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Yoshida, M.;  Turner, P.R.;  Cabral, J.D. Intervertebral Disc Tissue Engineering with Additive Manufacturing. Encyclopedia. Available online: https://encyclopedia.pub/entry/40078 (accessed on 02 July 2024).
Yoshida M,  Turner PR,  Cabral JD. Intervertebral Disc Tissue Engineering with Additive Manufacturing. Encyclopedia. Available at: https://encyclopedia.pub/entry/40078. Accessed July 02, 2024.
Yoshida, Minami, Paul Richard Turner, Jaydee Dones Cabral. "Intervertebral Disc Tissue Engineering with Additive Manufacturing" Encyclopedia, https://encyclopedia.pub/entry/40078 (accessed July 02, 2024).
Yoshida, M.,  Turner, P.R., & Cabral, J.D. (2023, January 11). Intervertebral Disc Tissue Engineering with Additive Manufacturing. In Encyclopedia. https://encyclopedia.pub/entry/40078
Yoshida, Minami, et al. "Intervertebral Disc Tissue Engineering with Additive Manufacturing." Encyclopedia. Web. 11 January, 2023.
Intervertebral Disc Tissue Engineering with Additive Manufacturing
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This entry is adapted from the peer-reviewed paper 10.3390/gels9010025

Intervertebral disc (IVD) degeneration is one of the major causes of lower back pain, a common health condition that greatly affects the quality of life. With an increasing elderly population and changes in lifestyle, there exists a high demand for novel treatment strategies for damaged IVDs. Researchers have investigated IVD tissue engineering (TE) as a way to restore biological and mechanical functions by regenerating or replacing damaged discs using scaffolds with suitable cells. These scaffolds can be constructed using material extrusion additive manufacturing (AM), a technique used to build three-dimensional (3D), custom discs utilising computer-aided design (CAD). Structural geometry can be controlled via the manipulation of printing parameters, material selection, temperature, and various other processing parameters

intervertebral disc additive manufacturing tissue engineering 3D printing biomaterials

1. Introduction

Back pain statistics are stark; more than 80% of the adult population is affected by lower back pain, causing a huge socioeconomic burden, especially in developed countries [1][2]. Forty percent of this lower back pain is associated with intervertebral disc (IVD) degeneration, which manifests in 97% of the population greater than 50 years old [3].
Healthy IVDs serve several purposes and are uniquely structured to perform them. They cushion the stacked vertebrae and so must be resistant to compressive load, but still be flexible enough to allow spinal movement.
To meet these demands, the IVD consists of three parts; an internal type II collagen and proteoglycan-rich compartment (nucleus pulposus, NP), a fibrous outer part (annulus fibrosus, AF) composed of repeating layers of type I and II collagen-rich sheets (lamellae), and the cartilaginous end plates (CEPs) that are bound to both the vertebrae and disc and control nutrient import [4].

2. Regenerative Medicine

The regenerative medicine approach, using tissue-engineering scaffolds for IVD replacement, if successful, would be superior to current treatment strategies by alleviating pain, allowing short-term repair and long-term tissue regeneration, decreasing immune rejection and re-herniation, as well as preserving disc height and restoring the natural range of motion [5][6]. Over the last 20 years, researchers have successfully fabricated IVD constructs, with some focusing on the use of soft, injectable biomaterials to serve as carriers of cells and/or biomolecules to be delivered to the injury site; [7] however, none have managed to fully mimic the unique micro-scale architecture of native AF tissue. Although it is believed that utilizing biomaterials similar in composition to the natural ECM of native tissue would be ideal, combining two distinct fibrous and gelatinous tissues is problematic. Therefore, an adequate combination of biomaterials, fabrication methods, cells, and biochemical and mechanical factors must all be investigated for the development of successful IVD constructs [3].
The field of regenerative medicine is vast—a Medline search results in over 95,000 hits—and excellent reviews on the topic abound [8][9] with the incorporation of vasculature a key highlight [10].

