically-mediated failure mechanisms of artificial discs. We provide evidence here that TDRs exhibit surface damage such as rim fracture, delamination, polyethylene (PE) penetration and in-vivo oxidation. We have established methods to quantify linear wear and volumetric wear in TDR components using microCT analysis. Moreover, we have a method to evaluate the volume, shape and size of wear particles in periprosthetic tissues using environmental scanning electron microscopy and have shown a positive correlation between the amount of debris and the extent of the inflammatory and histopathologic changes, which { may contribute to the major reasons for TDR failure, e.g. heterotopic ossification (HO) and intractable pain. } To investigate the potential failure modes of TDRs, we propose to elucidate mechanisms of in vivo degradation and the contribution of wear debris to biologically-mediated failure mechanisms. First, we will evaluate physical changes of TDR implants to determine if there are significant differences in wear and wear rate among three TDR designs (two contemporary designs and a historical control). The physical changes that are significant with respect to implant wear will be established for the three TDR designs. Second, we will evaluate the volume, shape and size distribution of wear particles in periprosthetic tissue of retrieved TDRs and determine if these findings are significantly correlated to TDR design. Lastly, we will evaluate the inflammatory { (osteo- and neuro-inflammatory mediators) } and histological responses in periprosthetic tissues and correlate these changes to the presence of PE wear debris { and clinical TDR failure. } Successful achievement of the proposed specific aims will provide essential information about implant performance and design, { and potential biological mediators that can be targeted to prevent the loss of implant mobility and the need for revision surgery due to pain. In addition, it } will provide essential information needed for informed health care decisions.

Public Health Relevance

Total disc replacement (TDR) was conceived in 1960 and now, after two decades of clinical use in Europe and a decade in the United States, the long-term and short-term outcomes of TDR and implant design can be assessed. A fundamental objective of our device retrieval research is to understand successful implants and assess failures through explant, tissue and clinical analysis. Thus, successful achievement of the proposed research will provide essential information on TDR implant performance and on clinical outcomes, which are needed for informed health care decisions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR056264-03
Application #
8212061
Study Section
Skeletal Biology Structure and Regeneration Study Section (SBSR)
Program Officer
Panagis, James S
Project Start
2010-02-18
Project End
2015-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$302,629
Indirect Cost
$86,629
Name
Drexel University
Department
None
Type
Schools of Engineering
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Cipriani, E; Bracco, P; Kurtz, S M et al. (2013) In-vivo degradation of poly(carbonate-urethane) based spine implants. Polym Degrad Stab 98:1225-1235
Punt, Ilona M; Austen, Shennah; Cleutjens, Jack P M et al. (2012) Are periprosthetic tissue reactions observed after revision of total disc replacement comparable to the reactions observed after total hip or knee revision surgery? Spine (Phila Pa 1976) 37:150-9
Punt, Ilona; Baxter, Ryan; van Ooij, Andre et al. (2011) Submicron sized ultra-high molecular weight polyethylene wear particle analysis from revised SB Charite III total disc replacements. Acta Biomater 7:3404-11
Ianuzzi, Allyson; Kurtz, Steven M; Kane, William et al. (2010) In vivo deformation, surface damage, and biostability of retrieved Dynesys systems. Spine (Phila Pa 1976) 35:E1310-6