39 results on '"Plomp, Saskia"'
Search Results
2. Composition, architecture and biomechanical properties of articular cartilage in differently loaded areas of the equine stifle.
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Fugazzola, Maria, Nissinen, Mikko T., Jäntti, Jiri, Tuppurainen, Juuso, Plomp, Saskia, Te Moller, Nikae, Mäkelä, Janne T. A., and van Weeren, Rene
- Abstract
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- 2024
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3. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment
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Kearney, Clodagh M., primary, Korthagen, Nicoline M., additional, Plomp, Saskia G. M., additional, Labberté, Margot C., additional, de Grauw, Janny C., additional, van Weeren, P. René, additional, and Brama, Pieter A. J., additional
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- 2023
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4. Prolonged inhibition of inflammation in osteoarthritis by triamcinolone acetonide released from a polyester amide microsphere platform
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Rudnik-Jansen, Imke, Colen, Sascha, Berard, Julien, Plomp, Saskia, Que, Ivo, van Rijen, Mattie, Woike, Nina, Egas, Annelies, van Osch, Gerjo, van Maarseveen, Erik, Messier, Ken, Chan, Alan, Thies, Jens, and Creemers, Laura
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- 2017
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5. Histological tissue healing following high-power laser treatment in a model of suspensory ligament branch injury
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Pluim, Mathilde, Heier, Annabelle, Plomp, Saskia, Boshuizen, Berit, Gröne, Andrea, van Weeren, P René, Vanderperren, Katrien, Martens, Ann, Dewulf, Jeroen, Chantziaras, Ilias, Koene, Marc, Luciani, Antonio, Oosterlinck, Maarten, Van Brantegem, Leen, Delesalle, Cathérine, Equine Musculoskeletal Biology, dES RMSC, LS Pharma, VP pathologie, dPB CR, dPB I&I, Dep Clinical Sciences, dES AVR, LS Equine Internal Medicine, CS_Locomotion, Equine Musculoskeletal Biology, dES RMSC, LS Pharma, VP pathologie, dPB CR, dPB I&I, Dep Clinical Sciences, dES AVR, LS Equine Internal Medicine, and CS_Locomotion
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collagen ,tendon ,TENDINOPATHY ,LEVEL ,INDUCED CORE LESIONS ,HORSES ,THERAPY ,histology ,ligament ,Animals ,Horses ,Veterinary Sciences ,ACHILLES TENDINITIS ,Mammals ,REPAIR ,Factor VIII ,Ligaments ,TENDONS ,Equine ,General Medicine ,IRRADIATION ,horse ,fibre ,Eosine Yellowish-(YS) ,Horse Diseases ,Joint Diseases - Abstract
Background High-power laser therapy gained popularity recently as a regenerative treatment for tendinitis and desmitis in the horse. However, studies evaluating the effects of laser therapy on tissue repair at the histological level in large mammals are lacking. Objectives To evaluate the effects of high-power laser therapy on suspensory desmitis healing, using a model of suspensory ligament branch injury. Study design In vivo experiments. Methods Standardised lesions were surgically induced in all four lateral suspensory branches of 12 healthy Warmblood horses. Laser therapy (class 4, 15W) was applied daily on two of four induced lesions for four consecutive weeks. Horses were randomly assigned to either short-term study (horses were sacrificed after 4 weeks) or long-term study (6 months). Suspensory ligament samples were scored after staining with haematoxylin-eosin and immunostaining for collagen 1- collagen 3- and factor VIII. Results In the short-term study, significantly better (lower) scores for variation in density (17% above cut-off score in treated lesions vs. 31% above cut-off score in controls, P = .03), shape of nuclei (54% vs 92%, P = .02), fibre alignment (32% vs 75%, P = .003) and fibre structure (38% vs 71%, P = .02) were found in laser-treated lesions when compared to controls. Collagen 3 expression was significantly higher (32% vs 19%, P = .006) in control lesions. In both short- and long-term studies combined, parameters lesion size (44% vs 56%, P = .02) and shape of nuclei (53% vs 84%, P = .05) scored significantly better in treated lesions. Long-term, significantly better (lower) scores were found in the laser-treated group for lesion size (15% vs 45%, P = .008) and a higher percentage above cut-off score for density of the nuclei (27% vs 9%, P = .02), compared to controls. Main limitations The model of suspensory branch injury is not an exact representation of clinical overstrain lesions. Conclusions These results suggest that high-power laser therapy enables better lesion healing than conservative treatment.
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- 2022
6. No Effects of Hyperosmolar Culture Medium on Tissue Regeneration by Human Degenerated Nucleus Pulposus Cells Despite Upregulation Extracellular Matrix Genes
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Krouwels, Anita, Popov-Celeketic, Jelena, Plomp, Saskia G.M., Dhert, Wouter J.A., Öner, F. Cumhur, Bank, Ruud A., and Creemers, Laura B.
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- 2018
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7. Treatment Effects of Intra-Articular Allogenic Mesenchymal Stem Cell Secretome in an Equine Model of Joint Inflammation
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Kearney, Clodagh M., primary, Khatab, Sohrab, additional, van Buul, Gerben M., additional, Plomp, Saskia G. M., additional, Korthagen, Nicoline M., additional, Labberté, Margot C., additional, Goodrich, Laurie R., additional, Kisiday, John D., additional, Van Weeren, P. R., additional, van Osch, Gerjo J. V. M., additional, and Brama, Pieter A. J., additional
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- 2022
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8. Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization
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Bergmann, Wilhelmina, de Lest, Chris van, Plomp, Saskia, Vernooij, Johannes C M, Wijnberg, Inge D, Back, Willem, Gröne, Andrea, Delany, Mark W, Caliskan, Nermin, Tryfonidou, Marianna A, Grinwis, Guy C M, Dep Pathobiologie, VPDC pathologie, dPB CR, Equine Musculoskeletal Biology, Veterinaire biochemie, dB&C FR-RMSC RMSC, dES RMSC, CS_Locomotion, FAH Evidence based Veterinary Medicine, dFAH AVR, Equine Internal Medicine, dES AVR, CS_Welfare & emerging diseases, VP pathologie, dPB I&I, Chirurgie, dCSCA RMSC-1, Veterinair Pathologisch Diagnostisch Cnt, LS Pathologie, Dep Pathobiologie, VPDC pathologie, dPB CR, Equine Musculoskeletal Biology, Veterinaire biochemie, dB&C FR-RMSC RMSC, dES RMSC, FAH Evidence based Veterinary Medicine, dFAH AVR, Equine Internal Medicine, dES AVR, VP pathologie, dPB I&I, Chirurgie, dCSCA RMSC-1, CS_Locomotion, CS_Welfare & emerging diseases, Veterinair Pathologisch Diagnostisch Cnt, and LS Pathologie
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General Veterinary ,intervertebral disc degeneration ,fibrosis ,scoring ,pentosidine ,musculoskeletal system ,veterinary(all) ,horse ,histology ,Dogs ,hydroxylysine ,glycosaminoglycan ,Animals ,Horse Diseases ,Collagen ,Dog Diseases ,Horses ,Intervertebral Disc - Abstract
Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.
