POLISH NATIONAL PROJECT

NEW MATERIALS AND TECHNOLOGIES FOR BIOMEDICAL ENGINEERING
co-ordinator: Professor Jan Chłopek

The aim of the project is elaboration and manufacture of new biomaterials designed for the treatment of human tissues and organs. The project tasks will be realized according to the newest research trends, in three thematic groups, within which the following problems are specified:

I. Metallic biomaterials with surface layers
1. Improvement of biological and tribological properties of metallic implants by modification their microstructure and the surface.
2. Shaping a structure of the shape memory alloys and the hyperelastic alloys intended for medical applications.
3. Preparation of Ti – based new metallic biomaterials with the appropriated modulus of elasticity covered with ceramic, ceramic-polymer, passive-carbon, oxides and nitrides layers, having improved corrosion resistance and biological activity.

II. Resorbable polymers and composites.
1. Elaboration of new methods of biodegradable polymers’ synthesis using non-toxic initiators.
2. Modeling of carbon and resorbable polymers scaffolds’ microstructure for tissue regeneration.
3. Shaping a structure and useful properties of constructional implants made of resorbable polymers modified with the fibres and particles as biomaterials for the controlled osseointegration

III. Bioactive phosphate-siliceous materials
1. Calcium phosphates – based multifunctional ceramics
2. Manufacture and shaping of the properties of new bioglass and glass-ceramics as highly – bioactive materials.
3. Bioactive ceramic layers.
4. Ceramic bone cements.

Specified materials can be used for: hip endoprothesis, implants to osseointegration, corrective medical devices, bone stabilizers, stents for blood vessels - artery and aorta, oesophagus, bronchi, trachea and urinary system, bone and tissue substitutes, scaffolds for tissue regeneration.

Main tasks of the project
1. Elaboration of the medical technology for the production of new biomaterials
2. Determination of biomedical requirements and physico-chemical characteristics of biomaterials.
3. Elaboration of the test methods and standards for biomaterials that are compatible with European medical regulations.
4. Determination of material and constructional requirements for the implants.
5. Publication of the obtained results of the project in international magazines.
6. Presentation of the obtained results at foreign and domestic conferences

Determination of tribological characteristics of materials for hip endoprothesis

prof. J. R. Dąbrowski, Białystok Technical University,
lena@pb.bialystok.pl

Capabilities of powder metallurgy methods will be employed in this project, in order to design and produce materials of planned applied characteristics. The main scientific goals are:
- to develop a composite material based on the implant alloys (cobalt or titanium) with solid lubricant additions; the material should have good tribological properties – minimal frictional resistance and tribological wear;
- to develop modifications of tribological properties of friction faces by the method of surface engineering (e.g. ion implantation, thin wear-resistant coatings);
- to develop a conception, mathematical model as well as experimental verification of self-lubricating friction pair of hip joint endoprosthesis; the usage of natural and artificial synovial liquid as a lubricant will be provided; artificial synovial liquids will be prepared on a base of chosen cholesterol esters.
The strength of the project is the fact, that technology of produce sintered materials, among them – composites based of Co-Cr-Mo alloy, were worked out in advance. The main functional aspect of the project will be the development of a new generation of biomaterials and constructional-technological solution of joint endoprosthesis friction pair. The realization of and a preliminary biological evaluation of hip joint endoprosthesis prototype is anticipated, using achieved materials and technologies.

Plasma modification of surface layers biocompatibility of implants based on Ti-alloys, intended for heart-vascular system

Prof. A. Sysa, Polish Mother’s Memorial Hospital, Research Institute
sysakard@mail.p.lodz.pl

The beginning of therapy of blood circulation system using implants (artificial heart valves, vessel stents) mainly made of titanium alloys created many problems because of their unbiological character. They concern among others surface which has direct contact with tissue. One of the them is the problem with upkeep of mechanical properties on elements which have very complicated shapes. Another very important task is biocompatibility of implant surface with blood and surrounding tissues.
The aim of the investigation task is assessment of modified by nanocrystalline diamond layer (NCD) implant surfaces including analysis of physical properties and determination of bioactivity on surface of these implants (mechanical valve, vessel stents).
In the project the elaboration of technology of deposition of nanocrystalline diamond on implants with complex geometry and undergoing a deformation after deposition of NCD layer will be investigated.For deposition the RF PCVD and MW-RF PCVD method will be used.
Later the analysis of physicochemical properties including microcorrosion phenomenon and analysis of surface using scanning microscope, atom force microscope and analysis of adhesion of NCD layer under straining using scratch tests will be done. The heart valves will be put under simulate work and then the assessment of their surfaces will be done. In the investigations of bioactivity the elements of implants with NCD layer will be assessed by the allergy tests and adhesion of blood platelets.
It is assumed that as the result of investigations carried out the advantageous mechanical and biocompatibility features of NCD layers deposited on heart-vessel will be established
Cooperated units::
• Technical University of Łódź
• Warsaw University of Technology

