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2. Drug retention after intradiscal administration.

Author

Rudnik-Jansen, Imke, Du, Jie, Karssemakers-Degen, Nina, Tellegen, Anna R., Wadhwani, Parvesh, Zuncheddu, Daniele, Meij, Björn P., Thies, Jens, Emans, Pieter, Öner, Fetullah C., Mihov, George, Garcia, Joao Pedro, Ulrich, Anne S., Grad, Sibylle, Tryfonidou, Marianna A., Ingen, Hugo van, and Creemers, Laura B.

Subjects
DRUG delivery systems, KNEE joint, INTERVERTEBRAL disk, LABORATORY rats, NUCLEAR magnetic resonance
Abstract

Intradiscal drug delivery is a promising strategy for treating intervertebral disk degeneration (IVDD). Local degenerative processes and intrinsically low fluid exchange are likely to influence drug retention. Understanding their connection will enable the optimization of IVDD therapeutics. Release and retention of an inactive hydrophilic fluorine-19 labeled peptide (19F-P) as model for regenerative peptides was studied in a whole IVD culture model by measuring the 19F-NMR (nuclear magnetic resonance) signal in culture media and IVD tissue extracts. In another set-up, noninvasive near-infrared imaging was used to visualize IR-780, as hydrophobic small molecular drug model, retention upon injection into healthy and degenerative caudal IVDs in a rat model of disk degeneration. Furthermore, IR-780-loaded degradable polyester amide microspheres (PEAM) were injected into healthy and needle pricked degenerative IVDs, subcutaneously, and in knee joints with and without surgically-induced osteoarthritis (OA). Most 19F-P was released from the IVD after 7 days. IR-780 signal intensity declined over a 14-week period after bolus injection, without a difference between healthy and degenerative disks. IR-780 signal declined faster in the skin and knee joints compared to the IVDs. IR-780 delivery by PEAMs enhanced disk retention beyond 16 weeks. Moreover, in degenerated IVDs the IR-780 signal was higher over time than in healthy IVDs while no difference between OA and healthy joints was noted. We conclude that the clearance of peptides and hydrophobic small molecules from the IVD is relatively fast. These results illustrate that development of controlled release formulations should take into account the target anatomical location and local (patho)biology. Highlights: Tissue degeneration alters molecule retention in tissues with a low fluid clearance Extrapolating retention between different anatomical locations is not recommended Drug delivery platforms should be customized to anatomical location Drug delivery platforms should be customized to existing pathophysiology [ABSTRACT FROM AUTHOR]

Published
2024
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3. Pulmonary cryptococcoma in a Friesian horse in the Netherlands

Author

MMB, MMB Medische Staf, van Eijk, Nadiah M.H.A., Houben, Rosa M.A.C., Tellegen, Anna R., Hagen, Ferry, Ankringa, Nynke, MMB, MMB Medische Staf, van Eijk, Nadiah M.H.A., Houben, Rosa M.A.C., Tellegen, Anna R., Hagen, Ferry, and Ankringa, Nynke

Published
2024

4. Pulmonary cryptococcoma in a Friesian horse in the Netherlands

Author

VPDC pathologie, Equine Internal Medicine, CS_Welfare & emerging diseases, Diagnostische beeldvorming, Pathology, van Eijk, Nadiah M.H.A., Houben, Rosa M.A.C., Tellegen, Anna R., Hagen, Ferry, Ankringa, Nynke, VPDC pathologie, Equine Internal Medicine, CS_Welfare & emerging diseases, Diagnostische beeldvorming, Pathology, van Eijk, Nadiah M.H.A., Houben, Rosa M.A.C., Tellegen, Anna R., Hagen, Ferry, and Ankringa, Nynke

Published
2024

5. Pulmonary cryptococcoma in a Friesian horse in the Netherlands

Author

van Eijk, Nadiah M. H. A., Houben, Rosa M. A. C., Tellegen, Anna R., Hagen, Ferry, Ankringa, Nynke, van Eijk, Nadiah M. H. A., Houben, Rosa M. A. C., Tellegen, Anna R., Hagen, Ferry, and Ankringa, Nynke

Abstract

A 6-year-old female Friesian horse was admitted with pyrexia, dullness, weight loss, watery faeces and mild bilateral mucoid nasal discharge. Radiographic and ultrasonographic examination of the thorax indicated a large mid-thoracic soft tissue mass, and the horse was euthanased because of a poor prognosis. At postmortem examination, it was found that the lung tissue was partly replaced by multiple to coalescing soft tissue lesions with a yellow gelatinous aspect, varying in size up to 15 ? 15 ? 20 cm. Histologically, the mass showed mild pyogranulomatous inflammation associated with large numbers of globular encapsulated 10?20 ?m yeasts with or without narrow-based budding, consistent with multiple coalescing cryptococcomas. Quantitative PCR testing of formalin-fixed paraffin-embedded tissue led to the identification of Cryptococcus gattii species complex. To the authors? knowledge, this is the first case reported in the Netherlands of pulmonary cryptococcomas due to C. gattii sensu lato in a horse that had never travelled abroad.

Published
2024

6. Prevalence of presumed endplate junction failure at the lumbosacral intervertebral junction in dogs on computed tomography.