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- 2022
9. Folate Receptor Expression by Human Monocyte-Derived Macrophage Subtypes and Effects of Corticosteroids
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Warmink, Kelly, Siebelt, Michiel, Low, Philip S, Riemers, Frank M, Wang, Bingbing, Plomp, Saskia G M, Tryfonidou, Marianna A, van Weeren, P René, Weinans, Harrie, Korthagen, Nicoline M, Chirurgie, dCSCA RMSC-1, Equine Musculoskeletal Biology, dES RMSC, Dep Clinical Sciences, CS_Locomotion, Chirurgie, dCSCA RMSC-1, Equine Musculoskeletal Biology, dES RMSC, Dep Clinical Sciences, CS_Locomotion, and Orthopedics and Sports Medicine
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Physical Therapy ,Macrophage Colony-Stimulating Factor ,M1/M2 ,Biomedical Engineering ,Granulocyte-Macrophage Colony-Stimulating Factor ,Physical Therapy, Sports Therapy and Rehabilitation ,Sports Therapy and Rehabilitation ,corticosteroids ,macrophages ,disease marker ,Folic Acid ,SDG 3 - Good Health and Well-being ,FR-beta ,Adrenal Cortex Hormones ,Humans ,Immunology and Allergy ,Folate Receptor 2 ,Biomarkers - Abstract
Objective Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β+ macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-β expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid. Design Human monocyte–derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-β expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). Results FR-β expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-β expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-β+ phenotype. Conclusions As corticosteroids skewed monocytes toward an FR-β-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-β has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-β expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-β+ macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity.
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- 2022
10. sj-docx-1-car-10.1177_19476035221081469 ��� Supplemental material for Folate Receptor Expression by Human Monocyte���Derived Macrophage Subtypes and Effects of Corticosteroids
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Warmink, Kelly, Siebelt, Michiel, Low, Philip S., Riemers, Frank M., Wang, Bingbing, Plomp, Saskia G. M., Tryfonidou, Marianna A., van Weeren, P. Ren��, Weinans, Harrie, and Korthagen, Nicoline M.
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FOS: Clinical medicine ,FOS: Biological sciences ,110323 Surgery ,110604 Sports Medicine ,FOS: Health sciences ,69999 Biological Sciences not elsewhere classified ,110314 Orthopaedics - Abstract
Supplemental material, sj-docx-1-car-10.1177_19476035221081469 for Folate Receptor Expression by Human Monocyte���Derived Macrophage Subtypes and Effects of Corticosteroids by Kelly Warmink, Michiel Siebelt, Philip S. Low, Frank M. Riemers, Bingbing Wang, Saskia G. M. Plomp, Marianna A. Tryfonidou, P. Ren�� van Weeren, Harrie Weinans and Nicoline M. Korthagen in CARTILAGE
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- 2022
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11. sj-docx-2-car-10.1177_19476035221081469 ��� Supplemental material for Folate Receptor Expression by Human Monocyte���Derived Macrophage Subtypes and Effects of Corticosteroids
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Warmink, Kelly, Siebelt, Michiel, Low, Philip S., Riemers, Frank M., Wang, Bingbing, Plomp, Saskia G. M., Tryfonidou, Marianna A., van Weeren, P. Ren��, Weinans, Harrie, and Korthagen, Nicoline M.
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FOS: Clinical medicine ,FOS: Biological sciences ,110323 Surgery ,110604 Sports Medicine ,FOS: Health sciences ,69999 Biological Sciences not elsewhere classified ,110314 Orthopaedics - Abstract
Supplemental material, sj-docx-2-car-10.1177_19476035221081469 for Folate Receptor Expression by Human Monocyte���Derived Macrophage Subtypes and Effects of Corticosteroids by Kelly Warmink, Michiel Siebelt, Philip S. Low, Frank M. Riemers, Bingbing Wang, Saskia G. M. Plomp, Marianna A. Tryfonidou, P. Ren�� van Weeren, Harrie Weinans and Nicoline M. Korthagen in CARTILAGE
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- 2022
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12. Supplemental Material, sj-pdf-1-vet-10.1177_03009858211067463 - Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization
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Bergmann, Wilhelmina, de Lest, Chris van, Plomp, Saskia, Vernooij, Johannes C. M., Wijnberg, Inge D., Back, Willem, Gr��ne, Andrea, Delany, Mark W., Caliskan, Nermin, Tryfonidou, Marianna A., and Grinwis, Guy C. M.
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70706 Veterinary Medicine ,FOS: Clinical medicine ,FOS: Veterinary sciences ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified - Abstract
Supplemental Material, sj-pdf-1-vet-10.1177_03009858211067463 for Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization by Wilhelmina Bergmann, Chris van de Lest, Saskia Plomp, Johannes C. M. Vernooij, Inge D. Wijnberg, Willem Back, Andrea Gr��ne, Mark W. Delany, Nermin Caliskan, Marianna A. Tryfonidou and Guy C. M. Grinwis in Veterinary Pathology
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- 2022
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13. Dual‐contrast micro‐CT enables cartilage lesion detection and tissue condition evaluation ex vivo.
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Honkanen, Miitu K. M., Mohammadi, Ali, te Moller, Nikae C. R., Ebrahimi, Mohammadhossein, Xu, Wujun, Plomp, Saskia, Pouran, Behdad, Lehto, Vesa‐Pekka, Brommer, Harold, van Weeren, P. René, Korhonen, Rami K., Töyräs, Juha, and Mäkelä, Janne T. A.