Metallic biomaterials with modified structure and specific mechanical features (modulus of elasticity, shape-memory and hyperplasticity) with surface layers of good mechanical and corrosion properties and biotolerance intended for making new generation implants for reconstruction and elastic osteosynthesis.

prof. J. Marciniak, Silesian University of Technology in Gliwice, Center of Biomedical Engineering
janmar@zeus.polsl.gliwice.pl

The aim of the task is to work out the technology of making new generation metallic biomaterials with surface layers intended for surgical implants for reconstruction and elastic osteosynthesis. Implants of perspective importance were selected for endoscopic operations (stents for treatment of narrowing of blood vessels - artery and aorta, oesophagus, bronchi, trachea and urinary system made of FeCrNiMo alloys nad NiTi shape memory and hyperelastic alloys with passive - carbon layers) and nails for intramedullar osteosynthesis made of FeCrNiMo and TiAlNb alloys with passive - carbon layers as well as fixators used for spine illness and injury made of TiAlNb or TiNbTaZr alloys of specific modulus of elasticity, with surface layers modified with elements such as O, C and N.
The project assumes stress and strain analyses for selected forms and geomeric features of implants realized with the use of computational mechanics methods (due) to describe optimal mechanical properties of a metallic biomaterial and surface layers. The selection of optimal structures and mechanical properties of the metallic biomaterial as well as physical and chemical properties of surface layers for specified functional forms of implants, their conditions of use and applied operation technique is a key problem (both scientific and application) in the suggested task.
Tests of biomaterials with surface layers as well as finished products (which will be made by selected manufacturers) will be carried out in "in vitro" conditions adequate to clinical ones. Furthermore, sterilization techniques of implants and criteria of quality assessment of applied biomaterials, surface layers and finished products taking UE directives into consideration will be worked out. Additionally, recommendations for the operation technique for these products will be also carried out.

New titanium-based biomaterials produced by surface engineering methods with the possibility of controlling their biocompatibility

prof. T. Wierzchoń, Warsaw University of Technology
twierz@inmat.pw.edu.pl

Titanium and its alloys belong to the most prospective metallic biomaterials. Their distinguishing features are:
- the highest resistance to biological corrosion,
- relatively good mechanical properties accompanied by a low density - twice as low as that of austenitic steel and that of Co-Cr-Mo alloys.
- the smallest Young modulus, which is particularly important in the fabrication of human bone implants.
Just as is the case with the metallic biomaterials mentioned above, the use of titanium and its alloys is however limited by their low frictional wear resistance and by the possibility of the release of their constituents into the surrounding biological environment. The investigations performed thus far indicate that the possibility of improving the biotolerance of and mechanical properties of biomaterials by modifying their chemical and phase composition has been exhausted. The other difficulties reported in the literature lie in achieving a good bond between the bone implant and the tissues that surround it, and, when moving artificial body parts and medical instruments are in question, in ensuring a low cell adhesion. Now, the only way in which these problems can be solved is to develop new methods of materials engineering such that permit producing surface layers with a precisely specified microstructure, chemical and phase composition, surface topography, hardness and residual stress state, prevent the release of the material constituents into the surrounding tissues, and in addition are characterized by a good resistance to frictional wear and corrosion and, in consequence, by a good biocompatibility tailored according to a given destination of the biomaterial.
The basic goal of the project is to develop technologies that permit optimizing the properties of titanium alloys, both used at the present and those being in the stage of development, that are intended to be used for the fabrication of orthopedic implants, heart valves, backbone stabilizers, bone screws and plates and medical instruments, by employing new, even in the world-wide scale, methods of surface engineering, such as glow discharge assisted carbonitriding and nitriding combined with Pulsed Laser Deposition (PLD), or with autocatalytic deposition of nickel-phosphorus coatings. The project has an innovative character because of the novel surface engineering techniques employed, the new types of the surface layer produced, such as composite layers of the Ti(C,N) + Ti2N + ΑTi(N)+hydroxyapatite, TiN + (Ti,Ni)3P + Ti3P + (Ti,Ni) or (Ti,Ni)3P + Ti3P + (Ti,Ni) types formed on the Ti6Al4V titanium alloy, the innovative methods used for examining the layer structures, the improved properties of the layers, and the possibility of controlling their morphology. Another important advantage is that the layers can be produced on parts of sophisticated shapes. The research goals of the project will thus be concentrated on the fabrication of a new generation of titanium-based biomaterials that combine the good physical and mechanical properties of titanium and its alloys with the properties, advantageous for the biochemical behavior of the implant, of the surface layers with controlled biocompatibility and biofunctionality. The project comprises a wide spectrum of research tasks, beginning from the development of the technology of the surface layers, through the examinations necessary to verify their biocompatibility, and ending with the preparation of the fundamental recommendations concerning the application of the layers.
The technologies developed during the realization of the project can be applied for the fabrication of bone implants designed to operate in contact with blood or with soft tissues, and for the production of medical instruments.

