Fabrication of a novel whole tissue-engineered intervertebral disc for intervertebral disc regeneration in the porcine lumbar spine

Yang, Fei; Xiao, Dongqin; Zhao, Qiao; Chen, Zhu; Liu, Kang; Chen, Shixiao; Sun, Xiao; Yue, Qiuju; Zhang, Ruolan; Feng, Gang

doi:10.1039/c8ra06943c

Cited by 15 publications

(9 citation statements)

References 44 publications

(50 reference statements)

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“…However, the natural complexity of the AF structure and composition is uniquely designed to resist an amazing variety of mechanical loads, both in nature and magnitude, which makes AF TE particularly challenging [ 363 , 364 ]. Indeed, integrated replacement strategies for the whole IVD are also commonly explored targeting both the NP and the AF, through highly hydrated composites [ 365 , 366 , 367 ]. Evidence has been predominantly collected in vitro/ex vivo, whereas in vivo studies comprise a far smaller proportion, which relates to the need for development of appropriate animal models previous to clinical trials.…”

Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

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Intervertebral disc (IVD) degeneration is a major risk factor of low back pain. It is defined by a progressive loss of the IVD structure and functionality, leading to severe impairments with restricted treatment options due to the highly demanding mechanical exposure of the IVD. Degenerative changes in the IVD usually increase with age but at an accelerated rate in some individuals. To understand the initiation and progression of this disease, it is crucial to identify key top-down and bottom-up regulations’ processes, across the cell, tissue, and organ levels, in health and disease. Owing to unremitting investigation of experimental research, the comprehension of detailed cell signaling pathways and their effect on matrix turnover significantly rose. Likewise, in silico research substantially contributed to a holistic understanding of spatiotemporal effects and complex, multifactorial interactions within the IVD. Together with important achievements in the research of biomaterials, manifold promising approaches for regenerative treatment options were presented over the last years. This review provides an integrative analysis of the current knowledge about (1) the multiscale function and regulation of the IVD in health and disease, (2) the possible regenerative strategies, and (3) the in silico models that shall eventually support the development of advanced therapies.

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Section: Ivd Regeneration Strategies: Biological Targets and Biomamentioning

confidence: 99%

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Baumgartner

Wuertz‐Kozak

Maitre

et al. 2021

IJMS

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“…After 4 and 8 weeks of implantation the cell-scaffold construct retained its original height and showed a histological gross appearance that resembled that of the native tissue. Moreover, the compressive Young’s modulus of the construct was 58.4 ± 12.9 MPa, similar to that measured for the native tissue (71.5 ± 18.2 MPa) [140]. Under a similar concept, Choy et al studied the potential of biphasic scaffolds for full IVD tissue engineering.…”

Section: Tissue Engineering and Regeneration Strategiesmentioning

confidence: 52%

“…Therefore, the gap between the translation of this research to the clinic still remains fairly large with many hurdles to overcome, leading to the need for future research [127,144]. With degenerative disc disease posing such a large problem for individuals and society, and no current ideal treatment options that come without complications, there is a welcoming for future research in the field of tissue engineered biomaterials for the solution of total intervertebral disc replacement [128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144].…”

Section: Discussionmentioning

confidence: 99%

“…In the last few years, tissue engineered scaffolds for total intervertebral disc replacement have risen to the forefront of current biomaterial literature and research in order to address the challenges mentioned above [123,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143,144]. Scaffolds have been fabricated using both natural and synthetic materials, as well as most containing embedded cells for natural tissue growth and integration [127].…”

Section: Tissue Engineering and Regeneration Strategiesmentioning

confidence: 99%

“…Although this first study shows an interesting 3D printing approach, the final scaffold represents a rather homogeneous construct and not the clearly compartmented native organ. Yang et al overcame this issue by designing and fabricating a triphasic scaffolds that aimed at recapitulating the three main structures of native IVD, the nucleus pulposus and the inner and outer rings of the annulus fibrosus, while targeting the mechanical properties of human IVD [140]. The authors used a chitosan hydrogel to mimic the inner nucleus pulposus that was then surrounded by a poly(butylene succinate-co-terephthalate) (PBST) fiber film and a poly(ether ether ketone) (PEEK) ring to mimic the inner and outer annulus fibrosus, respectively.…”

Section: Tissue Engineering and Regeneration Strategiesmentioning

confidence: 99%

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Materials for the Spine: Anatomy, Problems, and Solutions

2019

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Disc degeneration affects 12% to 35% of a given population, based on genetics, age, gender, and other environmental factors, and usually occurs in the lumbar spine due to heavier loads and more strenuous motions. Degeneration of the extracellular matrix (ECM) within reduces mechanical integrity, shock absorption, and swelling capabilities of the intervertebral disc. When severe enough, the disc can bulge and eventually herniate, leading to pressure build up on the spinal cord. This can cause immense lower back pain in individuals, leading to total medical costs exceeding $100 billion. Current treatment options include both invasive and noninvasive methods, with spinal fusion surgery and total disc replacement (TDR) being the most common invasive procedures. Although these treatments cause pain relief for the majority of patients, multiple challenges arise for each. Therefore, newer tissue engineering methods are being researched to solve the ever-growing problem. This review spans the anatomy of the spine, with an emphasis on the functions and biological aspects of the intervertebral discs, as well as the problems, associated solutions, and future research in the field.

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Flexible support material maintains disc height and supports the formation of hydrated tissue engineered intervertebral discs in vivo

Fidai,

Kim,

Lintz

et al. 2024

JOR Spine

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BackgroundMechanical augmentation upon implantation is essential for the long‐term success of tissue‐engineered intervertebral discs (TE‐IVDs). Previous studies utilized stiffer materials to fabricate TE‐IVD support structures. However, these materials undergo various failure modes in the mechanically challenging IVD microenvironment. FlexiFil (FPLA) is an elastomeric 3D printing filament that is amenable to the fabrication of support structures. However, no present study has evaluated the efficacy of a flexible support material to preserve disc height and support the formation of hydrated tissues in a large animal model.MethodsWe leveraged results from our previously developed FE model of the minipig spine to design and test TE‐IVD support cages comprised of FPLA and PLA. Specifically, we performed indentation to assess implant mechanical response and scanning electron microscopy to visualize microscale damage. We then implanted FPLA and PLA support cages for 6 weeks in the minipig cervical spine and monitored disc height via weekly x‐rays. TE‐IVDs cultured in FPLA were also implanted for 6 weeks with weekly x‐rays and terminal T2 MRIs to quantify tissue hydration at study endpoint.ResultsResults demonstrated that FPLA cages withstood nearly twice the deformation of PLA without detrimental changes in mechanical performance and minimal damage. In vivo, FPLA cages and stably implanted TE‐IVDs restored native disc height and supported the formation of hydrated tissues in the minipig spine. Displaced TE‐IVDs yielded disc heights that were superior to PLA or discectomy‐treated levels.ConclusionsFPLA holds great promise as a flexible and bioresorbable material for enhancing the long‐term success of TE‐IVD implants.

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Fabrication of a novel whole tissue-engineered intervertebral disc for intervertebral disc regeneration in the porcine lumbar spine

Abstract: A novel whole tissue-engineered IVD consisting of a triphasic scaffold demonstrated excellent biocompatibility and mechanical properties in the porcine lumbar spine.

Cited by 15 publications

References 44 publications

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Multiscale Regulation of the Intervertebral Disc: Achievements in Experimental, In Silico, and Regenerative Research

Materials for the Spine: Anatomy, Problems, and Solutions

Flexible support material maintains disc height and supports the formation of hydrated tissue engineered intervertebral discs in vivo

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