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Summary: Background: Post‐traumatic osteoarthritis is a frequent joint disease in the horse. Currently, equine medicine lacks effective methods to diagnose the severity of chondral defects after an injury. Objectives: To investigate the capability of dual‐contrast‐enhanced computed tomography (dual‐CECT) for detection of chondral lesions and evaluation of the severity of articular cartilage degeneration in the equine carpus ex vivo. Study design: Pre‐clinical experimental study. Methods: In nine Shetland ponies, blunt and sharp grooves were randomly created (in vivo) in the cartilage of radiocarpal and middle carpal joints. The contralateral joint served as control. The ponies were subjected to an 8‐week exercise protocol and euthanised 39 weeks after surgery. CECT scanning (ex vivo) of the joints was performed using a micro‐CT scanner 1 hour after an intra‐articular injection of a dual‐contrast agent. The dual‐contrast agent consisted of ioxaglate (negatively charged, q = −1) and bismuth nanoparticles (BiNPs, q = 0, diameter ≈ 0.2 µm). CECT results were compared to histological cartilage proteoglycan content maps acquired using digital densitometry. Results: BiNPs enabled prolonged visual detection of both groove types as they are too large to diffuse into the cartilage. Furthermore, proportional ioxaglate diffusion inside the tissue allowed differentiation between the lesion and ungrooved articular cartilage (3 mm from the lesion and contralateral joint). The mean ioxaglate partition in the lesion was 19 percentage points higher (P < 0.001) when compared with the contralateral joint. The digital densitometry and the dual‐contrast CECT findings showed good subjective visual agreement. Main limitations: Ex vivo study protocol and a low number of investigated joints. Conclusions: The dual‐CECT methodology, used in this study for the first time to image whole equine joints, is capable of effective lesion detection and simultaneous evaluation of the condition of the articular cartilage. [ABSTRACT FROM AUTHOR]
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- 2023
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14. Dual‐contrast micro‐CT enables cartilage lesion detection and tissue condition evaluation ex vivo
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Honkanen, Miitu K. M., primary, Mohammadi, Ali, additional, Moller, Nikae C. R., additional, Ebrahimi, Mohammadhossein, additional, Xu, Wujun, additional, Plomp, Saskia, additional, Pouran, Behdad, additional, Lehto, Vesa‐Pekka, additional, Brommer, Harold, additional, Weeren, P. René, additional, Korhonen, Rami K., additional, Töyräs, Juha, additional, and Mäkelä, Janne T. A., additional
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- 2022
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15. Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG1000]-b-[PLLA] Multi-Block Copolymers in Healthy Horse Joints
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Cokelaere, Stefan M., Groen, Wilhelmina M.G.A.C., Plomp, Saskia G.M., Grauw, Janny C. de, Midwoud, Paul M. van, Weinans, Harrie H., Lest, Chris H.A. van de, Tryfonidou, Marianna A., Weeren, P. René van, Korthagen, Nicoline M., LS Heelkunde, LS Equine Muscoskeletal Biology, Equine Musculoskeletal Biology, dES RMSC, Anesthesiologie, dES AVR, Chirurgie, dCSCA RMSC-1, Dep Clinical Sciences, CS_Locomotion, CS_Locomotion, Equine Musculoskeletal Biology, Anesthesiologie, Veterinaire biochemie, Chirurgie, and Dep Clinical Sciences
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musculoskeletal diseases ,medicine.medical_treatment ,Arthritis ,Pharmaceutical Science ,chemical and pharmacologic phenomena ,Cartilage metabolism ,Pharmacology ,Article ,Tacrolimus ,chemistry.chemical_compound ,synovial fluid ,Pharmacy and materia medica ,White blood cell ,Hyaluronic acid ,medicine ,Synovial fluid ,tacrolimus ,Saline ,equine ,prolonged-action preparation ,Chemistry ,Equine ,biomarkers ,medicine.disease ,Prolonged-action preparation ,Controlled release ,RS1-441 ,medicine.anatomical_structure ,surgical procedures, operative ,arthritis ,Biomarkers - Abstract
There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG1000]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>, 20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<, 0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals.
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- 2021
16. The Complexity of Joint Regeneration: How an Advanced Implant could Fail by Its In Vivo Proven Bone Component
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Diloksumpan, Paweena, primary, Abinzano, Florencia, additional, de Ruijter, Mylène, additional, Mensinga, Anneloes, additional, Plomp, Saskia, additional, Khan, Ilyas, additional, Brommer, Harold, additional, Smit, Ineke, additional, Dias Castilho, Miguel, additional, van Weeren, P. René, additional, Malda, Jos, additional, and Levato, Riccardo, additional
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- 2021
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17. Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9‐month equine groove model study
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Moller, Nikae C. R., primary, Mohammadi, Ali, additional, Plomp, Saskia, additional, Serra Bragança, Filipe M., additional, Beukers, Martijn, additional, Pouran, Behdad, additional, Afara, Isaac O., additional, Nippolainen, Ervin, additional, Mäkelä, Janne T. A., additional, Korhonen, Rami K., additional, Töyräs, Juha, additional, Brommer, Harold, additional, and Weeren, P. René, additional
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- 2021
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18. Long-Term in Vivo Performance of Low-Temperature 3D-Printed Bioceramics in an Equine Model
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Bolaños, Rafael Vindas, Castilho, Miguel, de Grauw, Janny, Cokelaere, Stefan, Plomp, Saskia, Groll, Jürgen, van Weeren, P. René, Gbureck, Uwe, Malda, Jos, Anesthesiologie, dES AVR, dES RMSC, LS Heelkunde, Equine Musculoskeletal Biology, Dep Clinical Sciences, CS_Locomotion, Anesthesiologie, dES AVR, dES RMSC, LS Heelkunde, Equine Musculoskeletal Biology, Dep Clinical Sciences, CS_Locomotion, Orthopaedic Biomechanics, EAISI Health, and ICMS Affiliated
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3d printed ,Bone Regeneration ,Biomedical Engineering ,Biomaterials ,In vivo ,Medicine ,Animals ,Horses ,three-dimensional printing ,EQUINE MODELS ,EQUINOS ,ENFERMEDADES OSEAS ,business.industry ,CABALLOS ,Temperature ,CALCIO ,equine model ,osteoinduction ,Term (time) ,calcium phosphates ,in vivo ,osteoconduction ,Three dimensional printing ,REGENERACIÓN BIOLÓGICA ,Three-Dimensional ,Bone Substitutes ,Printing, Three-Dimensional ,Printing ,business ,Porosity ,Biomedical engineering - Abstract