Controlled modification of metallic surface layers with carbon ions.

prof. S. Mitura, Technical University of Łódź
mitura@p.lodz.pl

The aim of the project was to develop the technology of deposition of thin carbon films which would fulfill special requirements as the layers on medical implants made of Ti6A14V alloy.
Diamond is the most biocompatible material and because of this reason it was used in the project as the basic material, which properties investigated in earlier researches had shown its biocompatibility.
In this project the RF PCVD method will be improved, the resources of control of biocompatibility of diamond will be extended and the protective interlayer against metalosis in case of incidental damages of diamond layer will be produced.
The improvement of RF PCVD method consist in application of complex process of deposition: RF PCVD and MW PCVD which should enable better rate of ionization of plasma without damage of control of autopotential and temperature of surface and increase of the area of uniform plasma composition which is important for phenomenon stability.
The second alternative of the improvement of RF PCVD method consist in utilization of ceramic film for controlled profiling of surface morphology from nano scale to micro scale.

Microstructure and texture optimum parameters in respect to the biocompatibility and mechanical properties of titanium –based semi-roducts produced by deep-drawing with the final surface treatment

Prof. B. Major, Aleksander Krupkowski Institute of Metallurgy and Materials Science
nmmajor@imim-pan.krakow.pl

Interest in titanium and its alloys is connected with their good mechanical properties joined with the corrosion resistance and bio-compatibility which is the best among metallic materials. The further increase of the bio-compatibility as well as mechanical properties could be obtained by application of the suitable final surface treatment. Good ductility of titanium and its alloys, despite the hexagonal structure, makes possible fabrication of semi-products with complicated shapes by application of chosen technologies of plastic deformation.
The goal of the project is to elaborate a method of fabrication of titanium-based semi-products with complicated shapes by application of mechanical and hydro-mechanical deep-drawing with subsequent surface treatment using glow discharge methods and laser technologies.
Beside the conventional method of deep-drawing, the hydro-mechanical process will be applied, too. This last method is recently used in the world to produce parts with complicated shapes. In this technological process, the material is being formed into hollow bodies with the aid of an additional fluid. The tension-pressure combination increases the plastifying properties of the material to be deep-drawn and allows the manufacture of complicated work-pieces from the metallic materials. Further increase of physical and chemical parameters of titanium and its alloys could be obtained by application of the respectively chosen modern technology of surface engineering. It is planned to applied the following technologies:
- glow discharge nitriding; fabrication of titanium nitride surface layer
- pulsed laser deposition; producing coatings on the basis of nitrides, oxides and hydroxyapatite (HA) and diamont like carbon (DLC).
The research activity will be realised in the integrated net-work with co-operation of:
- Institute of Metallurgy and Materials Science, Polish Academy of Science in Cracow; complex structural and properties diagnostic
- Faculty of Non-Ferrous Metals, University of Mining and Metallurgy in Cracow; mechanical and hydro-mechanical deep drawing
- Institute of Optoelectronic MUT in Warsaw; pulsed laser deposition
- Faculty of Materials Science Warsaw University of Technology in Warsaw; glow discharge technologies.
Semi-products for application as element of hip-joint and dental implants are planned to be fabricated.