3. Additive Manufacturing in IVD Tissue Engineering

Additive manufacturing, also known as rapid prototyping or solid free-form technique, forms 3D objects in a layer-by-layer manner to produce a three-dimensional structure based on computer-aided design (CAD) data [11][12]. Some of the major additive manufacturing technologies used for tissue engineering are fused deposition modelling (FDM), 3D bioprinting, selective laser sintering, stereolithography and melt electrowriting (MEW) [12][13]. The advantages of rapid prototyping are high efficiency, scaffold reproducibility and printability; and the ability to construct complex, biomimetic architectures and structures [14]. Additive manufacturing also allows researchers to control the mechanical and biological properties, as well as the biodegradation rate of the scaffold by controlling porosity and infill structure in addition to biomaterial selection [15].
More and more research facilities have started utilising additive manufacturing technologies for tissue engineering purposes. IVD tissue engineering is not an exception. The technique is highly advantageous to produce personalised IVD scaffolds, as IVD shapes are unique between individuals and IVDs have a highly complex architecture. In addition, rapid prototyping can integrate with imaging techniques, such as computed tomography scanning, to create scaffolds with a customised structure.
Although currently, a majority of the IVD tissue engineering studies utilise polymer electrospinning or hydrogel moulding, some of them have employed additive manufacturing technologies. Composite structures using multiple AM techniques, such as 3D melt extrusion and 3D bioprinting together, along with growth factor (GF) delivering nanoparticles (NPs) encapsulated within the bioink are used to recreate IVD complexity [16].
Three-dimensional printing is an extrusion-based, additive manufacturing technique that extrudes ink/bioink through a nozzle in a layer-by-layer manner to create 3D structure. It includes FDM and 3D bioprinting, which employ different ways of preparing ink (e.g., polymer solutions, molten thermoplastic polymers and cell-laden hydrogels) for extrusion.
FDM is used in tissue engineering due to its affordability and ease of scaffold manufacturing [17]. Unlike other additive manufacturing methods, FDM does not require any solvents and uses easy-to-handle materials [18]. The FDM process starts by slicing the 3D CAD data into layers. Then, the filaments or pellets of the thermoplastic materials are heated to extrude through the nozzle in specific configurations specified by the CAD model. The molten polymers are deposited in a layer-by-layer manner, fusing each layer to the previously printed layers [17]. The extrusion nozzle continues to move in the horizontal x-y plane while the build platform moves vertically down [19]. To print scaffolds with highly complex structures, the use of water-soluble support material is common. After printing is complete, the support materials are removed [19]. FDM is more common and inexpensive compared to selective laser sintering. Scaffolds fabricated with FDM technology tend to have high precision and mechanical strength [11]. The raw materials it can handle are limited to thermoplastic polymers, however, such as polycaprolactone (PCL), polylactic acid (PLA), acrylonitrile butadiene styrene, polyester, and polycarbonate. Encapsulation of other polymers in these materials has also been investigated for tissue engineering purposes [20].
For tissue engineering the whole IVD, FDM is also commonly used, mainly to provide mechanical strength to withstand the physical loads that are expected to be applied to the IVD scaffolds. The biomaterials used in this field are PCL, PLA, and FlexiFil PLA (FPLA) filaments [15][16][21][22][23][24][25]. The scaffolds created with the FDM technique have been used as CEP, AF region, structural support for the IVD, or for the whole IVD with different infill density between AF and NP regions. Other studies also employed FDM indirectly to create moulds to crosslink hydrogels to make IVD scaffold solely out of hydrogels, or to produce angular patterns simulating the collagen fibre orientation of the AF [26][27].
3D bioprinting is a type of 3D printing which uses hydrogels that encapsulate cells as a bioink. The printed scaffold is typically cured/crosslinked using UV light or other chemicals after the printing is complete. Similar to FDM and other extrusion-based 3D printing, the bioink is extruded through a nozzle and deposited onto a platform that typically, is cooled [14]. Some of the advantages of 3D bioprinting are that it allows zone-specific distribution of cells, and the encapsulated cells have high cell viability [11]. Although hydrogels tend to have insufficient mechanical properties for use in IVD tissue engineering, some studies have presented sufficient results utilising double network crosslinking or the addition of nanofibers [2][24].
Several studies bioprinted cell-laden hydrogels such as alginate, gellan gum–poly (ethylene glycol) diacrylate (GG–PEGDA), and gelatin–hyaluronic acid–sodium alginate seeded with chondrocytes and bone marrow stromal cells [15][16][21][24][25]. In these studies, hydrogels were used as part of the NP along with FDM scaffolds. The use of hydrogels generally increases the biocompatibility of the scaffolds and enhances cell adhesion and proliferation, hence it is a valid method for fabricating large tissue constructs such as IVDs [16].
Melt electrowriting is a newly emerging technique, that combines the best of both worlds of 3D printing and electrospinning. It deposits electrically controlled fine microfibres onto the platform to fabricate precise layer-by-layer scaffolds. The main feature of MEW is that it uses heat-molten biomaterials, but with much finer strands deposited compared to FDM. MEW also allows control over the microarchitecture of the scaffold unlike electrospinning [28]. This is particularly good for mimicking the microarchitecture of the native AF tissue.

