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1.

001-es BibID:BIBFORM118410
035-os BibID:(cikkazonosító)2300931 (Scopus)85168319047 (WOS)001049575600001
Első szerző:Gao, Liang
Cím:A Photopolymerizable Biocompatible Hyaluronic Acid Hydrogel Promotes Early Articular Cartilage Repair in a Minipig Model In Vivo / Liang Gao, Riccardo Beninatto, Tamás Oláh, Lars Goebel, Ke Tao, Rebecca Roels, Steffen Schrenker, Julianne Glomm, Jagadeesh K. Venkatesan, Gertrud Schmitt, Ebrar Sahin, Ola Dahhan, Mauro Pavan, Carlo Barbera, Alba Di Lucia, Michael D. Menger, Matthias W. Laschke, Magali Cucchiarini, Devis Galesso, Henning Madry
Dátum:2023
ISSN:2192-2640 2192-2659
Megjegyzések:Articular cartilage defects represent an unsolved clinical challenge. Photopolymerizable hydrogels are attractive candidates supporting repair. This study investigates the short-term safety and efficacy of two novel hyaluronic acid (HA)-triethylene glycol (TEG)-coumarin hydrogels photocrosslinked in situ in a clinically relevant large animal model. It is hypothesized that HA-hydrogel-augmented microfracture (MFX) is superior to MFX in enhancing early cartilage repair, and that the molar degree of substitution and concentration of HA affects repair. Chondral full-thickness defects in the knees of adult minipigs are treated with either 1) debridement (No MFX), 2) debridement and MFX, 3) debridement, MFX, and HA hydrogel (30% molar derivatization, 30 mg mL?1 HA; F3) (MFX+F3), and 4) debridement, MFX, and HA hydrogel (40% molar derivatization, 20 mg mL?1 HA; F4) (MFX+F4). After 8 weeks postoperatively, MFX+F3 significantly improves total macroscopic and histological scores compared with all other groups without negative effects, besides significantly enhancing the individual repair parameters "defect architecture," "repair tissue surface" (compared with No MFX, MFX), and "subchondral bone" (compared with MFX). These data indicate that photopolymerizable HA hydrogels enable a favorable metastable microenvironment promoting early chondrogenesis in vivo. This work also uncovers a mechanism for effective HA-augmented cartilage repair by combining lower molar derivatization with higher concentrations.
Tárgyszavak:Orvostudományok Gyógyszerészeti tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
cartilage defects
cartilage repairs
hyaluronic acid
hydrogels
large animal model
photo-crosslinkin
Megjelenés:Advanced Healthcare Materials. - 12 : 26 (2023), p. 2300931. -
További szerzők:Beninatto, Riccardo Oláh Tamás (1983-) (élettanász) Goebel, Lars Tao, Ke Roels, Rebecca Schrenker, Steffen Glomm, Julianne Venkatesan, Jagadeesh K. Schmitt, Gertrud Sahin, Ebrar Dahhan, Ola Pavan, Mauro Barbera, Carlo Lucia, Alba Di Menger, Michael D. Laschke, Matthias W. Cucchiarini, Magali Galesso, Devis Madry, Henning
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2.

001-es BibID:BIBFORM115442
035-os BibID:(WoS)000469480000024 (Scopus)85053303109
Első szerző:Gao, Liang
Cím:Asymptomatic focal calcium pyrophosphate crystal deposition within partially failed repair tissue after matrix-assisted autologous chondrocyte implantation / Liang Gao, Tamás Oláh, Magali Cucchiarini, Henning Madry
Dátum:2018
ISSN:0942-2056
Megjegyzések:Possible failures of autologous chondrocyte implantation (ACI), a cell-based technique for articular cartilage repair, are not always clinically apparent and the underlying mechanisms largely remain unknown. This case report presents the first scenario in the literature highlighting an association of a medium-term partial failure of an advanced ACI procedure (matrix-assisted ACI) in the knee with focal asymptomatic calcium pyrophosphate deposition disease, a common inflammatory pyrophosphate arthropathy. The specific presence of CPPDs, resulting from increased biomechanical stresses in the repair tissue?cartilage and repair tissue?subchondral bone integration sites, together with the absence of cartilage regeneration was identified and possibly contributed to the partial failure.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Matrix-assisted autologous chondrocyte implantation
Calcium pyrophosphate deposition disease
Asymptomatic failure
Mid-term outcome
Knee
Megjelenés:Knee Surgery Sports Traumatology Arthroscopy. - 27 : 6 (2018), p. 1939-1942. -
További szerzők:Oláh Tamás (1983-) (élettanász) Cucchiarini, Magali Madry, Henning
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3.

