External events of interest
Prof. Matteo Santin
Brighton Studies in Tissue-mimicry and Aided Regeneration, School of Pharmacy & Biomolecular Sciences, University of Brighton
The recent development of magnetic scaffolds for bone tissue engineering has paved the way towards the development of magnetic carriers facilitating the efficient uploading and delivery of stem cells throughout their porosity. In addition, the differentiation of the stem cells into osteoblasts, as well as the long-term viability of bone formed through the support of biomaterial scaffolds, depends on the extent of tissue vascularisation. The vascular endothelial growth factor (VEGF) is the most effective promoter of angiogenesis. Indeed, this growth factor is capable of stimulating blood vessel sprouting through a delicate balance of concentration and gradient. Therefore, controlled angiogenesis in bone regeneration cannot be achieved by spontaneous endogenous processes or by injection of soluble VEGF.
The seminar will provide an overview of a novel technology developed at University of Brighton for the magnetization of both stem cells and VEGF for their controlled delivery in tissue engineering scaffolds. Magnetic iron nanoparticles (MNP) were functionalised with hyperbranched poly(epsilon-lysine) dendrons obtained by a solid-phase synthesis method. The dendron was designed to present a three branching generations of lysine (G3K) which were tethered at their uppermost branching generation with monomers of carboxybetaine, a highly hydrophilic modified amino acid. The resulting dendron (C G3KCB16) was grafted onto the surface of the MNP through di-sulfide bonds.
The results of the in vitro studies clearly showed the ability of these biocompetent magnetic carriers to magnetise MSCs with an efficiency of up to 80% of the original MSC population after 5 min of incubation. Unlike other types of MNP which are internalised by cells, the magnetization by these novel biocompetent magnetic carriers occurred through their interaction with the cell surface thus reducing any potential risk of cytotoxicity and genotoxicity. Indeed, the biocompetent NMP did not compromise MSC viability and differentiation potential into osteoblasts. When tested as carriers for VEGF, these biocompetent magnetic drivers bound VEGF at a rate of 3.5 ug/mg of NMP and they were shown to drive endothelial cell sprouting in both 2D and 3D models of angiogenesis.