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uKnee: a 3D miniaturized in vitro platform to screen candidate anti-osteoarthritis drugs

Applicant Occhetta Paola
Number 178261
Funding scheme Bridge - Proof of Concept
Research institution
Institution of higher education University of Basel - BS
Main discipline Other disciplines of Engineering Sciences
Start/End 01.01.2018 - 30.06.2019
Approved amount 195'000.00
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Keywords (6)

3R; in vitro pre-clinical models; drug screening; osteoarthritis; microfluidics; organs-on-chip

Lay Summary (Italian)

L’Osteoartrite (OA) è la più comune patologia del sistema muscoloscheletrico e ad oggi non esiste una trattamento farmacologico efficace in grado di ripristinare le funzioni di un'articolazione affetta da OA. Questa mancanza è almeno parzialmente imputabile alla mancanza di modelli preclinici su cui testare nuovi candidati farmaci. Grazie a questo progetto abbiamo sviluppato e validato un modello in vitro miniaturizzato di cartilagine osteoartitica, uKnee.
Lay summary

L’Osteoartrite (OA) è la più comune patologia del sistema muscoloscheletrico, colpendo il 75% della popolazione sopra i 55 anni. A causa dell’invecchiamento globale, è stato stimato che l’OA diventerà un peso economico sempre maggiore per il sistema sanitario mondiale. La situazione peggiora considerando che non esistono trattamenti farmacologici in grado di curare la patologia. La mancanza di farmaci in grado di curare l’OA è almeno parzialmente imputabile alla mancanza di modelli preclinici su cui testare nuovi candidati. I sistemi di coltura cellulare tradizionali sono troppo semplificativi, mentre i modelli animali seppur più complessi introducono problematiche etiche. La recente legge sul principio delle 3R (2010/63/EU) sta, infatti, spingendo le aziende farmaceutiche all’utilizzo di modelli alternative agli animali. Questo rende estremamente urgente la realizzazione di modelli in vitro avanzati in grado di riprodurre la patologia osteoartritica con cellule umane. Questo progetto ha contributo allo sviluppo di un modello in vitro miniaturizzato di cartilagine osteoartitica, uKnee. uKnee si basa su una tecnologia brevettata in grado di coltivare cellule umane in un ambiente tridimensionale e di applicare ad esse una stimolazione meccanica controllata. Grazie alle sue dimensioni miniaturizzate, uKnee permette inoltre di ridurre tempo, reagenti permettendo quindi un risparmio generale. All'interno di questo progetto abbiamo dimostrato le potenzialità di uKnee come modello preclinico per testare l’efficacia di nuove molecole candidate come farmaci anti-OA. Proseguiremo ora con lo sviluppo di un prodotto commercializzabile, aprendo la strada ad un futuro lancio sul mercato.

Direct link to Lay Summary Last update: 19.07.2019

Responsible applicant and co-applicants



Group / person Country
Types of collaboration
Fidia Farmaceutici Italy (Europe)
- Industry/business/other use-inspired collaboration
BiomimX S.r.l. Italy (Europe)
- Industry/business/other use-inspired collaboration
Novartis Institutes for BioMedical Research (NIBR) Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Gordon Research Conference on Cartilage Biology and Pathology Talk given at a conference Hyper-Physiological Compression Triggers Osteoarthritic features in a Cartilage-on-Chip Model 17.03.2019 Hotel Galvez in Galveston, TX United States., United States of America Occhetta Paola;
LS2 Cardiovascular Research Meeting 2019 Talk given at a conference A microfluidic model to study the interaction between cardiomyocytes and fibroblasts in cardiac scar formation 14.03.2019 Swiss Integrative Center for Human Health SA in Fribourg, Switzerland Occhetta Paola;
World Termis 2018 Talk given at a conference Modeling Osteoarthritis in a Chip through Hyper-Physiological Compression of a 3D Cartilage Model 04.09.2018 Kyoto International Conference Center, Kyoto, Japan, Japan Occhetta Paola;

Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
«Regenerate Mobility!» workshop Workshop 06.05.2019 Universität Basel Innovation Space – Gewerbestrasse 24, 3rd Floor, 4123, Allschwill, Switzerland Occhetta Paola;


Osteoarthritis (OA) is the most common human musculoskeletal disease, affecting 75% of people older than 55. Due to population aging, OA is expected to be a heavy economic burden on world-wide healthcare systems. No definitive pharmacological treatments are currently available and only medical option is often surgical intervention. The shortage in OA disease modifying (DMOA) drugs development is partially related to the absence of valid pre-clinical models. Traditional in vitro cell cultures are too simplistic, while animal models often fail in predicting the human response. Furthermore, recent legislation about 3R principle (Directive 2010/63/EU) is pushing Pharma industries towards methods alternative to animals. In this scenario, the demand for innovative in vitro tools able to reliably predict drug efficacy already in the pre-clinical phase is urgent, especially for high prevalence pathologies like OA. In the last years, my collaborators and I developed uKnee, an in vitro miniaturized platform able to replicate the complex 3D architecture of human joint and the mechano-phatological OA environment. uKnee builds on a new technology (I’m inventor of the patent), enabling for culturing 3D cellular constructs within microfluidic platforms and subjecting them to controlled mechanical stimulation. Moreover, thanks to its miniaturized scale uKnee permits to considerably reduce experimental time, reagents and money consumption. In this project proposal, I aim at providing the proof-of-principle of the potentiality of uKnee to be commercialized as in vitro platform for pre-clinical DMOA candidates screening. To achieve this vision, three key measures will be pursued in this proof-of-concept study. First, uKnee will be validated as in vitro tool to predict anti-OA putative compounds efficacy: a match between uKnee outcomes and existing anti-OA compound-associated preclinical data will prove the accuracy of our model. Second, a higher throughput version of uKnee hosting multiple independent replicates will be realized to finally target Pharma as main customers, adequate to perform drug screening and extract dose-response curves of candidate compounds. Third, a business plan will be elaborated focusing on finalizing the collection of information on market size, customer segments and competitors, carrying on a risk analysis and performing a Freedom to Operate (FTO) analysis for the commercialization of uKnee. The success of this proof of concept study will allow moving form the existing lab prototype to a first concept of a market version of uKnee, paving the way for an extensive program leading to the future launch of uKnee in the market.