Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model

Endres, Michaela; Abbushi, Alexander; Thomale, Ulrich W.; Čabraja, Mario; Kroppenstedt, Stefan; Morawietz, Lars; Casalis, Pablo Ariel; Zenclussen, María Laura; Aj, Lemke; Horn, Peter A.; Kaps, Christian; Woiciechowsky, Christian

doi:10.1016/j.biomaterials.2010.03.078

Cited by 48 publications

(42 citation statements)

References 27 publications

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“…These mechanisms seem to be more pronounced in heavily loaded discs of large adult animal models offering higher human like body weights. Smaller and younger animals achieve better results in regenerative disc therapies due to biomechanical, anatomical, and cellular differences offering higher regenerative potential [1,10,[12][13][14][15]. However, portability to the human situation seems to be more doubtful in small animal models and therapeutic strategies should finally be evaluated on large models with biomechanical properties similar to humans.…”

Section: Discussionmentioning

confidence: 99%

“…In a rabbit model of disc degeneration, a cell-free PGA/HA nucleus implant facilitated the formation of nucleus pulposus repair tissue and limited the loss of disc height [13]. In a recent rabbit study of disc degeneration, cell-free PGA hyaluronan implants accelerated the healing process and were able to induce disc regeneration with cell migration into the defect [14]. Another rabbit study found promising results after application of a novel cross-linked hyaluronate hydrogel and cross-linked chondroitin sulphate hydrogel [15].…”

Section: Introductionmentioning

confidence: 99%

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Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

et al. 2012

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Introduction Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model. Materials and methods 12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done. Results Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged. Conclusion Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

et al. 2012

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“…Badylak et al, 1995;Dejardin et al, 2001;Jonsson et al, 2011;Kim et al, 2012;Kim et al, 2014b ; Ledet et al, 2009;Visage et al, 2006 Danhier et al, 2012;El-Amin et al, 2003;Endres et al, 2010;Feng et al, 2011;Kim et al, 2014a;Lai et al, 2014;Liang et al, 2013;Mizuno et al, 2004;Ruan et al, 2010 Poly-ε- Sinha et al, 2004;Silva et al, 2007;Li et al, 2005a;Lopez et al, 2010;Koepsell et al, 2011a ;Koepsell et al, 2011b;Martin et al, 2014 Martino et al, 2005). However, chitosan gels tend to be much softer and...…”

Section: Natural Solid Biomaterialsmentioning

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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“…Because of the importance of nucleus pulposus to the normal function of the disk, this has been a logical area for study, particularly with a view of preventing degenerative changes following diskectomy of a herniated nucleus pulpous. Collagen-incorporated hydrogels [21,22] and polymer-linked hydrogels [23] have also been used; none of these products have been successfully used in humans to date.…”

Section: Spinal Surgerymentioning

confidence: 99%

Clinical Translation in Tissue Engineering—The Surgeon’s View

et al. 2015

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Tissue engineering has raised the hopes of many surgeons to provide products, to restore the functionality of tissues and organs. The orthopedic surgeon could use these products to replace missing tissue due to trauma, infection, or surgical removal of necrotic or neoplastic tissue. Although research has shown large interest in TE, and number of publications in this field has increased tremendously in the last decade, there are still very few products available.This review provides the view of leading surgeons and their view of TE in their area of expertise. Looking at spinal surgery, cartilage repair, tendon/ligament/muscle repair, large bone defects, and biomaterials, these experts report about the current demand, the current achievements, and the future of tissue engineering in the perspective of the surgeon. Furthermore, the difficulties of translating research results to usable products will be discussed.

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Intervertebral disc regeneration after implantation of a cell-free bioresorbable implant in a rabbit disc degeneration model

Cited by 48 publications

References 27 publications

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

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

Clinical Translation in Tissue Engineering—The Surgeon’s View

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