D'Amora, Ugo (2013) A NOVEL ROUTE TOWARDS THE DESIGN OF 3D MORPHOLOGICALLY CONTROLLED MAGNETIC SCAFFOLDS FOR ADVANCED BONE TISSUE ENGINEERING. [Tesi di dottorato]

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Abstract

Tissue engineering is an interdisciplinary field that has the goal of creating new tissues and organs. Ideal bone scaffold, which is the key element,should possess important chemical, biochemical and biophysical properties, whilst the biomechanical environment introduces another level of complexity. Scaffold needs to be able to withstand external forces, and it is known that bone regeneration, modeling and remodeling is mediated by mechanical stimuli known as mechanotransduction. Mechanical stimuli transferred by scaffolds to cells rely exclusively on intrinsic scaffold properties, such as material stiffness and architecture. Consequently, the introduction of rapid prototyping technologies in the biomedical field has allowed to obtain scaffolds characterized by a precise control of its internal architecture, including precise pore size, pore geometry, spatial distribution of pores and interconnectivity, which may be considered as critical features to the their in vivo, biological and mechanical performances. In order to obtain a complete histomorphologically and biologically mature tissue, as bone, the restoration of the mechanical resistance to physiological stresses should be also followed by angiogenesis, which is a crucial aspect in the development of regenerative medicine approaches that require rapid vascularization of tissue-engineered structures. The main driving idea of this work is creating a conceptually new type of bioactive scaffold able to be manipulated in situ by means of magnetic forces in order to repair large bone and osteochondral defects. As first step, the design of 3D fiber deposited poly(ε-caprolactone)/iron oxide nanocomposite scaffolds has been described. The effect of iron oxide nanoparticle inclusion on morphological, mechanical, magnetic and biological performances has been assessed. Successively, in order to avoid the dangerous problem of leaving any non bioresorbable magnetic inclusion (for example, magnetite) inside the repaired tissue, poly(ε-caprolactone)/iron-doped hydroxyapatite substrates were designed and characterized using different polymer-to-particle weight ratios. The effect of iron-doped hydroxyapatite nanoparticle inclusion on morphological, mechanical, magnetic and biological performances has been assessed. This has allowed to choose the optimal polymer-to-particle weight ratio. In particular, a nanoparticle amount of 20% by weight embedded into the polymeric matrix has shown the best compromise between all the above reported features and then, 3D morphologically controlled nanocomposite magnetic scaffolds have been manufactured. The effect of a sinusoidal magnetic stimulation on adhesion and proliferation of cells seeded on 3D scaffolds has been studied. Future works will be focused on the effect of a variable magnetic field on cell differentiation. This work may represent a first approach towards the design of morphologically controlled and fully biodegradable nanocomposite magnetic scaffolds, which should be able to improve cell recruitment and cell loading efficiency. Furthermore, preliminary histological analyses have highlighted very interesting results.

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