Study on interaction of body fluids with artificial surfaces predicted for use in medical implant

prof. B. Walkowiak, Medical Academy in Łódź
bogdan01@csk.am.lodz.pl

The use of medical implants allows for improvement of health condition of people suffering from different diseases. One of the most difficult problem to solve is a proper selection of structural materials and/or materials coating an implant. It is important to reduce unfavourable reactions resulting from contact of body fluids with the surfaces. It is generally accepted, that titanium and its alloys are the best tolerated materials which introduce the lowest amount of unfavourable changes in the body. But currently the most promising coating layer, in respect to the biocompatibility, seems to be carbon formed in very thin layers of diamond-like carbon (DLC). The newest technologies in material engineering allow for production of coatings in the form of nanocrystalline diamond (NCD), which posses much better mechanical, chemical and tribological properties. The technology for coating metal substrates with NCD layers was developed in the Institute of Materials Sciences and Engineering of Technical University of Lodz. This technology was already successfully used in the bone surgery (screws and nails). At present this technology is transferred into implants predicted for permanent contact with blood (stents, heart valves).
The aim of the proposed project is estimation of phenomena taking place at the surface of NCD layer coating medical steel, titanium alloys, and other metallic materials, during contact with flowing blood. We will estimate a susceptibility of the selected surfaces (layer of NCD coating medical steel and for comparison surface modified by nitriding titanium alloy) for deposition of plasma proteins, mainly fibrinogen, and platelet adhesion. The separate aim is estimation of reactivity of blood platelets after contact with the studied surfaces, and all the above will allow us for estimation of thrombogenity of NCD layers. The next aim of the project is estimation of electro-physical phenomena occurring at the NCD surface during contact with body fluids. Especially interesting is possibility to apply an electron processes, occurring in the contact zone, for specific detection of polar chemical compounds, what should bring a new biosensor with a high chemiselectivity.
Interaction of components of blood with the selected surfaces will be studied with two techniques. The first one uses the SPR biosensors working in BiaCore X system, and it allows for real time observation of protein deposition and platelet adhesion onto the studied surface and their identification and also quantitative analysis. The second one, allowing for long time contact of blood with the studied surfaces, leans on fluorescence or enzymatic immunostaining. Moreover, the studied surfaces will be subjected to scanning electron microscope (SEM) inspection. Platelet reactivity after contact with the studied surfaces will be tested with routine aggregation and adhesion tests and also by estimation of P-selectin at the platelet membrane. The scheduled study will be carried out in research laboratories of the Department of Molecular and Medical Biophysics (Medical University of Lodz) and the Department of Biophysics Institute of Materials Science and Engineering (Technical University of Lodz). Studies on electron structure and properties of the surfaces are planed to be done in laboratories of Institute of Microelectronics and Optoelectronics of Warsaw Technical University.
The research task of the project has a multidisciplinary nature and is an unique in the world scale. The importance of the project can be underlined by establishment of the Excellence Centre „New technologies for medical applications: studying and production of carbon surfaces allowing for controllable bioactivity” where our team is an important part of the Centre. Our team consists of biophysicists, physicists, biologists and engineers specialised in materials sciences and electronics.

Tribological researches of the new titanium biomaterials with superficial layers

prof. M.Gierzyńska Dolna, Technical University of Częstochowa
sekret@iop.pcz.czest.pl

Owing to an insufficient state of tribological researches, within the confines of the Project, the following aims are expected to be executed:
1. Determination of tribological characteristics of titanium alloys exposed to the different kinds of surface treatment.
2. Testing of the amount and form of wear products occurring in the frictional pairs: “head – acetabular cup”.
3. Identification and description of the wear mechanisms in the different tribological systems.
4. Working out the recommendation for the expected application of titanium alloys, exposed to the surface treatment, in implantation.
Ti6Al4V dual-phase titanium alloy exposed to the following surface treatments:
- diffusion ion nitriding,
- coating with composite materials of different phases,
- coating with nanocrystalline layers of carbon on different sublayers
The surface treatment will be carried out in the Faculty of Materials Science and Engineering at the Warsaw University of Technology, according to the production technology by prof. T.Wierzchoń. Tribological tests will be carried out on the simulators of hip and knee joints which are at the Technical University of Częstochowa. Determination of the tribological characteristics of titanium alloys exposed to the different kinds of the surface treatment will contribute to increase in using the alloys in implantation. It results from the fact that the tribological processes play a dominant role in a loss of the endoprostheses stability. A limiting of wear of the frictional elements by surface treatment allow to increase in the implant durability.