Author

Tellegen, Anna R., Beukers, Martijn, Meij, Björn P., Tryfonidou, Marianna A., and Veraa, Stefanie

Abstract

Lumbosacral intervertebral disc herniation (IVDH) is a common cause of lower back pain in dogs and humans. In humans, the vertebral endplate to annulus fibrosus (AF) attachment was implicated as an alternative failure site besides rupture through the dorsal AF (AFF). Endplate junction failure (EPJF) is characterized by IVDH, accompanied by endplate irregularities (type A), rim avulsions (type B), or larger bony avulsions on one (type C) or both endplates (type D), associated with an adjacent endplate defect. This retrospective study reports the CT prevalence of presumed EPJF in dogs and its associations with signalment and other lumbosacral CT abnormalities. CT scans, including the lumbosacral spine of dogs obtained at two institutions, were assessed, yielding 324 scans. Presumed EPJF was found in 69 dogs (21%) and AFF in 68 dogs (21%), commonly at the caudal endplate of the last lumbar vertebra (71%). The remaining 187 dogs did not show presumed EPJF or AFF. Presumed EPJF type A occurred in 49/69, type B in 19/69, and type C in 1/69 dogs. Univariable logistic regression showed that presumed EPJF was associated with significantly higher IVDH grades than AFF. In the multiple regression model, presumed EPJF and AFF remained associated with increasing age and spondylosis deformans. Presumed EPJF was associated with vertebral endplate sclerosis and AFF with zygapophyseal joint osteoarthritis. In conclusion, presumed EPJF was observed on CT in 21% of dogs with lumbosacral IVDH. Prospective studies correlating EPJF on CT with clinical, surgical, and histopathological findings are needed for a better understanding of the underlying pathology and clinical relevance. [ABSTRACT FROM AUTHOR]

Published
2024
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9. A Novel Standardized Method for Aiding to Determine Left Atrial Enlargement on Lateral Thoracic Radiographs in Dogs

Author

Szatmári, Viktor, Hofman, Zelie M M, van Bijsterveldt, Nynke J, Tellegen, Anna R, Vilaplana Grosso, Federico R, CS_Welfare & emerging diseases, Interne geneeskunde GD, Klinische infectiologie en microb. lab., and Diagnostische beeldvorming

Subjects
myxomatous mitral valve degeneration, heart failure, pimobendan, dyspnea, stage B
Abstract

BACKGROUND: Left atrial enlargement indicates severe cardiac disease. Although the gold standard for determining left atrial size is echocardiography, many veterinary practices lack the necessary equipment and expertise. Therefore, thoracic radiography is often used to differentiate cardiogenic pulmonary edema from primary respiratory diseases and to facilitate distinguishing dogs with stage B1 and B2 mitral valve degeneration. METHODS: The goal was to test a new standardized method for identifying radiographic left atrial enlargement. On a lateral radiograph, a straight line was drawn from the dorsal border of the tracheal bifurcation to the crossing point of the dorsal border of the caudal vena cava and the most cranial crus of the diaphragm. If a part of the left atrium extended this line dorsally, it was considered enlarged. Echocardiographic left atrial to aortic ratio (LA:Ao) was used as a reference. Thirty-nine observers with various levels of experience evaluated 90 radiographs, first subjectively, then applying the new method. RESULTS: The new method moderately correlated with LA:Ao (r = 0.56-0.66) in all groups. The diagnostic accuracy (72-74%) of the subjective assessment and the new method showed no difference. CONCLUSIONS: Though the new method was not superior to subjective assessment, it may facilitate learning and subjective interpretation.

Published
2023

10. Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Author

Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, Tryfonidou, Marianna A, Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, and Tryfonidou, Marianna A

Abstract

Objective: Drug delivery platforms that allow for gradual drug release after intra-articular administration have become of much interest as a treatment strategy for osteoarthritis (OA). The aim of this study was to investigate the safety and efficacy of an intra-articular sustained release formulation containing celecoxib (CXB), a cyclooxygenase-2 (COX-2) selective inhibitor. Methods: Amino acid-based polyesteramide microspheres (PEAMs), a biodegradable and non-toxic platform, were loaded with CXB and employed in two in vivo models of arthritis: an acute inflammatory arthritis model in rats (n = 12), and a randomized controlled study in chronic OA dog patients (n = 30). In parallel, the bioactivity of sustained release of CXB was evaluated in monolayer cultures of primary dog chondrocytes under inflammatory conditions. Results: Sustained release of CXB did not alleviate acute arthritis signs in the rat arthritis model, based on pain measurements and synovitis severity. However, in OA dog patients, sustained release of CXB improved limb function as objective parameter of pain and quality of life based on gait analysis and owner questionnaires. It also decreased pain medication dependency over a 2-month period and caused no adverse effects. Prostaglandin E2 levels, a marker for inflammation, were lower in the synovial fluid of CXB-treated dog OA patients and in CXB-treated cultured dog chondrocytes. Conclusion: These results show that local sustained release of CXB is less suitable to treat acute inflammation in arthritic joints, while safe and effective in treating pain in chronic OA in dogs.

Published
2023

11. A Novel Standardized Method for Aiding to Determine Left Atrial Enlargement on Lateral Thoracic Radiographs in Dogs

Author

CS_Welfare & emerging diseases, Interne geneeskunde GD, Klinische infectiologie en microb. lab., Diagnostische beeldvorming, Welfare & Emerging Diseases, Szatmári, Viktor, Hofman, Zelie M M, van Bijsterveldt, Nynke J, Tellegen, Anna R, Vilaplana Grosso, Federico R, CS_Welfare & emerging diseases, Interne geneeskunde GD, Klinische infectiologie en microb. lab., Diagnostische beeldvorming, Welfare & Emerging Diseases, Szatmári, Viktor, Hofman, Zelie M M, van Bijsterveldt, Nynke J, Tellegen, Anna R, and Vilaplana Grosso, Federico R

Published
2023

12. Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Author

Diagnostische beeldvorming, Chirurgie, CS_Cancer, CS_Locomotion, Equine Musculoskeletal Biology, Dep Clinical Sciences, Locomotion - Equine Sciences, Locomotion - Surgery (CA), OnGo, Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, Tryfonidou, Marianna A, Diagnostische beeldvorming, Chirurgie, CS_Cancer, CS_Locomotion, Equine Musculoskeletal Biology, Dep Clinical Sciences, Locomotion - Equine Sciences, Locomotion - Surgery (CA), OnGo, Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, and Tryfonidou, Marianna A

