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Contract number
14.W03.31.0014
Time span of the project
2017-2021

As of 01.11.2022

8
Number of staff members
41
scientific publications
2
Objects of intellectual property
General information

Name of the project: Developing biocompatible materials based on chemically modified cellulose



Goals and objectives

Research directions: Chemical technologies

Project objective: Developing and optimization of methodological approach to synthesis of biocompatible materials based on chemically modified cellulose

The practical value of the study

Scientific results:

  1. The main scientific result of the conducted research is the development of a method of 3D printing of acrylic hydrogels reinforced with bacterial cellulose, whose laboratory production has been launched in the Institute of Macromolecular Compounds of the Russian Academy of Sciences as part of the implementation of the project. The basis of the developed method is disintegrating bacterial cellulose mass with the use of UV-hardened ionic liquid. The produced materials are potentially of interest as an artificial replacement of cartilage tissue. At the same time, a distinctive feature of the technology is its orientation towards personalized medicine by forming products of specified shape and additive manufacturing.
  2. The research conducted by the Laboratory allows to determine the parameters that define the mechanical characteristics of products manufactured by 3D printing, which allows  for targeted modification of their rigidity and strength. The work performed by the Laboratory are currently related to increasing the precision of the process of printing, namely the correspondence between the geometrical parameters of the model and the final product. The problem thus solved is that ionic liquids which are able to disintegrate bacterial cellulose in the most efficient way lead to the degradation of its crystalline structure and a decrease in the degree of polymerization. This negatively affects the mechanical properties of the system. The use of less active ionic liquid, even though it allows to perform 3D printing, leads to the surface of the products being abrasive and to inhomogeneities in the volume, which is related to the periodical clogging of the nozzle of the printer with agglomerates of nanofibers of bacterial cellulose. To solve this problem, the Laboratory has developed a method for modifying the surface of nanofibers of bacterial cellulose with (trimethoxysilyl)propyl methacrylate. This modifier forms a layer on the surface that stabilizes them in dispersion and, additionally, due to the presence of methacrylate groups, is able to covalently integrate into a polycrylic material that is formed during the UV hardening of the product after the process of printing. The latter factor positively affects the mechanical characteristics of produced items.
  3. Our researchers have developed polymer biocompatible and biodegradable composite materials based on complex polyesters of aliphatic hydroxy acids that are characterized by osteoconductive properties and characteristics similar to those of a number of bone tissues, which allows to use them to replenish differing sizes and a wide range of  tissue defects and to accelerate bone tissue regeneration. The achievement of this result is caused by the use of the produced particles of modified amphiphilic anionic poly(amino acid) nanocrystalline cellulose as the filler for the polymer basis. These particles provide an improved distribution of the filler in a hydrophobic polymer matrix and the binding of calcium ions, moreover, regulating the content of nanoparticles of the filler and the type of the used polymer basis allows to control the final properties of the material (mechanical properties, rate of biodegradation, osteoconductivity). The conducted studies with the use of model systems, as well as in vitro and in vivo experiments, have demonstrated a significant improvement of biomineralization, an absence of acute inflammation and an acceleration of the formation of proper bone tissue when these composites are used.
  4. We have developed a number of composite materials for scaffolds of cartilage and bone tissue. The joint use of theoretical research, multi-scale modeling and experimental research allowed to develop a methodological approach to the comprehensive study of nanocomposite materials based on bacterial cellulose, to determine the molecular mechanisms that define the properties of the developed products and to synthesize materials with enhanced properties. 

Implemented results of research: 

The developed materials based on complex polyesters and cellulose nanocrystals are currently tested for toxicity and biocompatibility using model animals at Saint Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of Russia to prepare these materials for clinical testing. 

Education and career development:

  • 10 bachelor’s and master’s degree theses have been prepared and defended.
  • A lecture course and practical classes have been developed on the use of the Python programming language in academic work. It is taught at the Institute of Chemistry of Saint Petersburg State University.

  • Foreign master’s degree students are completing internships at the laboratory.