001-es BibID:BIBFORM115263
035-os BibID:(WoS)000573288100006 (Scopus)85091542378 (cikkazonosító)eaba9481
Első szerző:Haberkamp, Sophie
Cím:Analysis of spatial osteochondral heterogeneity in advanced knee osteoarthritis exposes influence of joint alignment / Sophie Haberkamp, Tamás Oláh, Patrick Orth, Magali Cucchiarini, Henning Madry
Dátum:2020
ISSN:1946-6234
Megjegyzések:Osteoarthritis (OA) is considerably affected by joint alignment. Here, we investigate the patterns of spatial osteochondral heterogeneity in patients with advanced varus knee OA together with clinical data. We report strong correlations of osteochondral parameters within individual topographical patterns, highlighting their fundamental and location-dependent interactions in OA. We further identify site-specific effects of varus malalignment on the lesser loaded compartment and, conversely, an unresponsive overloaded compartment. Last, we trace compensatory mechanisms to the overloaded subarticular spongiosa in patients with additional high body weight. We therefore propose to consider and to determine axial alignment in clinical trials when selecting the location to assess structural changes in OA. Together, these findings broaden the scientific basis of therapeutic load redistribution and weight loss in varus knee OA.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Osteoarthritis
Subchondral Bone
Cancellous Bone
Megjelenés:Science Translational Medicine. - 12 : 562 (2020), p. eaba9481. -
További szerzők:Oláh Tamás (1983-) (élettanász) Orth, Patrick Cucchiarini, Magali Madry, Henning
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4.

001-es BibID:BIBFORM114886
035-os BibID:(Scopus)85169976718 (WoS)001054969100001 (cikkazonosító)4495697
Első szerző:Liu, Wei
Cím:Effects of rAAV-Mediated Overexpression of sox9 and TGF-β via Alginate Hydrogel-Guided Vector Delivery on the Chondroreparative Activities of Human Bone Marrow-Derived Mesenchymal Stromal Cells / Wei Liu, Jagadeesh K. Venkatesan, Mahnaz Amini, Tamás Oláh, Gertrud Schmitt, Henning Madry, Magali Cucchiarini
Dátum:2023
ISSN:1932-7005
Megjegyzések:Recombinant adeno-associated virus (rAAV) vectors have a strong potential to promote the healing of traumatic cartilage defects and osteoarthritic lesions upon delivery and overexpression of therapeutic genes from suitable biomaterials that support a controlled release of the candidate constructs. The goal of the present work is to examine whether the administration of chondrogenic rAAV sox9 and rAAV TGF-? gene vehicles via alginate hydrogel-guided vector delivery stimulates the biological and chondroreparative activities of human bone marrow-derived mesenchymal stromal cells (hMSCs) as a source of improved reparative cells for future implantation in sites of cartilage damage. The delivery of rAAV using an alginate (AlgPH155) hydrogel system is successfully achieved in hMSCs over time (21?days), leading to the effective overexpression of sox9 and TGF-? that significantly increases the proliferation and chondrogenic differentiation activities of the cells relative to control (marker lacZ) gene transfer while advantageously preventing premature hypertrophy, osteogenesis, and mineralization. This study reveals the potential of alginate hydrogel-based systems to control the delivery of rAAV (sox9 and TGF-?) gene vectors to adeptly trigger the chondroreparative activities of hMSCs for future applications that aim at improving cartilage repair.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Journal of Tissue Engineering and Regenerative Medicine. - 2023 (2023), p. 4495697. -
További szerzők:Venkatesan, Jagadeesh K. Amini, Mahnaz Oláh Tamás (1983-) (élettanász) Schmitt, Gertrud Madry, Henning Cucchiarini, Magali
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Intézményi repozitóriumban (DEA) tárolt változat
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5.

