Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration

Rudnik-Jansen, Imke; Tellegen, Anna R.; Beukers, Martijn; Öner, F. Cumhur; Woike, Nina; Mihov, George; Thies, Jens; Meij, Björn P.; Tryfonidou, Marianna A.; Creemers, Laura B.

doi:10.1016/j.spinee.2018.10.014

Cited by 23 publications

(23 citation statements)

References 77 publications

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“…One reason why BMPs may fail to induce NP regeneration may reside in the limited number and/or capacity of degenerated NP cells to adequately respond to growth factor stimulation. NP cell collection from non-extruded discs for isolation and expansion may induce (further) disc degeneration, as nucleotomy is a well-known method of inducing degeneration [28] and hence is not considered a feasible clinical approach. To this end, mesenchymal stromal cells (MSCs) are being clinically employed for NP regeneration.…”

Section: Introductionmentioning

confidence: 99%

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Krouwels

Iljas

Kragten

et al. 2020

IJMS

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Matrix production by nucleus pulposus (NP) cells, the cells residing in the center of the intervertebral disc, can be stimulated by growth factors. Bone morphogenetic proteins (BMPs) hold great promise. Although BMP2 and BMP7 have been used most frequently, other BMPs have also shown potential for NP regeneration. Heterodimers may be more potent than single homodimers, but it is not known whether combinations of homodimers would perform equally well. In this study, we compared BMP2, BMP4, BMP6, and BMP7, their combinations and heterodimers, for regeneration by human NP cells. The BMPs investigated induced variable matrix deposition by NP cells. BMP4 was the most potent, both in the final neotissue glysosaminoglycan content and incorporation efficiency. Heterodimers BMP2/6H and BMP2/7H were more potent than their respective homodimer combinations, but not the BMP4/7H heterodimer. The current results indicate that BMP4 might have a high potential for regeneration of the intervertebral disc. Moreover, the added value of BMP heterodimers over their respective homodimer BMP combinations depends on the BMP combination applied.

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Section: Introductionmentioning

confidence: 99%

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Krouwels

Iljas

Kragten

et al. 2020

IJMS

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“…To ensure successful clinical translation, the safety and efficacy of the formulation should be tested in an animal model that accurately mimics these conditions. Therefore, in the future, the proposed therapeutic strategy will be tested in dogs with experimentally induced and/or naturally occurring mild/moderate IVD degeneration [51,52]. On the other hand, the proposed therapeutic strategy may not be suitable as a single treatment for the advanced stages of DDD, where proteoglycans of the NP are degraded and disc cells are disappearing.…”

Section: Discussionmentioning

confidence: 99%

Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc

et al. 2019

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Locally delivered anti-inflammatory compounds can restore the homeostasis of the degenerated intervertebral disc (IVD). With beneficial effects on IVD cells, epigallocatechin 3-gallate (EGCG) is a promising therapeutic candidate. However, EGCG is prone to rapid degradation and/or depletion. Therefore, the purpose of this study was to develop a method for controlled EGCG delivery in the degenerated IVD. Primary IVD cells were isolated from human donors undergoing IVD surgeries. EGCG was encapsulated into microparticles by electrospraying of glutaraldehyde-crosslinked gelatin. The resulting particles were characterized in terms of cytocompatibility and anti-inflammatory activity, and combined with a thermoresponsive carrier to produce an injectable EGCG delivery system. Subsequently, electrospraying was scaled up using the industrial NANOSPIDER™ technology. The produced EGCG microparticles reduced the expression of inflammatory (IL-6, IL-8, COX-2) and catabolic (MMP1, MMP3, MMP13) mediators in pro-inflammatory 3D cell cultures. Combining the EGCG microparticles with the carrier showed a trend towards modulating EGCG activity/release. Electrospray upscaling was achieved, leading to particles with homogenous spherical morphologies. In conclusion, electrospray-based encapsulation of EGCG resulted in cytocompatible microparticles that preserved the activity of EGCG and showed the potential to control EGCG release, thus favoring IVD health by downregulating local inflammation. Future studies will focus on further exploring the biological activity of the developed delivery system for potential clinical use.

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“…[ 150 ] IVD degeneration in dogs can be triggered by an annular puncture [ 151 ] or nucleotomy. [ 152 ] Rudnik‐Jansen et al, has used the nucleotomized IVDs of beagles to assess the potential of the sustained release of corticosteroids in LBP symptoms relive. The release of triamcinolone acetonide by poly(esteramide) microspheres resulted in decreased NGF expression, suggesting its potential applicability for pain relief, although no beneficial effects could be observed on the degenerated tissue.…”

Section: Advanced Models Of Inflammation For Ivd Degenerationmentioning

confidence: 99%

“…The release of triamcinolone acetonide by poly(esteramide) microspheres resulted in decreased NGF expression, suggesting its potential applicability for pain relief, although no beneficial effects could be observed on the degenerated tissue. [ 152 ] Canine veterinary patients (beagles) suffering from spontaneous IVD degeneration and chronic low back pain have also been used to address the feasibility of COX‐2 inhibitor celecoxib loaded on a thermoresponsive hydrogel to treat IVD degeneration. The authors were able to demonstrate that quality of life of these patients was improved.…”

Section: Advanced Models Of Inflammation For Ivd Degenerationmentioning

confidence: 99%

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

Teixeira

Pereira

Almeida

et al. 2020

Adv Funct Materials

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The burden of chronic inflammatory diseases of joints and the spine is increasing with population ageing and unhealthy lifestyles. Articular cartilage and intervertebral discs (IVDs) are avascular and aneural tissues with abundant extracellular matrix, low cell density, and reduced regenerative capacity after damage or degeneration. The most advanced in vitro and ex vivo cell-/tissue-/biomaterial-based models and technologies to improve physiological mimicry are discussed, focusing on the impact of inflammation on articular repair/regeneration. In addition, in vivo models, developed to study cartilage and IVD repair/regeneration are addressed. While animal models continue to provide crucial mechanistic and preclinical data, more advanced and robust in vitro/ex vivo cartilage and IVD models, with appropriate extracellular matrix cues and allowing for cellular crosstalk, have seen an exponential growth in the last decade. Due to the complexity of articular microenvironments, adequate in vitro/ex vivo/in vivo models are essential to study the molecular mechanisms underlying articular diseases and develop new therapies for repair/regeneration.

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Safety of intradiscal delivery of triamcinolone acetonide by a poly(esteramide) microsphere platform in a large animal model of intervertebral disc degeneration

Cited by 23 publications

References 77 publications

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Bone Morphogenetic Proteins for Nucleus Pulposus Regeneration

Electrospray-Based Microencapsulation of Epigallocatechin 3-Gallate for Local Delivery into the Intervertebral Disc

Articular Repair/Regeneration in Healthy and Inflammatory Conditions: From Advanced In Vitro to In Vivo Models

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