Periodic Reporting for period 1 - CREATION (Mechanobiological optimization of regeneration in cell-enriched construct implants within degenerative Cartilages: a defect Repair method through restoring Energy AbsorpTION)
Okres sprawozdawczy: 2020-09-01 do 2022-08-31
Tissue engineering methods propose solutions to OA by implanting chondrocyte cell-enriched hydrogel/scaffold constructs within degenerative cartilage defects. By applying mechanical loads to stimulate the cells within the constructs, they initiate cartilage extracellular matrix (ECM) synthesis. The mechanical environment of the cell-seeded construct has a crucial role in defining the quality and quantity of the regenerated ECM. This will determine the mechanical performance of the cartilage tissue. Indeed, any repair method has to aim at restoring the unique cartilage mechanics, in particular, the energy absorption capacity.
This project aims at restoring energy absorption of degenerative cartilage by optimizing regeneration in cell-enriched construct implants. The goal was pursued by developing an in-silico framework for mechanobiological modelling of the regeneration and degeneration in the cartilage-implant compound during loading. The in silico models can then be used in optimization schemes to minimize differences between the energy absorption of construct implants and native human cartilage.
Moreover, a mechanical characterization protocol to optimally identify the properties of hydrogel constructs and cartilage explants using simple unconfined compression experiments was developed. The protocol was developed based on an in silico parameter sensitivity analysis (published in: https://www.sciencedirect.com/science/article/pii/S1751616121004367). The developed protocol was also presented in a book chapter (Unconfined compression experimental protocol for cartilage explants and hydrogel constructs: from sample preparation to mechanical characterization. In: M. Stoddart, A. Armiento, E. Della Bella (editors) Cartilage Tissue Engineering, In-Press.). Moreover, the loading results of the longitudinal bioreactor experiments on healthy cartilage samples were used to determine the time-dependent changes in the absorbed energy by native cartilage explants.
The key outcome of this project is the in silico framework for further understanding of OA disease progression and optimization of treatment approaches. The key stakeholders in general are the OA community, tissue engineering and biomedical engineering researchers. The stakeholders have been reached through publishing the results in top-ranked peer-reviewed scientific journals of the relevant communities including Osteoarthritis and Cartilage, Frontiers in Bioengineering and Biotechnology and Journal of Mechanical Behavior of Biomedical Materials in addition to the methodological book chapter that is in press in Cartilage Tissue Engineering book. Following Horizon 2020 guidelines, open access was ensured to all the publications by paying for the open access fee and by self-archiving the articles in the KUL OpenAIRE compliant repository ‘Lirias’. Furthermore, the results were presented in 11 relevant conferences on computational (bio)mechanics (WCCM, CMBBE, VPH), orthopaedics (EORS, OARSI and ORS) and biomechanics (ESB, ISB, WCB). This selection of conferences disseminated the project results to experts in mechanics, biology and modelling and clinicians. The researcher also acted as Marie Curie Ambassador, visiting research groups within and outside of the collaboration network with similar research interests, to give invited talks on the findings of the project. Research results were disseminated to the project partner through project meetings held at the University of Eastern Finland (Finland) before (online) and during the secondment. During the visit to Utrecht University (Netherlands), the results have been presented to the group of Prof. Jos Malda, a leading European group in the field of bio-printing for cartilage tissue engineering. The project updates were also shared through LinkedIn and Twitter by the researcher, supervisor and collaborators.