BrainMap

Iuliana Caras

- INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO”

Researcher

Curriculum Vitae (11/07/2023)

Expertise & keywords

Design of new nanocellulose-based gas-carrier systems Call name: P 4 - Proiecte de cercetare exploratorie - PCE-2021
PN-III-P4-PCE-2021-0435 2022 - 2024

Role in this project:

Coordinating institution: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti

Project partners: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO)

Affiliation:

Project website: https://icechim.ro/celgas-en/

Abstract:

Severe oxygen deprivation can cause significant problems in chronic wounds, during organ preservation and implantation, or in cases of trauma, hemorrhagic shock, or viral pneumonia. Oxygen prevents wound infection, increases cell viability after implantation and could be an effective treatment in viral pneumonia. Currently, there is no viable solution to deliver oxygen to the grafts during the healing period and to administrate a large volume of oxygen to patients who suffered profound oxygen deprivation. The scope of the CELGAS project is to develop innovative oxygen-carrying systems capable of supplying oxygen in a controlled manner to injured tissue/ implants or intravenously. The innovative oxygen-carrying systems will ensure controlled release of oxygen for long periods of time, will have a high stability, biodegradability, will not be cytotoxic and will have a nanometric size, essential for intravenous administration to avoid vascular obstruction. In CELGAS, the problem will be addressed using nanocellulose and nanocellulose/biopolymer to encapsulate oxygen-generating species or to obtain oxygen-containing nanobubbles. The biopolymers to be used are selected from poly (3-hydroxybutyrate), medium chain length polyhydroxyalkanoates and polylactic acid. The design of the new systems will be based on improved methods and an efficient characterization that will allow the achievement of the objectives.

Polyoxazoline hydrogels - pluripotent carriers of antimicrobials for local treatment of osteomyelitis Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2021-2544 2022 - 2024

Role in this project: Key expert

Coordinating institution: INSTITUTUL DE CHIMIE ORGANICĂ ŞI SUPRAMOLECULARĂ "COSTIN D.NENIŢESCU"

Project partners: INSTITUTUL DE CHIMIE ORGANICĂ ŞI SUPRAMOLECULARĂ "COSTIN D.NENIŢESCU" (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Affiliation:

Project website: https://www.icoscdn.ro/index.php/proiecte/polyamos

Abstract:

The present project aims at developing a pluripotent carrier, based on poly(2-isopropenyl-2-oxazoline) (PiPOx) hydrogels, incorporating multiple antimicrobial agents with different mechanisms of action against aerobic and anaerobic microorganism, showing controlled drug release for the local treatment of osteomyelitis infections. One of the main challenges in developing efficient treatments against osteomyelitis infections is its complex microbial etiology. Extensive treatments with prolonged systemic intravenous antibiotic treatment lasting for many weeks have been implemented, but these induce high patient discomfort and can be toxic due to high doses applied over a long period of time. As alternative, herein, we propose the use of PiPOx to develop advanced functional hydrogel materials, combined with antimicrobial agents that will endow the hydrogels with antiseptic properties to alleviate the problems associated with bacterial infection in osteomyelitis. Two distinct antibiotics, nafcillin and metronidazole, will be conjugated to PiPOx matrix, while the antimicrobial peptides, will be physically entrapped in the hydrogel in a synergistic antimicrobial approach. Via the herein proposed objectives and activities, the multidisciplinary team of researchers undertook the challenge to demonstrate that PiPOx conjugated hydrogels may represent a feasible solution in the construction of advanced drug-delivery systems for sustained release. The proposed material is expected to degrade slow in contact with simulated body fluids, exhibiting resorbable behavior. The starting TRL of the project is 2 and targets a final TRL 4 in the innovation chain demonstrating the use of PiPOx hydrogel as degradable drug delivery system for the advanced treatment of osteomyelitis infections.

Biopolymer structures obtained by plasma treatment for wounds healing Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2021-2559 2022 - 2024

Role in this project:

Coordinating institution: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti

Project partners: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO); INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Affiliation:

Project website: https://icechim.ro/project/biopolymer-structures-obtained-by-plasma-treatment-for-wounds-healing-bioplasm/

Abstract:

Chronic wounds, severe burns or infected wounds are among the most painful diseases that require long-term expensive treatment. Currently, the clinical management of chronic wounds is difficult due to the increasing risk of infection with antibiotic-resistant bacteria and the shortcomings of current therapies. A novel technology for the manufacture of bilayer wound dressings, based on nanocellulose and cold plasma processing, will be developed in BIOPLASM project. The scope of the project is to obtain effective dressings for the treatment of infected wounds by developing antibacterial nanocellulose nanocarriers deposited on an aliphatic polyester substrate.

