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An In Vitro Engineered Osteochondral Model as Tool to Study Osteoarthritis Environment

Lookup NU author(s): Dr Annachiara ScalzoneORCiD, Dr Xiao WangORCiD, Dr Ana Ferreira-DuarteORCiD, Professor Kenneth Dalgarno, Dr Piergiorgio GentileORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2022 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.Osteoarthritis (OA) is a joint degenerative pathology characterized by mechanical and inflammatory damages affecting synovium, articular cartilage (AC), and subchondral bone (SB). Several in vitro, in vivo, and ex vivo models are developed to study OA, but to date the identification of specific pharmacological targets seems to be hindered by the lack of models with predictive capabilities. This study reports the development of a biomimetic in vitro model of AC and SB interface. Gellan gum methacrylated and chondroitin sulfate/dopamine hydrogels are used for the AC portion, whereas polylactic acid functionalized with gelatin and nanohydroxyapatite for the SB. The physiological behavior of immortalized stem cells (Y201s) and Y201s differentiated in chondrocytes (Y201-Cs), respectively, for the SB and AC, is demonstrated over 21 days of culture in vitro in healthy and pathological conditions, whilst modeling the onset of cytokines-induced OA. The key metrics are: lower glycosaminoglycans production and increased calcification given by a higher Collagen X content, in the AC deep layer; higher expression of pro-angiogenic factor (vegf) and decreased expression of osteogenic markers (coll1, spp1, runx2) in the SB. This novel approach provides a new tool for studying the development and progression of OA.


Publication metadata

Author(s): Scalzone A, Cerqueni G, Wang X-N, Ferreira-Duarte A, Dalgarno K, Mattioli-Belmonte M, Gentile P

Publication type: Article

Publication status: Published

Journal: Advanced Healthcare Materials

Year: 2022

Volume: 12

Issue: 2

Pages: 2202030

Print publication date: 13/01/2023

Online publication date: 27/10/2022

Acceptance date: 27/09/2022

Date deposited: 22/11/2022

ISSN (print): 2192-2640

ISSN (electronic): 2192-2659

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/adhm.202202030

DOI: 10.1002/adhm.202202030

PubMed id: 36300892


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Funding

Funder referenceFunder name
21156VERSUS Arthritis (formerly Arthritis Research UK)
EP/R51309X/1
EPSRC. Grant Number: EP/R51309X/1
Versus Arthritis. Grant Number: 21156

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