Bone has great self-healing capacity, but above a certain critical size, bone defects will not heal spontaneously, requiring intervention to achieve full healing. Among the synthetic calcium phosphate (CaP) bone replacement materials, brushite (CaHPO4·2H2O)-based materials are of particular interest because of their degree of solubility and the related high potential to promote bone regeneration after dissolution. They can be produced tailor-made using modern three-dimensional (3D) printing technology. Although this type of implant has been widely tested in vitro, there are only limited in vivo data and less so in a relevant large animal model. In this study, material properties of a 3D-printed brushite-based scaffold are characterized, after which the material is tested by in vivo orthotopic implantation in the equine tuber coxae for 6 months. The implantation procedure was easy to perform and was well tolerated by the animals, which showed no detectable signs of discomfort. In vitro tests showed that compressive strength along the vertical axis of densely printed material was around 13 MPa, which was reduced to approximately 8 MPa in the cylindrical porous implant. In vivo, approximately 40% of the visible volume of the implants was degraded after 6 months and replaced by bone, showing the capacity to stimulate new bone formation. Histologically, ample bone ingrowth was observed. In contrast, empty defects were filled with fibrous tissue only, confirming the material’s osteoconductive capacity. It is concluded that this study provides proof that the 3D-printed brushite implants were able to promote new bone growth after 6 months’ implantation in a large animal model and that the new equine tuber coxae bone model that was used is a promising tool for bone regeneration studies. El hueso tiene una gran capacidad de autocuración, pero por encima de un cierto tamaño crítico, los defectos óseos no se curan espontáneamente, por lo que es necesario intervenir para lograr una curación completa. Entre los materiales sintéticos de sustitución ósea de fosfato de calcio (CaP), los materiales a base de brusquitos (CaHPO4-2H2O) son de particular interés por su grado de solubilidad y el elevado potencial que presentan para promover la regeneración ósea después de la disolución. Pueden producirse a medida utilizando la moderna tecnología de impresión tridimensional (3D). Aunque este tipo de implante ha sido ampliamente probado in vitro, sólo hay datos limitados in vivo y menos en un modelo relevante de animal grande. En este estudio se caracterizan las propiedades del material de un andamiaje tridimensional impreso a base de grafito, tras lo cual el material se prueba mediante la implantación ortotópica in vivo en el tubérculo equino coxae durante 6 meses. El procedimiento de implantación fue fácil de realizar y fue bien tolerado por los animales, que no mostraron ningún signo detectable de molestia. Las pruebas in vitro demostraron que la resistencia a la compresión a lo largo del eje vertical del material densamente impreso era de alrededor de 13 MPa, que se redujo a aproximadamente 8 MPa en el implante cilíndrico poroso. En vivo, aproximadamente el 40% del volumen visible de los implantes se degradó después de 6 meses y fue reemplazado por hueso, lo que demuestra la capacidad de estimular la formación de nuevo hueso. Histológicamente, se observó un amplio crecimiento del hueso. En cambio, los defectos vacíos se llenaron sólo con tejido fibroso, confirmando la capacidad osteoconductiva del material. Se llega a la conclusión de que este estudio aporta pruebas de que los implantes de grafito tridimensional fueron capaces de promover el crecimiento de nuevo hueso después de 6 meses de implantación en un modelo de animal grande y que el nuevo modelo de hueso de tubérculo equino coxae que se utilizó es una herramienta prometedora para los estudios de regeneración ósea. Universidad Nacional, Costa Rica Escuela de Medicina Veterinaria
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- 2020
19. Treatment effects of intra‐articular triamcinolone acetonide in an equine model of recurrent joint inflammation
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Kearney, Clodagh M., primary, Korthagen, Nicoline M., additional, Plomp, Saskia G. M., additional, Labberté, Margot C., additional, Grauw, Janny C., additional, Weeren, P. R., additional, and Brama, Pieter A. J., additional
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- 2020
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20. Structural, compositional, and functional effects of blunt and sharp cartilage damage on the joint: A 9‐month equine groove model study.
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te Moller, Nikae C. R., Mohammadi, Ali, Plomp, Saskia, Serra Bragança, Filipe M., Beukers, Martijn, Pouran, Behdad, Afara, Isaac O., Nippolainen, Ervin, Mäkelä, Janne T. A., Korhonen, Rami K., Töyräs, Juha, Brommer, Harold, and van Weeren, P. René
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CARTILAGE ,JOINTS (Anatomy) ,SYNOVIAL fluid ,ARTICULAR cartilage ,HOMEOSTASIS - Abstract
This study aimed to quantify the long‐term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8‐week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait analysis. Macroscopic, microscopic, and biomechanical evaluation of the cartilage and assessment of subchondral bone parameters were performed ex vivo. Grooved cartilage showed higher OARSI microscopy scores than the contra‐lateral sham‐operated controls (p < 0.0001). Blunt‐grooved cartilage scored higher than sharp‐grooved cartilage (p = 0.007) and fixed charge density around these grooves was lower (p = 0.006). Equilibrium and instantaneous moduli trended lower in grooved cartilage than their controls (significant for radiocarpal joints). Changes in other tissues included a threefold to sevenfold change in interleukin‐6 expression in synovium from grooved joints at week 23 (p = 0.042) and an increased CPII/C2C ratio in synovial fluid extracted from blunt‐grooved joints at week 35 (p = 0.010). Gait analysis outcome revealed mild, gradually increasing lameness. In conclusion, blunt and, to a lesser extent, sharp grooves in combination with a period of moderate exercise, lead to mild degeneration in equine carpal cartilage over a 9‐month period, but the effect on overall joint health remains limited. [ABSTRACT FROM AUTHOR]
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- 2021
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21. Treatment effects of intra‐articular triamcinolone acetonide in an equine model of recurrent joint inflammation.
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Kearney, Clodagh M., Korthagen, Nicoline M., Plomp, Saskia G. M., Labberté, Margot C., de Grauw, Janny C., van Weeren, P. R., and Brama, Pieter A. J.