The use of cold plasma for nanocellulose and biopolymers processing in view of medical application is an effervescent field, with important benefits related to eco-friendliness, lack of secondary or waste products, sterilization and large functionalization capabilities. Cold plasma treatment of liquid suspensions of nanocellulose is a concept developed by ICECHIM and INFLPR in a previous project. This will serve as a starting point together with the functionalization and processing of nanocellulose and aliphatic polyesters for building a new technological approach to fabricate bilayer wound dressings. The new technology will be validated by in vitro and in vivo studies. The project will be implemented by a skilled group of researchers from ICECHIM, INFLPR and Cantacuzino Institute.

Synthetic nanogel antibodies molecularly imprinted with the Spike S1 protein Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente - TE-2021
PN-III-P1-1.1-TE-2021-1239 2022 - 2024

Role in this project:

Coordinating institution: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti

Project partners: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO)

Affiliation:

Project website: https://icechim.ro/project/antispike-ro

Abstract:

SARS-CoV-2 is a new coronavirus type and it is responsible for causing COVID 2019 in humans, with very high contagion rate all over the world. The viral entry of SARS-CoV-2 is conferred by the presence of Spike S1 protein on the surface that can direct attachment and enter the plasma membrane of the human cell. The Spike protein through its location is a significant therapeutic target, and targetable using antibodies. Despite recent technological developments, effective and safe therapies are currently not available for treating the infected victims. Thereby, the general objective of the project targets the synthesis of synthetic nanogel antibodies molecularly imprinted with Spike S1 (MIP-SNAs) for recognizing and retaining coronavirus-originated Spike S1 proteins. In this respect, the MIP-SNAs are able to recognize and bond to the Spike S1 proteins, acting as nanogel caps, and thus inhibiting the activity of SARS-CoV-2 antigen to penetrate the human cells. Hence, ANTISPIKE holds significant influence upon the scientific community by new concepts and methodologies for ligand-free delivery systems as MIP-SNAs (short-term impact: scientific ISI papers and communications, and national patent claim) and by opening new research directions associated with the side-benefits of the research (like new immuno-therapies) as long term impact. Implementation of this project will also bring specific scientific, economic and social benefits at the national and international level.

Next Generation Viral Hepatitis B and C vaccine development in plants and algae using advanced biotechnological tools Call name: EEA Grants - Proiecte Colaborative de Cercetare
EEA-RO-NO-2018-0078 2019 - 2024

Role in this project:

Coordinating institution: INSTITUTUL DE BIOCHIMIE

Project partners: INSTITUTUL DE BIOCHIMIE (RO); Norwegian Institute of Bioeconomy Research (NO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); Center for Infection & Immunity of Lille (FR)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: https://www.smartvac.ro

Abstract:

Hepatitis B (HBV) and C viruses (HCV) infect the human liver, triggering persistent inflammation and eventually cirrhosis and hepatocellular carcinoma (HCC), the second leading cause of cancer-related mortality worldwide. Currently, more than 500 million people are chronically infected with HBV or HCV and at high risk of developing end stage liver disease and HCC. Collectively, HBV and HCV infections are responsible for about 1.3 million deaths annually. HBV infection is not curable with the treatment available today due to the nuclear replication form not being eliminated from infected hepatocytes. There is no doubt that vaccination remains the most effective strategy to limit HBV spreading and control the disease. Administration of the standard recombinant vaccine containing the small (S) HBV envelope protein produced in yeast (the HBsAg) had a major impact on HBV-related liver disease and death. Unfortunately, about 10% of vaccinated people do not develop protective antibody titers and remain vulnerable to infection. Moreover, the duration of the immunity conferred by the 3-dose intramuscular administration of the HBsAg is unclear, several studies indicating that administration of booster doses might be needed at 15 years post primary vaccination. A strategy to overcome these issues has considered the development of improved adjuvants. Other approaches have investigated the possibility to incorporate the more immunogenic middle (M) and large (L) HBV envelope proteins in the standard vaccine. However, the high costs associated with expression of these proteins in mammalian cells prevented the widespread use of the novel generation of HBV vaccines.