001-es BibID:BIBFORM114889
035-os BibID:(cikkazonosító)e745 (WOS)000761353600001
Első szerző:Michaelis, Jana Christin
Cím:A high-resolution cross-species comparative analysis of the subchondral bone provides insight into critical topographical patterns of the osteochondral unit / Jana Christin Michaelis, Tamás Oláh, Steffen Schrenker, Magali Cucchiarini, Henning Madry
Dátum:2022
ISSN:2001-1326
Tárgyszavak:Orvostudományok Elméleti orvostudományok szerkesztői levél
folyóiratcikk
Megjelenés:Clinical and Translational Medicine. - 12 : 2 (2022), p. e745. -
További szerzők:Oláh Tamás (1983-) (élettanász) Schrenker, Steffen Cucchiarini, Magali Madry, Henning
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6.

001-es BibID:BIBFORM118408
035-os BibID:(WoS)001070595600001 (Scopus)85172002316
Első szerző:Oláh Tamás (élettanász)
Cím:Subchondral bone remodeling patterns in larger animal models of meniscal injuries inducing knee osteoarthritis - a systematic review / Tamás Oláh, Magali Cucchiarini, Henning Madry
Dátum:2023
ISSN:0942-2056
Megjegyzések:Purpose: Elucidating subchondral bone remodeling in preclinical models of traumatic meniscus injury may address clinically relevant questions about determinants of knee osteoarthritis (OA). Methods: Studies on subchondral bone remodeling in larger animal models applying meniscal injuries as standardizing entity were systematically analyzed. Of the identified 5367 papers reporting total or partial meniscectomy, meniscal transection or destabilization, 0.4% (in guinea pigs, rabbits, dogs, minipigs, sheep) remained eligible. Results: Only early or mid-term time points were available. Larger joint sizes allow reporting higher topographical details. The most frequently reported parameters were BV/TV (61%), BMD (41%), osteophytes (41%) and subchondral bone plate thickness (39%). Subchondral bone plate microstructure is not comprehensively, subarticular spongiosa microstructure is well characterized. The subarticular spongiosa is altered shortly before the subchondral bone plate. These early changes involve degradation of subarticular trabecular elements, reduction of their number, loss of bone volume and reduced mineralization. Soon thereafter, the previously normal subchondral bone plate becomes thicker. Its porosity first increases, then decreases. Conclusion: The specific human topographical pattern of a thinner subchondral bone plate in the region below both menisci is present solely in the larger species (partly in rabbits), but absent in rodents, an important fact to consider when designing animal studies examining subchondral consequences of meniscus damage. Large animal models are capable of providing high topographical detail, suggesting that they may represent suitable study systems reflecting the clinical complexities. For advanced OA, significant gaps of knowledge exist. Future investigations assessing the subchondral bone in a standardized fashion are warranted.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Meniscus
Meniscal tear
Subchondral bone
Animal model
Osteoarthritis
Systematic review
Megjelenés:Knee Surgery Sports Traumatology Arthroscopy. - 31 : 12 (2023), p. 5346-5364. -
További szerzők:Cucchiarini, Magali Madry, Henning
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7.

001-es BibID:BIBFORM115440
035-os BibID:(Scopus)85040458576 (WOS)000419442500012 (cikkazonosító)75
Első szerző:Oláh Tamás (élettanász)
Cím:Reliable landmarks for precise topographical analyses of pathological structural changes of the ovine tibial plateau in 2-D and 3-D subspaces / Tamás Oláh, Jan Reinhard, Liang Gao, Lars K. H. Goebel, Henning Madry
Dátum:2018
ISSN:2045-2322
Megjegyzések:Selecting identical topographical locations to analyse pathological structural changes of the osteochondral unit in translational models remains difficult. The specific aim of the study was to provide objectively defined reference points on the ovine tibial plateau based on 2-D sections of micro-CT images useful for reproducible sample harvesting and as standardized landmarks for landmark-based 3-D image registration. We propose 5 reference points, 11 reference lines and 12 subregions that are detectable macroscopically and on 2-D micro-CT sections. Their value was confirmed applying landmark-based rigid and affine 3-D registration methods. Intra- and interobserver comparison showed high reliabilities, and constant positions (standard errors?<?1%). Spatial patterns of the thicknesses of the articular cartilage and subchondral bone plate were revealed by measurements in 96 individual points of the tibial plateau. As a case study, pathological phenomena 6 months following OA induction in vivo such as osteophytes and areas of OA development were mapped to the individual subregions. These new reference points and subregions are directly identifiable on tibial plateau specimens or macroscopic images, enabling a precise topographical location of pathological structural changes of the osteochondral unit in both 2-D and 3-D subspaces in a region-appropriate fashion relevant for translational investigations.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Scientific Reports. - 8 : 1 (2018), p. 75. -
További szerzők:Reinhard, Jan Gao, Liang Goebel, Lars Madry, Henning
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Intézményi repozitóriumban (DEA) tárolt változat
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8.

