3D direct ink writing (robocasting) of bioceramic porous scaffolds: towards a new generation of bone graft substitutes (ROBONEGRAFT)


Project Director: Dr. George Stan

Project ID:  PN-III-P1-1.1-TE-2019-0463

Project Director:  Dr. George Stan

Project Type: National

Project Program: HUMAN RESOURCES, Young Teams

Funded by:  Romanian National Authority for Scientific Research, UEFISCDI

Contractor: National Institute of Materials Physics

Project Status: In progress

Start Date: 1 January, 2021

End Date: 30 December, 2022

 

Project summary: 

Bone transplantation demand stems from tissue deficiency or a substantial skeletal loss, and has multiple causes: age, severe trauma, chronical bone disorders/infections, tumor resections, congenital bone defects. Bone grafting evolved in the last decade into a distinct biomedical segment, which will continuously expand. Responding to this necessity, the project proposal aims to delineate series of innovative architectural solutions of porous bone graft substitutes (BGSs) to be fabricated by accessible and performant 3D robocasting technologies, from bioactive and/or piezoelectric ceramics. Their functional performance will be assessed to prospect their potential for developing a new generation of BGSs capable to satisfy the mechanical and biological requirements of both trabecular and the more demanding cortical bone regions. New routes for endowing angiogenesis, osteogenesis and antibacterial capabilities to both the bioactive and piezoceramic BGSs, such as to enable their rapid, safe and long-lasting osseointegration, will be explored and implemented. Not least the proposal will tackle another highly important issue: the lack of standard in vitro protocols for uniform cell seeding of porous scaffolds.
Innovative and original fundamental and technological elements are expected to emerge: (a) design of bioactive ceramics with controlled degradability and therapeutic ion release, (b) coupling of mechanical strong piezoelectric ceramics with biofunctional materials and (c) in vitro testing of piezoelectric effect on cells behavior under dynamical mechanical stress conditions. The project will lead to the creation of an independent research team of young scientists with complementary skills, and strive to (i) attract human resources in the national research; (ii) create opportunities of professional formation for young researchers, and (iii) generate premises for the future formation of a larger scientific community with skills and knowledge in materials for medicine.

 

Project Objectives: 

General Objective: Opening New Perspectives Towards a New Generation of Ceramic Bone Graft Substitutes Based on Bioactive and Piezoelectric Ceramics

Specific objectives:

O1: Synthesis of alkali-free silica-based bioactive glass (SBG), calcium phosphates (CaP) and piezoelectric ceramic powders by melt-quenching, co-precipitation, and conventional ceramic technology (solid-state)/hydrothermal synthesis, respectively. – Realized [RST 1/2021].

O2: Electing the most promising bioactive and piezoelectric ceramics for 3D printing based on multi-parametrical structural, piezoelectric, surface energy, mechanical and in vitro biological evaluations. – Realized [RST 1/2021].

O3: Fabrication of 3D bioactive and/or piezoelectric bone graft substitutes by robocasting with different filament distribution geometries and pore sizes.

O4: Exploratory studies of coating the 3D porous bone substitutes constructs based on piezoelectric ceramics with sacrificial bio-functional layers by chemical and physical deposition techniques.

O5: Cross-examination of the physical-chemical, mechanical and bio-functional (degradability, ion release, bioactivity, uniform cell seeding, cytocompatibility, angiogenesis and osteogenesis capability) features of the fabricated porous scaffolds by multi-parametric analyses. Optimization.

O6: Rational selection of the best scaffold designs dedicated to the substitution of cortical and trabecular bones, ensuring a functional compromise between porosity, biofunctionality and mechanical performance.

O7: Consolidation and strengthening of the research team by addition of young researchers with complementary skills and active interests in field of 3D printing and/or bone regeneration prospective solutions, and creation of an independent research program. Dissemination of relevant scientific results. – Partially realized [RST 1/2021].

Stage I summary:

Project PN-III-P1-1.1-TE-2019-0463 (contract TE135/2020) aims to open perspectives for the realization of a new generation of synthetic bone graft substitutes (scaffolds) based on bioactive and piezoelectric ceramics. Starting from this general objective, Stage I of the PN-III-P1-1.1-TE-2019-0463 (2021.01.01 - 2021.12.31) research project was dedicated to both (1) the preparation, characterization and selection of future source materials [e.g., silicate and phosphate bioactive glasses, doped with Zn, Sr, Cu and/or Ga, synthesized by the melt-quenching; piezoelectric ceramics (based on: KNbO3; LiNbO3; LiTaO3; BaTiO3 simple and doped with Zr; and solid solutions from the Ba(Ti0.8Zr0.2)TiO3 – (Ba0.7Ca0.3)TiO3) binary system manufactured by the solid-state reaction conventional ceramic technology; simple, binary and ternary calcium phosphates, doped with Mn, Sr, Mg and/or Ga, prepared by co-precipitation/hydrothermal synthesis or derived from biological and mineral resources] for either scaffolds and/or bioactive functionalization layers, and (2) the first experiments of 3D printing, using the robocasting technology (direct ink writing) – primary, and by incorporating agents porous (vegetable fibers, whose thermal combustion will generate micro- and macro-pores and inter-canaliculi) – secondarily, of macro-porous synthetic bone graft substitutes from the ceramic materials selected based on the multi-parametric physical-chemical and in vitro biological evaluations. Part of the results obtained in this stage of the project were disseminated by presentations at international conferences (1) and articles published/accepted in/to Web of Science®-indexed journals (5).

