Towards engineering distinct multi‐lamellated outer and inner annulus fibrosus tissues

Iu, Jonathan; Santerre, J. Paul; Kandel, Rita A.

doi:10.1002/jor.23793

Cited by 16 publications

(10 citation statements)

References 50 publications

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“…However, the ECM composition of AF tissue changes between the outer region, which is abundant in collagen type I with little proteoglycans, and the inner region, which is rich in collagen type II and proteoglycans 88 . Supplementation of culture media with insulin transferrin‐selenium, proline, dexamethasone, and pyruvate to a multi‐lamellated outer and inner AF engineered tissue was able to promote the accumulation of collagen type I in the outer region and aggrecan and collagen type II the in inner region, replicating the ECM distribution of the native tissue 89 …”

Section: Electrospinningmentioning

confidence: 96%

“…88 Supplementation of culture media with insulin transferrin-selenium, proline, dexamethasone, and pyruvate to a multi-lamellated outer and inner AF engineered tissue was able to promote the accumulation of collagen type I in the outer region and aggrecan and collagen type II the in inner region, replicating the ECM distribution of the native tissue. 89 Considering the beneficial effects on ECM components in maintaining and/or directing cell phenotype, 90 and degradation rate. 91 Given the importance of mechanical loading in disc degeneration and regeneration, bioreactor systems have been utilized to provide more physiologically relevant conditions for the development of functional IVD substitutes.…”

Section: Optimization Of Cells and Cues For Ivd Tementioning

confidence: 99%

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Electrospinning and 3D bioprinting for intervertebral disc tissue engineering

et al. 2020

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Intervertebral disc (IVD) degeneration is a major cause of low back pain and represents a massive socioeconomic burden. Current conservative and surgical treatments fail to restore native tissue architecture and functionality. Tissue engineering strategies, especially those based on 3D bioprinting and electrospinning, have emerged as possible alternatives by producing cell-seeded scaffolds that replicate the structure of the IVD extracellular matrix. In this review, we provide an overview of recent advancements and limitations of 3D bioprinting and electrospinning for the treatment of IVD degeneration, focusing on future areas of research that may contribute to their clinical translation.

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Section: Electrospinningmentioning

confidence: 96%

Section: Optimization Of Cells and Cues For Ivd Tementioning

confidence: 99%

Electrospinning and 3D bioprinting for intervertebral disc tissue engineering

et al. 2020

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“…Inclusion of an endplate region to stimulate integration of tissue‐engineered discs in vitro and in vivo has also been attempted in constructs composed of layered electrospun polycarbonate urethane for the AF region, surrounding a calcium polyphosphate cylinder seeded directly with NP cells . These constructs were cultured for 2 weeks in serum‐containing media prior to implantation in a defect created in the bovine caudal disc space and adjacent vertebral body for 4 weeks .…”

Section: Progress In Whole Disc Tissue Engineeringmentioning

confidence: 99%

“…After Inclusion of an endplate region to stimulate integration of tissueengineered discs in vitro and in vivo has also been attempted in constructs composed of layered electrospun polycarbonate urethane for the AF region, surrounding a calcium polyphosphate cylinder seeded directly with NP cells. 53,66 These constructs were cultured for 2 weeks in serum-containing media prior to implantation in a defect created in the bovine caudal disc space and adjacent vertebral body for 4 weeks. 48 While there was histological evidence of integration between the engineered disc components after in vivo implantation, these constructs were not sized to replace the whole bovine caudal disc, and there was evidence of subsidence into the vertebral body.…”