Metallic materials with modified surface layers

prof. H. Morawiec, Silesian University of Technology
morawiec@us.edu.pl

The scientific aim of this project is to create a basis for clinical applications in this country implants with shape memory effect and superelasticity of NiTi alloys.
The fundamental range of research to be carried out in the frame of this project is focused on the tailoring the structure of alloys to achieve the needed properties to made clamps for bone fracture healing and distractors for bone elongation using the shape recovery and superelastic properties of the NiTi alloys.
In order to obtain the proper microstructure and parameters of the implants it is necessary to choose the proper chemical compositions, the appropriate thermo-mechanical treatment or ageing. This will serve to work out models of clamps and springs for distractors designed for surgical healing facial and cranial bones and clamps for spine surgery. To ensure the best biocompatibility of these implants it is essential to work out the optimal method of passivation and alternatively covering the surfaces of these implants with diamond like carbon or proper polymer (PTFE) layers. The evaluation of passivation quality would based on the results of the potentiodynamic polarization testing. The corrosion behavior of the implants would be tested in vitro in a biological environmental solutions and the reaction on the implants surface will be studied by SEM and Auger electron spectroscopy.
The results of this studies would be transferred to surgical clinics which are include for cooperation as well as to some specialized in implants production companies in order to undertake the production of implants to make use of the shape memory and superelastic effects.

Developing of the stabilization system of bone graft in reconstructive and revised alloplasty of the hip joint

PhD Bogdan Stodolnik, Technical University of Częstochowa
itm@itm.pcz.czest.pl

The aim of the research task named: “Developing of the stabilization system of bone graft in reconstructive and revised alloplasty of the hip joint” is to develop effective method of stabilization and implantation of human frozen bone graft with metal implants. Implants in the form of rings, meshes and clamping rings made of titanium sheet covered with bioceramics enable load transfer and fast healing of the grafts in the event of secondary alloplasty of a hip. Scope of the research covers:
- Developing of the construction and technological documentation of implants for osteosynthesis,
- Manufacture the instrumentation, tools and the pre-production batch of the implants,
- Developing and performing heat and surface treatment of the implants batch with bioceramic coatings (ceramic hydroxy apatite, titania),
- Determining the biomechanical characteristic of the stabilizing implant-bone tissue system in laboratory conditions,
- Developing the surgical procedure technique of the bone grafts with use of stabilizing implants.
Developed method of stabilization with use of implants for bone grafts is expected to be much cheaper and better then the methods used presently abroad. It will allow creating domestic back-up in the form of coherent osteosynthesis system in the reconstructive surgical procedures of the hip joint for domestic orthopedic departments of clinical hospitals purposes.

New ecological method of synthesis of poly (aspartic acid)

prof. J. Pielichowski, Cracow University of Technology
pielich@usk.pk.edu.pl

The aim of the project is to develop a new, environmentally-safe method of synthesis of poly(aspartic acid) (PAA) and its derivatives by thermal polymerization of aspartic or aminomaleic acid under microwave irradiation. It is assumed that time of polyreaction will be shortened in relation to classical methods of PAA synthesis from tens to ca. one hour, as well as there will be no need for using a catalyst - ortofosforic acid.
Polymerization method (in bulk or in chosen solvents) as well as optimal conditions of the polymerization process will be the subject of investigation. The obtained PAA shall be characterized towards its chemical structure (NMR, UV, IR methods), molecular weight (GPC), morphology (microscopy), thermal ((MT)DSC, TGA) and mechanical properties. Studies on modification and cross-linking of PAA in order to obtain products with high molecular weight - hydrogels, and application tests of PAA-based macromolecular compounds in biomedical materials, acting as (i) agents facilitating integration of tissue with an implant, or (ii) improving mechanical stability of constructional implants.
Obtained results will be applied to design an ecologically-friendly technology of PAA synthesis in microwave reactor in an industrial scale.

Developing of new methods of synthesis of biodegradable polymers using non-toxic initiators

prof. Z. Jedliński, Center of Polymer Chemistry, Polish Academy of Science
polymer@uranos.cto.us.edu.pl

The novel multifunctional materials and new production processes are based on the principles of nanotechnology and nanosciences. These synthetic polymeric materials having the chemical structure of natural polyhydroxybutyrate (PHB) which is produced in the cells of some microorganisms are completely nontoxic and biocompatible.
These synthetic polymers developed in the framework of this grant proposal will be used in tissue engineering and also applied as drug carriers in the therapy of some human diseases also in the cancer therapy. These new materials will be patented in Poland and in foreign countries.