References

  1. Whatley, B.R.; Kuo, J.; Shuai, C.; Damon, B.J.; Wen, X. Fabrication of a biomimetic elastic intervertebral disk scaffold using additive manufacturing. Biofabrication 2011, 3, 015004.
  2. Costa, J.B.; Silva-Correia, J.; Ribeiro, V.P.; da Silva Morais, A.; Oliveira, J.M.; Reis, R.L. Engineering patient-specific bioprinted constructs for treatment of degenerated intervertebral disc. Mater. Today Commun. 2019, 19, 506–512.
  3. Nerurkar, N.L.; Sen, S.; Huang, A.H.; Elliott, D.M.; Mauck, R.L. Engineered disc-like angle-ply structures for intervertebral disc replacement. Spine 2010, 35, 867.
  4. Mizuno, H.; Roy, A.K.; Vacanti, C.A.; Kojima, K.; Ueda, M.; Bonassar, L.J. Tissue-engineered composites of anulus fibrosus and nucleus pulposus for intervertebral disc replacement. Spine 2004, 29, 1290–1297.
  5. Stergar, J.; Gradisnik, L.; Velnar, T.; Maver, U. Intervertebral disc tissue engineering: A brief review. Bosn. J. Basic Med. Sci. 2019, 19, 130.
  6. Van Uden, S.; Silva-Correia, J.; Correlo, V.; Oliveira, J.; Reis, R. Custom-tailored tissue engineered polycaprolactone scaffolds for total disc replacement. Biofabrication 2015, 7, 015008.
  7. Ligorio, C.; Hoyland, J.A.; Saiani, A. Self-Assembling Peptide Hydrogels as Functional Tools to Tackle Intervertebral Disc Degeneration. Gels 2022, 8, 211.
  8. Henry, N.; Clouet, J.; Le Bideau, J.; Le Visage, C.; Guicheux, J. Innovative strategies for intervertebral disc regenerative medicine: From cell therapies to multiscale delivery systems. Biotechnol. Adv. 2018, 36, 281–294.
  9. Baumgartner, L.; Wuertz-Kozak, K.; Le Maitre, C.L.; Wignall, F.; Richardson, S.M.; Hoyland, J.; Ruiz Wills, C.; González Ballester, M.A.; Neidlin, M.; Alexopoulos, L.G.; et al. Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research. Int. J. Mol. Sci. 2021, 22, 703.
  10. Tian, A.; Yi, X.; Sun, N. Application of mesenchymal stem cells combined with nano-polypeptide hydrogel in tissue engineering blood vessel. Regen. Ther. 2022, 21, 277–281.
  11. Shen, S.; Chen, M.; Guo, W.; Li, H.; Li, X.; Huang, S.; Luo, X.; Wang, Z.; Wen, Y.; Yuan, Z. Three dimensional printing-based strategies for functional cartilage regeneration. Tissue Eng. Part B Rev. 2019, 25, 187–201.
  12. Subia, B.; Kundu, J.; Kundu, S. Biomaterial scaffold fabrication techniques for potential tissue engineering applications. In Tissue Engineering; InTech: London, UK, 2010.
  13. Yoshida, M.; Turner, P.R.; Ali, M.A.; Cabral, J.D. Three-Dimensional Melt-Electrowritten Polycaprolactone/Chitosan Scaffolds Enhance Mesenchymal Stem Cell Behavior. ACS Appl. Bio Mater. 2021, 4, 1319–1329.
  14. Ventola, C.L. Medical applications for 3D printing: Current and projected uses. Pharm. Ther. 2014, 39, 704.
  15. Hu, D.; Wu, D.; Huang, L.; Jiao, Y.; Li, L.; Lu, L.; Zhou, C. 3D bioprinting of cell-laden scaffolds for intervertebral disc regeneration. Mater. Lett. 2018, 223, 219–222.
  16. Sun, B.; Lian, M.; Han, Y.; Mo, X.; Jiang, W.; Qiao, Z.; Dai, K. A 3D-Bioprinted dual growth factor-releasing intervertebral disc scaffold induces nucleus pulposus and annulus fibrosus reconstruction. Bioact. Mater. 2021, 6, 179–190.
