Biomimetic Lumbar Artificial Intervertebral Disc

Rapid Prototyping of a Biomimetic Lumbar Artificial Intervertebral Disc for Total Disc Replacement Arthroplasty

Abstract

Intervertebral discs (IVDs) are soft tissues that provide flexibility to the vertebral column by transmitting and distributing the large loads that act on the spine. Degeneration of any of the IVD components may cause low back pain (LBP) in a significant amount of the world’s population due to change in the entire disc’s mechanics. IVD arthroplasty or total disc replacement (TDR) is an alternative to spinal fusion by allowing some movement to be restored to the patient. Existing artificial disc replacements (AIDs) have not the same properties of a normal biological IVDs, and may cause further complications such as metallosis, osteolysis, and implant dislodgement. Currently, there exist no AIDs that allow the same range of motion, mechanical performance, and comparable life span to a biological IVD. This projects seeks to create a soft and flexible biomimetic AID with equivalent mechanical properties by rapid prototyping to be able to personalize the implant to suit the anatomical characteristics of each individual.

Background

The spinal column provides rigidity and stability to the skeleton; it is divided into 4 distinct spinal regions: cervical (C1 – C7), thoracic (T1 – T12), lumbar (L1 – L5), and sacral (S1 – S5). Each section of the spine is composed of osseous elements called vertebrae separated by intervertebral discs (IVD) attached to the surfaces of the vertebral bodies. IVDs are composed of soft tissue with three main components: the gelatinous nucleus pulposus (NP) at the centre, the surrounding concentric collagen layers of the annulus fibrosus (AF), and the cartilaginous endplates that attach the NP and the AF to the vertebral bodies. Degeneration of any of these soft tissues will cause the mechanical behaviour of the entire disc to change [1]. In particular, degeneration of the nucleus pulposus causes the loss of osmotic pressure and hydration. Consequently, the fluid exchange is reduced and affects the tissue’s cellular function and disc height diminution. Producing as a result an increase in disc instability and impingement of the roots of the spine triggering discogenic pain [2] [3].

IVD degeneration in any of the spinal regions directly contributes to instability, axial back pain [3]. The strongest compression forces that affect the components of the spine are experienced at the height of the lumbar-sacral regions (L4-L5 and L5-S1) [4] [5] [6] often resulting in lumbar or low back pain (LBP) [3]. LBP is the second most frequent reason for a medical intervention in the USA [7], affecting an estimated 80% [6] of the world’s population at some point of their lives; with an estimated economic impact of approximately $100 billion in the USA [8] [9], and £12 billion in the UK [10] per annum.

While surgery is not the first choice to treat discogenic pain, it is considered after a six month period of conservative pain management fails to ease the patient’s pain [3] [6]. Surgical options for LBP include dynamic stabilization, spinal fusion, and total disc replacement (TDR) surgery [3] [6]. TDR is an alternative treatment that may be used in some patients instead of spinal fusion [3]; it consists removing the damaged IVD and using a mechanical device to replace it and restore movement to the affected zone [1] [3] [11]. This method aims to restore movement to the spine and prevent early degeneration and disease of adjacent segments that may be caused by the load and motion redistribution of a fused spinal segment [3] [12]; TDR has a significantly reduced surgery time, shorter postoperative recuperation, improved patient recovery, and acceptable level of morbidity [3] [11] [13]. Among the most used artificial intervertebral discs (AIDs) commercially available now include: Charite artificial discs (Depuy, Johnson and Johnson) [14] [13], ProDisc-L (DePuy Synthes) [3] [13].

1. Statement of the Problem

AIDs are more commonly made from “hard” materials, such as metals, ceramics and hard polymers [11] [13] [15], but these experience wear and may even result in metallosis, osteolysis and implant dislodgement [11] [16] Current technologies consist mostly of superposed metallic plates with another core material acting as the nucleus pulposus. The surfaces of the implants connected to the vertebras may lead to the formation of tight bonds that cause clashing movements between the plate and core materials hindering the implant-bone interface. In reality, these AIDs have limited mobility compared to normal biological IVDs, and may further deteriorate the patient’s condition by dislodging from the vertebral bodies or releasing debris from the wear and friction of the implant [11] [17]. Flexible AIDs made from polymeric materials have been deemed as unable to sustain the high mechanical loads of the spine [15].

