Effect of crystallization on dissolution and biocompatibility of bioactive scaffolds

Abstract

Event Abstract Back to Event Effect of crystallization on dissolution and biocompatibility of bioactive scaffolds Virginia Melli1, Elena Boccardi1, 2, Elena Canciani3, Andrea Cochis3, Elena Varoni3, Luigi De Nardo1, Stéphanie Grenier4, Lia Rimondini5, Lina Altomare1 and Louis-Philippe Lefebvre4 1 Politecnico di Milano, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", Italy 2 University of Erlangen-Nuremberg, Institute of Biomaterials, Germany 3 Università degli studi di Milano, Clinica Odontoiatrica A.O. San Paolo, Italy 4 National Research Council Canada, Medical Device, Canada 5 Università del Piemonte Orientale Amedeo Avogadro, Italy Introduction: Numerous approaches have been proposed to manufacture porous bioactive glass scaffolds for load bearing applications, often resulting in inadequate compressive strengths[1]. To obtain suitable mechanical properties, the consolidation of the scaffolds often requires a thermal treatment that results in a fine dispersion of crystalline phases within a glassy matrix. This study provides a better understanding of the effects of crystallization on dissolution and biocompatibility. Materials and Methods: Bioglass foams (24.5Na2O-24.5CaO-6P2O5-45SiO2 wt%) were fabricated using a powder technology process consisting of mixing powders (i.e. bioglass powder, polymeric binder and foaming agent), molding the powder blend followed by foaming, debinding and sintering[2]. Foams were characterized before and after dissolution using scanning electron microscopy, micro-computed tomography, uniaxial compression, inner gas fusion (i.e. chemical composition), weight and density measurements, ion release and x-ray diffraction. To evaluate dissolution kinetics and impact of dissolution on the structure and properties, foams were immersed in simulated body fluid (SBF) or deionized water (DW) for a period up to 28 days. To assess in vivo response, samples were implanted percutaneously in a murine model for 6 weeks. Results and Discussion: The scaffolds showed an open network of porosity (fig.1). Depending on the powder formulation and processing conditions, porosities ranging from 55 to 77% and pore sizes between 100-500 µm were obtained, as required for bone ingrowth. The material specific surface area averages 45 mm2/mm3 (measured by image analysis on µCT reconstruction) and provides large surface for cells proliferation. After sintering, crystalline structures identified as combeite and rhenanite were observed. The binder and foaming agent decomposed well and leaves low amount of residues as measured by inert gas fusion (carbon and sulfur concentration under 0.03 and 0.05% respectively). Compressive strengths varied from 5-40 MPa depending on porosity. Immersion in SBF caused immediate Na and Si ion release and the formation of a Ca-P coating within 2 days. Crystalline peaks on XRD patterns disappeared over time suggesting amorphization of the base material and solubility of the crystalline phases. Compressive strengths decreased mostly due to the dissolution of the material but foams retained structural integrity even after 28 days of immersion. Sample weight significantly decreased in the first 2 weeks and stabilized thereafter. Immersion in DW revealed that the crystalline and amorphous phases dissolve with different kinetics but produced a constant weight loss rate. Percutaneous implantation in a murine model showed good tissue ingrowth, vascularization and the absence of inflammatory response (fig.2). Fig. 1. Scanning electron micrograph of bioactive glass foam prior to dissolution, scale bar = 500 µm with embedded 2D section extracted from µCT reconstruction. Fig. 2. Percutaneous implantation in a murine model showed absence of inflammatory response, good tissue ingrowth and vascularization and after 6 weeks (coloration: blue of Toluene and Pironina G). Conclusion: Crystallization did not inhibit Bioglass foam dissolution and bioactivity was confirmed by the deposition of a Ca-P rich layer. Despite 28 days of immersion in SBF, the compressive strength of partially dissolved foams was comparable to cancellous bone values and remained higher than values reported on pristine scaffolds prepared by sol-gel foaming or replica techniques using polyurethane foam as sacrificial template. The proposed technology shows great promise for bone regeneration applications.