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Spanish scientists design a bioreactor that allows to monitor through ultrasound the maturation of human cartilage grown in 3D

The UGR leads this research with the participation of specialists from the fields of medicine, biology, mathematics, physics and engineering, which has allowed the generation of human cartilage tissues in four weeks

A team of Spanish scientists has designed a bioreactor that allows to grow, in four weeks, human cartilage tissues in scaffolds generated by 3D printing. Likewise, said bioreactor allows real‑time monitoring through the analysis of ultrasonic signals. The team of researchers is composed of doctors, biologists, physicists and engineers led by the University of Granada UGR).

Engineered cartilage tissue is at present one of the most promising treatments for articular cartilage pathologies, caused by ruptures and sports injuries, genetic factors or other diseases (such as some types of arthritis).

In this study, published in the journal Sensors and Actuators B, ‘scaffolds’ of polylactic acid (a biocompatible and resorbable substance) were 3D‑printed and seeded with human chondrocytes (human cartilage cells) obtained from patients. Then, they were cultured in an ultrasound (US)‑integrated bioreactor.

The readings from the ultrasonic sensors were analyzed by numerical models of the ultrasound‑tissue interaction and by a stochastic treatment to infer the extracellular matrix (ECM) evolution. To reconstruct the velocity and attenuation from the recorded signals, the scientists combined a computational process (based on genetic algorithms on the biomechanics of the tissue) with the processing of the propagation of the wave.

The ultrasonic data were validated against evolution measurements of the in vitro 3D chondrocyte cultures assessed by proliferation and morphological observations, qualitative and quantitative biochemical parameters and gene expression analysis.

The parameters reconstructed by the scientists from the ultrasonic monitoring (such as p‑wave velocity, attenuation, cell density changes) were proved useful to indirectly determine cell culture proliferation parameters in a non‑invasive manner.

The new US evaluation method developed is presented as a precise and non‑invasive procedure that can be automated and which provides real‑time information on the functionality of primary human chondrocytes. This method could monitor and evaluate, in a clinical context, the progression of the lesion after the treatment in patients with osteoarthritis.

This work has counted with the participation of researchers from the universities of Granada and Jaen belonging to the Unit of Excellence “Modeling Nature: from nano to macro” of the UGR, as well as researchers from the Complutense University of Madrid and the Biosanitary Research Institute of Granada (ibs.GRANADA).

Bibliographic references:

Melchor, Juan & López Ruiz, Elena & Soto Rueda, Juan & Jiménez González, Gema & Antich, C & Peran, Macarena & Baena, José Manuel & Marchal, J.A. & Rus, Guillermo. (2018). In-bioreactor ultrasonic monitoring of 3D culture human engineered cartilage. Sensors and Actuators B: Chemical. 266.

DOI: 10.1016/j.snb.2018.03.152

1. The researchers that carried out this study. From left to right: Carlos Chocarro, Cristina Antich,  Elena López Ruiz, Gema Jiménez, Juan Antonio Marchal, Guillermo Rus, Macarena Perán, Juan Melchor y Antonio Callejas.

The researchers that carried out this study. From left to right: Carlos Chocarro, Cristina Antich, Elena López Ruiz, Gema Jiménez, Juan Antonio Marchal, Guillermo Rus, Macarena Perán, Juan Melchor y Antonio Callejas.

2. The ultrasonic biorreactor and the peristaltic pumps.

The ultrasonic biorreactor and the peristaltic pumps.

 

3. Coloured green, the cartilage cells (chondrocytes) after a month growing on the scaffold in the biorreactor.

Coloured green, the cartilage cells (chondrocytes) after a month growing on the scaffold in the biorreactor.

 

Contact info:

Juan Antonio Marchal Corrales

Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada

Phone number: (+34) 958 241 000 Ext. 20080 – (+34) 958 249 321

E‑mail: jmarchal@ugr.es

 

Guillermo Rus Carlborg

Department of Structural Mechanics, Politécnico de Fuentenueva, University of Granada

Phone number: (+34) 958 240 037

E‑mail: grus@ugr.es