Published
2023

13. Sustained release of locally delivered celecoxib provides pain relief for osteoarthritis: a proof of concept in dog patients

Author

Orthopaedie Onderzoek, MKA/BT Onderzoek, CTI Eijkelkamp, Brain, Child Health, Infection & Immunity, Cancer, ORT Research, Regenerative Medicine and Stem Cells, Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, Tryfonidou, Marianna A, Orthopaedie Onderzoek, MKA/BT Onderzoek, CTI Eijkelkamp, Brain, Child Health, Infection & Immunity, Cancer, ORT Research, Regenerative Medicine and Stem Cells, Tellegen, Anna R, Rudnik-Jansen, Imke, Utomo, Lizette, Versteeg, Sabine, Beukers, Martijn, Maarschalkerweerd, Roelof, van Zuilen, Dick, van Klaveren, Nicoline J, Houben, Kaat, Teske, Erik, René van Weeren, P, Karssemakers-Degen, Nina, Mihov, George, Thies, Jens, Eijkelkamp, Niels, Creemers, Laura B, Meij, Björn P, and Tryfonidou, Marianna A

Published
2023

14. Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

Author

Chirurgie, CS_Locomotion, Diagnostische beeldvorming, Du, Jie, Garcia, João P, Bach, Frances C, Tellegen, Anna R, Grad, Sibylle, Li, Zhen, Castelein, René M, Meij, Björn P, Tryfonidou, Marianna A, Creemers, Laura B, Chirurgie, CS_Locomotion, Diagnostische beeldvorming, Du, Jie, Garcia, João P, Bach, Frances C, Tellegen, Anna R, Grad, Sibylle, Li, Zhen, Castelein, René M, Meij, Björn P, Tryfonidou, Marianna A, and Creemers, Laura B

Published
2022

15. Intradiscal injection of human recombinant BMP-4 does not reverse intervertebral disc degeneration induced by nuclectomy in sheep

Author

ORT Research, Other research (not in main researchprogram), MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Du, Jie, Garcia, João P., Bach, Frances C., Tellegen, Anna R., Grad, Sibylle, Li, Zhen, Castelein, René M., Meij, Björn P., Tryfonidou, Marianna A., Creemers, Laura B., ORT Research, Other research (not in main researchprogram), MS Orthopaedie Algemeen, Regenerative Medicine and Stem Cells, Du, Jie, Garcia, João P., Bach, Frances C., Tellegen, Anna R., Grad, Sibylle, Li, Zhen, Castelein, René M., Meij, Björn P., Tryfonidou, Marianna A., and Creemers, Laura B.

Published
2022

16. Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

Author

Wiersema, Tijn, Tellegen, Anna R, Beukers, Martijn, van Stralen, Marijn, Wouters, Erik, van de Vooren, Mandy, Woike, Nina, Mihov, George, Thies, Jens C, Creemers, Laura B, Tryfonidou, Marianna A, Meij, Björn P, Chirurgie, Diagnostische beeldvorming, dCSCA AVR, LS Algemene chirurgie, dCSCA RMSC-1, Chirurgie, Diagnostische beeldvorming, dCSCA AVR, LS Algemene chirurgie, and dCSCA RMSC-1

Subjects
040301 veterinary sciences, Analgesic, Pharmaceutical Science, Physical examination, Disc protrusion, Placebo, Article, 0403 veterinary science, Biomaterials, 03 medical and health sciences, 0302 clinical medicine, Pharmacy and materia medica, Degenerative lumbosacral stenosis, medicine, Back pain, Controlled release, non-steroidal anti-inflammatory drugs, medicine.diagnostic_test, intervertebral disc degeneration, business.industry, Modic changes, 04 agricultural and veterinary sciences, medicine.disease, Low back pain, Microspheres, RS1-441, microspheres, Anesthesia, Celecoxib, medicine.symptom, Intervertebral disc degeneration, degenerative lumbosacral stenosis, business, controlled release, 030217 neurology & neurosurgery, Non-steroidal anti-inflammatory drugs, medicine.drug, biomaterials
Abstract

Back pain affects millions globally and in 40% of the cases is attributed to intervertebral disc degeneration. Oral analgesics are associated with adverse systemic side-effects and insufficient pain relief. Local drug delivery mitigates systemic effects and accomplishes higher local dosing. Clinical efficacy of intradiscally injected celecoxib (CXB)-loaded polyesteramide microspheres (PEAMs) was studied in a randomized prospective double-blinded placebo controlled veterinary study. Client-owned dog patients suffering from back pain were treated with CXB-loaded (n = 20) or unloaded PEAMs (“placebo”) (n = 10) and evaluated by clinical examination, gait analysis, owners’ questionnaires, and MRI at 6 and 12 weeks follow-up. At 6 and 12 weeks, CXB-treated dogs experienced significantly less pain interference with their daily life activities compared to placebo. The risk ratio for treatment success was 1.90 (95% C.I. 1.24–2.91, p = 0.023) at week 6 and 1.95 (95% C.I. 1.10–3.45, p = 0.036) at week 12. The beneficial effects of CXB-PEAMs were more pronounced for the subpopulation of male dogs and those with no Modic changes in MRI at inclusion in the study, disc protrusion did not affect the outcome. It remains to be determined whether intradiscal injection of CXB-PEAMs, in addition to analgesic properties, has the ability to halt the degenerative process in the long term or restore the disc.