- Abstract
Background: Intra‐articular triamcinolone acetonide is a widely used treatment for joint inflammation despite limited scientific evidence of its efficacy. Objectives: To investigate if intra‐articular triamcinolone acetonide has sustained anti‐inflammatory effects using an equine model of repeated joint inflammation. Study design: Randomised controlled experimental study. Method: For three consecutive cycles 2 weeks apart, inflammation was induced in both middle carpal joints of eight horses by injecting 0.25 ng lipopolysaccharide (LPS). After the first LPS injection only, treatment with 12 mg triamcinolone acetonide (TA) followed in one randomly assigned joint, while the contralateral joint was treated with sterile saline (control). Clinical parameters (composite welfare scores, joint effusion, joint circumference) were recorded and synovial fluid samples were analysed for various biomarkers (total protein, WBCC; PGE2; CCL2; TNFα; MMP; GAGs; C2C; CPII) at fixed timepoints (post injection hours 0, 8, 24, 72 and 168). The effects of time and treatment on clinical and synovial fluid parameters and the presence of time–treatment interactions were tested using a linear mixed model for repeated measures with horse as a random effect, and time and treatment as fixed effects. Results: The TA treated joints showed significantly higher peak synovial GAG concentrations (Difference in means 283.1875 µg/mL, 95% CI 179.8, 386.6, P < 0.000), and PGE2 levels (Difference in means 77.8025 pg/mL, 95% CI 21.2, 134.4, P < 0.007) after the first inflammation induction. Significantly lower TP levels were seen with TA treatment after the second induction (Difference in means −7.5 g/L, 95% CI −14.8, −0.20, P < 0.04). Significantly lower WBCC levels were noted with TA treatment after the first (Difference in means −23.7125 × 109 cells/L, 95% CI −46.7, −0.7, P < 0.04) and second (Difference in means −35.95 × 109 cells/L, 95% CI −59.0, −12.9, P < 0.002) inflammation inductions. Significantly lower general MMP activity was also seen with TA treatment after the second inflammation inductions (Difference in means −51.65 RFU/s, 95% CI −92.4, −10.9, P < 0.01). Main limitations: This experimental study cannot fully reflect natural joint disease. Conclusions: In this model, intra‐articular TA seems to have some anti‐inflammatory activity (demonstrated by reductions in TP, WBCC and general MMP activity) up to 2 weeks post treatment but not at 4 weeks. This anti‐inflammatory effect appeared to outlast a shorter‐lived, potentially detrimental effect illustrated by increased synovial GAG and PGE2 levels after the first induction. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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22. Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model
- Author
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Cokelaere, Stefan M, Plomp, Saskia G M, de Boef, Esther, de Leeuw, Mike, Bool, Sophie, van de Lest, Chris H A, van Weeren, René, Korthagen, Nicoline M, Dep Gezondheidszorg Paard, LS Equine Muscoskeletal Biology, LS Heelkunde, dES AVR, dES RMSC, LS Veterinaire biochemie, dB&C FR-RMSC RMSC, Dep Gezondheidszorg Paard, LS Equine Muscoskeletal Biology, LS Heelkunde, dES AVR, dES RMSC, LS Veterinaire biochemie, and dB&C FR-RMSC RMSC
- Subjects
0301 basic medicine ,Lipopolysaccharides ,Male ,musculoskeletal diseases ,040301 veterinary sciences ,Polyesters ,Pharmaceutical Science ,Inflammation ,Osteoarthritis ,Pharmacology ,Injections, Intra-Articular ,Polyethylene Glycols ,0403 veterinary science ,03 medical and health sciences ,Synovitis ,Synovial Fluid ,medicine ,Synovial fluid ,Animals ,Humans ,Horses ,Adverse effect ,business.industry ,Equine ,Slow release ,Anti-Inflammatory Agents, Non-Steroidal ,Hydrogels ,04 agricultural and veterinary sciences ,General Medicine ,medicine.disease ,Disease Models, Animal ,Hydrogel ,030104 developmental biology ,Celecoxib ,Joint pain ,Rheumatoid arthritis ,Delayed-Action Preparations ,Female ,LPS model ,medicine.symptom ,business ,Biomarkers ,Biotechnology ,medicine.drug - Abstract
Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals.
- Published
- 2018
23. Early Signs of Bone and Cartilage Changes Induced by Treadmill Exercise in Rats
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Moshtagh, Parisa R, Korthagen, Nicoline M, Plomp, Saskia G, Pouran, Behdad, Castelein, Rene M, Zadpoor, Amir A, Weinans, Harrie, LS Equine Muscoskeletal Biology, and dES RMSC
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OSTEOARTHRITIS ,ANIMAL MODELS ,BONE MODELING AND REMODELING ,EXERCISE ,BIOMECHANICS - Abstract
This study aims to investigate the earliest alterations of bone and cartilage tissues as a result of different exercise protocols in the knee joint of Wistar rats. We hypothesize that pretraining to a continuous intense running protocol would protect the animals from cartilage degeneration. Three groups of animals were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with gradually increasing velocity and time of running followed by a constant running program (6 weeks of 1.12 km/hour running per day); (ii) a non-adaptive running (constant running) group that initially rested for 8 weeks followed by 6 weeks of constant running; and (iii) a non-running (control) group. At weeks 8, 14, and 20 bone and cartilage were analyzed. Both running groups developed mild symptoms of cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in different cartilage zones, in particular after the adaptive running protocol. As a result of physical training in the adaptive running exercise a dynamic response of bone was detected at week 8, where bone growth was enhanced. Conversely, the thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced due to the constant running in the period between 8 and 14 weeks. Finally, the intermediate differences between the two running groups disappeared after both groups had a resting period (from 14 to 20 weeks). The adaptive running group showed an increase in aggrecan gene expression and reduction of MMP2 expression after the initial 8 weeks running. Thus, the running exercise models in this study showed mild bone and cartilage/chondrocyte alterations that can be considered as early-stage osteoarthritis. The pretraining adaptive protocol before constant intense running did not protect from mild cartilage degeneration. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Published
- 2018
24. Early signs of bone and cartilage changes induced by treadmill exercise in rats
- Author
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Rahnamay Moshtagh, P., Korthagen, Nicoline M., Plomp, Saskia G., Pouran, B., Castelein, Rene M., Zadpoor, A.A., and Weinans, H.H.
