Novel, Bio-Inspired Superparamagnetic Hybrid Microspheres for Bone Tissue Engineering

Abstract

The available strategies for the treatment of complex bone defects are limited and do not effectively promote bone tissue regeneration. Smart biomaterials have been investigated and designed as a suitable tool for application in degenerative diseases. In particular, magnetic materials are a class of smart biomaterials that showed promising results in bone tissue regeneration or as a diagnostic use. Therefore, the development of biomaterials with magnetic properties is an emerging field of research. The present work describes the application of biomineralisation process, to develop novel biocompatible and bioactive hybrid biomaterials with superparamagnetic properties. Collagen type I-like peptide matrix (RCP) was mineralised with Fe+2/Fe3+-doped hydroxyapatite and engineered into hybrid microspheres (RCPFeHA) by using an appositely developed and optimized emulsification process. Thorough investigation of physicochemical, morphological, thermal, magnetic and biologic properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, designed shape and size, tailored magnetization, good cytocompatibility and significant activity in inducing osteogenic differentiation and expression of genes relevant for bone tissue formation. Microspheres were stable in physiological and inflammatory-mimicking conditions and delivered calcium and iron ions, which could be related to the osteogenic differentiation of murine pre-osteoblasts cells and human mesenchymal stem cells. On the other hand, the effect of microspheres composition on the release of important growth factor in bone tissue regeneration (i.e. rhBMP-2) was studied under static and pulsed electromagnetic field, and bioactive and slow release over the time was obtained. The unique features exhibited by the new hybrid magnetic microspheres are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, that might be addressed to smart and personalized applications in medicine, particularly in bone tissue regeneration or smart drug delivery systems.