Published
2021

17. Prospective Evaluation of Local Sustained Release of Celecoxib in Dogs with Low Back Pain

Author

Chirurgie, Diagnostische beeldvorming, dCSCA AVR, LS Algemene chirurgie, dCSCA RMSC-1, Wiersema, Tijn, Tellegen, Anna R, Beukers, Martijn, van Stralen, Marijn, Wouters, Erik, van de Vooren, Mandy, Woike, Nina, Mihov, George, Thies, Jens C, Creemers, Laura B, Tryfonidou, Marianna A, Meij, Björn P, Chirurgie, Diagnostische beeldvorming, dCSCA AVR, LS Algemene chirurgie, dCSCA RMSC-1, Wiersema, Tijn, Tellegen, Anna R, Beukers, Martijn, van Stralen, Marijn, Wouters, Erik, van de Vooren, Mandy, Woike, Nina, Mihov, George, Thies, Jens C, Creemers, Laura B, Tryfonidou, Marianna A, and Meij, Björn P

Published
2021

18. Prospective evaluation of local sustained release of celecoxib in dogs with low back pain

Author

Beeldverwerking ISI, ORT Research, Regenerative Medicine and Stem Cells, Wiersema, Tijn, Tellegen, Anna R., Beukers, Martijn, van Stralen, Marijn, Wouters, Erik, van de Vooren, Mandy, Woike, Nina, Mihov, George, Thies, Jens C., Creemers, Laura B., Tryfonidou, Marianna A., Meij, Björn P., Beeldverwerking ISI, ORT Research, Regenerative Medicine and Stem Cells, Wiersema, Tijn, Tellegen, Anna R., Beukers, Martijn, van Stralen, Marijn, Wouters, Erik, van de Vooren, Mandy, Woike, Nina, Mihov, George, Thies, Jens C., Creemers, Laura B., Tryfonidou, Marianna A., and Meij, Björn P.

Published
2021

19. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

Author

Bach, Frances C, Tellegen, Anna R, Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A M, de Vries, Stefan A H, Creemers, Laura B, Benz, Karin, Meij, Björn P, Ito, Keita, Tryfonidou, Marianna A, Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming, Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming, and Orthopaedic Biomechanics

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, regenerative medicine, canine, Matrix (biology), SDG 3 – Goede gezondheid en welzijn, Regenerative medicine, Canine, Extracellular matrix, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Notochordal cells, medicine, human, Bone regeneration, Demineralized bone matrix, business.industry, Mesenchymal stem cell, Intervertebral disc, Chondrogenesis, notochordal cells, 030104 developmental biology, medicine.anatomical_structure, Oncology, intervertebral disc, business, Research Paper, Human
Abstract

The socioeconomic burden of chronic back pain related to intervertebral disc (IVD) disease is high and current treatments are only symptomatic. Minimally invasive strategies that promote biological IVD repair should address this unmet need. Notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) during IVD maturation and degeneration. The regenerative potential of NC-secreted substances on CLCs and mesenchymal stromal cells (MSCs) has already been demonstrated. However, identification of these substances remains elusive. Innovatively, this study exploits the regenerative NC potential by using healthy porcine NC-derived matrix (NCM) and employs the dog as a clinically relevant translational model. NCM increased the glycosaminoglycan and DNA content of human and canine CLC aggregates and facilitated chondrogenic differentiation of canine MSCs in vitro. Based on these results, NCM, MSCs and NCM+MSCs were injected in mildly (spontaneously) and moderately (induced) degenerated canine IVDs in vivo and, after six months of treatment, were analyzed. NCM injected in moderately (induced) degenerated canine IVDs exerted beneficial effects at the macroscopic and MRI level, induced collagen type II-rich extracellular matrix production, improved the disc height, and ameliorated local inflammation. MSCs exerted no (additive) effects. In conclusion, NCM induced in vivo regenerative effects on degenerated canine IVDs. NCM may, comparable to demineralized bone matrix in bone regeneration, serve as 'instructive matrix', by locally releasing growth factors and facilitating tissue repair. Therefore, intradiscal NCM injection could be a promising regenerative treatment for IVD disease, circumventing the cumbersome identification of bioactive NC-secreted substances.

Published
2018
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20. Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter

Author

Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, Tryfonidou, Marianna A, Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, and Tryfonidou, Marianna A

Abstract

Osteoarthritis (OA) is a degenerative joint disease associated with chronic pain and disability in humans and companion animals. The canine species can be subdivided into non-chondrodystrophic (NCD) and chondrodystrophic (CD) dogs, the latter having disproportionally short limbs due to disturbance in endochondral ossification of long bones. This phenotype is associated with retrogene insertions of the fibroblast growth factor 4 (FGF4) gene, resulting in enhanced fibroblast growth factor receptor 3 (FGFR3) signaling. The effect on cartilage is unknown and in experimental studies with dogs, breeds are seemingly employed randomly. The aim of this study was to determine whether CD- and NCD-derived cartilage differs on a structural and biochemical level, and to explore the relationship between FGF4 associated chondrodystrophy and OA. Cartilage explants from CD and NCD dogs were cultured for 21 days. Activation of canonical Wnt signaling was assessed in primary canine chondrocytes. OA and synovitis severity from an experimental OA model were compared between healthy and OA samples from CD and NCD dogs. Release of glycosaminoglycans, DNA content, and cyclooxygenase 2 (COX-2) expression were higher in NCD cartilage explants. Healthy cartilage from NCD dogs displayed higher cartilage degeneration and synovitis scores, which was aggravated by the induction of OA. Dikkopf-3 gene expression was higher in NCD cartilage. No differences in other Wnt pathway read outs were found. To conclude, chondrodystrophy associated with the FGF4 retrogene seems to render CD dogs less susceptible to the development of OA when compared with NCD dogs. These differences should be considered when choosing a canine model to study the pathobiology and new treatment strategies of OA. © 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:2550-2560, 2019.

Published
2019

21. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Author

Rudnik-Jansen, Imke, Tellegen, Anna R., Pouran, Behdad, Schrijver, Karin, Meij, Björn P., Emans, Pieter J., de Gendt, Erin, Thomas, Rachel E., Kik, Marja J.L., de Visser, Huub M., Weinans, Harrie, Egas, Annelies, van Maarseveen, Erik, Woike, Nina, Mihov, George, Thies, Jens, Tryfonidou, Marianna A., Creemers, Laura B., Rudnik-Jansen, Imke, Tellegen, Anna R., Pouran, Behdad, Schrijver, Karin, Meij, Björn P., Emans, Pieter J., de Gendt, Erin, Thomas, Rachel E., Kik, Marja J.L., de Visser, Huub M., Weinans, Harrie, Egas, Annelies, van Maarseveen, Erik, Woike, Nina, Mihov, George, Thies, Jens, Tryfonidou, Marianna A., and Creemers, Laura B.

