Novel Antimicrobial Graphene Oxide-Lanthanide- Hydroxyapatite Composites as Therapeutic Materials in Bone Infection and Repair

Project Information

NOVA

Grant agreement ID: 753636

DOI

10.3030/753636

Project closed

EC signature date 24 February 2017

Start date 1 March 2017

End date 28 February 2019

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 195 454,80

EU contribution

€ 195 454,80

Coordinated by

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Periodic Reporting for period 1 - NOVA (Novel Antimicrobial Graphene Oxide-Lanthanide- Hydroxyapatite Composites as Therapeutic Materials in Bone Infection and Repair)

Reporting period: 2017-03-01 to 2019-02-28

Summary of the context and overall objectives of the project

Orthopaedic infections are associated with long-term disability and together with antimicrobial resistance pose an increasing threat to public health. A review on the antimicrobial resistance estimated around 0.7M deaths worldwide each year with a possibility to rise to 10M a year by 2050 having a cumulative 66 trillion-pound economic impact due to the costs associated with the rise of drug-resistant infections. It is therefore vital and necessary to develop some alternative approaches for a better society. To build new multi-functional systems that can exhibit antimicrobial properties for bone related applications is both challenging and desirable. The overall aim is to develop antimicrobial lanthanide containing ceramic composites to address emerging bone and antimicrobial issues.
WP 1: Development and characterisation of innovative Lanthanide glasses and doped HA
WP 2: Development and characterisation of GO-Ln-HA composites
WP 3: In vitro osteoblastic cell culture, cytotoxicity and antimicrobial studies of GO and GO-Ln-HA composites.
The aims and objectives of NOVA have been successfully achieved and reported in Tech. Report Part B.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Lanthanides have the ability to modulate bone metabolism and express an affinity to the calcium interaction site. The inclusion of Ln3+ ions in bone substitute materials, such as glass reinforced hydroxyapatites (HA), has been considered and shown to influence the biological response. This has led to the application of Lanthanides in the development of smart materials, which can play multi-purpose roles in innovative designs for biomedical and luminescence applications.
Luminescence applications:
The following 7 elements in the periodic table: La3+, Sm3+, Eu3+, Gd3+,Tb3+, Dy3+ and Tm3+ were incorporated in a series of borate glass compositions for luminescence applications.
The time-resolved luminescence and EEM measurements of three different lanthanides glasses Gadolinium, Gd3+; Terbium, Tb3+; and Dysprosium, Dy3+ doped borate glasses were studied. Similarly, Europium and Thulium host glasses were studied and a bright reddish-orange colour was observed from all samples. Thulium host glasses exhibit a strong blue emission in the reported glasses.
Biomedical applications:
We reported the biological response of tellurite (Te) containing glass reinforced hydroxyapatite composites. These were developed with distinct chemical compositions, ranging from Te-0.5La-HA to Te-4La-HA, and HA was used as a control. These composites were assayed with human bone marrow-derived stromal cells (hBMSCs). The cells presented a characteristic morphology, with a higher number of proliferating cells was observed. The materials were also evaluated for antibacterial activity with S. aureus.
Exploitation and dissemination of results
Participation in conferences:
1.S.Nandyala et.al. “Synthesis of bioactive Tellurite-La reinforced hydroxyapatite composites for biomedical and luminescence applications, Oct.26-29 2018 - BIOCERAMICS 30, Nagoya, Japan. KEYNOTE LECTURE.
2.S.Nandyala et.al. Antimicrobial and Luminescence properties of La ions doped glassy hydroxyapatite composite materials, Jan 8-10, 2018 - ICBHE’18, Sathyabama Institute of Science and Technology, Chennai, India. INVITED LECTURE.
3.S.Nandyala et.al. "Biological and Luminescence Response of Tellurite- La-Reinforced Hydroxyapatite Composites" JULY 24-28, 2018 - BioMET 2018 , VIT University, Vellore, India, INVITED LECTURE
4.S.Nandyala et.al. Development of La-reinforced Hydroxyapatite composites: MG63 Cells behaviour and Antimicrobial response., July 9-13, 2018, PNCS-ESG 2018 - 15th Int. Conf. on the Physics of Non-Crystalline Solids, Saint-Malo, France. ORAL
5.S.Nandyala et.al. Development of La-doped zinc borate glass fibres for biomedical applications, Oct 25-27, 2017 - BIOCERAMICS 29, Toulouse, France. ORAL
6.S.Nandyala et.al. Decay measurements of emission and upconversion transitions: Dy3+ doped silver zinc borate glasses, April 24-26, 2017 - FLUOR0 FEST Workshop - Glasgow, UK. POSTER
7.S.Nandyala et.al. Time-resolved and Fluorescence Excitation-Emission Matrix Measurements of Gd3+&Tb3+ doped Silver Zinc Borate Glasses for Biomedical Applications, Oct 25-27, 2017- BIOCERAMICS 29, Toulouse, France. POSTER

