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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: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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3.

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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4.

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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5.

001-es BibID:BIBFORM114717
035-os BibID:(WoS)000953912600001 (Scopus)85144755733
Első szerző:Schrenker, Steffen
Cím:In vivo rAAV-mediated human TGF-β overexpression reduces perifocal osteoarthritis and improves osteochondral repair in a large animal model at one year / S. Schrenker, M. Cucchiarini, L. Goebel, T. Olah, J. K. Venkatesan, G. Schmitt, S. Speicher-Mentges, J. Maihofer, L. Gao, D. Zurakowski, M. D. Menger, M. W. Laschke, H. Madry
Dátum:2023
ISSN:1063-4584
Megjegyzések:Objective: Osteoarthritis (OA) is a serious consequence of focal osteochondral defects. Gene transfer of human transforming growth factor beta (hTGF-β) with recombinant adeno-associated virus (rAAV) vectors offers a strategy to improve osteochondral repair. However, the long-term in vivo effects of such rAAV-mediated TGF-β overexpression including its potential benefits on OA development remain unknown. Method: Focal osteochondral defects in minipig knees received rAAV-lacZ (control) or rAAV-hTGF-β in vivo. After one year, osteochondral repair and perifocal OA were visualized using validated macroscopic scoring, ultra-high-field MRI at 9.4 T, and micro-CT. A quantitative estimation of the cellular densities and a validated semi-quantitative scoring of histological and immunohistological parameters completed the analysis of microarchitectural parameters. Results: Direct rAAV-hTGF-β application induced and maintained significantly improved defect filling and safranin O staining intensity and overall cartilage repair at one year in vivo. In addition, rAAV-hTGF-β led to significantly higher chondrocyte densities within the cartilaginous repair tissue without affecting chondrocyte hypertrophy and minimized subarticular trabecular separation. Of note, rAAV-hTGF-β significantly improved the adjacent cartilage structure and chondrocyte density and reduced overall perifocal OA development after one year in vivo. Conclusions: rAAV-hTGF-β treatment improves long-term osteochondral repair and delays the progression of perifocal OA in a translational model. These findings have considerable potential for targeted molecular approaches to treat focal osteochondral defects.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Osteochondral defects
Osteoarthritis
rAAV
Large animal model
Cartilage repair
TGF-β
Megjelenés:Osteoarthritis And Cartilage. - 31 : 4 (2023), p. 467-481. -
További szerzők:Cucchiarini, Magali Goebel, Lars Oláh Tamás (1983-) (élettanász) Venkatesan, Jagadeesh K. Schmitt, Gertrud Speicher-Mentges, Susanne Maihöfer, J. Gao, L. L. Zurakowski, D. Menger, Michael D. Laschke, Matthias W. Madry, Henning
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