Abstract

Background and Purpose: Corticosteroids are intra-articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial-based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. Experimental Approach: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. Key Results: Intra-articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability-induced OA cartilage degeneration, synovitis, nor the OA-related bone phenotype was affected. However, biomaterial microsphere-based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. Conclusions and Implications: We conclude that short-term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage-associated joint instability, but not of brief exposure.

Published
2019

22. Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter

Author

Orthopedie en neurochirurgie, Biochemisch laboratorium, dCSCA RMSC-1, LS Algemene chirurgie, dCSCA AVR, LS Equine Muscoskeletal Biology, Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, Tryfonidou, Marianna A, Orthopedie en neurochirurgie, Biochemisch laboratorium, dCSCA RMSC-1, LS Algemene chirurgie, dCSCA AVR, LS Equine Muscoskeletal Biology, Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, and Tryfonidou, Marianna A

Published
2019

23. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Author

Rudnik‐Jansen, Imke (author), Tellegen, Anna R. (author), Pouran, B. (author), Schrijver, Karin (author), Meij, Björn P. (author), Emans, Pieter J. (author), de Gendt, Erin (author), Thomas, Rachel E. (author), Kik, Marja J.L. (author), de Visser, Huub M. (author), Weinans, H.H. (author), Egas, Annelies (author), van Maarseveen, Erik (author), Woike, Nina (author), Mihov, George (author), Thies, Jens (author), Tryfonidou, Marianna A. (author), Creemers, Laura B. (author), Rudnik‐Jansen, Imke (author), Tellegen, Anna R. (author), Pouran, B. (author), Schrijver, Karin (author), Meij, Björn P. (author), Emans, Pieter J. (author), de Gendt, Erin (author), Thomas, Rachel E. (author), Kik, Marja J.L. (author), de Visser, Huub M. (author), Weinans, H.H. (author), Egas, Annelies (author), van Maarseveen, Erik (author), Woike, Nina (author), Mihov, George (author), Thies, Jens (author), Tryfonidou, Marianna A. (author), and Creemers, Laura B. (author)

Abstract

Background and Purpose: Corticosteroids are intra-articularly injected to relieve pain in joints with osteoarthritis (OA) or acute tissue damage such as ligament or tendon tears, despite its unverified contraindication in unstable joints. Biomaterial-based sustained delivery may prolong reduction of inflammatory pain, while avoiding harmful peak drug concentrations. Experimental Approach: The applicability of prolonged corticosteroid exposure was examined in a rat model of anterior cruciate ligament and medial meniscus transection (ACLT + pMMx) with ensuing degenerative changes. Key Results: Intra-articular injection of a bolus of the corticosteroid triamcinolone acetonide (TAA) resulted in enhanced joint instability in 50% of the joints, but neither instability-induced OA cartilage degeneration, synovitis, nor the OA-related bone phenotype was affected. However, biomaterial microsphere-based extended TAA release enhanced instability in 94% of the animals and induced dystrophic calcification and exacerbation of cartilage degeneration. In healthy joints, injection with TAA releasing microspheres had no effect at all. In vitro, TAA inhibited cell migration out of joint tissue explants, suggesting inhibited tissue healing in vivo as mechanisms for enhanced instability and subsequent cartilage degeneration. Conclusions and Implications: We conclude that short-term TAA exposure has minor effects on surgically induced unstable joints, but its extended presence is detrimental by extending instability and associated joint degeneration through compromised healing. This supports a contraindication of prolonged corticosteroid exposure in tissue damage-associated joint instability, but not of brief exposure., Biomaterials & Tissue Biomechanics

Published
2019
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24. Dog as a Model for Osteoarthritis: The FGF4 Retrogene Insertion May Matter

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Kuball, Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, Tryfonidou, Marianna A, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Lab Reumatologie/Klinische Immunologie, CTI Kuball, Tellegen, Anna R, Dessing, Aileen J, Houben, Kaat, Riemers, Frank M, Creemers, Laura B, Mastbergen, Simon C, Meij, Björn P, Miranda-Bedate, Alberto, and Tryfonidou, Marianna A

Published
2019

25. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Author

Other research (not in main researchprogram), Orthopaedie Onderzoek, Zorgeenheid Orthopaedie Medisch, Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, Apotheek KF TDM, Apotheek Klinische Farmacie, Rudnik-Jansen, Imke, Tellegen, Anna R, Pouran, Behdad, Schrijver, Karin, Meij, Björn P, Emans, Pieter J, de Gendt, Erin, Thomas, Rachel E, Kik, Marja J L, de Visser, Huub M, Weinans, Harrie, Egas, Annelies, van Maarseveen, Erik, Woike, Nina, Mihov, George, Thies, Jens, Tryfonidou, Marianna A, Creemers, Laura B, Other research (not in main researchprogram), Orthopaedie Onderzoek, Zorgeenheid Orthopaedie Medisch, Orthopaedie Opleiding, Regenerative Medicine and Stem Cells, Apotheek KF TDM, Apotheek Klinische Farmacie, Rudnik-Jansen, Imke, Tellegen, Anna R, Pouran, Behdad, Schrijver, Karin, Meij, Björn P, Emans, Pieter J, de Gendt, Erin, Thomas, Rachel E, Kik, Marja J L, de Visser, Huub M, Weinans, Harrie, Egas, Annelies, van Maarseveen, Erik, Woike, Nina, Mihov, George, Thies, Jens, Tryfonidou, Marianna A, and Creemers, Laura B