New composite materials used in dentistry for permanent fillings

prof. dr hab. inż. K. Sikorski, Warsaw University of Technology, Faculty of Material Science and Engineering
sikorski@inmat.pw.edu.pl

Until quite lately, an amalgam was the main material used for permanent fillings (PF) in dentistry. It was because of its good mechanical characteristics (high compression strength, good wear resistance) and good adhesion to the tooth tissue. However, its disadvantages e.g. toxicity of mercury vapour, high thermal conductivity, possibility of galvanic cell forming with the other metals, as well as unsatisfied colour of fillings, motivate to widespread investigations of new materials which could replace the amalgam.
In the group of various materials used for fillings in dentistry the composites seems the most perspective. In spite of intensive studies and considerable development in the latest years, a few elaborated so far composites can not compare with the amalgam. Besides their polymerising contraction cause the forming of crevices on the tooth-filling boundary, which promote of decay in these places.
The aim of this work is to develop new composites that better will fulfil the requirements for permanent fillings. It is expected that high strength and wear resistant material can be obtained by suitable type and form of reinforcing particles and polymerising contraction could be considerably diminished by appropriate combination of two polymers self compensating volumetric changes during polymerisation. The calculations of the residual stresses (performed by FEM simulation) in the composite together with the quantitative analysis of the microstructure and mechanical testing of the samples could allow to design the optimum microstructure of the composite in question.
Various, advanced methods and techniques of material investigations will be used to characterise the behaviour of the composites in the conditions simulating the oral cavity conditions to which PF are exposed to. The contact area between the composite filling and the tooth tissue will be examined from the point of view of the metabolism products promoting of decay. The obtained composites should meet ISO standards. Their clinical studies are planned and the materials developed will be commercialised ones in with pre-selected companies.
Cooperating units:
• Białystok Technical University, Faculty of Mechanical Engineering, Chair of Materials Technology
• Glass and Ceramics Institute
• Warsaw University of Technology, Faculty of Chemistry
• Warsaw University of Technology, Institute of Material Science and Mechanics
• Medical Academy of Warsaw, Department of Preservative Dentistry

Hard tissue reconstruction by means of tissue engineering – biomaterial scaffolds for autologous cell transplantation

dr hab. inż. M. Lewandowska-Szumieł, Center of Research – Functional Materials, Warsaw University of Technology (consortium of 10 units),
mszumiel@ib.amwaw.edu.pl

The idea of tissue reconstruction by means of tissue engineering (TE) is extremely up-to-date. One of the TE method is transplantation of patient own cells isolated from the health part of the tissue, proliferated, differentiated in vitro, settled on 3 dimensional (3D) scaffold and stimulated to produce extracellular matrix.
In Poland the consortium consisting of 10 institutions has been established in order to elaborate the optimal implantable constructions of this type.
Specialists in material engineering representing all biomaterial fields (polymers, ceramics, metals and composites) are represented in the consortium and will work on carriers for cell transplantation. Candidate scaffolds will be tested in vitro in the culture of human cells harvested from bone, cartilage and marrow. Two radiation centers experienced with sterilization of medical products are also involved in the venture in order to resolve problems with sterilization of all the products as well as to use radiation as a method of desirable modifications of material properties. All scaffolds are to be designed in strong collaboration with orthopedic and laryngological surgeons. The main expectation is to work out TE constructions dedicated to the specific clinical situations. Due to the certainly interdisciplinary character of the consortium we do believe to be able to accomplish the result faster then it could be achieved in many small bilateral collaborations.
We are open for collaboration with partners engaged in the field of Tissue Engineering and/or Regenerative Medicine

Resorbable polymers and composites. Bioactive phosphate-siliceous materials (packet)

prof. J. Chłopek, AGH University of Science and Technology, Cracow
chlopek@agh.edu.pl

1. Developing of new methods of synthesis of biodegradable polymers using non-toxic initiators

Prof. M. Bero, Center of Polymer Chemistry, Polish Academy of Science
cordbd@cchp-pan.zabrze.pl