001-es BibID:BIBFORM115267
035-os BibID:(Scopus)85071741811 (WoS)000484406300004 (cikkazonosító)eaax6775
Első szerző:Oláh Tamás (élettanász)
Cím:Topographic modeling of early human osteoarthritis in sheep / Tamás Oláh, Jan Reinhard, Liang Gao, Sophie Haberkamp, Lars K. H. Goebel, Magali Cucchiarini, Henning Madry
Dátum:2019
ISSN:1946-6234
Megjegyzések:Articular cartilage damage occurring during early osteoarthritis (OA) is a key event marking the development of the disease. Here, we modeled early human OA by gathering detailed spatiotemporal data from surgically induced knee OA development in sheep. We identified a specific topographical pattern of osteochondral changes instructed by a defined meniscal injury, showing that both cartilage and subchondral bone degeneration are initiated from the region adjacent to the damage. Alterations of the subarticular spongiosa arising locally and progressing globally disturbed the correlations of cartilage with subchondral bone seen at homeostasis and were indicative of disease progression. We validated our quantitative findings against human OA, showing a similar pattern of early OA correlating with regions of meniscal loss and an analogous late critical disturbance within the entire osteochondral unit. This translational model system can be used to elucidate mechanisms of OA development and provides a roadmap for investigating regenerative therapies.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Science Translational Medicine. - 11 : 508 (2019), p. eaax6775. -
További szerzők:Reinhard, Jan Gao, Liang Haberkamp, Sophie Goebel, Lars Cucchiarini, Magali Madry, Henning
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9.

001-es BibID:BIBFORM115032
035-os BibID:(WoS)000610869000010 (Scopus)85096209629 (cikkazonosító)151630
Első szerző:Oláh Tamás (élettanász)
Cím:Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part II: Small animals / Tamás Oláh, Xiaoyu Cai, Jana Christin Michaelis, Henning Madry
Dátum:2021
ISSN:0940-9602
Megjegyzések:Background Small animal models are critical to model the complex disease mechanisms affecting a functional joint leading to articular cartilage disorders. They are advantageous for several reasons and significantly contributed to the understanding of the mechanisms of cartilage diseases among which osteoarthritis. Methods Literature search in Pubmed. Results and discussion This narrative review summarizes the most relevant anatomical structural and functional characteristics of the knee (stifle) joints of the major small animal species, including mice, rats, guinea pigs, and rabbits compared with humans. Specific characteristics of each species, including kinematical gait parameters are provided and compared with the human situation. When placed in a proper context respecting their challenges and limitations, small animal models are important and appropriate models for articular cartilage disorders.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Small animal model
knee
human
osteochondral unit
articular cartilage
subchondral bone
range of motion
Megjelenés:Annals Of Anatomy-Anatomischer Anzeiger. - 234 (2021), p. 151630. -
További szerzők:Michaelis, Jana Christin Cai, Xiaoyu Cucchiarini, Magali Madry, Henning
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10.