Published
2019

26. Local controlled release of corticosteroids extends surgically induced joint instability by inhibiting tissue healing

Author

Rudnik‐Jansen, Imke, primary, Tellegen, Anna R., additional, Pouran, Behdad, additional, Schrijver, Karin, additional, Meij, Björn P., additional, Emans, Pieter J., additional, Gendt, Erin, additional, Thomas, Rachel E., additional, Kik, Marja J.L., additional, Visser, Huub M., additional, Weinans, Harrie, additional, Egas, Annelies, additional, Maarseveen, Erik, additional, Woike, Nina, additional, Mihov, George, additional, Thies, Jens, additional, Tryfonidou, Marianna A., additional, and Creemers, Laura B., additional

Published
2019
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28. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix : From bench towards bedside

Author

Bach, Frances C., Tellegen, Anna R., Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A.M., de Vries, Stefan A.H., Creemers, Laura B., Benz, Karin, Meij, Björn P., Ito, Keita, Tryfonidou, Marianna A., Bach, Frances C., Tellegen, Anna R., Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A.M., de Vries, Stefan A.H., Creemers, Laura B., Benz, Karin, Meij, Björn P., Ito, Keita, and Tryfonidou, Marianna A.

Published
2018

29. Intradiscal application of a PCLA–PEG–PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines : What's in it for humans?

Author

Tellegen, Anna R., Willems, Nicole, Beukers, Martijn, Grinwis, Guy C.M., Plomp, Saskia G.M., Bos, Clemens, van Dijk, Maarten, de Leeuw, Mike, Creemers, Laura B., Tryfonidou, Marianna A., Meij, Björn P., Tellegen, Anna R., Willems, Nicole, Beukers, Martijn, Grinwis, Guy C.M., Plomp, Saskia G.M., Bos, Clemens, van Dijk, Maarten, de Leeuw, Mike, Creemers, Laura B., Tryfonidou, Marianna A., and Meij, Björn P.

Published
2018

30. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: from bench towards bedside

Author

Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming, Bach, Frances C, Tellegen, Anna R, Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A M, de Vries, Stefan A H, Creemers, Laura B, Benz, Karin, Meij, Björn P, Ito, Keita, Tryfonidou, Marianna A, Orthopedie en neurochirurgie, dCSCA RMSC-1, LS Equine Muscoskeletal Biology, Onderzoek, dCSCA AVR, LS Algemene chirurgie, Diagnostische beeldvorming, Bach, Frances C, Tellegen, Anna R, Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A M, de Vries, Stefan A H, Creemers, Laura B, Benz, Karin, Meij, Björn P, Ito, Keita, and Tryfonidou, Marianna A

Published
2018

31. Biologic canine and human intervertebral disc repair by notochordal cell-derived matrix: From bench towards bedside

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Bach, Frances C., Tellegen, Anna R., Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A.M., de Vries, Stefan A.H., Creemers, Laura B., Benz, Karin, Meij, Björn P., Ito, Keita, Tryfonidou, Marianna A., Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Bach, Frances C., Tellegen, Anna R., Beukers, Martijn, Miranda-Bedate, Alberto, Teunissen, Michelle, de Jong, Willem A.M., de Vries, Stefan A.H., Creemers, Laura B., Benz, Karin, Meij, Björn P., Ito, Keita, and Tryfonidou, Marianna A.

Published
2018

32. Intradiscal application of a PCLA–PEG–PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Author

Researchgr. Beeldg. Moleculaire Interv., Cancer, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Tellegen, Anna R., Willems, Nicole, Beukers, Martijn, Grinwis, Guy C.M., Plomp, Saskia G.M., Bos, Clemens, van Dijk, Maarten, de Leeuw, Mike, Creemers, Laura B., Tryfonidou, Marianna A., Meij, Björn P., Researchgr. Beeldg. Moleculaire Interv., Cancer, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Tellegen, Anna R., Willems, Nicole, Beukers, Martijn, Grinwis, Guy C.M., Plomp, Saskia G.M., Bos, Clemens, van Dijk, Maarten, de Leeuw, Mike, Creemers, Laura B., Tryfonidou, Marianna A., and Meij, Björn P.

Published
2018

33. Inflammatory profiles in canine intervertebral disc degeneration

Author

Willems, Nicole, Tellegen, Anna R, Bergknut, Niklas, Creemers, Laura B, Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C M, Tryfonidou, Marianna A, Meij, Björn P, dCSCA RMSC-1, dCSCA AVR, Opleiding chirurgie, Orthopedie en neurochirurgie, Sub Neurologie, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, dPB CR, dCSCA RMSC-1, dCSCA AVR, Opleiding chirurgie, Orthopedie en neurochirurgie, Sub Neurologie, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, and dPB CR

Subjects
0301 basic medicine, Chemokine, Pathology, Prostaglandin, medicine.medical_treatment, Intervertebral Disc Degeneration, Degeneration (medical), 0403 veterinary science, Dog, Medicine, Dog Diseases, Non-U.S. Gov't, Herniation, Non-chondrodystrophic, PGE, biology, Research Support, Non-U.S. Gov't, Interleukin, 04 agricultural and veterinary sciences, General Medicine, musculoskeletal system, Extracellular Matrix, medicine.anatomical_structure, Cytokine, Tumor necrosis factor alpha, PGE2, Inflammation Mediators, medicine.symptom, Intervertebral Disc Displacement, Research Article, musculoskeletal diseases, medicine.medical_specialty, 040301 veterinary sciences, Inflammation, CCL2, Research Support, Osteochondrodysplasias, 03 medical and health sciences, Dogs, Journal Article, Animals, Low back pain, General Veterinary, business.industry, Intervertebral disc, veterinary(all), 030104 developmental biology, Cyclooxygenase 2, biology.protein, Chondrodystrophic, business
Abstract