Trimethylen carbonate/glycolide, trimethylen carbonate/lactide or trimethylen carbonate/ ?-caprolactone copolymers are known as a good biocompatible and biodegredable material used in manufacturing of temporary surgery implants (surgery screws, threads and fabrics). Until now, produced copolymers unfortunately consist strongly toxic stanous compounds, used as initiator in polymerization. As it was proved in the presented papers, even very small concentrations of these compounds have strongly toxic influence on human organism.
The aim of our project is to work out new methods of trimethylen carbonate copolymers and 2,2 dimethyl trimethylen carbonate copolymers synthesis with the use of non-toxic or low-toxic calcium, iron and zirconnium compounds. Such choice of the kind of initiator makes it possible to minimise the toxic influence of the metal compounds remnants, which cannot be removed from the final product. First of all, we will use acetylacetonates of those metals as initiators, as in the methods of the oxycyclic monomers copolymerization we had previously worked out they emerged very good initiators. Apart from the choice of optimal initiators and copolymerization conditions, in the project we plan to find the methods of chain microstructure analysis of the obtained copolymers. This will enable us to define the connections between the chain microstructure and the thermal and mechanical properties of the obtained materials, as well as the influence of the kind of initiator on the final chain microstructure.
Another essential task will be the synthesis of the glycolide/lactide copolymers with the use of non-toxic initiator (Zr(acac)4) in a large scale, according to a method previously worked out by our group for the project (forming of applicable structural implants and the scaffolds).
The results of the project should lead to obtaining of a new method of the synthesis of a lot biodegradable copolymers, which would have a long degradation time, consisting carbonate groups in the chain, not consisting the toxic stanous compounds. The appropriate choice of the copolymer composition, as well as the kind of the initiator would make it possible to set the mechanical and degradational properties of the obtained materials, depending on the plans of their application. The produced copolymers with interesting application properties will be given to the Faculty of Material Science and Ceramics at the University of Mining and Metallurgy for further investigation on forming the biodegradable screws and other surgical elements. The ?-caprolactone/carbonates copolymers will probably be an interesting material for forming flexible implants for application in neurosurgery (nerve guides).

2. Modelling of scaffold microstructure for tissue regeneration using carbon fibrous materials and modified resorbable polymers

Prof. M. Błażewicz, AGH University of Science and Technology, Cracow
mblazew@agh.edu.pl

The aim of this project are the researches on the design and elaboration of supporting materials for tissue engineering. It is intended to investigate and to manufacture the materials with optimal spatial architecture and properties allowing to culture in vitro and in vivo the cells of hard and soft tissues. The synthetic substrates will be used in the treatment and in the reconstruction of hard and soft tissue.
The project is directed to develop new approach in the treatment of tissues by combining the tissue engineering methods with biomaterials engineering. The concept is that some functions of organs or tissues are difficult to be rebuilt by using single phases or constituents (ex. metals) and such functions can be restored in part, by synthetic composite phases. These composite phases can be designed and manufactured using different biocompatible, non – metallic constituents (carbon fibres, tissues, fabrics, polymers) allowing for closer approach to the natural tissue and restoring better mechanical functions whereas another tissue can be cultured within the three- dimensional scaffold integrally bonded with composite phase.
The project deals with the two major problems. The first one is fundamental in nature, and will deal with the modeling 3D scaffolds as cell and tissue carriers based on biocompatible various forms of surface- modified carbon fibers, whereas the second task will concern to developing an implant for trachea reconstruction. The implant in the form of flattened tube will be made from material constituting a scaffold for epithelial growth cell, whilst the outer layer will act as inert constructional phase with the anisotropic structural behavior.

3. Modelling of structure and usable properties of structural implants using resorbable polymers modified with fibres and particles, suitable for controlled bone adhesion.

prof. J. Chłopek, AGH University of Science and Technology, Cracow
chlopek@agh.edu.pl

The aim of the study is to elaborate technological basis for obtaining structural implants of resorbable and inert polymers modified with fibres and particles. To realize this, modeling of composite’s microstructure for fulfilling particular biomechanical function is required. Fundamental problem for practical application is to estimate the relationship between mechanical stability of composites and resorption time and kinetics of bone union.
Obtained results should allow to obtain polymer composites with controlled mechanical and biological composites and on their basis resorbable and biostable joints in the form of plates, screws, nails and other shapes. The last stage of this task would be estimation of their usefulness in vitro and in vivo studies.

