Laboratory for Clinical Smart Nano-technologies

Scientific results:

The project is focused on the development of a breakthrough smart nanotechnology for the treatment of osteoarthritis, based on the application of extracellular matrix-bound nanovesicles (MBVs) that effectively regulate local inflammatory responses and stimulate regeneration, functionalized with magnetic nanoparticles. The developed nanosystem, in combination with traditionally applied magnetic physiotherapy in orthopedics, will enable targeted impact on damaged tissues and immune cells, providing effective personalized solutions in regenerative medicine and nanomedicine for osteoarthritis treatment.

The project is being implemented by a team from a new world-class laboratory - the "Laboratory of Clinical Smart Nanotechnologies" at the Institute of Regenerative Medicine, Biomedical Science and Technology Park of the Federal State Autonomous Educational Institution of Higher Education Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University). It is led by leading scientists, including Professor Xin-Jie Liang, a unique specialist in the formation of "smart" nanosystems for targeted delivery of biologically active substances and magnetic nanoparticles, and Dr. Peter Sergeevich Timashev, a unique specialist in 3D biofabrication in regenerative medicine and scientific director of the Biomedical Science and Technology Park.

The project brings together leading experts in the fields of biomedicine, nanotechnology, engineering, materials science, and orthopedics, as well as preclinical and clinical research centers, ensuring the effective integration of innovative technologies into the healthcare system. The main advantage of the development for osteoarthritis treatment is the non-invasive targeted impact on damaged joint tissues and immune cells. The innovative approach to osteoarthritis therapy will increase the speed and efficiency of rehabilitation.

Scientific developments have been carried out in the following areas:

• Obtaining, isolating, and biobanking MBVs.

• MBVs as specific mediators of inflammation regulation and regeneration stimulation.

• Modification of MBVs with magnetic nanoparticles (MNPs) and the method of controlling modified MBVs using an external magnetic field.

• Establishing the safety, tropism to the site of cartilage tissue damage, and efficacy of modified MBVs in an animal model.

• A unique expert-level computer analyzer based on artificial intelligence for the automatic detection of hip joint pathology.

Methods have been developed for isolating multipotent mesenchymal stromal cells from various sources. Methods have been developed to stimulate the synthesis and accumulation of extracellular matrix and MBVs by cells. A method for obtaining MBVs from monolayer cell cultures and cell spheroids has been developed. A comparative analysis of MBVs accumulation depending on the type of cells and their cultivation conditions has been conducted. The peak diameter of MBVs isolated from different cell types under various cultivation conditions ranges from 40-120 nm. A biobanking protocol for MBVs has been developed without destroying their structure.

Unique proteomic and transcriptomic profiles of MBVs have been studied, ensuring their functional activity in regulating intercellular communication, modulating regenerative processes, and inflammatory response.

To develop control of modified MBVs using an external magnetic field and non-invasive registration of MNPs, new ultra-sensitive thin-film nanostructured sensors of weak magnetic fields with a threshold resolution of ≤10 nT have been used. Optimal concentrations for in vivo visualization of modified MBVs by X-ray microtomography have been found.

An analysis of the safety and efficacy of modified MBVs was conducted in experimental models of cartilage tissue damage in rats and mini pigs. After therapy, there was a reduction in dystrophic changes in chondrocytes and inflammatory response. It was established that for the targeted delivery of the developed nanocomposite, the magnitude and direction of the magnetic field created by the magnetic bandage design, with a maximum scalar magnitude of the external magnetic field around 3000 Gs, ensured a field of at least 1000 Gs in the synovial fluid environment. The minimum magnetic field magnitude during exposure did not drop below 100 Gs, which is sufficient to retain the necessary amount of modified MBVs in the affected joint area and significantly improve therapy efficacy. The application of modified MBVs in the experimental osteoarthritis model contributed to the normalization of the morphological structure and functional state of the cartilage tissue in the affected joint.

For early diagnosis, prediction of osteoarthritis progression, and assessment of therapy efficacy, a unique expert-level computer analyzer based on artificial intelligence was created. An extensive image database, already comprising more than 5,000 MRI studies, was developed and validated with methods for automatic image segmentation. The computer model for automatic hip joint pathology detection has already allowed the analysis of more than 200 real clinical cases.

Implementation of research results:

Personalized technology for the treatment of osteoarthritis based on the use of a new type of biologically active regulators of inflammation and regeneration—secreted by matrix-bound nanovesicles (MBV) cells, and their functionalization with magnetic nanoparticles has been developed. A new method has been developed and patented for the production of specific mediators for inflammation regulation and regeneration stimulation—MBV from monolayer cell cultures and cellular spheroids.

A method for controlling modified MBV with an external magnetic field has been developed. 

Biosensors for visualization of nanovesicles have been developed, and approaches to the visualization of biological tissues with high spatial resolution have been improved. 