Background Intervertebral disc (IVD) disease is a common spinal disorder in dogs and degeneration and inflammation are significant components of the pathological cascade. Only limited studies have studied the cytokine and chemokine profiles in IVD degeneration in dogs, and mainly focused on gene expression. A better understanding is needed in order to develop biological therapies that address both pain and degeneration in IVD disease. Therefore, in this study, we determined the levels of prostaglandin E2 (PGE2), cytokines, chemokines, and matrix components in IVDs from chondrodystrophic (CD) and non-chondrodystrophic (NCD) dogs with and without clinical signs of IVD disease, and correlated these to degeneration grade (according to Pfirrmann), or herniation type (according to Hansen). In addition, we investigated cyclooxygenase 2 (COX-2) expression and signs of inflammation in histological IVD samples of CD and NCD dogs. Results PGE2 levels were significantly higher in the nucleus pulposus (NP) of degenerated IVDs compared with non-degenerated IVDs, and in herniated IVDs from NCD dogs compared with non-herniated IVDs of NCD dogs. COX-2 expression in the NP and annulus fibrosus (AF), and proliferation of fibroblasts and numbers of macrophages in the AF significantly increased with increased degeneration grade. GAG content did not significantly change with degeneration grade or herniation type. Cytokines interleukin (IL)-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, immune protein (IP)-10, tumor necrosis factor (TNF)-α, and granulocyte macrophage colony-stimulating factor (GM-CSF) were not detectable in the samples. Chemokine (C-C) motif ligand (CCL)2 levels in the NP from extruded samples were significantly higher compared with the AF of these samples and the NP from protrusion samples. Conclusions PGE2 levels and CCL2 levels in degenerated and herniated IVDs were significantly higher compared with non-degenerated and non-herniated IVDs. COX-2 expression in the NP and AF and reactive changes in the AF increased with advancing degeneration stages. Although macrophages invaded the AF as degeneration progressed, the production of inflammatory mediators seemed most pronounced in degenerated NP tissue. Future studies are needed to investigate if inhibition of PGE2 levels in degenerated IVDs provides effective analgesia and exerts a protective role in the process of IVD degeneration and the development of IVD disease. Electronic supplementary material The online version of this article (doi:10.1186/s12917-016-0635-6) contains supplementary material, which is available to authorized users.

Published
2016
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34. Intradiscal application of a PCLA–PEG–PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Author

Tellegen, Anna R., primary, Willems, Nicole, additional, Beukers, Martijn, additional, Grinwis, Guy C.M., additional, Plomp, Saskia G.M., additional, Bos, Clemens, additional, Dijk, Maarten, additional, Leeuw, Mike, additional, Creemers, Laura B., additional, Tryfonidou, Marianna A., additional, and Meij, Björn P., additional

Published
2017
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35. Pedicle screw-rod fixation: a feasible treatment for dogs with severe degenerative lumbosacral stenosis

Author

Tellegen, Anna R, Willems, Nicole, Tryfonidou, Marianna A, Meij, Björn P, Regenerative Medicine, Stem Cells & Cancer, Applied Veterinary Research, dCSCA AVR, dCSCA RMSC-1, Orthopedie en neurochirurgie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, Regenerative Medicine, Stem Cells & Cancer, Applied Veterinary Research, dCSCA AVR, dCSCA RMSC-1, Orthopedie en neurochirurgie, Sub Neuro/Tandheelkunde, and LS Algemene chirurgie

Subjects
Male, Discospondylitis, medicine.medical_specialty, Spinal stenosis, Lumbosacral fixation, Bone Screws, Pedicle screws, Fixation (surgical), Dogs, Spinal Stenosis, Degenerative lumbosacral stenosis, Dog, medicine, Animals, Dog Diseases, General Veterinary, business.industry, Lumbosacral Region, Retrospective cohort study, General Medicine, medicine.disease, veterinary(all), Surgery, Clinical trial, Stenosis, Radiological weapon, Female, Implant, Intervertebral disc degeneration, business, Lumbosacral joint, Research Article
Abstract

BACKGROUND: Degenerative lumbosacral stenosis is a common problem in large breed dogs. For severe degenerative lumbosacral stenosis, conservative treatment is often not effective and surgical intervention remains as the last treatment option. The objective of this retrospective study was to assess the middle to long term outcome of treatment of severe degenerative lumbosacral stenosis with pedicle screw-rod fixation with or without evidence of radiological discospondylitis. RESULTS: Twelve client-owned dogs with severe degenerative lumbosacral stenosis underwent pedicle screw-rod fixation of the lumbosacral junction. During long term follow-up, dogs were monitored by clinical evaluation, diagnostic imaging, force plate analysis, and by using questionnaires to owners. Clinical evaluation, force plate data, and responses to questionnaires completed by the owners showed resolution (n = 8) or improvement (n = 4) of clinical signs after pedicle screw-rod fixation in 12 dogs. There were no implant failures, however, no interbody vertebral bone fusion of the lumbosacral junction was observed in the follow-up period. Four dogs developed mild recurrent low back pain that could easily be controlled by pain medication and an altered exercise regime. CONCLUSIONS: Pedicle screw-rod fixation offers a surgical treatment option for large breed dogs with severe degenerative lumbosacral stenosis with or without evidence of radiological discospondylitis in which no other treatment is available. Pedicle screw-rod fixation alone does not result in interbody vertebral bone fusion between L7 and S1.

