Tissue Engineering Based on Injectable Intra-arterial Micro-carrier
Delivery System for Cardiac Muscle Regeneration
Cardiovascular disease is one of the leading causes for morbidity and mortality in the
developed countries. Cardiac tissue engineering is a promising novel approach in the
regenerative medicine field aimed to provide a reparative solution for the damaged
myocardium and restore heart function. However, functional donor-to-host integration of
the engineered tissue constructs remains a critical challenge. The overall objective of this
work is to design an optimal delivery system for cells and growth factors for cardiac
treatment, taking into account several parameters for better integration of the engineered
construct within the host tissues, including a preferable mode of implantation, superior
pro-angiogenic properties and reduced foreign body response. In this context, we
developed MRI/fluorescence bi-modal imaging to document the integration of the
hydrogel implants in vivo in a non-invasive and continuous manner. We focused on the
characterization of the scaffold’s dissolution, resorption and host response as a function
of the hydrogel’s chemical composition, 3D geometry and implantation strategy. We
found that each type of implant configuration had very different dissolution kinetics and
distinct bi-phasic release profile of degradation products into the surrounding tissues.
Moreover, the stability, the host-implant response and the biodegradation mechanism
were significantly modulated by the hydrogel composition. Next, we incorporated
vascular endothelial growth factor (VEGF) within the hydrogel network and investigated
the pro-angiogenic properties of the hydrogels. We demonstrated the controlled release of
this growth factor from the hydrogel scaffolds, with subsequent pronounced proangiogenic effect in vivo when PEG-Fibrinogen micro-beads were used as a delivery
platform. Finally, we adapted PEG-Fibrinogen micro-beads for injection into a
myocardial infarction model in rats. Feasibility in vivo studies demonstrated that injected
micro-beads remained localized and stable at the injection site, as was evident by the
MRI and histology.
Overall, we demonstrated that using different hydrogel modalities can have a
significant effect on the implant integration. As such, implantation strategy should be a
major consideration when designing tissue engineered constructs and delivery systems,
particularly for challenging applications in myocardial repair. The PEG-Fibrinogen
micro-beads provide a preferred platform for the implantation in this regard, because of
the controllable and reproducible preparation, injectable mode of implantation, as well as
superior integration and pro-angiogenic properties.