Delivered results:

  • 1 study scientific study on the methods of synthesis of oxide-based source powder materials (bioactive ceramics and glasses, piezoelectric ceramics) to be employed for the further fabrication of bone graft substitutes by the robocasting printing technology;
  • 1 presentation (poster type) held at the E-MRS 2021 Fall Meeting international conference;
  • 1 article published in a journal indexed in Web Science®, without impact factor;
  • 4 articles published/accepted in/to journals indexed in Web of Science®, with impact factor, one situated in the Q2 quartile and three in the Q1 quartile.

The scientific report cannot be yet divulged on the project website, as the results are in the process of being published, but it can be accessed upon request at UEFISCDI.

2021: THE SYNTHETIC SCIENTIFIC REPORT no. 1 in .pdf format is available at UEFISCDI, and can be accessed by request.

  • 2021: Ioana Cristina Tudor, student, 2nd year of study, Faculty of Medical Engineering, University Politehnica of Bucharest, effectuated 360 hours of scientific practice in the field of synthesis and physical-chemical and in vitro biological characterization of ceramic materials in both bulk and thin film forms, under the coordination of Dr. George Stan (Project director of TE135/2021).

Web of Science® articles - published or accepted:

  • 01. A.C. Mocanu, F. Miculescu*, G.E. Stan^, R.C. Ciocoiu, M.C. Corobea, M. Miculescu, L.T. Ciocan, Preliminary studies on graphene-reinforced 3D products obtained by the one-stage sacrificial template method for bone reconstruction applications; J FUNCT BIOMATER 12 (2021) 13. https://doi.org/10.3390/jfb12010013.
  • 02. A.C. Mocanu, F. Miculescu*, G.E. Stan^, A.M. Pandele, M.A. Pop, R.C. Ciocoiu, S.I. Voicu, L.T. Ciocan, Fiber-templated 3D calcium-phosphate scaffolds for biomedical applications: The role of the thermal treatment ambient on physico-chemical properties; MATERIALS 14 (2021) 2198. https://doi.org/10.3390/ma14092198.
  • 03. I.M. Chirica^, A.M. Enciu, T. Tite*, M. Dudau, L. Albulescu, S.I. Iconaru, D. Predoi, I. Pasuk, M. Enculescu, C. Radu, C. Mihalcea, A.C. Popa^, N. Rusu, S. Nita, C. Tanase*, G.E. Stan*,^,  The physico-chemical properties and exploratory real-time cell analysis of hydroxyapatite nanopowders substituted with Ce, Mg, Sr and Zn (0.5–5 at.%); MATERIALS 14 (2021) 3808. https://doi.org/10.3390/ma14143808.
  • 04. A. Gaddam*, A.A. Allu, S. Ganisetti, H.R. Fernandes, G.E. Stan^, C.C. Negrila, A.P. Jamale, F. Mear, L. Montagne, J.M.F. Ferreira; Effect of vanadium oxide on the structure and Li-Ion conductivity of lithium silicate glasses; J PHYS CHEM C 125 (2021) 16843. https://doi.org/10.1021/acs.jpcc.1c05059
  • 05. B.W. Stuart*, G.E. Stan^, A.C. Popa^, M.J. Carrington, I. Zgura, M. Necsulescu, D.M. Grant*, New solutions for combatting implant bacterial infection based on silver nano-dispersed and gallium incorporated phosphate bioactive glass sputtered films: A preliminary study; BIOACTIVE MATER 8 (2022) 325. https://doi.org/10.1016/j.bioactmat.2021.05.055.

International Conferences:

  • 01. T. Tite, A.C. Popa^, I.M. Chirica^, B.W. Stuart, A.C. Galca, L.M. Balescu, G. Popescu-Pelin, D.M. Grant, J.M.F. Ferreira, G.E. Stan^; Tuning the cross-area uniformity, structure and biological response of sputtered phosphate bioglass films by the gas pressure, E-MRS 2021 Fall Meeting, Symposium J: „Materials and technological solutions preventing biofilms and antimicrobial resistance”, 20–23 September 2021, online (poster).

*corresponding author

^project team member

GEORGE E. STAN, PhD in Materials Engineering

Senior Researcher I

Telephone: +40-(0)21-2418 128 or +40-(0)21-2418 153

Department: Laboratory of Multifunctional Materials and Structures


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