Posttraumatic Osteoarthritis Development and Progression in an Ovine Model of Partial Anterior Cruciate Ligament Transection and Effect of Repeated Intra-articular Methylprednisolone Acetate Injections on Early Disease

Barton, Kristen I; Heard, Bryan J.; Sevick, Johnathan L; Martin, Claude; Shekarforoush, Seyed Mohammad Mehdi; Chung, May; Achari, Yamini; Frank, Cyril B.; Shrive, Nigel G.; Hart, David A.

doi:10.1177/0363546518765098

Cited by 21 publications

(25 citation statements)

References 60 publications

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“…The release of the remaining MET has occurred in 90 days. According to previous literature (Naghizadeh et al, 2018a, 2018b), MET can be helpful for the first 3 days and relieve early inflammation (Barton et al, 2018; Tobar‐Grande et al, 2013). However, the beneficial effect of MEL has also been reported to be effective from 3 to 21 days (Pei, He, Wei, & Rawson, 2009; Gao et al, 2018).…”

Section: Resultsmentioning

confidence: 91%

“…The release of the remaining MET has occurred in F I G U R E 3 Time dependence of storage modulus G′ and loss modulus G″ of hydrogel/microparticle F I G U R E 4 Cumulative release of melatonin (MEL) and methylprednisolone (MET) from the hydrogel/microparticle at 37°C F I G U R E 5 (a) Scanning electron micrographs of hydrogel/microparticle seeded with adipose-derived mesenchymal stem cells (AdSCs). Cytocompatibility determination by (b) acridine orange/ propidium iodide (AO/PI) staining, and (c) 4′,6-diamidino-2-phenylindole (DAPI) staining of the hydrogel/microparticle 2018a, 2018b), MET can be helpful for the first 3 days and relieve early inflammation (Barton et al, 2018;Tobar-Grande et al, 2013).…”

Section: Drug Deliverymentioning

confidence: 99%

“…One of these molecules with a substantial effect on chondrogenic differentiation of MSCs is melatonin (MEL). On the other hand, methylprednisolone (MET) has also been effective in repairing cartilage inflammation in cartilage tissue repair (Barton et al, 2018; Tobar‐Grande et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Cartilage regeneration with dual‐drug‐releasing injectable hydrogel/microparticle system: In vitro and in vivo study

Naghizadeh

Karkhaneh

Nokhbatolfoghahaei

et al. 2020

Journal Cellular Physiology

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In this study, we developed an injectable in situ forming hydrogel/microparticle system consisting of two drugs, melatonin and methylprednisolone, to investigate the capability of the system for chondrogenesis in vitro and in vivo. The chemical, mechanical, and rheological properties of the hydrogel/microparticle were investigated. For in vitro evaluation, the adipose-derived stem cells might be mixed with hydrogel/microparticles, then cellular viability was analyzed by acridine orange/propidium iodide and 4′,6-diamidino-2-phenylindole staining and also dimethylmethylene blue assay were conducted to find the amount of proteoglycan. The real-time polymerase chain reaction for aggrecan, sex-determining region Y-Box 9, collagen I (COL1), and COL2 gene expression was performed after 14 and 21 days. For evaluation of cartilage regeneration, the samples were implanted in rabbit knees with cartilaginous experimental defects. Defects were created in both knees of three groups of rabbits. Group 1 was the control with no injection, and Groups 2 and 3 were loaded with hydrogel/cell and hydrogel/microparticle/cell; respectively. Then, after 3 and 6 months, histological evaluations of the defected sites were carried out. The amount of glycosaminoglycans after 14 and 21 days increased significantly in hydrogels/microparticles loaded with cells. The expression of marker genes was also significant in hydrogels/microparticles loaded with cells. According to histology analysis, the hydrogels/microparticles loaded with cells showed the best cartilage regeneration. Overall, our study revealed that the developed injectable hydrogel/microparticle can be used for cartilage regeneration.

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Section: Resultsmentioning

confidence: 91%

Section: Drug Deliverymentioning

confidence: 99%

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Cartilage regeneration with dual‐drug‐releasing injectable hydrogel/microparticle system: In vitro and in vivo study

Naghizadeh

Karkhaneh

Nokhbatolfoghahaei

et al. 2020

Journal Cellular Physiology

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“…13 Skeletally mature, 3- to 5-year-old female Suffolk cross sheep (average weight, 74.4 kg) were used for the p-ACL Tx model. 3 The animals were allocated into 3 groups: nonoperative controls (n = 6), 20 weeks after p-ACL Tx (n = 5), and 40 weeks after p-ACL Tx (n = 6). Briefly, 3 all surgical procedures were accomplished to the right stifle joint.…”