Section: In Vivo Evaluation Of Engineered Discs In the Spinementioning

confidence: 99%

Promise, progress, and problems in whole disc tissue engineering

Gullbrand

Smith

et al. 2018

JOR Spine

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Intervertebral disc degeneration is frequently implicated as a cause of back and neck pain, which are pervasive musculoskeletal complaints in modern society. For the treatment of end stage disc degeneration, replacement of the disc with a viable, tissue-engineered construct that mimics native disc structure and function is a promising alternative to fusion or mechanical arthroplasty techniques. Substantial progress has been made in the field of whole disc tissue engineering over the past decade, with a variety of innovative designs characterized both in vitro and in vivo in animal models. However, significant barriers to clinical translation remain, including construct size, cell source, culture technique, and the identification of appropriate animal models for preclinical evaluation. Here we review the clinical need for disc tissue engineering, the current state of the field, and the outstanding challenges that will need to be addressed by future work in this area. K E Y W O R D Sanimal models, biomaterials, biomechanics, disc degeneration, mesenchymal stem cells | INTRODUCTIONBack and neck pain place a significant social and economic burden on modern society, affecting nearly 1 in 2 individuals annually. In the United States alone, these conditions are associated with an estimated $194 billion in yearly medical costs and lost wages. Back pain is commonly associated with degenerative disc disease, a progressive condition with complex underlying etiology, during which component tissues undergo an array of cellular and structural changes that ultimately compromises biomechanical function.Although the pathological manifestations of disc degeneration are well characterized, the underlying causes and the origins of discogenic pain are still not well understood, impeding the development of effective therapies. Current treatments for disc degeneration do not restore native disc structure and function, and thus exhibit limited long-term efficacy. Tissue engineering offers the promise of generating de novo, living structures that recapitulate the form, function, and biology of healthy host tissues with the potential to treat a variety musculoskeletal disorders, including disc degeneration. Here, we review recent progress in the field of whole disc tissue engineering as well as the barriers that will need to be addressed for the successful clinical translation of engineered discs. | INTERVERTEBRAL DISC STRUCTURE AND MECHANICAL FUNCTIONThe intervertebral discs of the spine are composite structures composed of the central nucleus pulposus (NP), the peripheral annulus fibrosus (AF), and the superior and inferior cartilaginous end plates.The extracellular matrix (ECM) of the NP is composed primarily of proteoglycans and type II collagen; the high proteoglycan content of | INTERVERTEBRAL DISC DEGENERATION AND TREATMENTDegeneration of the intervertebral discs may occur with aging or following injury. While the exact pathophysiology of disc degeneration remains unclear, it is known to involve a progressive cascade of cellular,...

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“…Several studies have combined two different biomaterials to create an engineered whole disc replacement. ,− One composite whole disc replacement, using PLA mesh for the AF and alginate gel for the NP, exhibited increased ECM over time in vitro , some integration between the two regions after 12 weeks in culture, an increase in mechanical properties over time, and shows promise in maintaining disc height in an animal model. , Another composite whole disc replacement using electrospun PCL for the AF and agarose for the NP observed compressive stress relaxation behavior and an increase in compressive modulus over weeks in culture. Additional animal studies of this implant highlighted the need for integration into the surrounding anatomy, so engineered end plates of an additional material were added to the design. , These types of complex tissue engineered whole disc approaches recapitulate anatomical and some mechanical properties of the disc and show promise for restoring disc height .…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional-Printed Flexible Scaffolds Have Tunable Biomimetic Mechanical Properties for Intervertebral Disc Tissue Engineering

Marshall

Jacobsen

Emsbo

et al. 2021

ACS Biomater. Sci. Eng.

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The intervertebral disc (IVD) exhibits complex structure and biomechanical function, which supports the weight of the body and permits motion. Surgical treatments for IVD degeneration (e.g., lumbar fusion, disc replacement) often disrupt the mechanical environment of the spine which lead to adjacent segment disease. Alternatively, disc tissue engineering strategies, where cell-seeded hydrogels or fibrous biomaterials are cultured in vitro to promote matrix deposition, do not recapitulate the complex IVD mechanical properties. In this study, we use 3D printing of flexible polylactic acid (FPLA) to fabricate a viscoelastic scaffold with tunable biomimetic mechanics for whole spine motion segment applications. We optimized the mechanical properties of the scaffolds for equilibrium and dynamic moduli in compression and tension by varying fiber spacing or porosity, generating scaffolds with de novo mechanical properties within the physiological range of spine motion segments. The biodegradation analysis of the 3D printed scaffolds showed that FPLA exhibits lower degradation rate and thus has longer mechanical stability than standard PLA. FPLA scaffolds were biocompatible, supporting viability of nucleus pulposus (NP) cells in 2D and in FPLA+hydrogel composites. Composite scaffolds cultured with NP cells maintained baseline physiological mechanical properties and promoted matrix deposition up to 8 weeks in culture. Mesenchymal stromal cells (MSCs) cultured on FPLA adhered to the scaffold and exhibited fibrocartilaginous differentiation. These results demonstrate for the first time that 3D printed FPLA scaffolds have de novo viscoelastic mechanical properties that match the native IVD motion segment in both tension and compression and have the potential to be used as a mechanically stable and biocompatible biomaterial for engineered disc replacement.

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Towards engineering distinct multi‐lamellated outer and inner annulus fibrosus tissues

Cited by 16 publications

References 50 publications

Electrospinning and 3D bioprinting for intervertebral disc tissue engineering

Electrospinning and 3D bioprinting for intervertebral disc tissue engineering

Promise, progress, and problems in whole disc tissue engineering

Three-Dimensional-Printed Flexible Scaffolds Have Tunable Biomimetic Mechanical Properties for Intervertebral Disc Tissue Engineering

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