Shikinami et al pioneered a flexible 3D woven fabric AID made form bioinert ultrahigh molecular weight polyethylene (UHMWPE) [16]. Their AID consisted of mimicking the collagenous fibre arrangement of a normal biological IVD using a triaxial fibre arrangement able to exhibit similar mechanical properties to a human IVD; however, they acknowledged that wear debris occurred at the bone-implant interface in vitro and their fixation method could cause direct bonding to the vertebral bodes or cause fibrous connective tissues to cover the interface [17]. The Bonassar group at Cornell University have devised a composite AID made form TE-TDR and ovine AF and NP cell. After being implanted in the rat caudal lumbar spine for six months, it was shown to maintain adequate disc height (78%) and ECM deposition into the vertebral bodies and endplate. Nevertheless, this composite AID was only tested axially and it is not known if such composite would be able to resist bending and torsion [18].

More recently, a fused deposition modelling (FDM) 3D printed composite TE-TDR PCL scaffold was created to replicate a rabbit IVD [19]. Their results show that their model exhibited higher compressive stiffness than that of a human IVD and prove that personalised implants created by rapid prototyping are promising in the future. However, their proposed implant does not mimic the internal structure of a normal biological IVD. Thus far, there are no commercial AID implants that cater to the unique anatomical features of each individual. Furthermore, current soft AID implants being investigated have the following concerns: these seldom mimic the radially alternating lamellas of the AF, have been thoroughly tested in the six degrees of freedom that the human spine endures, or promote appropriate implant – vertebral body integration.

2. Research Objectives

The guiding research question is: Would a 3D printed “soft” biomimetic AID be able to have the same mobility and mechanical properties of a normal biological IVD? This involves the following specific objectives:

1. To create an accurate 3D printed biomimetic implant mimicking the radially alternating lamellas of the annulus fibrosus.
2. Assess the implant’s endurance and fatigue resistance.
3. To promote cellular integration of the implant’s top and bottom surfaces into the vertebral bodies without hindering the implant’s performance.
4. Compare the biomimetic implant to commercially available AIDs implants.

3. Methodology

The research plan will proceed in two phases. During the first phase, 1) I will collect anthropometric data to generate a geometrically accurate IVD model from CT/MRI databases using Materialise Mimics (Materialise NV). From this model, 2) I will create a CAD model of a biomimetic IVD implant mimicking the AF lamellas , and 3) perform FEA on the model to determine if the chosen materials will be able to sustain the in vivo loads a natural IVD experiences. In this first phase, I will also perform FEA analysis of commercially available artificial disc implants and compare them to our biomimetic IVD implant. The final step of the first phase is to 3D print the biomimetic model and if needed 4) optimize it to account for any warping or curling of the material, or any other defects caused by the rapid prototyping.

During the second phase, 5) I will test implant wear, endurance, and other mechanical properties and 6) biocompatibility and osseous integration to the top and bottom surfaces of the biomimetic IVD and assess cellular attachment to the vertebras. I will also 7) compare our biomimetic IVD to commercially available artificial discs such as Charite (Depuy, Johnson and Johnson) and ProDisc-L (DePuy Synthes).

4. Tentative Timeline

Phase 1: Green Phase 2: Blue

2018

2019

2020

Fall

Spring

Fall

Spring

Fall

Spring

Fall

Finalize project description

1) Anthropometric data acquisition

2) Biomimetic CAD model of IVD implant.