Section: Methodsmentioning

confidence: 99%

“…In an ovine knee injury model, altered kinematics 4 and degradation of cartilage 3 have been observed at 20 and 40 weeks after partial ACL transection (p-ACL Tx) surgery of the AM band. However, for the injured knee as an adaptive organ system, 23 biological changes to the intact PL band and posterior cruciate ligament (PCL) after AM band Tx remain to be characterized.…”

mentioning

confidence: 99%

Structural Consequences of a Partial Anterior Cruciate Ligament Injury on Remaining Joint Integrity: Evidence for Ligament and Bone Changes Over Time in an Ovine Model

et al. 2021

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Background: Severe injury to the knee joint often results in accelerated posttraumatic osteoarthritis (PTOA). In an ovine knee injury model, altered kinematics and degradation of the cartilage have been observed at 20 and 40 weeks after partial anterior cruciate ligament (ACL) transection (p-ACL Tx) surgery. However, changes to the integrity of the remaining intact intra-articular ligaments (posterolateral [PL] band and posterior cruciate ligament [PCL]) as well as the subchondral bone after anteromedial (AM) band Tx remain to be characterized. Purpose: (1) To investigate histological alterations to the remaining intact intra-articular ligaments, the synovium, and the infrapatellar fat pad (IPFP) and (2) to quantify subchondral bone changes at the contact surfaces of the proximal tibia at 20 and 40 weeks after AM band Tx. Study Design: Descriptive laboratory study. Methods: Mature female Suffolk cross sheep were allocated into 3 groups: nonoperative controls (n = 6), 20 weeks after partial ACL transection (p-ACL Tx; n = 5), and 40 weeks after p-ACL Tx (n = 6). Ligament, synovium, and IPFP sections were stained and graded. Tibial subchondral bone microarchitecture was assessed using high-resolution peripheral quantitative computed tomography. Results: p-ACL Tx of the AM band led to significant change in histological scores of the PL band and the PCL at 20 weeks after p-ACL Tx ( P = .031 and P = .033, respectively) and 40 weeks after p-ACL Tx ( P = .011 and P = .029) as compared with nonoperative controls. Alterations in inflammatory cells and collagen fiber orientation contributed to the greatest extent of the combined histological score in the PL band and PCL. p-ACL Tx did not lead to chronic activation of the synovium or IPFP. Trabecular bone mineral density was strongly inversely correlated with combined gross morphological damage in the top and middle layers of the subchondral bone in the lateral tibial plateau for animals at 40 weeks after p-ACL Tx. Conclusion: p-ACL Tx influences the integrity (biology and structure) of remaining intact intra-articular ligaments and bone microarchitecture in a partial knee injury ovine model. Clinical Relevance: p-ACL Tx leads to alterations in structural integrity of the remaining intact ligaments and degenerative changes in the trabecular bone mineral density, which may be detrimental to the injured athlete’s knee joint in the long term.

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Corticosteroid injections for the treatment of osteoarthritis present a wide spectrum of effects ranging from detrimental to disease‐modifying: A systematic review of preclinical evidence by the ESSKA Orthobiologic Initiative

Bensa,

Salerno,

Boffa

et al. 2024

Knee surg. sports traumatol. arthrosc.

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PurposeAim of this systematic review of preclinical evidence was to determine the effects of intra‐articular corticosteroid (CS) injections in joints affected by osteoarthritis (OA).MethodsA systematic review was performed on animal studies evaluating intra‐articular CS injections for OA joints. The search was performed on PubMed, Cochrane, and Web of Science databases. A synthesis of the results was performed investigating CS effects by evaluating studies comparing CS with control groups. Morphological, histological, immunohistochemistry evaluations, clinical outcomes, biomarkers and imaging results were evaluated. The risk of bias was assessed according to the Systematic Review Centre for Laboratory Animal Experimentation's tool.ResultsThirty‐two articles analysing CS effects in OA animal models were included (1079 joints), 18 studies on small and 14 on large animals. CS injections showed overall positive effects in at least one of the outcomes in 68% of the studies, while 16% reported a deleterious effect. CS improved cartilage and synovial outcomes in 68% and 60% of the studies, but detrimental effects were documented in 11% and 20% of the studies, respectively. Clinical parameters evaluated in terms of pain, lameness or joint swelling improved in 63% of the studies but deteriorated in 13%. Evidence is limited on imaging and biomarkers results, as well as on the best CS type, dose, formulation and injection protocol. The risk of bias assessment revealed a 28% low and an 18% high risk of bias.ConclusionIntra‐articular CS injections induced a wide range of results on OA joints in experimental animal models, from disease‐modifying and positive effects on pain and joint function at short‐term evaluation to the lack of benefit or even negative effects. This underlines the need to identify more specific indications and treatment modalities to avoid possible detrimental effects while maximising the anti‐inflammatory properties and the benefits of intra‐articular CS in OA joints.Level of EvidenceLevel II.

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Posttraumatic Osteoarthritis Development and Progression in an Ovine Model of Partial Anterior Cruciate Ligament Transection and Effect of Repeated Intra-articular Methylprednisolone Acetate Injections on Early Disease

Abstract: A p-ACL injury leads to slow and progressive PTOA-like joint damage, and multiple repeated injections of glucocorticoids may be detrimental to the knee joint in the long term.

Cited by 21 publications

References 60 publications

Cartilage regeneration with dual‐drug‐releasing injectable hydrogel/microparticle system: In vitro and in vivo study

Cartilage regeneration with dual‐drug‐releasing injectable hydrogel/microparticle system: In vitro and in vivo study

Structural Consequences of a Partial Anterior Cruciate Ligament Injury on Remaining Joint Integrity: Evidence for Ligament and Bone Changes Over Time in an Ovine Model

Corticosteroid injections for the treatment of osteoarthritis present a wide spectrum of effects ranging from detrimental to disease‐modifying: A systematic review of preclinical evidence by the ESSKA Orthobiologic Initiative

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