In the case of HCV, innovative direct acting antiviral cocktails which can achieve sustained virological response in more than 90% of treated patients have considerably advanced current therapy. Despite this success, the high treatment costs, the emergence of resistant mutants and the susceptibility to reinfection, underline the urgency for the development of a protective HCV vaccine that is still missing. Early clinical trials are ongoing for prophylactic B and T-cell based vaccines. A vaccine formulation based on HCV envelope proteins E1E2 heterodimer elicited cross-neutralizing antibodies in a minority of immunized patients despite its efficacy in animals. Although there is proof of concept in humans that HCV vaccination is possible, the design of the ideal antigen able to trigger protective immune response across HCV genotypes remains a major scientific challenge in the field.

The ultimate goal of prophylactic treatment in HBV and HCV infection is virus eradication, which can be achieved by conducting universal vaccination programs. However, these programs are financially very challenging and most low-income countries, which are confronted with the highest rates of infection, cannot afford them. Production of cost-effective vaccines would alleviate the economic burden on public health systems and increase availability to vulnerable societies.

In this context, our project proposal aims to: a) build upon our experience and knowledge accumulated in our previous collaboration on plant expression of HBV/HCV proteins (GreenVac project 2014-2017 funded by the EEA Norway-Romania Program) and produce high yields of novel HBV/HCV antigens with superior immunogenic properties based on innovative molecular design; b) take this experience a step forward and establish in premiere an advanced biotechnological platform for production of HBV/HCV antigens in algae; c) take advantage of the multiple recombinant protein expression systems developed in the consortium and perform systematic, comparative characterization of the biochemical and functional properties of the new antigens in relation to their immunogenicity; d) develop institutional networking around innovative plant and microalgae biotechnologies and train human resources in protein science in applied research in Romania and Norway.

Antimicrobial Nano-Functionalization of Peptide-enriched Silk Fibroin matrices to prevent bone infections and to enhance implant osseointegration in orthopaedics and dentistry Call name: P 3 - SP 3.2 - Proiecte ERA.NET - COFUND
COFUND-ERANET EURONANOMED 3-ANNAFIB 2019 - 2023

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO”

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); IRCCS Galeazzi Orthopaedic Institute (IT); Silk Biomaterials srl (IT); National Centre for Scientific Research “Demokritos” (GR); Tel Aviv University (IL)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: https://cantacuzino.mapn.ro/webroot/fileslib/upload/files/Proiectul%20ANNAFIB%20din%20cadrul%20Programului%20European%20-%20ERA-NET%20EuroNanoMed%20III%20(2)(1)(2).pdf

Abstract:

Implant-related infections represent a big burden in orthopaedics and dental implantology.

Bacterial biofilm formation is one of the leading causes of these infections leading to severe

consequences, such as implant loosening. Current antibiotic prophylaxis/therapy is inadequate to

prevent the biofilm formation and generates antibiotic resistance. Thus, the development of novel

biomimetic antibiotic-enriched matrices has an invaluable potential to achieve both the local

delivery of antimicrobial agents and the osseointegration of implanted devices. This project aims

at inhibiting the biofilm formation and restoring the damaged bone and periodontal tissues in the

case of implant-related infections. To do this, the project will investigate in vitro and in vivo the

function and efficacy of antimicrobial nano-functionalized peptide-enriched silk fibroin matrices

(ANF-PSF) fabricated and used both as drug delivery and regenerative materials. Peptide-enriched

silk fibroin matrices will be nano-functionalized with antibiotics and assessed for drug

encapsulation efficiency and release to be tested in animal models of infected fractures,

periodontitis and implant-related infections. The local delivery of antibiotics with controlled

release profiles and the modification of implant devices with osteoinductive properties represent

an innovative and synergistic approach to simultaneously promote bone-implant integration

before bacterial adhesion, thus preventing biofilm formation and its severe complications. ANFPSF

could be employed as membranes in infected fractures or periodontitis, or loaded within

porous metal devices for joint prostheses and dental implants. At the end of the investigations,

this project will validate a novel therapeutic strategy to prevent or treat both bone and

periodontal infections. The results of this project will exploited and disseminated through targeted

activities, i.e. events for investors, scientific community and patients.

New polyoxazoline conjugates for cancer chemo-immunotherapy Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-0745 2020 - 2022

Role in this project:

Coordinating institution: INSTITUTUL DE CHIMIE ORGANICĂ ŞI SUPRAMOLECULARĂ "COSTIN D.NENIŢESCU"

Project partners: INSTITUTUL DE CHIMIE ORGANICĂ ŞI SUPRAMOLECULARĂ "COSTIN D.NENIŢESCU" (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: https://ccocdn.ro/index.php?id=82

Abstract:

The present project aims at developing an innovative platform for tumor drug delivery based on poly(2-isopropenyl-2-oxazoline) (PiPOx) and doxorubicin (DOX) as chemo-immuno therapeutic agent. PiPOx emerged as a novel and versatile platform to develop advanced functional materials, reported recently in literature by Jerca’s group, showing high potential to be used in the development of biomaterials. The versatility of PiPOx polymer consists in its hydrophilic and biocompatible character, and in the fact that it can be synthesized with well-defined characteristics via anionic polymerization, using “in house” developed protocols. In addition, PiPOx can be easily modified by ring opening addition reactions in the presence of various reactive groups, thus, enabling the possibility to be used to conjugate hydrophobic drugs, such as DOX, which is a well-known drug used in chemotherapy. Polymer conjugates have been developed to overcome the drawbacks of conventional chemotherapy, such as resistance to therapy, high therapeutic doses, and inherent major side effects. Via the herein proposed objectives and activities, the multidisciplinary team of specialists undertook the challenge to demonstrate that PiPOx-DOX conjugates may represent a versatile and superior alternative in the construction of advanced drug-delivery systems for cancer therapy. The proposed model is expected to enhance the activity and/or decrease the high systemic toxicity of free DOX, allowing for lower therapeutic doses to be used, and be applied in precision medicine. Based on the previous findings on PiPOx polymer and the expertise of our team in cancer immunology and cytotoxicity testing, the starting technology readiness level of the proposal is high, TRL 3, and the final target technology readiness level is TRL 4 (proof-of-concept).

The development in oncology of novel radiopharmaceuticals and nuclear techniques for diagnostic imaging and personalized treatment at molecular level Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0769 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH

Project partners: INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA SI INGINERIE NUCLEARA " HORIA HULUBEI " - IFIN - HH (RO); INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); UNIVERSITATEA BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO); INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU TEHNOLOGII IZOTOPICE SI MOLECULARE I N C D T I M (RO); UNIVERSITATEA DE MEDICINA SI FARMACIE "CAROL DAVILA" (RO); INSTITUTUL CLINIC FUNDENI (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: https://www.nipne.ro/proiecte/pn3/9-proiecte.html

Abstract:

The ONCORAD project and the associated technological platform in Radiobiology, is built on the concepts of translational medicine and has as main objective the development of innovative targeted radiopharmaceuticals and nuclear medicine techniques for diagnostic imaging and improved radiotherapy in cancer. ONCORAD is based on the unique expertise of the coordinator (IFIN Horia Hulubei, Magurele) ) in the field of radioisotopes and radiopharmaceuticals, complemented by the exquisite know how of partner institutions in the field of biomedical research (INCD Victor Babes, Cantacuzino National Research Institute and Biochemistry Institute, Bucharest) and clinics (Fundeni Clinical Institute and Colentina Clinical Hospital, Bucharest), along with the expertise of INCD for Isotopic and molecular Techniques, Cluj-Napoca in nanotechnologies/nanomedicine. The multidisciplinary effort is focused in 4 interconnected research projects in the field of oncology and nuclear medicine. Additionally, the ONCORAD project will sustain the development of the partner institutions by supporting new jobs for young researchers and their extensive training, infrastructure development, and transfer of knowhow, technologies and good laboratory practices among partners and towards interested third parties. ONCORAD will build an organizational structure for enhanced interdisciplinary collaboration in the field of radiobiology, in the benefit of research, patients and oncologists. The project is a premise for future participation of the consortium in large-scale projects and in European networks/platforms in the field of nuclear medicine and nanomedicine, enlarge the research services and technological transfer for clinical applications.

Genomic mapping of population from polluted area with radioactivity and heavy metals to increase national security Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0737 2018 - 2021

Role in this project:

Coordinating institution: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU"

Project partners: UNIVERSITATEA DE MEDICINA SI FARMACIE "IULIU HATIEGANU" (RO); INSTITUTUL ONCOLOGIC PROF.DR.I.CHIRICUTA CLUJ-NAPOCA (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO); INSTITUTUL DE BIOCHIMIE (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: http://www.umfcluj.ro/component/content/article/8-ro/532-genomic-mapping-of-population-from-polluted-area-with-radioactivity-and-heavy-metals-to-increase-national-security-artemis?Itemid=216

Abstract:

The ARTEMIS project represents a complex approach to major environmental issues.ARTEMIS aims to follow new ways of controlling the population exposure to polluting agents(presents in water and soil),with a major role in cancer occurrence,following the evolution of genomic alterations,in the population that inhabits the NW of ROMANIA.The proposed consortium is composed of 5 well-known members of Romania’s research community,which are planning to develop innovative technologies for the prevention of oncological pathologies,following environmental pollution.The consortium,by being balanced between National Research and Development Institutes, Research Institutes belonging to the Academy of Medical Science and Universities create collaboration at national level in the study of molecular profiles among the affected population versus the cancer incidence from areas with clean environment.The consequence of a clean environment is followed by an improved quality of life of the population from decontaminated areas and a greater national security.The disease occurrences due to the contamination of the main natural resources with I-131 and heavy metals, with direct effects on the accumulation of mutations at the genomic level,could be limited through ARTEMIS.Chernobyl or the mine exploitation are in close connection with the reported higher incidence of cancer.The main objective is the identification of genome alterations and evaluation of the cancer tendency to be more frequent in the analyzed population.The consortium proposes 5 ARTEMIS projects,which approach a new and complex perspective of environmental resources pollution,considering the development of a regional strategy for reducing pollution.The final results are:the initiation of an inter-institutional collaboration with a common agenda and research interests,creating new jobs for the young researchers at the early stage of their career,at European standards,and the creation of a population genomic map of NW Romania.

Integrated development project for advanced medical treatment technologies Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0728 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA

Project partners: INSTITUTUL NATIONAL DE CERCETARE DEZVOLTARE PENTRU FIZICA LASERILOR, PLASMEI SI RADIATIEI - INFLPR RA (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA BUCURESTI (RO); UNIVERSITATEA PITESTI (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: http://teramed.inflpr.ro/

Abstract:

In order to increase community’s quality of life, the aim of the project proposal entitled “Integrated development project for advanced medical treatment technologies” (TERAMED) is to develop novel technologies with respect to the treatment of osseous and cutaneous conditions and oncological disorders. Given our experience in healthcare research and the current requirements of multidisciplinary and interinstitutional collaboration towards the personalized treatment purpose, the TERAMED project aims genuine synthesis and processing of biomaterials, but also functional and therapeutic evaluation relevant for clinical trials. The main objectives of the “Medical devices functionalized by laser technologies and alternatives for enhanced osseous integration and regeneration” subproject are to design and produce inorganic, composite or hybrid coatings for superior osteoconductive and osteoinductive performances of titanium-based implants. Smart wound patches and polymeric gels functionalized with antimicrobial and wound healing biomolecules incorporated within micro- and nanoparticles constitute the purpose of the “Medical devices (patches and gels) based on composite biomaterials obtained by laser, plasma and radiation technologies and alternatives for enhanced healing of cutaneous injuries” subproject. The “Technologies based on magnetic triggered nanostructures for oncological therapy: early diagnosis and targeted treatment” subproject aims the development of multifunctional medical devices for specific and selective diagnosis and treatment of breast cancer and melanoma. The general impact of the TERAMED project ensues from the beneficial conjunction of the clinical potential of the proposed medical devices, the feasible technological transfer and the economic advantages of interinstitutional collaboration.

Strengthening the capacity in translational research: vaccine development from concept to preclinical evaluation Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0529 2018 - 2021

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO”

Project partners: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); INSTITUTUL DE BIOCHIMIE (RO); UNIVERSITATEA PENTRU STIINŢELE VIEŢII "ION IONESCU DE LA BRAD" DIN IAŞI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE CHIMICO - FARMACEUTICA - I.C.C.F. BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE IN DOMENIUL PATOLOGIEI SI STIINTELOR BIOMEDICALE "VICTOR BABES" (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: http://www.convac.ro

Abstract:

Benefits of vaccination are indisputable, at both individual and social levels. As a major strategic direction in public health, vaccination makes these benefits far outweighing individual protection against many infectious diseases by eliminating / eradicating / reducing morbidity and complications associated with infectious diseases.

However, even if the benefits of vaccination are evident in modern society where unfiltered information leads to lower confidence in the vaccine, scientific arguments need to be continually put forward to demonstrate the efficacy, safety of vaccines, and to improve the concepts of their use. Also, the current tendency to use a limited number of antigens in existing vaccines on the market may lead to a vaccine pressure limited to a subset of microorganisms which may generate an antigenic drift of circulating microorganisms and, consequently, reduce protection. It is therefore necessary to continuously develop new antigens and the reduced antigenicity of some microbial components requires the presence of suitable adjuvants in current formulations of vaccines available on the market.

This consortium provides the necessary framework for the development of the vaccine through studies involving better characterization of the antigen, optimization of its formulation, extension of the immunogenicity characterization modalities, evaluation of the protection and finally elaboration of non-clinical studies documentation according to pharmaceutical regulations, aiming at increasing and consolidating scientific performance in the field of vaccination.