Organizational and structural changes:

  • Technological base has been created to synthesize and study biocompatible polymer nanomaterials
  • We have purchased equipment to conduct microbiological synthesis of biopolymets at the Institute of Macromolecular Compounds of the Russian Academy of Sciences. This equipment allowed to launch production of new biomaterials for study at the Laboratory including biosynthesis of polymers, their further chemical modifications and creating composite materials from synthesized polymers. For instance, production of bacterial cellulose has been launched in volumes to complete the whole project
  • We have purchased a GeSiM BioScaffolder 3.2 3D printer to create 3D scaffolds. The printer is a system with open architecture. It allows for usage of various 3D printing technologies when creating new materials with unique characteristics. Various accessories for mixing composites allowed to synthesize composite materials directly in the process of printing. Technologies of the BioScaffolder 3.2 printer can allow to print live tissues and organs using encapsulated cells.

Other results: Employees of the Laboratory took part in organizing and running the Open competition of high school students of Saint Petersburg named after M.V. Wolkenstein, as well as in the all-Russian «Museums Night 2018» presenting the «Metamorphoses of Sciences» exhibition.

Collaborations:

Lappeenranta–Lahti University of Technology LUT, University of Helsinki (Finland), University of São Paulo (Brazil), TU Eindhoven (the Netherlands), University of Western Ontario (Canada): joint research.

We are also actively working with other laboratories of the Institute of Macromolecular Compounds of the Russian Academy of Sciences, the Institute of Chemistry and the Institute of Physics of Saint Petersburg State University,the Institute of Organic Chemistry and and Biochemistry (Russia).

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n. lukasheva, d. tolmachev, m. karttunen
Cellulose nanofibril phosphorylation: Surface structure and monovalent ions are crucial for optimizing calcium content, PCCP, 2019, 21, 1067-1077. Editors’ choice 2018 PCCP HOT Article
a.a. gurtovenko, m. karttunen,
Controlled on-off switching of tight binding hydrogen bonds between model cell membranes and acetylated cellulose surfaces, Langmuir, 2019, 35, 13753.
d.a. tolmachev, n.v. lukasheva, g.z. mamistvalov and m. karttunen
Influence of calcium binding on conformations and motions of anionic polyamino acids. length, Polymers, 2020, 12, 1279.
d.a. tolmachev, o.s. boyko, n.v. lukasheva, h. martinez-seara, and m. karttunen,
Overbinding, qualitative and quantitative changes caused by simple Na+ and K+ ions in polyelectrolyte simulations: comparison of force fields with and without NBFIX and ECC corrections, J. Chem. Theory Comput., 2020, 16, 677.
a.d. glova, s.g. falkovich, d.i. dmitrienko, a.v. lyulin, s.v. larin, v.m. nazarychev, m. karttunen, s.v. lyulin
Scale-Dependent Miscibility of Polylactide and Polyhydroxybutyrate: Molecular Dynamics Simulations. Macromolecules. 2018, 51, 2, 552.
m.a. smirnov, v.s. fedotova, m.p. sokolova, a.l. nikolaeva, v.y. elokhovsky, m. karttunen,
Polymerizable Choline- and Imidazolium-Based Ionic Liquids Reinforced with Bacterial Cellulose for 3D-Printing. Polymers, 2021, 13, 3044.
e.v. batishcheva, d.n. sokolova, v.s. fedotova, m.p. sokolova, a.l. nikolaeva, a.y. vakulyuk, c.y. shakhbazova, m.c.c. ribeiro, m. karttunen, m.a. smirnov
Strengthening Cellulose Nanopaper via Deep Eutectic Solvent and Ultrasound-Induced Surface Disordering of Nanofibers. Polymers, 2022, 14, 78.
i.v. averianov, m.a. stepanova, i.v. gofman, a.l. nikolaeva, v.a. korzhikov-vlakh, m. karttunen, e.g. korzhikova-vlakh
Chemical modification of nanocrystalline cellulose for enhanced interfacial compatibility with poly(lactic acid). Mendeleev Communications, 2019, 29, 220.
m. stepanova, i. averianov, m. serdobintsev, i. gofman, n. blum, n. semenova, y. nashchekina, t. vinogradova, v. korzhikov-vlakh, m. karttunen, e. korzhikova-vlakh
PGlu-Modified Nanocrystalline Cellulose Improves Mechanical Properties, Biocompatibility, and Mineralization of Polyester-Based Composites. Materials, 2019, 12, 3435.
a.a. gurtovenko, e.i. mukhamadiarov, a.yu. kostritskii, m. karttunen
Phospholipid-Cellulose Interactions: Insight from Atomistic Computer Simulations for Understanding the Impact of Cellulose-Based Materials on Plasma Membranes, J. Phys. Chem. B, 2018, 122, 9973-9981.
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