Surface nitridation improves bone cell response to melt-derived bioactive silicate/borosilicate glass composite scaffolds

Significance Statement

Biomaterials have long been used in the orthopaedic surgery to guide and assist bone repair. Nowadays, they also have the potential of being used as substrates for bone tissue engineering. Bioglasses like 45S5 present optimal bioactivity, but when sinterized into 3D monoliths they crystallize and partly loose their properties, mainly in vivo absorb ability. We have developed a novel bioglass, called ICIE16/BSG-NITRI, that not only overcomes this limitation but also displays improved reactivity and biocompatibility due to surface nitridation. ICIE16/SBG-NITRI was synthesized from a mixture of two melt-derived glasses through combined gel casting and foam replication techniques, followed by nitridation. It is highly porous but mechanically stable and mimics the architecture of bone tissue. Nitridation confers it improved reactivity and bioactivity facilitating its resorption and deposition of apatite (bone-like mineral) at its surface. The nitrided surface also improved its interaction with bone cells, which were found to attach better to ICIE16/SBG-NITRI and to differentiate earlier on its surface.

Figure legend: bone on the left and our ICIE16/BSG-Nitru bioglass on the right (in both cases bar is 500 µm).

Figure legend: merge of visible and fluorescent-blue channels to show cell distribution on the bioglass surface. The hoechst-stained nuclei can be seen as blue dots.

About the author

Felipe Orgaz, Ph. D.

Felipe Orgaz is a tenured researcher at the Glass and Ceramic Research Institute (Madrid, Spain). He obtained his Ph. D. from the University of Madrid on strengthening glasses by ion exchange, and then conducted his post-doctoral studies at Sheffield University (UK) on sol-gel process. He joined the Spanish company Explosivos Río Tinto, and then Encros as Head of the Department of Ceramic Technology, conducting projects on structural ceramics for aerospace applications. He has also worked for the Spanish Ministry of Science and Technology evaluating technology transfer activities. He has conducted research on glasses and coatings from sol-gel process, nano-structured materials, dynamic fracture of advanced materials, transparent ceramics for armors, mechanical behavior of silicon nitride structural ceramics, TiO2 catalysts, and ion-densified ceramic foams and materials. His current research is focused on surface nitridation and its effects on the interface of the materials with living tissues, including protein adsorption and cell response. He has authored 10 international patents and more than 55 articles, in national and international journals and conference proceedings. He has also been part of several technical committees of the International Commission on Glass (ICG). He has been member of the steering committee of Fundación Círculo para la Defensa y la Seguridad, he has been member of the editorial board of the Bulletin of the Spanish Society of Ceramics and Glass, and of the Journal of Sol-Gel Science and Technology. He is currently the president of the Education and Innovation Area of the Spanish Society of Glass and Ceramic.

About the author

Leonor Santos-Ruiz, Ph. D.

Leonor Santos-Ruiz is a Senior Researcher at the Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN, Spain), and part-time associate professor at the Faculty of Sciences of the University of Málaga (Spain). She earned her PhD degree in Regenerative Biology in 2001, from the University of Málaga, and completed her post-doctoral fellowship at the Advanced Biotechnology Centre (Genoa, Italy) and the Institute for Child Health (ICH-UCL; London, UK). Her research is focused on bone repair and seeks the application of regenerative biology principles to develop tissue engineering products that stimulate bone regeneration, particularly in individuals where bone endogenous natural repair is hampered due to age or disease. She is interested in conditions like osteoporosis, osteonecrosis and skeletal dysplasias, particularly craniosynostosis, and her work includes the use of adult and perinatal stem cells for stem cell therapy, and the development and evaluation of novel biomaterials to be used as cell carriers and/or drug deliverers. She is the author of 2 international patents and more than thirty articles in international journals and conference proceedings.

Journal Reference

Acta Biomater. 2016;29:424-34.

Orgaz F¹, Dzika A¹, Szycht O¹, Amat D^2,3, Barba F¹, Becerra J^3,4,5, Santos-Ruiz L^3,4,5.

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¹ Instituto de Cerámica y Vidrio, Consejo Superior de Investigaciones Científicas (ICV-CSIC), c/ Kelsen n° 5, 28049 Madrid, Spain

² Universidad de Málaga, Departamento de Anatomía y Medicina Legal, Facultad de Medicina, Campus de Teatinos, 29071 Málaga, Spain

³ Centro de Investigación Biomédica en Red. Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, c/ Monforte de Lemos 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain

⁴ Universidad de Málaga & IBIMA, Departamento de Biología Celular, Genética y Fisiología, Facultad de Ciencias, Campus de Teatinos, 29071 Málaga, Spain

⁵ BIONAND-Universidad de Málaga, c/ Severo Ochoa 35, Campanillas, 29590 Málaga, Spain [/expand]

Abstract

Novel bioactive amorphous glass-glass composite scaffolds (ICIE16/BSG) with interconnected porosity have been developed. Hierarchically interconnected porous glass scaffolds were prepared from a mixture of two melt-derived glasses: a ICIE16 bioactive glass that was previously developed by Wu et al. (2011) to prevent crystallization, and a borosilicate glass of composition 73.48 SiO2-11.35 B2O3-15.15 Na2O (wt%). The resulting melt derived glass-glass composite scaffolds (ICIE16/BSG) were subject to surface functionalization to further improve its interaction with biological systems. Surface functionalization was performed by a nitridation process with hot gas N2/ammonia at 550°C for 2h, obtaining the ICIE16/BSG-NITRI. Evaluation of the degradation rate and the conversion to hydroxyapatite after immersion in simulated body fluid predicted a good biological activity of all the scaffolds, but particularly of the nitrided ones. In vitro evaluation of osteoblastic cells cultured onto the nitrided and non-nitrided scaffolds showed cell attachment, proliferation and differentiation on all scaffolds, but both proliferation and differentiation were improved in the nitrided ICIE16/BSG-NITRI.

STATEMENT OF SIGNIFICANCE:

Biomaterials are often required in the clinic to stimulate bone repair. We have developed a novel bioglass (ICIE16/SBG-NITRI) that can be sintered into highly porous 3D scaffolds, and we have further improved its bioactivity by nitridation. ICIE16/SBG-NITRI was synthesized from a mixture of two melt-derived glasses through combined gel casting and foam replication techniques, followed by nitridation. To mimic bone, it presents high-interconnected porosity while being mechanically stable. Nitridation improved its reactivity and bioactivity facilitating its resorption and the deposition of apatite (bone-like mineral) on its surface and increasing its degradation rate. The nitrided surface also improved the bioglass’ interaction with bone cells, which were found to attach better to ICIE16/SBG-NITRI and to differentiate earlier on its surface.

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