In addition, the consortium's objectives will include the development and consolidation of laboratory animal model studies completed with an accredited research-development service and the expansion of scientific expertise in vaccine science through the training and specialization of young researchers.

Microfluidic platform for circulating tumour cells (CTCs) concentration through dielectrophoresis-magnetophoresis and analyzed via broadband dielectric spectroscopy and electrochemical impedance Call name: P 1 - SP 1.2 - Proiecte complexe realizate in consorții CDI
PN-III-P1-1.2-PCCDI-2017-0214 2018 - 2021

Role in this project:

Coordinating institution: UNIVERSITATEA TEHNICĂ "GHEORGHE ASACHI" IAŞI

Project partners: UNIVERSITATEA TEHNICĂ "GHEORGHE ASACHI" IAŞI (RO); INSTITUTUL NATIONAL DE CERCETARE- DEZVOLTARE PENTRU MICROTEHNOLOGIE - IMT BUCURESTI INCD (RO); INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO); UNIVERSITATEA TRANSILVANIA BRASOV (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE-DEZVOLTARE MEDICO-MILITARA „CANTACUZINO” (RO)

Project website: http://www.ucelldetect.ro

Abstract:

The overall objective (GO) of uCellDetect is assuming the development of a microfluidic platform which is to integrate electromanipulation (DEP dielectrophoresis) technologies combined with magnetomanipulation (MPA – magnetophoresis) allowing the improvement of sorting and trapping capacity of circulating tumour cells (CTCs) harvested and purified from surgically excised tumors. Simultaneously with the sorting and trapping, on the basis of CTCs’ specific properties (electrical magnetic, electrochemical and spin), at the level of microfluidic platform the characterization of CTCs through broadband dielectric spectroscopy, electrochemical impedance and spintronic detection will be possible, fact which will ensure the precocious diagnosis, minimally invasive, tumours stabilization, monitoring and assessment of therapeutical interventions. The innovative device which is to be developed within 24 months will represent a fast and cheap technology allowing patients to appeal to an affordable diagnosis technology in comparison with the conventional costly and laborious technologies. The Consortium is encompassing 4 partners (two universities, one nationa R&D center and a revival R&D center) which agreed to share expertise, scientific, human and material resources (R&D infrastructure) grant integral complimentary approaches within the Bionanotechnology domain with immediate application in biomedicine.

Ligand-free targeted delivery nanogels for phospholipase A2 retention Call name: P 1 - SP 1.1 - Proiecte de cercetare pentru stimularea tinerelor echipe independente
PN-III-P1-1.1-TE-2016-1876 2018 - 2020

Role in this project:

Coordinating institution: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti

Project partners: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO)

Affiliation: Institutul National de Cercetare-Dezvoltare pentru Chimie si Petrochimie - ICECHIM Bucuresti (RO)

Project website: https://icechim-rezultate.ro/proiect.php?id=32&lang=en

Abstract:

It is well known that the venom from the Hymenoptera insect class (bees, wasps, ants) are potent neurotoxic due to secreted phospholipase A2 enzyme (PLA2). For instance, bee venom PLA2 enzyme acts synergistically with the polyvalent cations (toxins) in the venom creating an increased haemolytic effect and a quick access of toxins into the blood flow, targeting important organs like the brain, kidney and liver. In spite of recent technological developments, effective and safe therapies are currently not available for treating the victims of mass insect attacks. Yet, thanks to advances in the fields of Nanotechnology, removing of PLA2 enzyme from sting zone, can be accomplished by targeted delivery systems called ligand-free nanogels. The proposed concept for preparing ligand-free nanogels is original and uses bifunctional macromonomers, small molecule cross-linkers and PLA2 template molecules to create antibody-like recognition sites for PLA2 subsequent retention. Hence, PLANano holds significant influence upon the scientific community by new concepts and methodologies for free-ligand nanogel targeted delivery systems (short-term impact: 3 ISI papers, minimum 3 communications, 1 national patent claim, web site of project) and by opening new research directions associated with the side-impacts of the research (like new imuno-therapies) as long term impact. Implementation of this project will also bring specific scientific, economic and social benefits at the national level and at the international level. The greatest impact is given by the health value, if taken in consideration the advantages of the innovative ligan-free nanogels over conventional antivenom production. Plus, the existing infrastructure of the Host Institution is appropriate to sustain the proposed tasks for PLANano successful implementation. But most importantly, the young research team composed of young specialist, post-docs and PhD fellows is highly qualified in this direction.