- Subjects
oesteoarthritis ,exercise ,bone modeling and remodeling ,animal models ,biomechanics - Abstract
This study aims to investigate the earliest alterations of bone and cartilage tissues as a result of different exercise protocols in the knee joint of Wistar rats. We hypothesize that pretraining to a continuous intense running protocol would protect the animals from cartilage degeneration. Three groups of animals were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with gradually increasing velocity and time of running followed by a constant running program (6 weeks of 1.12 km/hour running per day); (ii) a non‐adaptive running (constant running) group that initially rested for 8 weeks followed by 6 weeks of constant running; and (iii) a non‐running (control) group. At weeks 8, 14, and 20 bone and cartilage were analyzed. Both running groups developed mild symptoms of cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in different cartilage zones, in particular after the adaptive running protocol. As a result of physical training in the adaptive running exercise a dynamic response of bone was detected at week 8, where bone growth was enhanced. Conversely, the thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced due to the constant running in the period between 8 and 14 weeks. Finally, the intermediate differences between the two running groups disappeared after both groups had a resting period (from 14 to 20 weeks). The adaptive running group showed an increase in aggrecan gene expression and reduction of MMP2 expression after the initial 8 weeks running. Thus, the running exercise models in this study showed mild bone and cartilage/chondrocyte alterations that can be considered as early‐stage osteoarthritis. The pretraining adaptive protocol before constant intense running did not protect from mild cartilage degeneration.
- Published
- 2018
25. 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?
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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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26. Additional file 2: of Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model
- Author
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Willems, Nicole, Hsiao-Yin Yang, Langelaan, Marloes, Tellegen, Anna, Grinwis, Guy, Hendrik-Jan Kranenburg, Riemers, Frank, Plomp, Saskia, Craenmehr, Eric, Dhert, Wouter, Papen-Botterhuis, Nicole, BjĂśrn Meij, Creemers, Laura, and Tryfonidou, Marianna
- Abstract
Primers used for qPCR. (DOCX 19 kb)
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- 2015
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27. Additional file 3: of Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model
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Willems, Nicole, Hsiao-Yin Yang, Langelaan, Marloes, Tellegen, Anna, Grinwis, Guy, Hendrik-Jan Kranenburg, Riemers, Frank, Plomp, Saskia, Craenmehr, Eric, Dhert, Wouter, Papen-Botterhuis, Nicole, BjĂśrn Meij, Creemers, Laura, and Tryfonidou, Marianna
- Abstract
Power analysis of the studies in laboratory beagle dogs. (DOCX 16 kb)
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- 2015
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28. Additional file 1: of Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model
- Author
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Willems, Nicole, Hsiao-Yin Yang, Langelaan, Marloes, Tellegen, Anna, Grinwis, Guy, Hendrik-Jan Kranenburg, Riemers, Frank, Plomp, Saskia, Craenmehr, Eric, Dhert, Wouter, Papen-Botterhuis, Nicole, Bjรถrn Meij, Creemers, Laura, and Tryfonidou, Marianna
- Subjects
technology, industry, and agriculture ,complex mixtures - Abstract
Synthesis and degradation of poly-N-isopropylacrylamide (pNIPAAM) MgFe-LDH hydrogels and controlled release of CXB in vitro. (DOCX 89 kb)
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- 2015
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29. Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration
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Willems, Nicole, Bach, Frances C, Plomp, Saskia G M, van Rijen, Mattie Hp, Wolfswinkel, Jeannette, Grinwis, Guy Cm, Bos, Clemens, Strijkers, Gustav J, Dhert, Wouter Ja, Meij, Björn P, Creemers, Laura B, Tryfonidou, Marianna A, CSCA TR1, dPB CR, Regenerative Medicine, Stem Cells & Cancer, Orthopedie en neurochirurgie, LS Equine Muscoskeletal Biology, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Pathologie, PB AVM, Faculteit Diergeneeskunde, LS Algemene chirurgie, Sub Neuro/Tandheelkunde, CSCA TR1, dPB CR, Regenerative Medicine, Stem Cells & Cancer, Orthopedie en neurochirurgie, LS Equine Muscoskeletal Biology, Veterinair Pathologisch Diagnostisch Cnt, Dep Pathobiologie, Pathologie, PB AVM, Faculteit Diergeneeskunde, LS Algemene chirurgie, and Sub Neuro/Tandheelkunde
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Bone Morphogenetic Protein 7 ,Immunology ,Cell ,Intervertebral Disc Degeneration ,Research Support ,Polymerase Chain Reaction ,Glycosaminoglycan ,Dogs ,Rheumatology ,Tissue engineering ,In vivo ,Osteogenesis ,medicine ,Journal Article ,Immunology and Allergy ,Animals ,Non-U.S. Gov't ,business.industry ,Regeneration (biology) ,Research Support, Non-U.S. Gov't ,Intervertebral disc ,musculoskeletal system ,In vitro ,Bone morphogenetic protein 7 ,Disease Models, Animal ,medicine.anatomical_structure ,business ,Research Article - Abstract
Introduction Strategies for biological repair and regeneration of the intervertebral disc (IVD) by cell and tissue engineering are promising, but few have made it into a clinical setting. Recombinant human bone morphogenetic protein 7 (rhBMP-7) has been shown to stimulate matrix production by IVD cells in vitro and in vivo in animal models of induced IVD degeneration. The aim of this study was to determine the most effective dose of an intradiscal injection of rhBMP-7 in a spontaneous canine IVD degeneration model for translation into clinical application for patients with low back pain. Methods Canine nucleus pulposus cells (NPCs) were cultured with rhBMP-7 to assess the anabolic effect of rhBMP-7 in vitro, and samples were evaluated for glycosaminoglycan (GAG) and DNA content, histology, and matrix-related gene expression. Three different dosages of rhBMP-7 (2.5 μg, 25 μg, and 250 μg) were injected in vivo into early degenerated IVDs of canines, which were followed up for six months by magnetic resonance imaging (T2-weighted images, T1rho and T2 maps). Post-mortem, the effects of rhBMP-7 were determined by radiography, computed tomography, and macroscopy, and by histological, biochemical (GAG, DNA, and collagen), and biomolecular analyses of IVD tissue. Results In vitro, rhBMP-7 stimulated matrix production of canine NPCs as GAG deposition was enhanced, DNA content was maintained, and gene expression levels of ACAN and COL2A1 were significantly upregulated. Despite the wide dose range of rhBMP-7 (2.5 to 250 μg) administered in vivo, no regenerative effects were observed at the IVD level. Instead, extensive extradiscal bone formation was noticed after intradiscal injection of 25 μg and 250 μg of rhBMP-7. Conclusions An intradiscal bolus injection of 2.5 μg, 25 μg, and 250 μg rhBMP-7 showed no regenerative effects in a spontaneous canine IVD degeneration model. In contrast, intradiscal injection of 250 μg rhBMP-7, and to a lesser extent 25 μg rhBMP-7, resulted in extensive extradiscal bone formation, indicating that a bolus injection of rhBMP-7 alone cannot be used for treatment of IVD degeneration in human or canine patients. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0625-2) contains supplementary material, which is available to authorized users.
