Biomaterials and Bioanalogous Polymer Systems

Research People Equipment Publications

 
 

Research

Scope

The research in the Group of Biomaterials and Bioanalogous Systems is focused on the design of polymer biomaterials and functional bio/material interfaces that can be used as supporting structures (scaffolds) for regenerative medicine and tissue engineering, biosensors or devices for the controlled delivery of bioactive compounds. The team is formed by a dynamic group of scientists with multidisciplinary backgrounds, comprising organic chemistry, physical chemistry of polymers, chemical engineering, biophysics/biochemistry and physiology. The projects of the team are based on well-balanced chemical/material and biochemical/biological approaches and understanding the mechanisms and events at biomaterial/cell interfaces.


From the materials point of view, the work focuses mainly on fully bio-degradable polymers derived either from synthetic poly(amino acid)s or aliphatic polyesters, e.g. polylactides. Both hydrophobic polyester-based materials and hydrophilic, polypeptide-based enzymatically degradable hydrogels are being developed. Methods of controlled synthesis are used for preparation of well-defined amphiphilic block copolymers composed of polyester, poly(ethylene oxide) and/or polypeptide blocks. Functional copolymers carrying bioactive structures and their self-assembled supramolecular structures are used in the modification of biomaterial surfaces to control the interaction of biomaterials with cells and tissues.

The design and characterization of interfaces between the material surface and cells/biological fluids is a common objective of several projects in the group. In addition to the deposition of functional amphiphilic copolymers, other methods of surfaces modification, using covalent grafting of polymer brushes and click-chemistry for creation of non-fouling surfaces with specific biomimetic structures, are being developed.

Functional bio/material interfaces are also prepared through controlled deposition of biologically-active macromolecules, such as proteins and carbohydrates or glycoproteins on the material surfaces. Basic factors controlling the formation and stability of biomacromolecules assemblies deposited on the surfaces, using a layer-by-layer technique, are investigated. The organized assemblies of biomacromolecules are used in (a) immuno-sensors and diagnostic nanoparticles, (b) non-fouling biomaterials in contact with blood, and (c) biomimetic modification of polymer scaffolds for tissue engineering.

Current Research Topics

Biomimetic surfaces of polymer scaffolds for tissue regeneration and engineering. Polymer biomaterials are sought as scaffolds for regenerative medicine and tissue engineering. Besides tuned mechanical properties and a suitable three-dimensional architecture, a potential of the scaffolds to elicit and control specific interactions between the biomaterial and living cells is required. Adhesion, proliferation and differentiation of cells on polymer substrates can be modified by providing solid-state signals to the cells through molecular ligands exposed on the polymer surfaces.

Engineering of biomimetic surfaces on polyester-based biomaterials. Biomimetic surfaces are prepared by deposition of amphiphilic block copolymers composed of hydrophobic polyester (e.g. polylactide) and hydrophilic end-functionalized blocks, e.g. poly(ethylene oxide), PEO, on a polyester bulk support. While the polyester blocks serve to anchor the copolymer layer to the polyester bulk, the flexible hydrophilic PEO blocks expose functional groups, which could be either non-specific or cell-specific, such as peptide motifs of extra-cellular matrix molecules. Self-association and phase-separation phenomena of amphiphilic block copolymers in selective solvents and/or at a solid/liquid interface are explored for the creation of biomimetic and patterned surfaces. The relationships between the molecular parameters of the copolymers and their adsorption to surfaces, the resulting surface properties, morphology and surface pattern of functional groups, as well as the effect of these modifications on protein adsorption are studied by physical surface-sensitive methods, such as imaging ellipsometry, FT IR spectroscopy, electron- and scanning-probe microscopy (AFM). The relationships between various surface modifications and the adhesion, growth and expression of various cell types are evaluated.

 

The concept of using functional amphiphilic block copolymers is being developed as a versatile modular system providing for different types of bioactive patterned surfaces on polymer biomaterials, exhibiting selective interactions at biomaterial-cell interfaces.

