Biophysics

Physiologically relevant characterization of biomaterials in biomimetic bioreactors

September 14, 2018.

Lecturer

Prof. Dr. BOJANA OBRADOVIĆ
Faculty of Technology and Metallurgy, University of Belgrade

Date and time

Monday, September 24, 2018 at 11:00 AM

Location

Lecture Hall, III Wing, Ruđer Bošković Institute, Bijenička cesta 54, Zagreb

Abstract

Biomimetic bioreactors are primarily developed as 3D systems for cell and tissue cultures in conditions that imitate physiological conditions in the organism. In addition, these systems enable the physiologically relevant characterization of biomaterials in terms of stability, biomechanical characteristics, as well as interactions with cells and tissues, in order to predict the behavior and functionality of biomaterials in vivo. Cytotoxicity tests, especially of nanomaterials, are also suitable in these systems since traditional methods in 2D systems in cell monolayers have often proved difficult to compare with the results of in vivo tests. The reason is the greater sensitivity of the cells in the monolayer due to the loss of natural morphological characteristics, extracellular matrix and intercellular interactions. Biomimetic bioreactors should provide the main relevant biochemical (eg nutrients, gases, growth factors) and biophysical signals (eg strain, mechanical stresses, electrical signals) so that the design of these systems is specific for each tissue or organ. In this presentation, 2 biomimetic bioreactors and several examples of functional characterization of biomaterials will be presented. The flow bioreactor is one of the simplest systems for 3D cultures, which provides a continuous flow of media directly through a sample of biomaterial or tissue at interstitial speeds in the range of blood speeds in capillaries (1 – 100 nanom/s). These conditions are particularly relevant for bone tissue, where it has been shown that hydrodynamic shifts are the key stimulus for osteogenesis. The application of this bioreactor will be illustrated on the example of the formation of hydroxyapatite (HAp) in macroporous alginate hydrogel samples with beta-tricalcium phosphate particles as a precursor of the mineral phase in bone tissue.

Bioreactor with dynamic compression is the second biomimetic bioreactor system designed and constructed at the Faculty of Technology and Metallurgy in Belgrade. This bioreactor enables dynamic compression of samples in a regime relevant to cartilage tissue (5 – 10 % deformation, 0.1 – 1 Hz frequency) with continuous media flow. The use of this bioreactor was demonstrated in 2 different examples, in studies of the cytotoxicity of nanocomposites based on alginate and silver nanoparticles, and in the development of potential osteochondral implants. It was shown that the results of the cytotoxicity test in bioreactor cultures of calf cartilage tissue correspond to the results of the application of Ag/alginate nanocomposites in the treatment of second degree burns on rats, in contrast to the results of significant cytotoxicity obtained in the control study on cells in a monolayer. In another example, two-phase samples based on gellan gum hydrogel and bioactive glass particles were developed and tested in terms of stability and HAp formation in biomimetic conditions. From the above examples, it can be concluded that biomimetic bioreactors represent suitable instruments for the characterization and efficient selection of the best biomaterial candidates for further in vivo testing, which leads to a reduction in the number of necessary animal studies.

Bojana Obradović, full professor at the Faculty of Technology and Metallurgy of the University of Belgrade, was born in 1966 in Belgrade. She graduated from the Faculty of Technology and Metallurgy of the University of Belgrade in 1990 and received her master's degree in 1993 from the same faculty. She defended her second master's thesis in 1996 at the Department of Chemical Engineering, Tufts University, USA. She worked on her doctoral dissertation entitled "Bioreactor Studies of Tissue Engineered Cartilage" in collaboration with MIT, Harvard-MIT Division of Health Sciences and Technology, USA, and defended it in 1999 at the Department of Chemical Engineering, Tufts University. Study stays: MIT, USA, 2002 and 2004, Columbia University, USA, 2006, Faculty of Pharmacy, University of Cagliari, Italy, 2008 and 2010. Since 2000, she has been employed at the Faculty of Technology and Metallurgy of the University of Belgrade, where she was Head of the Department of Chemical Engineering from 2005 to 2006, and from 2006 to In 2012, she held the position of vice dean for human resources and doctoral studies, where she led the reform and accreditation of doctoral studies. The scientific and professional issues dealt with by Dr. Bojana Obradović are multidisciplinary and belong to the fields of chemical, biochemical and biomedical engineering, where the focus is on the design, characterization and development of new bioreactor systems and biomaterials for use primarily in tissue engineering and biomedicine. As part of her scientific research work, she has published 13 chapters in international books, 2 chapters in a prominent national collection, over 70 papers in scientific journals and a large number of papers presented at conferences of international and national importance printed in proceedings. She is the editor of 1 thematic collection of international importance "Cell and Tissue Engineering", which was purchased and republished by the international publishing house Springer. A total of 49 works by Dr. B. Obradović have been cited over 2500 times (SCOPUS, 2018). She is a co-author of one implemented patent and three patent applications. Since 2016, Dr. Bojana Obradović has been the editor-in-chief of the scientific journal Hemijska industrija, which is on the WoS list. So far, she has been the leader of 2 international projects, and has participated in over 20 international and national scientific projects, as well as in 4 projects of cooperation with the economy. She was a member of the Board of Directors for Europe (Continental Chapter Council) of the Tissue Engineering & Regenerative Medicine International Society (TERMIS) (2011-2012), and is also a member of the Board of Directors of the Serbian Chemical Society (2006-), as well as a member of the Board of Directors of the Association of Chemical Engineers of Serbia (2017-). Since 2016, he has been a corresponding member of the Academy of Engineering Sciences of Serbia (AINS).

*SEMINAR of the Croatian Biophysical Society

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