- Published
- 2014
30. 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
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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
- Full Text
- View/download PDF
31. Biocompatibility and intradiscal application of a thermoreversible celecoxib-loaded poly-N-isopropylacrylamide MgFe-layered double hydroxide hydrogel in a canine model
- Author
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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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32. Intradiscal application of rhBMP-7 does not induce regeneration in a canine model of spontaneous intervertebral disc degeneration
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Willems, Nicole, primary, Bach, Frances C, additional, Plomp, Saskia G M, additional, van Rijen, Mattie HP, additional, Wolfswinkel, Jeannette, additional, Grinwis, Guy CM, additional, Bos, Clemens, additional, Strijkers, Gustav J, additional, Dhert, Wouter JA, additional, Meij, Björn P, additional, Creemers, Laura B, additional, and Tryfonidou, Marianna A, additional
- Published
- 2015
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33. Sustained Intra-Articular Release and Biocompatibility of Tacrolimus (FK506) Loaded Monospheres Composed of [PDLA-PEG 1000 ]- b -[PLLA] Multi-Block Copolymers in Healthy Horse Joints.
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Cokelaere, Stefan M., Groen, Wilhelmina M.G.A.C., Plomp, Saskia G.M., de Grauw, Janny C., van Midwoud, Paul M., Weinans, Harrie H., van de Lest, Chris H.A., Tryfonidou, Marianna A., van Weeren, P. René, and Korthagen, Nicoline M.
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POLYMERSOMES ,LEUKOCYTE count ,PATHOLOGICAL physiology ,COPOLYMERS ,SYNOVIAL fluid ,BIOCOMPATIBILITY ,PROSTAGLANDIN receptors - Abstract
There is an increasing interest in controlled release systems for local therapy in the treatment of human and equine joint diseases, aiming for optimal intra-articular concentrations with no systemic side effects. In this study, the intra-articular tolerability and suitability for local and sustained release of tacrolimus (FK506) from monospheres composed of [PDLA-PEG
1000 ]-b-PLLA multiblock copolymers were investigated. Unloaded and tacrolimus-loaded (18.4 mg tacrolimus/joint) monospheres were injected into the joints of six healthy horses, with saline and hyaluronic acid (HA) in the contralateral joints as controls. Blood and synovial fluid were analysed for the tacrolimus concentration and biomarkers for inflammation and cartilage metabolism. After an initial burst release, sustained intra-articular tacrolimus concentrations (>20 ng/mL) were observed during the 42 days follow-up. Whole-blood tacrolimus levels were below the detectable level (<0.5 ng/mL). A transient inflammatory reaction was observed for all substances, evidenced by increases of the synovial fluid white blood cell count and total protein. Prostaglandin and glycosaminoglycan release were increased in joints injected with unloaded monospheres, which was mitigated by tacrolimus. Both tacrolimus-loaded monospheres and HA transiently increased the concentration of collagen II cleavage products (C2C). A histologic evaluation of the joints at the endpoint showed no pathological changes in any of the conditions. Together, these results indicate the good biocompatibility of intra-articular applied tacrolimus-loaded monospheres combined with prolonged local drug release while minimising the risk of systemic side effects. Further evaluation in a clinical setting is needed to determine if tacrolimus-loaded monospheres can be beneficial in the treatment of inflammatory joint diseases in humans and animals. [ABSTRACT FROM AUTHOR]- Published
- 2021
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34. Histological tissue healing following high-power laser treatment in a model of suspensory ligament branch injury.
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Pluim M, Heier A, Plomp S, Boshuizen B, Gröne A, van Weeren R, Vanderperren K, Martens A, Dewulf J, Chantziaras I, Koene M, Luciani A, Oosterlinck M, Van Brantegem L, and Delesalle C
- Subjects
- Animals, Eosine Yellowish-(YS), Factor VIII, Horses, Ligaments injuries, Mammals, Horse Diseases pathology, Joint Diseases veterinary
- Abstract
Background: High-power laser therapy gained popularity recently as a regenerative treatment for tendinitis and desmitis in the horse. However, studies evaluating the effects of laser therapy on tissue repair at the histological level in large mammals are lacking., Objectives: To evaluate the effects of high-power laser therapy on suspensory desmitis healing, using a model of suspensory ligament branch injury., Study Design: In vivo experiments., Methods: Standardised lesions were surgically induced in all four lateral suspensory branches of 12 healthy Warmblood horses. Laser therapy (class 4, 15W) was applied daily on two of four induced lesions for four consecutive weeks. Horses were randomly assigned to either short-term study (horses were sacrificed after 4 weeks) or long-term study (6 months). Suspensory ligament samples were scored after staining with haematoxylin-eosin and immunostaining for collagen 1- collagen 3- and factor VIII., Results: In the short-term study, significantly better (lower) scores for variation in density (17% above cut-off score in treated lesions vs. 31% above cut-off score in controls, P = .03), shape of nuclei (54% vs 92%, P = .02), fibre alignment (32% vs 75%, P = .003) and fibre structure (38% vs 71%, P = .02) were found in laser-treated lesions when compared to controls. Collagen 3 expression was significantly higher (32% vs 19%, P = .006) in control lesions. In both short- and long-term studies combined, parameters lesion size (44% vs 56%, P = .02) and shape of nuclei (53% vs 84%, P = .05) scored significantly better in treated lesions. Long-term, significantly better (lower) scores were found in the laser-treated group for lesion size (15% vs 45%, P = .008) and a higher percentage above cut-off score for density of the nuclei (27% vs 9%, P = .02), compared to controls., Main Limitations: The model of suspensory branch injury is not an exact representation of clinical overstrain lesions., Conclusions: These results suggest that high-power laser therapy enables better lesion healing than conservative treatment., (© 2022 EVJ Ltd.)