Improvement of biomedical implant properties by surface nano-architecturing and antibacterial protection Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-0855 2014 - 2017

Role in this project:

Coordinating institution: INSTITUTUL DE CHIMIE FIZICA - ILIE MURGULESCU

Project partners: INSTITUTUL DE CHIMIE FIZICA - ILIE MURGULESCU (RO); UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO); R&D CONSULTANTA SI SERVICII S.R.L. (RO); TEHNOMED IMPEX CO S.A. (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO)

Project website: http://www.icf.ro/pr_2014/PN-II-PT-PCCA-2013-4-0855/SursaDeFinantare.html

Abstract:

This project proposes the obtaining of a novel, advanced, biocompatible Ti-Ta-Ag bioalloy for orthopaedic and maxillofacial implants with complete innovative composition and properties. Two Research Institutes, one University and two SMEs will resolve in synergetic, multi and inter-disciplinary way the following main scientific objectives: a) elaboration of a novel, original ternary Ti-Ta-Ag bioalloy that contains only non-toxic and non-allergenic elements (Ti and Ta) and an antibacterial element (Ag), assuring increased corrosion resistance, very low ion release, high bioactivity and bacteriostatic activity to avoid adverse reactions in the human body; b) the functionalisation of the alloy surface by introduction of antibacterial nano-particles to increase the antibacterial properties; c) nano-architecturing of the alloy surface with nano /-tubes, /-channels, /-fibres which will stimulate the implant direct attachment and rapid bone healing; d) assessment of the alloy chemical composition and structural characteristics by high level techniques; e) determination of the alloy mechanical properties by static and dynamic tests; f) alloy long-term electrochemical behaviour and corrosion resistance in artificial human biofluids simulating the severe functional conditions of an implant, using modern electrochemical methods; g) monitoring of the quantity of ions (specially Ag+ ions) released into biofluids by high level techniques to know the release rate of Ag+ ions from the bulk alloy; h) establishment of the nano-architecture with the most optimal properties of the stability, roughness, porosity by world level techniques; i) determination of the bacteriostatic capacity of the new alloy before and after its surface functionalisation and nano-architecturing; j) evaluation of the alloy biocompatibility in as-cast, functionalised and nano-architectured state by in vitro and in vivo studies. The project technological objectives are: a) laboratory technology of the alloy synthesis by the modern melting method in vacuum levitation furnace with cold crucible; b) laboratory technology for the surface functionalisation with antibacterial nano-particles having suitable properties of the stability and antibacterial ability; c) laboratory technology for the surface nano-architecturing by the application of nano /-tubes, /-channels, /-fibres; e) two technologies for the orthopaedic and maxillofacial implants obtaining; d) fabrication of the orthopaedic and maxillofacial implants – demonstrator products. The original and innovative contributions of the project are: a) novel, biocompatible ternary Ti-Ta-Ag alloy; b) a new, complex functionalisation and nano-architecturing of the alloy surface; c) elaboration of the original mechanisms of electrochemical behaviour for the as-cast, functionalised and nano-architectured alloy in simulated physiological solutions; d) scientific novelties concerning the modelling of the physical processes at the interface between new bioalloy and simulated biofluids; e) monitoring of the bacteriostatic activity by the modern techniques; f) prime novelty determination of the bare and structured alloy biocompatibility by in vitro and in vivo tests; g) original data bank regarding physico-mechanical, electrochemical, anticorrosive, surface, biocompatible, antibacterial characteristics of the novel bioalloy. The obtained orthopaedic and maxillofacial implants will fulfill the multiple, complete functions and properties of a good implant, actually non-existing on market.

Differential diagnosis of meningitis by cytokine profiling using a point-of-care rapid measuring device Call name: Joint Applied Research Projects - PCCA 2013 - call
PN-II-PT-PCCA-2013-4-1836 2014 - 2017

Role in this project:

Coordinating institution: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO

Project partners: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO); C.Y.B.E.R. SRL (RO); SPITALUL DE BOLI INFECTIOASE "DR.VICTOR BABES" (RO); UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO)

Project website: http://projectmedicy.wordpress.com/

Abstract:

Objective:

The aim of this project is to develop a rapid multiparametric lab-on-a-chip antibody array platform allowing point-of-care differential diagnosis of meningitis by discrimination between bacterial and aseptic (viral) meningitis based on simultaneous detection of several cytokines and chemokines in cerebrospinal fluid (CSF) of patients in clinical condition indicative of meningitis.

Issue:

Meningitis is a life-threatening medical emergency, most often resulting from an invasive infection of the central nervous system caused by different etiologic agents, and still represents a major problem to health care systems worldwide. The high mortality rate and frequency of permanent neurological sequelae (epilepsy, paralysis, mental retardation, deafness etc.) in meningitis survivors impinge staggering costs on families, healthcare systems and society in general.

