Nova

NOVA is an innovative multi- and inter-disciplinary Fellowship hosted by the University of Birmingham in the UK with the primary aim to develop antimicrobial graphene oxide (GO)-lanthanide glasses (Ln)-hydroxyapatite (HA) composites for bone repair. The proposed research is a novel research direction, and there is no previously published research on what is proposed to be a new class of multi-functional composites. The research was conducted to address the following scientific questions:

(i) Will the developed innovative composites prevent bacterial adhesion and proliferation?

(ii) Can these materials influence osteoblastic cell behaviour regarding adhesion, proliferation, and differentiation?

(iii) Do the developed composites show any luminescence behaviour?

The aims and objectives of NOVA have been successfully achieved and are reported in detail in the technical report part B.

Orthopaedic infections are associated with long-term disability and together with antimicrobial resistance pose an increasing threat to the 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. In 2017, the World Health Organization reported that only eight antibiotics out of 51 that are currently in development would add value to the current arsenal of antibiotics. 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. Some commercial products such as Hydroxyapatite (HA) and bioactive glass may ease the situation. They do have advantages but there are also some drawbacks. Firstly, HA has poorer mechanical properties than natural bone and cannot be used for load bearing applications. Secondly, the glass is difficult to process into porous 3D scaffolds. Therefore, to improve HA, it may be reinforced with the incorporation of a small percentage of different low melting temperature host glasses. These host glasses are a source of specific ions (e.g. F^-, Mg²⁺, Na+, Zn²⁺, Mg²⁺, SiO₄^4-, Sr²⁺) and their presence in the HA matrix modulates its physicochemical and biological properties. In addition the incorporation of lanthanide glasses will offer essential antimicrobial properties to the composites. La³⁺, Sm³⁺, Eu³⁺, Gd³⁺,Tb³⁺, Dy³⁺ and Tm³⁺ are some of the lanthanide elements used in NOVA. The overall aim is to develop antimicrobial lanthanide containing ceramic composites to address emerging bone and antimicrobial issues as well as diagnostic challenges such as bio-imaging applications taking advantage of the luminescence properties of lanthanide materials.

Dr Sooraj Nandyala is a Marie Skłodowska-Curie Fellow with an Individual Fellowship in NOVA, University of Birmingham, United Kingdom. Currently, he is working as a technical research officer in the H2020-MSCA-ITN, DOC-3D Printing project. His scientific background is related to the area of lanthanide ion doped glasses and hydroxyapatite composites for antimicrobial, bone regenerative, luminescence and microfluidic applications. He also worked in the Marie Curie Research and Innovation Staff Exchange NEXT 3D project as a project manager in the same research group. So far, he has been published research findings in a high-quality impact peer-reviewed 54 research papers and 13 conference proceedings in the indexed journals. Also, he has contributed 10 book chapters and participated in 34 International Conferences. He has given a keynote lecture in Nagoya, Japan and several invited talks (8); Oral (12) and poster presentations (17). He edited a total of six monographs, one e-book and four more books are being prepared. He had total citations 1415 with h-index 23 (Google Scholar database). He has supervised 14 master students and he was the line manager for one research fellow. He will contribute towards optimisation of powders, experimental work and patent creation.

He had a significant experience in working with different reputable international laboratories & participating in the European Project POLARIS funded by FP7 at 3B’s (Biomaterials, Biodegradable, and Biomimetics) research group in the headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, University of Minho, Portugal. He has shown excellent capability to lead scientific projects. The Portuguese Ministry of Science & Technology (FCT) awarded one major nationwide project with funding of € 142,000 and developed some innovative work on lanthanide materials for photoluminescence, anti-infective and bone regenerative applications. And, two bilateral joint collaborative projects with DST (Department of Science and Technology)/Ministry of Science & Technology, India. He was a member of the research proposals evaluator committee, Republic of Kazakhstan.

He is acting as an editor in chief of the JBBBE, Journal of Biomimetics, Biomaterials, and Biomedical Engineering, TTP Publishers, Switzerland. He worked as one of the core group members of Technologies for Optofluidic Devices and working group leader for materials (soft, bio & nano) in the EU Cost Action MP1205 and participated in 8 EU Cost Action Meetings in EU (Belgium, Czech Republic, Ireland, Italy (2), Portugal, and Spain). Further, he had good industrial and international collaboration with the HORIBA, UK, Biosckin S.A., Porto, Hospital Sao Joao, Portugal and NASA Research Center, Hampton, USA.

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. The following applications were considered in NOVA:

Luminescence applications

The following seven 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 Excitation Emission Matrix (EEM) measurements of three different lanthanides glasses Gadolinium, Gd³⁺ (GdG); Terbium, Tb³⁺ (TbG); and Dysprosium, Dy³⁺ (DyG) doped borate glasses were studied. Pumping with an excitation source at 267 nm for GdG, we observed a UV transition at 310nm with a lifetime of 53.1µs. A green emission performance at 545 nm of the phosphorescence timescale was observed for the TbG glass at 371 nm of excitation. In the DyG glass, the decays associate spectra showed a bright yellow emission transition (⁴F_7/2-> ⁶H_9/2) at 571 nm with different average decay times of 0.062 ms, 0.148 ms, 0.337 ms and 0.701 ms. This is indicative of different emitting species contributing to the emission band and it is also noted that the trends of the peak were related to the decay times.

