Organization/Department
Principal Investigator
Centre for Regenerative Medicine, Danube University Krems

Biography
Vivek Jeyakumar, Ph.D. is a Principal investigator in orthopedic regenerative medicine at the Center for Regenerative Medicine, Danube University Krems. Vivek Jeyakumar graduated with a Ph.D. in Regenerative Medicine on June 2019, followed by a postdoctoral position from the Centre for Regenerative Medicine at the Danube University Krems. Vivek Jeyakumar is currently working on the Developmental Tissue Engineering Model of Endochondral Ossification for Bone Regeneration funded by the NFB Lower Austria (NÖ) and Karl Landsteiner University. In addition, he is pursuing further as a principal investigator in the projects for bioprinting cartilage and meniscus tissues.

Title of Talk
Functional Meniscus Tissue Regeneration by 3D-Bioprinting with Silk-Based Bioinks

Vivek Jeyakumar1, Christoph Bauer1, Andreas Teuschl2, Karl Schneider3, Paul Slezak4, Heinz Redl4, Stefan Nehrer1

1. Center for Regenerative Medicine, Department for Health Sciences, Medicine & Research, Donau Universität Krems, 3500, Krems, Austria

2. University of Applied Sciences Technikum Wien, Department of Biochemical Engineering, Höchstädtplatz 5, 1200 Vienna, Austria; The Austrian Cluster for Tissue Regeneration, Vienna, Austria.

3. Center for Biomedical Research, Ludwig Boltzmann Cluster for Cardiovascular Research, Medical University of Vienna, 1090, Vienna, Austria

4. Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA trauma research center, Austrian Cluster for Tissue Regeneration

Abstract
Meniscus defects caused by trauma or disease remain a significant challenge in orthopedic treatments. Current treatments such as allografts or clinically used biomaterials to restore or regenerate meniscus tissue is challenged by mechanical instability and lack of integration to the surrounding host bone tissue upon implantation. Tissue engineering holds a huge promise yet fails to stimulate defined anatomically relevant 3D architectures and functionality of native tissues within engineered substitutes. Despite several advances on optimizing architectures to improve the biological response of cells, it is still not clear as to which right architecture holds cues for the right substrate stiffness, pore size, interconnectivity of engineered scaffolds. Conventional fabrication techniques, deployed in meniscus tissue engineering, do not allow local control of the materials; an independent discrepancy of defined geometric structures, uniform cell seeding density and irregular distribution of cells throughout the scaffold, poor biomechanics and lubrication properties. To facilitate the development of advanced strategies for meniscus tissue regeneration (MTR) new techniques such as 3D bioprinting must be subjugated to fabricate geometrically precise and robust architectural scaffolds with tunable biomechanical properties. In the current proposal, we propose a strategy for MTR by developing a hybrid bioink that incorporates naturally derived polymers such as meniscus derived extracellular matrix (MD-ECM) with Silk fibroin (SF) bioprinted for native geometrical structures based on computational digital designs from micro-CT scans. MD-ECM/SF bioinks are printed with live cells such as fibrochondrocytes, chondrocytes obtained from human meniscus donors and biochemically/biomechanically stimulated in a hydrostatic pressure bioreactor. ECM matrix formation will be monitored by time-lapse micro-computed tomography (micro-CT) monitoring non-destructively with contrasting agents generating 3D segmented images, and biomechanical, biotribological testing of the scaffolds will be evaluated to determine the stiffness, strength of the engineered meniscus upon implantation in a defect model subcutaneously in nude mice. Biochemical analysis and histological observations will be validating these results additionally. To achieve the goals, an interdisciplinary team with expertise from biomaterial fabrication, 3D bioprinting, biomechanics, biotribology cell biology, in vivo models and high-resolution imaging have been congregated. This interdisciplinary approach will aid in a process instructing bioresponsive scaffolds to recapitulate natural meniscus repair mechanisms. This project will develop a prototype for the 3D bio-printing of cell-laden hydrogel scaffolds with controllable geometric structures and the cellular biological response towards engineering a functional meniscus tissue with high reproducibility and controllability.