Novel Bioengineering approaches for studying muscle tissue homeostasis and regeneration.
It is well known that extracellular stimuli from the microenvironment are crucial for cell adhesion, migration, proliferation and differentiation, and the ECM constitutes the very foundation of tissue homeostasis and development (Seliktar, 2012).
Despite this, the analysis of such cells/ECM interplays in vivo is hampered by the intrinsic complexity of the native environment. To overcome this limitation, we will we will use of a specific biosynthetic protein-polymer hydrogel as an ECM-analogue for culturing cells in 3D, with highly defined and precisely controllable density, microarchitecture, proteolytic susceptibility, compliance and bio functionality.
ESR11 will use this method to elucidate the dominant and influential physical factors affecting morphogenesis patterns, phenotypic states, and differentiation of various muscle progenitor cell types and will further identify the optimal environmental conditions for directing stem cells in vivo based on biophysical induction and mechanical stimulation.
ESR11 will also engineering bioactive materials and devices to reconstruct the muscle niche in vitro. Innovative biomaterials will also be exploited to optimize the in vivo delivery of either stem/progenitor cells or biological drugs in animal models of muscle diseases. In vivo administration of proteins/biological drugs require to: i) enable the protein to maintain its structure and activity over a prolonged period of time, and ii) control the release kinetics allowing the appropriate dose of protein to reach the site over a given period of time. ESR11 will use semi-synthetic biomaterials made by grafting synthetic polymers onto proteins such as collagen and fibrinogen in order to create stable, elastic gels (Seliktar, 2012).
The biosynthetic gels are inherently biocompatible and proteolytically degradable based on their protein backbone, making them amenable to cell-mediated remodelling and morphogenesis. The conjugated polymer provides exact control over the hydrogel’s material properties. Injectable polymer/protein biomaterials will be used to deliver different biopharma, in a controlled fashion. They will evaluate the optimal condition for in vivo delivery of the biological drugs in mouse models of acute (CTX) and chronic injury (mdx mice) (Iavarone et al., 2020) and assess their ability to improve muscle regeneration and eventually ameliorate the disease phenotype.
To use novel bioengineering approaches to elucidate the dominant and influential physical factors affecting proliferation/differentiation of different progenitor cells in muscle regeneration
To engineer biomaterial delivery vehicle for temporal and spatial control of therapeutic proteins/cells in muscle regeneration
Enrolment in Doctoral degree
PhD programme at the department of biomedical engineering at the Technion, Israel Institute of technology (http://www.graduate.technion.ac.il/eng/).
Iavarone, F., Guardiola, O., Scagliola, A., Andolfi, G., Esposito, F., Serrano, A., Perdiguero, E., Brunelli, S., Munoz-Canoves, P., and Minchiotti, G. (2020). Cripto shapes macrophage plasticity and restricts EndMT in injured and diseased skeletal muscle. EMBO Rep 21, e49075.
Seliktar, D. (2012). Designing cell-compatible hydrogels for biomedical applications. Science (New York, NY) 336, 1124-1128.