Similarly, Europium and Thulium host glasses were studied in order to examine the Zinc and Tellurium effect in the host matrix. A bright reddish-orange colour was observed from all samples since the spectra were dominated by two main transitions at 590 and 612nm. It was also found that there was no effect by adding ZnO and TeO₂ as network modifiers in the host glass. Finally, Thulium host glasses exhibits 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 high mitochondrial activity, and in comparison, to the control, a higher number of proliferating cells was observed. The materials were also evaluated for antibacterial activity with S. aureus. Bacteria grown over Te-containing composites presented an effective antibacterial activity against S. aureus, with a significantly reduced metabolic activity, as compared to the control (See figures in the attachment). The metabolic activity of the bacterial culture was found to decrease in relation to the increasing content of Te. 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.

Exploitation and dissemination of results

The EU funding has been acknowledged in all the communication and public engagement activities undertaken during the period of the fellowship, as well as in the publications that have been published or are currently under preparation. EU funding will be acknowledged in future activities as well as future publications resulting from the work undertaken by Dr Nandyala during the fellowship period.

To disseminate the results of the project, Dr Nandyala participated in the following conferences and research meetings as a keynote lecture (#1); invited talks # 2; Oral presentations # 2; and posters # 2.

Participation in conferences

H. Nandyala, P. Gomes, G. Hungerford, L. Grenho, M. H. Fernandes, A. Stamboulis, “Synthesis of bioactive Tellurite-Lanthanide-reinforced hydroxyapatite composites for biomedical and luminescence applications, Oct.26-29, 2018 - BIOCERAMICS 30, 30th Symposium and Annual Meetings of the International Society for Ceramics in Medicine Nagoya, Japan. KEYNOTE LECTURE.
H. Nandyala, P. Gomes, G. Hungerford, L. Grenho, M. H. Fernandes, A. Stamboulis, Antimicrobial and Luminescence properties of Lanthanide ions doped glassy hydroxyapatite composite materials, Jan 8-10, 2018 - ICBHE’18, International Conference on Bioengineering on Health and Environment, Sathyabama Institute of Science and Technology, Chennai, India. INVITED LECTURE.
H. Nandyala, P. Gomes, G. Hungerford, L. Grenho, M. H. Fernandes and A. Stamboulis, "Biological and Luminescence Response of Tellurite- Lanthanide-Reinforced Hydroxyapatite Composites" JULY 24-28, 2018 - BioMET 2018 – International conference on Bio-Materials, Bio-Engineering and Bio-Theranostics, VIT University, Vellore, India, INVITED LECTURE.
H. Nandyala, P. Gomes, G. Hungerford, L. Grenho , M.H. Fernandes, A. Stamboulis, Development of Lanthanides-reinforced Hydroxyapatite composites: MG63 Cells behaviour and Antimicrobial response., July 9-13, 2018, PNCS-ESG 2018 - 15th International Conference on the Physics of Non-Crystalline Solids & 14th European society of Glass Conference, Saint Malo, France. ORAL PRESENTATION.
H.Nandyala, P.Andrew, U. Petr, G. Hungerford, C. E. Grace,R.Michael, A. Stamboulis, Development of La³⁺doped zinc borate glass fibres for biomedical applications, Oct 25-27, 2017 - BIOCERAMICS 29, 29th Symposium and Annual Meetings of the International Society for Ceramics in Medicine Toulouse, France. ORAL PRESENTATION.
H.Nandyala, G.Hungerford, A.Stamboulis, Decay measurements of emission and upconversion transitions: Dy³⁺ doped silver zinc borate glasses, April 24-26, 2017-FLUOR0 FEST Workshop - Glasgow, Scotland, UK. POSTER PRESENTATION.
H.Nandyala, G.Hungerford, A.Stamboulis, Time-resolved and Fluorescence Excitation-Emission Matrix Measurements of Gd³⁺ and Tb³⁺ doped Silver Zinc Borate Glasses for Biomedical Applications, Oct 25-27, 2017- BIOCERAMICS 29, - 29th Symposium and Annual Meetings of the International Society for Ceramics in Medicine Toulouse, France. POSTER PRESENTATION.

Publications

Journals

Kabir , S.H.Nandyala, M. Rahaman, Md. A.Kabir, Z. Pikramenou, M. Laver, A. Stamboulis, Polyethylene glycol assisted facile sol-gel synthesis of lanthanum oxide nanoparticles: Structural characterizations and photoluminescence studies, Ceramics International, 45 (1)(2018) pp.424-431.

Appl. Phys. A (2018) 124, pp 820.

