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001-es BibID:BIBFORM118410
035-os BibID:(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
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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3.

001-es BibID:BIBFORM115267
035-os BibID:(Scopus)85071741811 (WoS)000484406300004
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
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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5.

001-es BibID:BIBFORM125450
035-os BibID:(scopus)85187934055 (wos)001185356800001
Első szerző:Peifer, Carolin
Cím:Locally Directed Recombinant Adeno- Associated Virus-Mediated IGF-1 Gene Therapy Enhances Osteochondral Repair and Counteracts Early Osteoarthritis In Vivo / Peifer Carolin, Oláh Tamás, Venkatesan Jagadeesh K., Goebel Lars, Orth, Patrick; Schmitt, Gertrud; Zurakowski, David; Menger, Michael D.; Laschke, Matthias W.; Cucchiarini, Magali; Madry, Henning
Dátum:2024
ISSN:0363-5465 1552-3365
Megjegyzések:Background: Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise. Hypothesis: Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo. Study Design: Controlled laboratory study. Methods: Osteochondral defects were created in the femoral trochlea of adult sheep and treated with rAAV-IGF-1 or rAAV-lacZ (control) (24 defects in 6 knees per group). After 6 months in vivo, osteochondral repair and perifocal OA were assessed by well-established macroscopic, histological, and immunohistochemical scoring systems as well as biochemical and micro?computed tomography evaluations. Results: Application of rAAV-IGF-1 led to prolonged (6 months) IGF-1 overexpression without adverse effects, maintaining a significantly superior overall cartilage repair, together with significantly improved defect filling, extracellular matrix staining, cellular morphology, and surface architecture compared with rAAV-lacZ. Expression of type II collagen significantly increased and that of type I collagen significantly decreased. Subchondral bone repair and tidemark formation were significantly improved, and subchondral bone plate thickness and subarticular spongiosa mineral density returned to normal. The OA parameters of perifocal structure, cell cloning, and matrix staining were significantly better preserved upon rAAV-IGF-1 compared with rAAV-lacZ. Novel mechanistic associations between parameters of osteochondral repair and OA were identified. Conclusion: Local rAAV-mediated IGF-1 overexpression enhanced osteochondral repair and ameliorated parameters of perifocal early OA. Clinical Relevance: IGF-1 gene therapy may be beneficial in repair of focal osteochondral defects and prevention of perifocal OA.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
osteochondral defects
recombinant adeno-associated viral (rAAV) vectors
IGF-1
osteoarthritis
large-animal model
Megjelenés:American Journal Of Sports Medicine. - 52 : 5 (2024), p. 1336-1349. -
További szerzők:Oláh Tamás (1983-) (élettanász) Venkatesan, Jagadeesh K. Goebel, Lars Orth, Patrick Schmitt, Gertrud Zurakowski, David Menger, Michael D. Laschke, Matthias W. Cucchiarini, Magali Madry, Henning
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Intézményi repozitóriumban (DEA) tárolt változat
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6.

001-es BibID:BIBFORM125448
035-os BibID:(scopus)85188051020 (wos)001244842000001
Első szerző:Reinhard, Jan
Cím:Modulation of early osteoarthritis by tibiofemoral re-alignment in sheep / Reinhard Jan, Oláh Tamás, Laschke Matthias W., Goebel Lars K. H., Schmitt Gertrud, Speicher-Mentges Susanne, Menger Michael D., Cucchiarini Magali, Pape Dietrich, Madry Henning
Dátum:2024
ISSN:1063-4584
Megjegyzések:Objective To investigate whether tibiofemoral alignment influences early knee osteoarthritis (OA). We hypothesized that varus overload exacerbates early degenerative osteochondral changes, and that valgus underload diminishes early OA. Method Normal, over- and underload were induced by altering alignment via high tibial osteotomy in adult sheep (n = 8 each). Simultaneously, OA was induced by partial medial anterior meniscectomy. At 6 weeks postoperatively, OA was examined in five individual subregions of the medial tibial plateau using Kellgren-Lawrence grading, quantification of macroscopic OA, semiquantitative histopathological OA and immunohistochemical type-II collagen, ADAMTS-5, and MMP-13 scoring, biochemical determination of DNA and proteoglycan contents, and micro-computed tomographic evaluation of the subchondral bone. Results Multivariate analyses revealed that OA cartilaginous changes had a temporal priority over subchondral bone changes. Underload inhibited early cartilage degeneration in a characteristic topographic pattern (P ? 0.0983 vs. normal), in particular below the meniscal damage, avoided alterations of the subarticular spongiosa (P ? 0.162 vs. normal), and prevented the disturbance of otherwise normal osteochondral correlations. Overload induced early alterations of the subchondral bone plate microstructure towards osteopenia, including significantly decreased percent bone volume and increased bone surface?to?volume ratio (all P ? 0.0359 vs. normal). Conclusion The data provide high-resolution evidence that tibiofemoral alignment modulates early OA induced by a medial meniscus injury in adult sheep. Since underload inhibits early OA, these data also support the clinical value of strategies to reduce the load in an affected knee compartment to possibly decelerate structural OA progression.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Knee osteoarthritis
Axial alignment
Overload
Unloading
Large animal model
Osteochondral unit
Megjelenés:Osteoarthritis And Cartilage. - 32 : 6 (2024), p. 690-701. -
További szerzők:Oláh Tamás (1983-) (élettanász) Laschke, Matthias W. Goebel, Lars Schmitt, Gertrud Speicher-Mentges, Susanne Menger, Michael D. Cucchiarini, Magali Pape, Dietrich Madry, Henning
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7.

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, David Menger, Michael D. Laschke, Matthias W. Madry, Henning
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Intézményi repozitóriumban (DEA) tárolt változat
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