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

Scalzone, Annachiara; Cerqueni, Giorgia; Wang, Xiao-Nong; Ferreira, Ana Marina; Dalgarno, Kenneth; Mattioli‐Belmonte, Monica; Gentile, Piergiorgio

doi:10.1002/adhm.202202030

Cited by 5 publications

(7 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 44 ] Type II Collagen and aggrecan which are modulated by Col2 α and ACAN genes are the main structural components of the extracellular matrix (ECM) of cartilage. [ 45 ] When cartilage is under inflammation, their expression levels in cartilage are decreased. Simultaneously, the expression levels of matrix metalloproteinase 1 (MMP1) that is involved in cartilage degeneration, [ 46 ] and tachykinin‐1 (TAC1) gene that is highly related with pain are abnormally increased.…”

Section: Resultsmentioning

confidence: 99%

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy

Gong

Chao

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Osteoarthritis (OA) is associated with lubrication failure of articular cartilage and severe inflammatory response of joint capsule. Synergistic therapy combining joint lubrication and anti-inflammation emerges as a novel treatment of OA. In this study, bioinspired by ultralow friction of natural articular synovial fluid and mussel adhesion chemistry, a biomimetic nanosystem with dual functions of enhanced lubrication and stimuli-responsive drug release is developed. A dopamine mediated strategy realizes one step biomimetic grafting of hyaluronic acid (HA) on fluorinated graphene. The polymer modified sheets exhibit highly efficient near-infrared absorption, and show steady lubrication with a long time under various working conditions, in which the coefficient of friction is reduced by 75% compared to H 2 O. Diclofenac sodium (DS) with a high loading capacity of 29.2% is controllably loaded, and responsive and sustained drug release is adjusted by near-infrared light. Cell experiments reveal that the lubricating nanosystem is taken up by endocytosis, and anti-inflammation results confirm that the nanosystem inhibits osteoarthritis deterioration by upregulating cartilage anabolic gene and downregulating catabolic proteases and pain-related gene. This work proposes a promising biomimetic approach to integrate polymer modified fluorinated graphene as a dual-functional nanosystem for effective synergistic therapy of OA.

show abstract

Section: Resultsmentioning

confidence: 99%

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy

Gong

Chao

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

show abstract

“…The development of a patho-physiologically relevant in vitro model for OA should reflect the complexity of the disease, characterised by AC degeneration accompanied by the whole joint inflammation ( Goldberg & Kresina, 1987 ). Herein, we obtained an OA-induced environment by adding to the culture media the main pro-inflammatory cytokines, released from the synovium cells and chondrocytes, during OA progression (IL-1β, TNFα and IL-6) to recreate a naturally diseased environment ( Scalzone et al, 2023 ). Compared to previous literature, the combination of a cocktail of cytokines allowed to obtain OA-like cell and tissue responses that more closely resemble the native disease at an early stage, particularly taking into consideration the importance of synovium-related inflammation effects in the model design, which results in the release of pro-inflammatory mediators ( Johnson et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…Human TERT immortalised bone marrow stromal cells (Y201) were supplied by Prof P. Genever (York University) and cultured at 37 °C and 5% CO 2 in Dulbecco's Modified Eagle Medium (DMEM) with low glucose content, supplemented with 10% Foetal bovine serum (FBS), 2 mM L-glutamine and a 1% Penicillin/Streptomycin (P/S). After the expansion, cells were differentiated in chondrocytes (Y201-C), as previously reported (Scalzone et al, 2022b).…”

Section: Cell Culture: Fcs and Y201-cmentioning

confidence: 99%

“…The use of a combination of cytokines would induce OA-like cell and tissue responses to closely resemble the native disease, particularly taking into consideration the importance of synovium effects in the model design (Johnson et al, 2016). This pathological model was based on a reliable in vitro model of healthy AC, developed in our previous work (Scalzone et al, 2022b), whereas cytokines concentration was selected according to their prevalence in OA synovial fluid (Sohn et al, 2012). The main features which distinguish Healthy and OA conditions were analyzed with primary human fetal chondrocytes (FC) and Y201 TERT mesenchymal stem cells differentiated chondrocytes (Y201-C) using a pathological in vitro OA model.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis

Scalzone

Cerqueni

Wang

et al. 2023

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Given the lack of in vitro models faithfully reproducing the osteoarthritis (OA) disease on-set, this work aimed at manufacturing a reliable and predictive in vitro cytokine-based Articular Cartilage (AC) model to study OA progression. Cell spheroids of primary human fetal chondrocytes (FCs) and h-TERT mesenchymal stem cells differentiated chondrocytes (Y201-C) were analysed in terms of growth kinetics, cells proliferation and apoptosis over 10 days of culture, in healthy condition or in presence of cytokines (interleukin-1ß, −6 and TNF-α). Then, the spheroids were assembled into chondrospheres using a bottom-up strategy, to obtain an in vitro cytokines-induced OA model. The resulting chondrospheres were evaluated for gene expression and anabolic ECM proteins. Compared to the healthy environment, the simulated OA environment induced chondrocyte hyperproliferation and apoptotic pathway, decreased expression of anabolic ECM proteins, and diminished biosynthetic activity, resembling features of early-stage OA. These characteristics were observed for both Y201-C and HC at high and low concentrations of cytokines. Both HC and Y201-C demonstrated the suitability for the manufacturing of a scaffold-free in vitro OA model to facilitate studies into OA pathogenesis and therapeutic strategies. Our approach provides a faithful reproduction of early-stage osteoarthritis, demonstrating the ability of obtaining different disease severity by tuning the concentration of OA-related cytokines. Given the advantages in easy access and more reproducible performance, Y201-C may represent a more favourable source of chondrocytes for establishing more standardized protocols to obtain OA models.

show abstract

“…Development of osteochondral models employing bioprinting approaches with functional hydrogels [156][157][158][159][160] to study osteoarthritis has been achieved. The hydrogels, paired with extrusion bioprinting, enhanced the potential of the construct as cell behavior and fate during osteoarthritis onset could be mimicked accurately, demonstrating the power of BTE approach employing hydrogels and bioprinting.…”

Section: Multi-materials and Dual Printingmentioning

confidence: 99%

Hydrogels and Bioprinting in Bone Tissue Engineering: Creating Artificial Stem‐Cell Niches for In Vitro Models

et al. 2023

View full text Add to dashboard Cite

Advances in bioprinting have enabled the fabrication of complex tissue constructs with high speed and resolution. However, there remains significant structural and biological complexity within tissues that bioprinting is unable to recapitulate. Bone, for example, has a hierarchical organization ranging from the molecular to whole organ level. Current bioprinting techniques and the materials employed have imposed limits on the scale, speed, and resolution that can be achieved, rendering the technique unable to reproduce the structural hierarchies and cell–matrix interactions that are observed in bone. The shift towards biomimetic approaches in bone tissue engineering, where hydrogels provide biophysical and biochemical cues to encapsulated cells, is a promising approach to enhance the biological function and development of tissues for in vitro modelling. A major focus in bioprinting of bone tissue for in vitro modelling is creating the dynamic microenvironmental niches to support, stimulate, and direct the cellular processes for bone formation and remodeling. Hydrogels are ideal materials for imitating the extracellular matrix since they can be engineered to present various cues whilst allowing bioprinting. Here, we review recent advances in hydrogels and 3D bioprinting towards creating a microenvironmental niche that is conducive to tissue engineering of in vitro models of bone.This review focuses on hydrogels and 3D bioprinting in bone tissue engineering for development of in vitro models of bone. It highlights challenges in recapitulating the biological complexity seen in bone and how synergistic application of dynamic hydrogels and innovative bioprinting pipelines could address these challenges to achieve bone models.This article is protected by copyright. All rights reserved

show abstract

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

Cited by 5 publications

References 53 publications

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy

A Biomimetic Lubricating Nanosystem with Responsive Drug Release for Osteoarthritis Synergistic Therapy

A cytokine-induced spheroid-based in vitro model for studying osteoarthritis pathogenesis

Hydrogels and Bioprinting in Bone Tissue Engineering: Creating Artificial Stem‐Cell Niches for In Vitro Models

Contact Info

Product

Resources

About