  17. Moroni, L.; Boland, T.; Burdick, J.A.; De Maria, C.; Derby, B.; Forgacs, G.; Groll, J.; Li, Q.; Malda, J.; Mironov, V.A. Biofabrication: A guide to technology and terminology. Trends Biotechnol. 2018, 36, 384–402.
  18. Bajaj, P.; Schweller, R.M.; Khademhosseini, A.; West, J.L.; Bashir, R. 3D biofabrication strategies for tissue engineering and regenerative medicine. Annu. Rev. Biomed. Eng. 2014, 16, 247–276.
  19. Zein, I.; Hutmacher, D.W.; Tan, K.C.; Teoh, S.H. Fused deposition modeling of novel scaffold architectures for tissue engineering applications. Biomaterials 2002, 23, 1169–1185.
  20. Yoshida, M.; Turner, P.R.; McAdam, C.J.; Ali, M.A.; Cabral, J.D. A comparison between β-tricalcium phosphate and chitosan poly-caprolactone-based 3D melt extruded composite scaffolds. Biopolymers 2022, 113, e23482.
  21. Schuurman, W.; Khristov, V.; Pot, M.W.; van Weeren, P.R.; Dhert, W.J.; Malda, J. Bioprinting of hybrid tissue constructs with tailorable mechanical properties. Biofabrication 2011, 3, 021001.
  22. Gloria, A.; Russo, T.; D’Amora, U.; Santin, M.; De Santis, R.; Ambrosio, L. Customised multiphasic nucleus/annulus scaffold for intervertebral disc repair/regeneration. Connect. Tissue Res. 2020, 61, 152–162.
  23. Marshall, S.L.; Jacobsen, T.D.; Emsbo, E.; Murali, A.; Anton, K.; Liu, J.Z.; Lu, H.H.; Chahine, N.O. Three-Dimensional-Printed Flexible Scaffolds Have Tunable Biomimetic Mechanical Properties for Intervertebral Disc Tissue Engineering. ACS Biomater. Sci. Eng. 2021, 7, 5836–5849.
  24. Zhu, M.; Tan, J.; Liu, L.; Tian, J.; Li, L.; Luo, B.; Zhou, C.; Lu, L. Construction of biomimetic artificial intervertebral disc scaffold via 3D printing and electrospinning. Mater. Sci. Eng. C 2021, 128, 112310.
  25. Wu, D.; Tan, J.; Yao, L.; Tian, J.; Luo, B.; Li, L.; Zhou, C.; Lu, L. Customized composite intervertebral disc scaffolds by integrated 3D bioprinting for therapeutic implantation. Compos. Part A Appl. Sci. Manuf. 2021, 147, 106468.
  26. Yang, J.; Wang, L.; Zhang, W.; Sun, Z.; Li, Y.; Yang, M.; Zeng, D.; Peng, B.; Zheng, W.; Jiang, X. Reverse Reconstruction and Bioprinting of Bacterial Cellulose-Based Functional Total Intervertebral Disc for Therapeutic Implantation. Small 2018, 14, 1702582.
  27. Moriguchi, Y.; Mojica-Santiago, J.; Grunert, P.; Pennicooke, B.; Berlin, C.; Khair, T.; Navarro-Ramirez, R.; Ricart Arbona, R.J.; Nguyen, J.; Härtl, R.; et al. Total disc replacement using tissue-engineered intervertebral discs in the canine cervical spine. PLoS ONE 2017, 12, e0185716.
  28. Turner, P.; Yoshida, M.; Ali, A.; Cabral, J. Melt electrowritten sandwich technique using sulforhodamine B to monitor stem cell behavior. Tissue Eng. Part C Methods 2020, 26, 519–527.
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Subjects: Materials Science, Biomaterials
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Minami Yoshida
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Paul Richard Turner
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Jaydee Dones Cabral
View Times: 391
Entry Collection: Biopharmaceuticals Technology
Revisions: 2 times (View History)
Update Date: 12 Jan 2023
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