Published
2015
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36. Inflammatory profiles in canine intervertebral disc degeneration

Author

dCSCA RMSC-1, dCSCA AVR, Opleiding chirurgie, Orthopedie en neurochirurgie, Sub Neurologie, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, dPB CR, Willems, Nicole, Tellegen, Anna R, Bergknut, Niklas, Creemers, Laura B, Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C M, Tryfonidou, Marianna A, Meij, Björn P, dCSCA RMSC-1, dCSCA AVR, Opleiding chirurgie, Orthopedie en neurochirurgie, Sub Neurologie, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, dPB CR, Willems, Nicole, Tellegen, Anna R, Bergknut, Niklas, Creemers, Laura B, Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C M, Tryfonidou, Marianna A, and Meij, Björn P

Published
2016

37. Inflammatory profiles in canine intervertebral disc degeneration

Author

Zorgeenheid Orthopaedie Zorg, Regenerative Medicine and Stem Cells, Willems, Nicole, Tellegen, Anna R., Bergknut, Niklas, Creemers, Laura B., Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C M, Tryfonidou, Marianna A., Meij, Björn P., Zorgeenheid Orthopaedie Zorg, Regenerative Medicine and Stem Cells, Willems, Nicole, Tellegen, Anna R., Bergknut, Niklas, Creemers, Laura B., Wolfswinkel, Jeannette, Freudigmann, Christian, Benz, Karin, Grinwis, Guy C M, Tryfonidou, Marianna A., and Meij, Björn P.

Published
2016

38. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model

Author

Willems, Nicole, Yang, Hsiao-Yin, Langelaan, Marloes L P, Tellegen, Anna R, Grinwis, Guy C M, Kranenburg, Hendrik-Jan C, Riemers, Frank M, Plomp, Saskia G M, Craenmehr, Eric G M, Dhert, Wouter J A, Papen-Botterhuis, Nicole E, Meij, Björn P, Creemers, Laura B, Tryfonidou, Marianna A, Willems, Nicole, Yang, Hsiao-Yin, Langelaan, Marloes L P, Tellegen, Anna R, Grinwis, Guy C M, Kranenburg, Hendrik-Jan C, Riemers, Frank M, Plomp, Saskia G M, Craenmehr, Eric G M, Dhert, Wouter J A, Papen-Botterhuis, Nicole E, Meij, Björn P, Creemers, Laura B, and Tryfonidou, Marianna A

Published
2015

39. Pedicle screw-rod fixation: a feasible treatment for dogs with severe degenerative lumbosacral stenosis

Author

Regenerative Medicine, Stem Cells & Cancer, Applied Veterinary Research, dCSCA AVR, dCSCA RMSC-1, Orthopedie en neurochirurgie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, Tellegen, Anna R, Willems, Nicole, Tryfonidou, Marianna A, Meij, Björn P, Regenerative Medicine, Stem Cells & Cancer, Applied Veterinary Research, dCSCA AVR, dCSCA RMSC-1, Orthopedie en neurochirurgie, Sub Neuro/Tandheelkunde, LS Algemene chirurgie, Tellegen, Anna R, Willems, Nicole, Tryfonidou, Marianna A, and Meij, Björn P

Published
2015

40. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model

Author

Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Willems, Nicole, Yang, Hsiao-Yin, Langelaan, Marloes L P, Tellegen, Anna R, Grinwis, Guy C M, Kranenburg, Hendrik-Jan C, Riemers, Frank M, Plomp, Saskia G M, Craenmehr, Eric G M, Dhert, Wouter J A, Papen-Botterhuis, Nicole E, Meij, Björn P, Creemers, Laura B, Tryfonidou, Marianna A, Orthopaedie Onderzoek, Regenerative Medicine and Stem Cells, Willems, Nicole, Yang, Hsiao-Yin, Langelaan, Marloes L P, Tellegen, Anna R, Grinwis, Guy C M, Kranenburg, Hendrik-Jan C, Riemers, Frank M, Plomp, Saskia G M, Craenmehr, Eric G M, Dhert, Wouter J A, Papen-Botterhuis, Nicole E, Meij, Björn P, Creemers, Laura B, and Tryfonidou, Marianna A

Published
2015

41. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model

Author

Willems, Nicole, primary, Yang, Hsiao-yin, additional, Langelaan, Marloes L. P., additional, Tellegen, Anna R., additional, Grinwis, Guy C. M., additional, Kranenburg, Hendrik-Jan C., additional, Riemers, Frank M., additional, Plomp, Saskia G. M., additional, Craenmehr, Eric G. M., additional, Dhert, Wouter J. A., additional, Papen-Botterhuis, Nicole E., additional, Meij, Björn P., additional, Creemers, Laura B., additional, and Tryfonidou, Marianna A., additional

Published
2015
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42. Intradiscal application of a PCLA-PEG-PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Author

Tellegen AR, Willems N, Beukers M, Grinwis GCM, Plomp SGM, Bos C, van Dijk M, de Leeuw M, Creemers LB, Tryfonidou MA, and Meij BP

Subjects
Animals, Dogs, Female, Biocompatible Materials, Chronic Pain diagnostic imaging, Chronic Pain drug therapy, Chronic Pain etiology, Chronic Pain veterinary, Cyclooxygenase 2 metabolism, Extracellular Matrix metabolism, Injections, Subcutaneous, Intervertebral Disc diagnostic imaging, Intervertebral Disc drug effects, Intervertebral Disc pathology, Magnetic Resonance Imaging, Mice, Inbred BALB C, Surveys and Questionnaires, Disease Models, Animal, Back Pain diagnostic imaging, Back Pain drug therapy, Back Pain etiology, Back Pain veterinary, Celecoxib pharmacology, Celecoxib therapeutic use, Hydrogels administration & dosage, Hydrogels chemical synthesis, Hydrogels chemistry, Intervertebral Disc Degeneration complications, Intervertebral Disc Degeneration diagnostic imaging, Intervertebral Disc Degeneration drug therapy, Intervertebral Disc Degeneration veterinary, Polyesters administration & dosage, Polyesters chemical synthesis, Polyesters chemistry, Polyethylene Glycols administration & dosage, Polyethylene Glycols chemical synthesis, Polyethylene Glycols chemistry
Abstract

Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain., (Copyright © 2017 John Wiley & Sons, Ltd.)

Published
2018
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