Issues currently addressed:

  • Synthesis of amphiphilic poly(ethylene oxide)/polylactide block copolymers containing various functional structures, e.g., cell-adhesive peptide sequences, at the end of the poly(ethylene oxide) block, using controlled polymerization techniques and solid-phase peptide synthesis approaches.
  • Studies on the solution behavior of amphiphilic poly(ethylene oxide)/polylactide block copolymers and their efficacy in the surface modification of polylactide-based biomaterials.
  • Surface pattern formation through deposition of self-assembled supramolecular structures of block copolymers and characterization of accessibility and distribution of biomimetic groups.
  • Development of biomimetic polymers for support of selective growth of vascular cells.
  • Development of biodegradable polymer scaffolds for engineering of autologous human cartilage and bone. 

Bioresorbable Superporous Hydrogels

 

Poly(alpha-amino acid)s, polyAA, due to their polypeptide backbone, have an inherent potential to be degraded in biological environments by enzyme-catalyzed hydrolysis. The enzyme specificity and the rate of degradation can be controlled by selecting suitable polypeptide composition. Novel approaches to polyAA synthesis, adopting controlled polymerization of amino acid N-carboxyanhydrides (NCA), offer  extended control over the polyAA composition and their molecular properties. Biodegradable hydrogels with controlled porosity, based on synthetic poly(AA)s, have been designed as scaffolds for soft tissue regeneration, e.g., spinal cord injury repair. The covalently crosslinked gels are formed by radical copolymerization of methacroylated polyAA, as multi-functional macromonomers, with a low-molecular-weight methacrylic comonomer, e.g., 2-hydroxyethyl methacrylate (HEMA). By incorporation of adhesion-peptide sequences, derived from laminin and fibronectin (RGDS, YIGSR), hydrogels with biomimetic structures were prepared.

The effects of hydrogel composition and the presence of specific adhesion-peptide groups on cell adhesion, cell spreading, and the development of adhesion pattern through focal adhesion plaques of pig mesenchymal stem cells grown on the gels are evaluated in cell cultures. The biocompatibility and cell migration into hydrogels are studied in vivo in rats and pigs.

Polymer-controlled drug release system for vascular stents
A novel method was developed for the surface coating of metallic medical implants with thin films of polyester polymer composite, and the feasibility of using the polymer coatings for the controlled release of biologically-active agents was evaluated. High adhesion and stability of the coating polymer layer were achieved by covalent grafting of an interfacial adhesion layer of polymer through grafting polymerization of lactone monomers.

Coronary vascular stents were coated by the new method and the sustained release of drugs, controlling the inflammation reaction and cell proliferation was investigated, and the relationships between the coating composition and physical properties and the drug-release profiles were described. The polymer-coated stents had very good biocompatibility with pig coronary arteries and good efficacy of the released drug in controlling the in-stent restenosis.


 

Cooperation

EXPERTISSUES- Institute of Excellence for Tissue Engineering and Regenerative Medicine EEIG (Headquarters: Caldas das Taipas, Guimaraes, Portugal)

Institute of Science & Technology in Medicine, Keele University Medical School, Stoke-on -Trent, UK (Prof. Alicia El Haj, Dr. Ying Yang)

Technion - Israel Institute of Technology, Haifa, Israel  (Prof. Noah Lotan, Prof. Michael Silverstein)

Tampere University of technology, Department of Biomedical Engineering, tampere , Finland (Prof. Minna Kellomäki)

Dept. of Growth and Differentiation of Cell Populations, Institute of Physiology ASCR, Prague  (Dr. Lucie Bacakova)

Institute of Animal Physiology and Genetics ASCR, Libechov (prof. Jan Motlik)

Institute of Haematology and Blood Transfusion, Prague (Dr. J. E. Dyr)

Institute of Experimental Medicine of the AS CR (prof. A. Hampl)

BIOpolymer POstdoctoral Laboratory and educational center - BIOPOL

Otto Wichterle Centre of Polymer Materials and Technologies - CPMTOW

Centre of Biomedicinal Polymers - CBMP

Centre of Polymer Sensors - CPS

Polymers for Power Engineering - Energolab


 

Institute of Macromolecular Chemistry AS CR, v.v.i.
Heyrovského nám. 2
CZ-162 06 Praha 6
Czech Republic
phone:+420 296 809 111
fax:+420 296 809 410

Strategie 21