Recent advances in biological therapies for disc degeneration: tissue engineering of the annulus fibrosus, nucleus pulposus and whole intervertebral discs

Hudson, Katherine; Alimi, Marjan; Grunert, Peter; Härtl, Roger; Bonassar, Lawrence J.

doi:10.1016/j.copbio.2013.04.012

Cited by 91 publications

(71 citation statements)

References 47 publications

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“…Hydrogels have been proposed as ideal scaffolds for NP replacement because of their similarity in mechanical properties to the native tissue (Yang and Li 2009). A number of natural biopolymers, including hyaluronic acid, alginate and collagen, have been explored as scaffold materials in order to meet the specific functional demands of the native NP (Nerurkar et al 2010;Iatridis et al 2013;Hudson et al 2013). Carboxymethylcellulose (CMC), a watersoluble polysaccharide derivative of cellulose (Klemm et al 2005), has also been evaluated as an NP tissue scaffold due to its biocompatibility, low-cost, FDAapproval and commercial availability in high purity forms (Ogushi et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Functional nucleus pulposus-like matrix assembly by human mesenchymal stromal cells is directed by macromer concentration in photocrosslinked carboxymethylcellulose hydrogels

Gupta

Nicoll

2014

Cell Tissue Res

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Intervertebral disc (IVD) degeneration is associated with several pathophysiologic changes of the IVD, including dehydration of the nucleus pulposus (NP). Tissue engineering strategies may be used to restore both biological and mechanical function of the IVD following removal of NP tissue during surgical intervention. Recently, photocrosslinked carboxymethylcellulose (CMC) hydrogels were shown to support chondrogenic, NP-like extracellular matrix (ECM) elaboration by human mesenchymal stromal cells (hMSCs) when supplemented with TGF-β3; however, mechanical properties of these constructs did not reach native values. Fabrication parameters (i.e., composition, crosslinking density) can influence the bulk mechanical properties of hydrogel scaffolds, as well as cellular behavior and differentiation patterns. The objective of this study was to evaluate the influence of CMC macromer concentration (1.5, 2.5 and 3.5 % weight/volume) on bulk hydrogel properties and NP-like matrix elaboration by hMSCs. The lowest macromer concentration of 1.5 % exhibited the highest gene expression levels of aggrecan and collagen II at day 7, corresponding with the largest accumulation of glycosaminoglycans and collagen II by day 42. The ECM elaboration in the 1.5 % constructs was more homogeneously distributed compared to primarily pericellular localization in 3.5 % gels. The 1.5 % gels also displayed significant improvements in mechanical functionality by day 42 compared to earlier time points, which was not seen in the other groups. The effects of macromer concentration on matrix accumulation and organization are likely attributed to quantifiable differences in polymer crosslinking density and diffusive properties between the various hydrogel formulations. Taken together, these results demonstrate that macromer concentration of CMC hydrogels can direct hMSC matrix elaboration, such that a lower polymer concentration allows for greater NP-like ECM assembly and improvement of mechanical properties over time.

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Section: Introductionmentioning

confidence: 99%

Functional nucleus pulposus-like matrix assembly by human mesenchymal stromal cells is directed by macromer concentration in photocrosslinked carboxymethylcellulose hydrogels

Gupta

Nicoll

2014

Cell Tissue Res

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“…In the laboratory, however, there are many studies investigating numerous scaffolds including chitosan, silk, collagen, alginate, polylactic acid, polygylcolic acid and polycaprolactone (PCL) (reviewed for the disc in Hudson et al, 2013;Kandel et al, 2008) and meniscus (Makris et al, 2011;Rongen et al, 2014;van Tienen et al, 2009). For both meniscus and intervertebral disc applications the addition of growth factors is also being studied.…”

Section: Tissue Engineeringmentioning

confidence: 99%

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

Roberts¹,

Turner²,

Evans³

2016

Comprehensive Biotechnology

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Synopsis/AbstractThe intervertebral disc in the spine and the meniscus in the knee are two fibrocartilaginous tissues which commonly are injured or become degenerate, causing significant clinical problems. The principals of tissue engineering, which are applicable elsewhere in the body, hold true for the disc and meniscus. Whilst there are some similarities with articular cartilage in terms of the molecules present, these fibrocartilages have their own peculiarities, some of which can be quite challenging. Following a description of the structure and anatomy of the disc and meniscus and the current clinical treatments, the different strategies for biological repair are described focusing particularly on cell therapy. The types of cells and scaffolds being investigated and how these can be modified are discussed.

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“…In addition to the medium-throughput screening of in vivo biocompatibility already available (Oliveira et al, 2014) further validation in ex vivo IVD organ culture models, preferably of clinically relevant sizes, may allow for standardised and reliable testing before finally using in vivo models (Hudson et al, 2013).…”

Section: Towards Efficient Biomaterials Designmentioning

confidence: 99%

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

Schutgens¹,

Tryfonidou²,

Smit³

et al. 2015

eCM

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Intervertebral disc (IVD) degeneration is associated with most cases of cervical and lumbar spine pathologies, amongst which chronic low back pain has become the number one cause of loss of quality-adjusted life years. In search of alternatives to the current less than optimal and usually highly invasive treatments, regenerative strategies are being devised, none of which has reached clinical practice as yet. Strategies include the use of stem cells, gene therapy, growth factors and biomaterial carriers. Biomaterial carriers are an important component in musculoskeletal regenerative medicine techniques. Several biomaterials, both from natural and synthetic origin, have been used for regeneration of the IVD in vitro and in vivo. Aspects such as ease of use, mechanical properties, regenerative capacity, and their applicability as carriers for regenerative and anti-degenerative factors determine their suitability for IVD regeneration. The current review provides an overview of the biomaterials used with respect to these properties, including their drawbacks. In addition, as biomaterial application until now appears to have been based on a mix of mere availability and intuition, a more rational design is proposed for future use of biomaterials for IVD regeneration. Ideally, high-throughput screening is used to identify optimally effective materials, or alternatively medium content comparative studies should be carried out to determine an appropriate reference material for future studies on novel materials.

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Recent advances in biological therapies for disc degeneration: tissue engineering of the annulus fibrosus, nucleus pulposus and whole intervertebral discs

Cited by 91 publications

References 47 publications

Functional nucleus pulposus-like matrix assembly by human mesenchymal stromal cells is directed by macromer concentration in photocrosslinked carboxymethylcellulose hydrogels

Functional nucleus pulposus-like matrix assembly by human mesenchymal stromal cells is directed by macromer concentration in photocrosslinked carboxymethylcellulose hydrogels

Tissue Engineering of Fibrocartilaginous Tissues: The Intervertebral Disc and the Meniscus

Biomaterials for intervertebral disc regeneration: past performance and possible future strategies

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