For early diagnosis, prediction of osteoarthritis development, and evaluation of therapy effectiveness, a unique expert-level computer analyzer based on artificial intelligence has been created in cooperation with PJSC "Vympel-Communications." An extensive image database has been created, already including more than 5,000 MRI studies, and methods for automatic image segmentation have been developed and validated. A computer model for the automatic detection of hip joint pathology with an accuracy of more than 80% has made it possible to analyze more than 200 real clinical cases.

Education and personnel occupational retraining:

• We have compiled and published the first handbook on regenerative medicine in Russia. Regenerative medicine: a handbook / Pyotr. V. Glybchenko, Yelena V. Zagaynova. – Moscow: GEOTAR-Media, 2023. – 456 p. - DOI:10/33029/9704-7535-5-REG-2023-1-456. ISBN 978-5-9704-7535-5.
• We have compiled and published Educational and methodological manuals “Fundamentals of biomedical statistics: educational and methodological manual”, “Histological and immunohistochemical staining of tissues: educational and methodological manual”.
• Four education programs have been developed and implemented into the education process for First Moscow State Medical University (Sechenov University) students majoring in Pediatrics: 1) «Biodesign and personalized medicine. Module 1. Mammalian embryology»; 2) «Biodesign and personalized medicine. Module 3. General tissue engineering»; 3) «Biodesign and personalized medicine. Module 5. Foundations of assisted reproductive technologies». 4. «Biodesign and personalized medicine. Module. “Tissue engineering”.
• We have developed and implemented into the education process the program «Synthetic biology and foundations of embryology» for First Moscow State Medical University (Sechenov University) master“s degree students majoring in Biology in the training direction «Synthetic biology and biodesign».
• We have developed and implemented into the education process 2 programs of additional professional education “Introduction to 3D bioprinting” were developed and introduced into the educational process; “Working with laboratory animals: general principles and capabilities of modern technologies.”
• Using the Zoom online platform, two times a month we conduct seminars «Modern Advances in Biomedicine and Biophotonics».
• Using the Zoom online platform, we organized and staged three annual international Russian-Chinese Symposium «Future Orthopedics: Nanotechnology and AI»).
• In 2021, four members of the academic team completed additional training at the Russian Medical Academy for Continuing Professional Training of the Ministry of Health of Russia in the additional training program «Fundamental directions of general pathology and pathophysiology».
• In 2022 five members of the academic team completed additional training: at Immanuel Kant Baltic Federal University in the additional training programs «Time management», «Adobe Illustrator. Part 2», «Adobe Illustrator. Part 1», «Adobe Photoshop. Part 1», «Adobe Photoshop. Part 2», «Autodesk 3ds Max», at the «Russian Medical Academy for Continuing Professional Training of the Ministry of Health of Russia» in the additional training programs «Current problems of modern biomedicine», at the Moscow School of Management «SKOLKOVO» in the additional training program «Basics of education ecosystem management».
• In 2023 eighteen members of the academic team completed additional training in the additional training programs “Psychological and pedagogical foundations of higher medical and pharmaceutical education”, “Advanced regenerative medicine”, “Implementation of projects on time and on budget”, “Setting up a system for implementing projects at the university”, “Advanced technologies of nuclear medicine for implementation in practice of high-tech centers of the Russian Federation”, “Digital signal processing in biomedical sensor networks”, “My first grant: how to get funding and successfully implement a project”, Self-development in conditions of uncertainty”, “Digital literacy”, “ Genetic technologies in modern research”, “Analysis of the properties of new genome editors”, “Analysis of genomic variants in bacteria”. “Management of human capital and organizational behavior in science and higher education”, “Development of personalized mathematical models of the cardiovascular system”, “Systems thinking”, “Training in the use of personal protective equipment”, “Providing first aid to victims at work”, “Training on general issues of labor protection and the functioning of the labor protection management system”, “Training in safe methods and techniques for performing work under the influence of harmful and dangerous production factors, hazard sources identified within the framework of the special labor safety standards and occupational risk assessment”.
• In 2023 internships for young members of the research team were successfully implemented at leading scientific or educational institutions in the laboratory of biological effects of nanomaterials and nanosafety under the guidance of Professor Xing-Jie Liang at the National Center for Nanoscience and Technology (Beijing, China) and at the Research Institute of Experimental Oncology and Biomedical Technologies of the Federal State Budgetary Educational Institution of Higher Education " Privolzhsky Research Medical University" of the Ministry of Health of Russia (Nizhny Novgorod, Russia).

Cooperation:

National Center for Nanoscience and Technology (Beijing, China), Royan Institute (Tehran, Iran), Sharif University of Technology (Tehran, Iran), Erciyes University (Kayseri, Turkey), Nicolae Testemitanu State University of Medicine and Pharmacy (Chisinau, Moldova), Center for Genetic Engineering and Biotechnology (Havana, Cuba), Lomonosov Moscow State University, Privolzhsky Research Medical University of the Ministry of Health of Russia, Nizhniy Novgorod State University, N.N. Semenov Federal Research Center for Chemical Physics of the Russian Academy of Sciences, «Vympel-Communications» PJSC (Russia): joint research and publications.