Vijay Singh; M. Seshadri; M. Radha; N. Singh; S H. Nandyala, Intense infrared, visible up and down emissions in Er³⁺/Yb³⁺ co-doped SrAl12O19 obtained by urea assisted combustion route, Journal of Materials Science: Materials in Electronics, October 2018, Volume 29, Issue 19, pp 16516-16522.

Book Chapters

H Nandyala, P. Gomes, G. Hungerford , L. Grenho, M. H. Fernandes, A. Stamboulis, “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, Chapter 12, (2018), pp.275-288. ISBN: 978-3-319-76567-9. Springer International Publishing AG, part of Springer Nature, USA.

Bhaskar Kumar, B. Vengla Rao, B.Chandra Babu, Graham Hungerford, S.H Nandyala, J.D. Santos, “Luminescence and Energy Transfer Phenomena in Lanthanide ions doped Phosphor and Glassy Materials” in “Current Trends on Lanthanide Glasses and Materials” Eds. N. Sooraj Nandyala, Chapter 7 (2017),pp 159-190, Materials Research Forum LLC, USA.

Chandra Babu, B. Vengala Rao, G. Bhaskar Kumar, G. Hungerford, S.H. Nandyala, Artemis Stamboulis, “Optical and Electrical Properties of Transition Metal Ion doped Sol-Gel Materials“ in “Advanced Materials and their Applications: Micro to nano scale”, Eds: Ishaq Ahmad, Paolo Di Sia, Rizwan Raza, Chapter 9, (2018), pp 195-218, (eBook): 978-1-910086-216,Publisher: One Central Press (OCP), Manchester, UK.

During NOVA, the luminescence, antibacterial and osteoblastic cell culture studies of Lanthanides Hydroxyapatite (Ln-HA) composites; Lanthanide Hydroxyapatite plus Graphene oxide mixed composites were successfully achieved. Results support the argument that lanthanum-doped hydroxyapatite composites present enhanced osteoblastic cell response and antibacterial activity - the two key features contributing to an improved biological outcome for the next-generation bone grafts. All developed materials presented antibacterial activity, as compared to the positive control (culture plate with no antibacterial activity). The lower values correlate with the highest antibacterial activity, as discussed. Most of the exploitation plans initially proposed have been achieved.

The REF rating and the quality of Dr Nandyala’s research work have been impacted and recognised by:

The organising committee of Bioceramics 30, Japan, have been invited for a Keynote Lecturer and Session chair on Oct 26-29, 2018, Nagoya, Japan.

Also, received two invited talks invitations from the international conferences organizers (BioMET’18 and ICBHE’18), India.

The Springer International Publishing AG, part of Springer Nature, USA, invited me to write a book Chapter on bone materials in “Tellurite Glass Smart Materials: Applications in Optics and Beyond”.

Optics and Laser 2019, the organising committee invited to deliver a keynote lecture in the International Summit on Optics, Photonics and Laser Technologies (Optics & Laser-2019) scheduled during June 3-5, 2019 in San Francisco, CA, USA.

SCON World Congress on Optics, Photonics and Laser Technologies to be held on the dates February 17-18, 2020 at the venue, Singapore.

Further, the organising committee of Materials Science & Smart Materials (MSSM-2019), UK, invited me to deliver a keynote lecturer on Smart Lanthanide Composites Materials for Biomedical and Luminescence Applications that will be held on 24-26 July 2019 at Aston University, Birmingham, UK.

Impact on Dr Nandyala’s career

Dr Nandyala developed friendly teamwork in the research group and trained students in the lab policies, good lab practice and procedures such as how to write COSHH forms, Risk Assessment and Standard Operating Procedure (SOP) and providing practical training such as Furnaces, 3D printers, Micro CT, FTIR, SEM, XRD instruments etc. In the duration of the NOVA, Dr Nandyala have been trained NMR and SPS instruments at Queen Mary University London. Dr Nandyala have been supervised the following two MSc Engineering students from May till September 2018.

Mr. Bibo Zhao ID: 1768886

Project: Development of Lanthanum doped glass reinforced hydroxyapatite composites

Mr. Chris Miller ID: 1578274

Project: The effect of lanthanides and glass formers on the structure and properties of a glass-ceramic hydroxyapatite composites.

The career objectives of the Dr Nandyala will be getting further research funding to keep developing his further research projects and goals. 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. Thanks to NOVA, Dr Nandyala’s number of citations has been increased to 1300 from 1000 since 2017. Dr Nandyala, has secured and started a new staff position at the School of Materials and Metallurgy, University of Birmingham as a technical research officer in the H2020-MSCA-ITN, DOC-3D Printing project as a technical support to train a new generation of Early-Stage Researchers.

Those who are interested to write book chapters in the following monographs please contact.

Current Trends on Microfluidic Research. Materials Research Forum LLC, USA.

Recent Advances in Emerging Nanomaterials and Biomaterials, Materials Research Forum LLC, USA.

Rare Earth - A tribute to the late Mr. Rare Earth, Professor Karl Gschneidner- Materials Research Forum LLC, USA.

Lanthanide Materials: Advances and Applications at the Macro- and Nanoscale, Pan Stanford Publishing, Singapore