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- 2022
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35. Intervertebral disc degeneration in warmblood horses: Histological and biochemical characterization.
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Bergmann W, de Lest CV, Plomp S, Vernooij JCM, Wijnberg ID, Back W, Gröne A, Delany MW, Caliskan N, Tryfonidou MA, and Grinwis GCM
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- Animals, Collagen, Dogs, Fibrosis, Horses, Hydroxylysine, Dog Diseases pathology, Horse Diseases pathology, Intervertebral Disc pathology, Intervertebral Disc Degeneration pathology, Intervertebral Disc Degeneration veterinary
- Abstract
Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.
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- 2022
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36. Folate Receptor Expression by Human Monocyte-Derived Macrophage Subtypes and Effects of Corticosteroids.
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Warmink K, Siebelt M, Low PS, Riemers FM, Wang B, Plomp SGM, Tryfonidou MA, van Weeren PR, Weinans H, and Korthagen NM
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- Biomarkers metabolism, Folic Acid metabolism, Humans, Macrophage Colony-Stimulating Factor metabolism, Macrophage Colony-Stimulating Factor pharmacology, Adrenal Cortex Hormones, Folate Receptor 2 metabolism, Granulocyte-Macrophage Colony-Stimulating Factor metabolism, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Macrophages
- Abstract
Objective: Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β
+ macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-β expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid., Design: Human monocyte-derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-β expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA)., Results: FR-β expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-β expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-β+ phenotype., Conclusions: As corticosteroids skewed monocytes toward an FR-β-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-β has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-β expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-β+ macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity.- Published
- 2022
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37. Long-Term in Vivo Performance of Low-Temperature 3D-Printed Bioceramics in an Equine Model.
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Bolaños RV, Castilho M, de Grauw J, Cokelaere S, Plomp S, Groll J, van Weeren PR, Gbureck U, and Malda J
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- Animals, Bone Regeneration, Horses, Porosity, Temperature, Bone Substitutes, Printing, Three-Dimensional
- Abstract
Bone has great self-healing capacity, but above a certain critical size, bone defects will not heal spontaneously, requiring intervention to achieve full healing. Among the synthetic calcium phosphate (CaP) bone replacement materials, brushite (CaHPO
4 ·2H2 O)-based materials are of particular interest because of their degree of solubility and the related high potential to promote bone regeneration after dissolution. They can be produced tailor-made using modern three-dimensional (3D) printing technology. Although this type of implant has been widely tested in vitro, there are only limited in vivo data and less so in a relevant large animal model. In this study, material properties of a 3D-printed brushite-based scaffold are characterized, after which the material is tested by in vivo orthotopic implantation in the equine tuber coxae for 6 months. The implantation procedure was easy to perform and was well tolerated by the animals, which showed no detectable signs of discomfort. In vitro tests showed that compressive strength along the vertical axis of densely printed material was around 13 MPa, which was reduced to approximately 8 MPa in the cylindrical porous implant. In vivo, approximately 40% of the visible volume of the implants was degraded after 6 months and replaced by bone, showing the capacity to stimulate new bone formation. Histologically, ample bone ingrowth was observed. In contrast, empty defects were filled with fibrous tissue only, confirming the material's osteoconductive capacity. It is concluded that this study provides proof that the 3D-printed brushite implants were able to promote new bone growth after 6 months' implantation in a large animal model and that the new equine tuber coxae bone model that was used is a promising tool for bone regeneration studies.- Published
- 2020
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38. Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.
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Cokelaere SM, Plomp SGM, de Boef E, de Leeuw M, Bool S, van de Lest CHA, van Weeren PR, and Korthagen NM
- Subjects
- Animals, Biomarkers analysis, Delayed-Action Preparations administration & dosage, Disease Models, Animal, Female, Horses, Humans, Hydrogels administration & dosage, Injections, Intra-Articular, Lipopolysaccharides immunology, Male, Polyesters, Polyethylene Glycols, Synovial Fluid chemistry, Synovitis immunology, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Celecoxib administration & dosage, Synovitis drug therapy
- Abstract
Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 h after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
39. Early Signs of Bone and Cartilage Changes Induced by Treadmill Exercise in Rats.
- Author
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Moshtagh PR, Korthagen NM, Plomp SG, Pouran B, Castelein RM, Zadpoor AA, and Weinans H
- Abstract
This study aims to investigate the earliest alterations of bone and cartilage tissues as a result of different exercise protocols in the knee joint of Wistar rats. We hypothesize that pretraining to a continuous intense running protocol would protect the animals from cartilage degeneration. Three groups of animals were used: (i) an adaptive (pretraining) running group that ran for 8 weeks with gradually increasing velocity and time of running followed by a constant running program (6 weeks of 1.12 km/hour running per day); (ii) a non-adaptive running (constant running) group that initially rested for 8 weeks followed by 6 weeks of constant running; and (iii) a non-running (control) group. At weeks 8, 14, and 20 bone and cartilage were analyzed. Both running groups developed mild symptoms of cartilage irregularities, such as chondrocyte hypertrophy and cell clustering in different cartilage zones, in particular after the adaptive running protocol. As a result of physical training in the adaptive running exercise a dynamic response of bone was detected at week 8, where bone growth was enhanced. Conversely, the thickness of epiphyseal trabecular and subchondral bone (at week 14) was reduced due to the constant running in the period between 8 and 14 weeks. Finally, the intermediate differences between the two running groups disappeared after both groups had a resting period (from 14 to 20 weeks). The adaptive running group showed an increase in aggrecan gene expression and reduction of MMP2 expression after the initial 8 weeks running. Thus, the running exercise models in this study showed mild bone and cartilage/chondrocyte alterations that can be considered as early-stage osteoarthritis. The pretraining adaptive protocol before constant intense running did not protect from mild cartilage degeneration. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
- Published
- 2018
- Full Text
- View/download PDF
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