Book Chapter:
S. Nandyala, et.al. “Development of Bioactive-Based Tellurite-Lanthanide Ions– Reinforced Hydroxyapatite Composites for Biomedical and Luminescence Applications”, in “Tellurite Glass Smart Materials: Applications in Optics and Beyond” Eds. R. El-Mallawany, Springer Int. Publishing AG, part of Springer Nature, USA. Chapter 12, (2018), p.275. (NOVA Preliminary results)

Collaborative work Journal publications:
1. Ceramics Int., 45 (1)(2018) p.424.
2. Appl. Phys. A (2018) 124, p.820
3. J.Mat.Sci: Mater. Electronics, 2018, Vol. 29(19), p. 16516.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Results supported the argument that lanthanum-doped hydroxyapatite composites presented enhanced osteoblastic cell response and antibacterial activity - the two key features contributing to an improved biological outcome for the next-generation bone grafts.
The career development activities of NOVA have also been communicated through other non-academic channels, including the project’s website (www.nova.sbrpc.co.uk). Most of the exploitation plans initially proposed have been achieved. During the Fellowship, Dr Nandyala developed research collaborations that led to the publication of three journal articles. He also created enough novelty that needs to be protected by a patent and he has submitted a record of the invention with the aim to file a patent in the near future. The patent deals with a novel antimicrobial ceramic composite powder that fulfils requirements for laser 3D printing Furthermore, we have submitted one funding applications with (i) Innovation to Commercialisation of University Research (ICURe) Midland Cohort C; (ii) EPSRC proof of concept funding application is under the submission stage.
Impact on Dr Nandyala’s career
In the duration of the NOVA, Dr Nandyala have been trained NMR and SPS instruments at QMUL. Dr Nandyala has been supervised the following two MSc students from May till Sept. 2018.
1: Mr. Bibo Zhao, ID: 1768886
Project: Development of Lanthanum doped glass reinforced hydroxyapatite composites
2: Mr. Chris Miller, ID: 1578274
Project: The effect of lanthanides and glass formers on the structure and properties of glass-ceramic hydroxyapatite composites.
Since completing his fellowship, Dr Nandyala has secured and started a new temporary staff position at the University of Birmingham as a technical research officer in the H2020-MSCA-ITN, DOC-3D Printing project as technical support to training a new generation of Early-Stage Researchers.
Further, Dr Nandyala has gained international visibility and made connections with other academics from the NASA collaboration and joint publications are under submission stage.
Furthermore, Dr Nandyala has received the first time an opportunity for a keynote lecture from Japan. Intellectually speaking, Dr Nandyala has acquired professional maturity during these two years, especially in connection with project design and collaborative work with other members in the department and other institutions. Thanks to NOVA, Dr Nandyala’s number of citations has been increased to 1292 from 1000 since 2017. Eventually, Dr Nandyala will be expecting a permanent teaching/research position at the UoB, UK.

Figure 1: Confocal Laser Scanning Microscope Image; Figure 2: Metabolic Activity