A three dimensional magnetic patterning of two cell types was realised in vitro inside an additive manufactured magnetic scaffold, as a conceptual precursor for the vascularised tissue. The realisation of separate arrangements of vascular and osteoprogenitor cells, labelled with biocompatible magnetic nanoparticles, was established on the opposite sides of the scaffold fibres under the effect of nonhomogeneous magnetic gradients and loading magnetic configuration. The magnetisation of the scaffold amplified the guiding effects by an additional trapping of cells due to short range magnetic forces. The mathematical modelling confirmed the strong enhancement of the magnetic gradients and their particular geometrical distribution near the fibres, defining the preferential cell positioning on the micro-scale. The manipulation of cells inside suitably designed magnetic scaffolds represents a unique solution for the assembling of cellular constructs organised in biologically adequate arrangements.Nanotechnology and nanomaterials provide numerous innovative solutions for tissue engineering, aiming at radical reinforcement and renovation of clinical practice. The rapidly growing field of tissue engineering points at the regeneration of damaged tissues, rather than their substitution, and promotes that by implanting templates for tissue regeneration, typically represented by ceramic or polymeric scaffolds 1 . The implantation of bare cell-free scaffolds has serious limitations, especially considering the regular development of the vascular network in the regenerated tissue 2,3 . The most promising solution to this problem is the in vitro pre-loading of scaffolds with cells and/or growth factors before the implantation. The realisation of a correct distribution of cells inside the three-dimensional scaffolds is a key element for the maximally complete regeneration 1,4 . On the other hand, the manipulation and seeding of cells throughout the whole volume of the scaffold is an extremely challenging task and can be partially achieved via technologically sophisticated platforms 5 , barely compatible with routine clinical practice. Moreover, most tissues and organs are composed of various types of cells, preferentially arranged in complex 3D architectures, where they interact with each other and with the organism as a whole 6,7 , complicating further the requisites for a correct pre-loading. A partial solution to this challenging demand consists in the employment of the predominant cell type which defines the main tissue function 8 . This approach is generally suitable for relatively homogeneous tissues, such as cartilage, where tissue development should not be actively supported by other cell types 9 . For other tissues the achievement of efficient vascularisation, cell migration and organisation of the extracellular matrix 10 should be necessarily supported by assembles of different cell types inside the scaffold before implantation 11 .In this paper we propose a new, versatile and easy-to-implement method promoting the three-...
Thermo switchable magnetic hydrogels undoubtedly have a great potential for medical applications since they can behave as smart carriers able to transport bioactive molecules to a chosen part of the body and release them on demand via magneto-thermal activation. We report on the ability to modify the lower critical solution temperature (LCST) of poly(N-isopropylacrylamide) (PNIPAM) on demand from 32 °C to LCST ≥ 37 °C. This was achieved by the absorption of controlled amounts of magnetite nanoparticles on the polymer chains. We show, through the effect on cell viability, that the resulting magnetic PNIPAM is able to trap and to release bio-active molecules, such as cell growth factors. The activities of the released bio molecule are tested on human umbilical vein endothelial cells culture. We demonstrate that the LCST of the magnetic PNIPAM can be reached remotely via inductive heating with an alternating magnetic field. This approach on magnetic PNIPAM clearly supports appealing applications in safe biomedicine.
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