Given the rapid decline in patients status and the importance of early treatment for improving patient outcome, medication is usually started early, empirically, based on indirect evidence (CSF macroscopic appearance, cytology, Gram stain) leading to frequent cases of improper therapy with associated health and economic impact.

A rapid and reliable test able to distinguish between aseptic and bacterial meningitis could facilitate choice of treatment regimen and ultimately improve patient outcome and reduce costs associated to both primary care and subsequent lifetime medical and social support.

Short description:

Starting from our own experimental results and previous literature reports, we propose development of a low cost, portable, lab-on-a-chip array suitable for multiparametric point-of-care detection of select cytokines and chemokines. The proposed diagnosis device would comprise of disposable cassettes containing the required fluidics for sample/reagent mixing and incubation while detection would be performed on a reusable fluorescent detector with limited optical complexity. To enhance portability, on-board software for image analysis and data interpretation would allow stand-alone data acquisition, interpretation and report generation.

Assay development will depend on cooperation of several research teams from complementary domains (immunology, microbiology, molecular biology, biotechnology and engineering) in order to cover the requirements of the specific objectives:

Develop antibody array allowing multiple cytokine detection in low sample volumes, combining test sample and assay controls

Develop readout device, transfer interface and data interpretation software

Develop multiparametric statistical algorithms allowing differential diagnosis of meningitis

Initial proof-of-concept validation of differential diagnosis of meningitis on clinical samples

Prepare commercial exploitation plan combining manufacturing and marketing

The consortium is formed by the “Cantacuzino” NIRDMI, responsible for molecular biology confirmation of etiological agent, array development and cross-validation of cytokine detection in CSF by conventional protein arrays, the "Dr. Victor Babes" Hospital for Infectious and Tropical Diseases handling hundreds of meningitis cases per year that will be responsible for sample selection and management and patient monitoring, the Electronic Research Group of University Politechnica of Bucharest with experience in design of optoelectronic circuits and microfluidic sensors and C.Y.B.E.R. Srl, a subsidiary of Biomedica Medizinprodukte GmbH & Co KG Vienna, with extensive experience in development and marketing of research and in vitro diagnostic immunoassays.

Bioactive Injectable Macroporous Biomaterials for Bone Regeneration Call name: Joint Applied Research Projects - PCCA-2011 call, Type 2
PN-II-PT-PCCA-2011-3.2-0885 2012 - 2016

Role in this project:

Coordinating institution: UNIVERSITATEA POLITEHNICA DIN BUCURESTI

Project partners: UNIVERSITATEA POLITEHNICA DIN BUCURESTI (RO); INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO); METAV - CERCETARE DEZVOLTARE S.R.L. (RO); MEDICAL ORTOVIT S.R.L. (RO); SPITALUL CLINIC "COLENTINA" BUCURESTI (RO)

Affiliation: INSTITUTUL NATIONAL DE CERCETARE CANTACUZINO (RO)

Project website: http://www.tsocm.pub.ro/en/cercetare/SmartBIMBBone/index.htm

Abstract:

Osteoporosis, bone degeneration in aging population as well as a multitude of traumatic and pathological bone defects justify the request for improved orthopaedic therapeutic products. The main aim of this project is to generate a novel concept of smart biomaterials for bone regeneration. The complex biomaterials developed in this project will present porous architectures typical to trabecular bone, self-assembling properties, eventually self-setting, and built-in bioactivity to promote angio- and osteo-genesis, additionally to injectability, controlled biodegradability, and sterilizability. Because these materials will be developed as injectable formulations, their application by minimally invasive surgery represents an important advantage for the comfort of patients. The new injectable smart biomaterials will be synthesized following different stages, and characterized with respect to their chemical and phase composition, micro- and nanostructure, chemical, mechanical, rheological properties, 3D porosity post-application, biodegradability and, when needed, in vitro and in vivo behavior. Rational criteria will be used to select the best scaffolds during an iterative approach. From all points of view these biomaterials will be advantageous alternatives to autologous bone grafts mainly due to their large availability and controlled fabrication and properties. Moreover, they will represent enhanced alternatives to the existing commercially available injectable products for bone repair/filling. The consortium has all necessary complementary competences to achieve this goal: obtaining of smart injectable scaffolds providing in situ nanostructured porous constructs with enhanced bioactivity. It is expected that this project will stimulate the production of biomaterials in Romania.

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List of research grants as project coordinator or partner team leader
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