3) FEA analysis of CAD model

4) 3D printing optimization of model

5) Mechanical testing of 3D printed model

6) Biocompatibility and integration of biomimetic IVD implant

7) Comparison to commercially available TDR implants

8) Preparing Thesis and Defense

Defense

X

5. References

[1]	D. H. Cortes and D. M. Elliot, “The Intervertebral Disc: Overview of Disc Mechanics,” in The Intervertebral Disc, Springer-Verlag Wien, 2014, pp. 17-31.
[2]	S. M. Richardson, A. J. Freemont and J. A. Hoyland, “Pathogenesis of Intervertebral Disc Degeneration,” in The Intervertebral Disc, Springer-Verlag Wien, 2014, pp. 177-200.
[3]	D. G. Sueki and B. Barcohana, “Lumbar Spine Disc Replacement,” in Rehabilitation for the Postsurgical Orthopedic Patient, St. Louis, Elsevier Mosby, 2013, pp. 335-360.
[4]	A. MRÓZ, K. SKALSKI and W. WALCZYK, “New lumbar disc endoprosthesis applied to the patient’s anatomic features,” Acta of Bioengineering and Biomechanics, vol. 17, no. 2, pp. 25-34, 2015.
[5]	J. L. Pinheiro-Franco and P. Roussouly, “The Importance of Sagittal Balance for the Treatment of Lumbar Degenerative Disk Disease,” in Advanced Concepts in Lumbar Degenerative Disk Disease, Spinger, 2016, pp. 703-724.
[6]	R. R. Patel, J. A. Rihn, R. K. Ponnoppan and T. J. Albert, “Surgical Indications for Lumbar Degenerative Disease,” in The Intervertebral Disc, Wien, Springer-Verlag, 2014, pp. 213-224.
[7]	A. Borthakur and R. Reddy, “Imaging Modalities for Studying Disc Pathology,” in The Intervertebral Disc, Wien, Springer-Verlag, 2014, pp. 201- 212.
[8]	K. JN, “Lumbar disc disorders and low-back pain: socioeconomic factors and consequences [review].,” J Bone Joint Surg Am, vol. 88, pp. 21-24, 2006.
[9]	W. T. Crow and D. R. Willis, “Estimating Cost of Care for Patients With Acute Low Back Pain: A Retrospective Review of Patient Records,” The Journal of the American Osteopathic Association, vol. 109, pp. 229-233, 2009.
[10]	D. G. T. Whitehurst, S. Bryan, M. Lewis, J. Hill and E. M. Hay, “Exploring the cost-utility of stratified primary care management for low back pain compared with current best practice within risk-defined subgroups,” Annals of the Rheumatic Diseases, vol. 17, pp. 1796-1802, 2012.
[11]	C. K. Lee and V. K. Goel, “Artificial disc prosthesis: design concepts and criteria,” The Spine Journal , vol. 4, pp. 209S-218S, 2004.
[12]	F. García Vacas, F. Ezquerro Juanco, A. Pérez de la Blanca, M. Prado Novoa and S. Postigo Pozo, “The flexion-extension response of a novel lumbar intervertebral disc prosthesis: A finite element study,” Mechanism and Machine Theory, vol. 73, pp. 273-281, 2013.
[13]	J. M. Vital and L. Boissiere, “Total Disc Replacement,” Orthopaedics & Traumatology: Surgery & Research , vol. 100, pp. S1-S14, 2014.
[14]	R. D. Guyer and D. D. Ohnmeiss, “A Prospective Randomized Comparison of Two Lumar Total Disk Replacements,” in Surgery for Low Back Pain, Springer-Verlag, 2010, pp. 193-197.
[15]	D. G. Kang, M. D. Helgeson and A. R. Vaccaro, “Spinal Motion Restoration Devices for the Degenerative Disc,” in The Intervertebral Disc, Springer-Verlag, 2014, pp. 225-246.
[16]	Y. Shikinami, Y. Kotani, B. W. Cunningham, K. Abumi and K. Kaneda, “A Biomimetic Artificial Disc with Improved Mechanical Properties Compared to Biological Intervertebral Discs,” Advanced Functional Materials, vol. 14, no. 11, 2004.
[17]	Y. Shikinami, Y. Kawabe, K. Yasukawa, K. Tsuta, Y. Kotani and K. Abumi, “A biomimetic artificial intervertebral disc system composed of a cubic three-dimensional fabric,” The Spine Journal, vol. 10, pp. 141-152, 2010.
[18]	R. D. Bowles, H. H. Gebhard, R. Hartl and L. J. Bonassar, “Tissue-engineered intervertebral discs produce new matrix, maintain disc height, and restore biomechanical function to the rodent spine,” Proceedings of the National Academy of Sciences, vol. 108, no. 32, p. 13106-13111, 2011.
[19]	S. Van Uden, J. Silva-Correia, V. M. Correlo, J. M. Oliveira and R. L. Reis, “Custom-Tailored Tissue Engineered Polycaprolactone Scaffolds for Total Disc Replacement,” Biofabrication, vol. 7, no. 1, 2015.