Ion-doped mesoporous bioactive glass nanoparticles for wound healing applications

Introduction. Bioactive glasses (BGs) have been extensively studied for bone repair. However, recent research has also shown their positive effects on wound healing. Among BGs, mesoporous bioactive glasses (MBGs), which combine the texture parameters of ordered mesoporous matrices with the properties of bioactive glasses, have received increasing attention as tissue-regeneration systems. Their high surface area and accessible pore volume give the possibility of incorporating and releasing therapeutic ions to impart biological properties, such pro-angiogenic effects (cerium [1], copper [2]) or antibacterial activities (copper) [3]. Materials and Methods. In this work, MBGs doped with two different ions (Ce3+, Cu2+) were synthesized following two different routes: a base-catalyzed sol-gel method [4] and an aerosol-assisted spray-drying procedure [5]. Ce and Cu-containing MBGs were characterized by FESEM coupled to EDS, XRD, N2 adsorption-desorption analysis and UV-vis spectroscopy. To study the release profiles of the therapeutic ions, nanoparticles were immersed in different media and maintained at 37°C in an orbital shaker for up to 14 days. Ion contents in the supernatants were measured by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Future studies will assess their antibacterial and angiogenic potential. Antibacterial tests will use both standard microbiological tests and they will also be assessed in a bacterial infected 3D human skin model [6]. The pro-angiogenic effects will be tested using a rat aortic ring assay. Results and Conclusions. The use of two different routes allowed us to obtain spherical MBGs based on SiO2-CaO system doped by therapeutic ions. Figure 1 shows samples characterized by different dimensions -between 500-5500 nm for spray-dryer samples and around 100 nm for sol-gel particles. High surface area and homogeneous pore size distribution (7nm for for spray-dryer samples and 3nm for sol-gel ones) permitted the incorporation of specific amount of ions, which were then released in a sustained way throughout 14 days. References [1] Garner JP, Heppell PS., Cerium nitrate in the management of burns, Burns 31 (2005) 539–547 [2] Hoppe et al., A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics, Biomaterials 32 (2011) 2757-74 [3] C. Wu et al., Copper-containing mesoporous bioactive glass scaffolds with multifunctional properties of angiogenesis capacity, osteostimulation and antibacterial activity, Biomaterials 34 (2013) 422-433 [4] M. Shi et al., Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis, Acta Biomater. 30 (2016) 334–344 [5] C.Vitale-Brovarone, L. Pontiroli, G. Novajra, I. Tcacencu, J. Reis, A. Manca, Spine-Ghost: a new bioactive Cement for Vertebroplasty, Key Eng Mat 631 (2015) 43-47 [6] Shepherd, J., Douglas, I., Rimmer, S., Swanson, L., & MacNeil, S. Development of three-dimensional tissue-engineered models of bacterial infected human skin wounds. Tissue Eng Part C Methods (2009), 475-484.