4. Multifunctional ceramics on the basis of calcium phosphates

prof. A. Ślósarczyk, AGH University of Science and Technology, Cracow
aslosar@uci.agh.edu.pl

Recently there has been considerable interest in the development of new bioceramic materials which can be used as potential multifunctional implants. In accordance with this trend of studies in our research we would like to prepare and to evaluate the new calcium phosphate based materials for bone substitution and local release of the drugs. This concept of the ceramic carriers overcomes the disadvantages of the other drug delivery systems.
Porous hydroxyapatite (HAP), whitlockite (TCP) or composite type implants with HAP and TCP as well as apatite cements including the incorporated drugs guarantee their sustained and slow release and a high local concentration in a long period.
Calcium phosphate based multifunctional implants with hetero- or homogenous profile thanks to their chemical and mineralogical similarity to bone apatites have very good biocompatibility to host tissues. After completion of drug release the implant is not removed but should serve as a scaffold for new bone formation. This drug delivery system may be an effective way used in the treatment of osteitis, rheumatism, bone tumors and osteoporosis with high therapeutic effectiveness.
The second aim of our work is to evaluate the interaction of different type implants on the basis of calcium phosphates with human cells in in vitro tests. The influence of the phase composition and microstructure on the cells proliferation and differentiation will be studied. The obtained results should be helpful in qualifying the ranges of application of these materials in medicine. Problems regarding the different bioactivity and biocompatibility of calcium phosphate based materials will be emphasized.

5. New generation of ceramic bioactive materials of higher bioactivity – bioglasses and glass-ceramics produced by sol-gel method

prof. M. Łączka, AGH University of Science and Technology, Cracow
mlaczka@poczta.fm

Bioactive glasses and glass-ceramics have great potential as bone substitutes in dentistry and medicine. They have the important property of bioactivity, permitting not only bonding to bone surfaces but also stimulation of bone formation. Both of these properties are clearly dependent on the material composition and reactivity of the surface, but it has thus far not been possible to identify the key parameters leading to bioactivity.
The project concerns the new generation of these biomaterials (glasses and glass-ceramics) produced by chemical sol-gel method. Gel-derived biomaterials are characterised by higher bioactivity, especially concerning their effect on the faster reconstruction of living tissues.
We will try to determine the mechanism of the interaction between gel-derived biomaterials and tissues as well as the kind of cell response on material action. Examinations will be carried out in vitro an in vivo conditions. The influence of various materials factors (chemical and phase composition, surface state, development of surface and other) on the behaviour of cells and tissue regeneration will be examined.

6. Bioactive ceramic overlayers

prof. dr hab. inż. M. Handke, AGH University of Science and Technology, Cracow
mhandke@agh.edu.pl

The project task is development in the field of implant technology connected with production of firm joint between implant and biological tissue which rely on the application of bioactive ceramic overlayers.
Preparation of new materials for the layers phosphate and phosphate-silica based is expected, as well as an improvement in the methods of preparation of phosphate or phosphate-carbonate materials applied already in our laboratory.
Ceramic bioactive layers will be deposited onto metal, ceramic or carbon implants using sol-gel, biomimetic and electrochemical techniques. Best conditions of the layers deposition and their thermal pretreatment will be establishhed. Interaction between the overlayers and the substrates as well as estimation of their corrosive resistance in synthetic body fluids „in vitro” will also be studied. Biological activity of the overlayers by means of the growth of bone cells on their sufrace will be evaluated.
It is expected that the bioactive ceramic overlayers formed according to procedures developed in the Project allow producing the non-concrete bonding between the implant and biologic neighborhood.

7. Composites with bioactive ceramic phases of natural and synthetic origin

prof. J. Chłopek, AGH University of Science and Technology, Cracow
chlopek@agh.edu.pl

The aim of the study is to elaborate the method of obtaining hydroxyapatite from animal bones, without organic phase, the method of obtaining sinters containing natural hydroxyapatite and estimating the way of obtaining gradient carbon-ceramic composites with different types of hydroxyapatites and bioglasses.
Structural analysis of natural and synthetic hydroxyapatites and carbon-phosphate composites prepared by heat treatment will allow to choose the most beneficial method of obtaining implants on the basis of these materials characterized with good physico-chemical properties, mainly their ability to fixate with bone tissue. Some in vitro research will also be done to estimate the kinetics of bone apatite growth on scaffolds made of these materials and to determine the level of cells viability.
Elaborated implants will be applied in dentistry and veterinary medicine.