001-es BibID:BIBFORM114910
035-os BibID:(WoS)000635677000012 (Scopus)85100454395 (cikkazonosító)151680
Első szerző:Oláh Tamás (élettanász)
Cím:Comparative anatomy and morphology of the knee in translational models for articular cartilage disorders. Part I: Large animals / Tamás Oláh, Xiaoyu Cai, Jana Christin Michaelis, Henning Madry
Dátum:2021
ISSN:0940-9602
Megjegyzések:Background: The human knee is a complex joint, and affected by a variety of articular cartilage disorders. Large animal models are critical to model the complex disease mechanisms affecting a functional joint. Species-dependent differences highly affect the results of a pre-clinical study and need to be considered, necessitating specific knowledge not only of macroscopic and microscopic anatomical and pathological aspects, but also characteristics of their individual gait and joint movements. Methods: Literature search in Pubmed. Results and discussion: This narrative review summarizes the most relevant anatomical structural and functional characteristics of the knee (stifle) joints of the major translational large animal species, comprising dogs, (mini)pigs, sheep, goats, and horses in comparison with humans. Specific characteristics of each species, including kinematical gait parameters are provided. Considering these multifactorial dimensions will allow to select the appropriate model for answering the research questions in a clinically relevant fashion.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Large animal model
Knee
Human
Osteochondral unit
Articular cartilage
Subchondral bone
Range of motion
Megjelenés:Annals Of Anatomy-Anatomischer Anzeiger. - 235 (2021), p. 151680. -
További szerzők:Cai, Xiaoyu Michaelis, Jana Christin Madry, Henning
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11.

001-es BibID:BIBFORM114906
035-os BibID:(Scopus)85123905875 (WOS)000747294800006 (cikkazonosító)eabn0179
Első szerző:Oláh Tamás (élettanász)
Cím:Axial alignment is a critical regulator of knee osteoarthritis / Tamás Oláh, Jan Reinhard, Matthias W. Laschke, Lars K. H. Goebel, Frédéric Walter, Gertrud Schmitt, Susanne Speicher-Mentges, Michael D. Menger, Magali Cucchiarini, Dietrich Pape, Henning Madry
Dátum:2022
ISSN:1946-6234
Megjegyzések:Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion. Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:Science Translational Medicine. - 14 : 629 (2022), p. eabn0179. -
További szerzők:Reinhard, Jan Laschke, Matthias W. Goebel, Lars Walter, Frédéric Schmitt, Gertrud Speicher-Mentges, Susanne Menger, Michael D. Cucchiarini, Magali Pape, Dietrich Madry, Henning
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Intézményi repozitóriumban (DEA) tárolt változat
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12.

001-es BibID:BIBFORM114887
035-os BibID:(WOS)000806728200001 (Scopus)85131298379 (cikkazonosító)2201692
Első szerző:Oláh Tamás (élettanász)
Cím:Quantifying the Human Subchondral Trabecular Bone Microstructure in Osteoarthritis with Clinical CT / Tamás Oláh, Xiaoyu Cai, Liang Gao, Frédéric Walter, Dietrich Pape, Magali Cucchiarini, Henning Madry
Dátum:2022
ISSN:2198-3844
Megjegyzések:Osteoarthritis (OA) is characterized by critical alterations of the subchondral bone microstructure, besides the well-known cartilaginous changes. Clinical computed tomography (CT) detection of quantitative 3D microstructural subchondral bone parameters is applied to monitor changes of subchondral bone structure in different stages of human OA and is compared with micro-CT, the gold standard. Determination by clinical CT (287 ?m resolution) of key microstructural parameters in tibial plateaus with mild-to-moderate and severe OA reveals strong correlations to micro-CT (35 ?m), high inter- and intraobserver reliability, and small relative differences. In vivo, normal, mild-to-moderate, and severe OA are compared with clinical CT (331 ?m). All approaches detect characteristic expanded trabecular structure in severe OA and fundamental microstructural correlations with clinical OA stage. Multivariate analyses at various in vivo and ex vivo imaging resolutions always reliably separate mild-to-moderate from severe OA (except mild-to-moderate OA from normal), revealing a striking similarity between 287 ?m clinical and 35 ?m micro-CT. Thus, accurate structural measurements using clinical CT with a resolution near the trabecular dimensions are possible. Clinical CT offers an opportunity to quantitatively monitor subchondral bone microstructure in clinical and experimental settings as an advanced tool of investigating OA and other diseases affecting bone architecture.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
3D microstructure
computed tomography
microcomputed tomography
multislice computed tomography
osteoarthritis of knee
subchondral bone
Megjelenés:Advanced Science. - 9 : 23 (2022), p. 2201692. -
További szerzők:Cai, Xiaoyu Gao, Liang Walter, Frédéric Pape, Dietrich Cucchiarini, Magali Madry, Henning
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Intézményi repozitóriumban (DEA) tárolt változat
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