Мedicine/7.
FSBEI HPE «Saratov state technical
university of a name Gagarin Yu.A.», Saratov, Russia
Article is prepared with support the grant President
of the Russian Federation
Biocompatible мetal-oxide
coverings with antiseptic properties on implants for traumatology and
orthopedics
Researches
in vivo rod orthopedic implants with biocompatible metal-oxide the coverings modified by silver and copper –
elements with antimicrobic activity are conducted. Basic possibility of
effective application metal-oxide
coverings with antiseptic properties on titanic and steel implants for an
external bone osteosynthesis is shown.
Keywords: orthopedic implants, biocompatible metal-oxide coverings, modifying, copper, silver, antiseptic properties.
Проведены
исследования in vivo стержневых ортопедических имплантатов
с биосовместимыми металлооксидными покрытиями, модифицированными серебром и
медью – элементами с антимикробной активностью. Показана принципиальная
возможность эффективного применения
металлооксидных покрытий с антисептическими свойствами на титановых и
стальных имплантатах для внешнего чрескостного остеосинтеза.
Ключевые слова: ортопедические
имплантаты, биосовместимые металлооксидные покрытия, модифицирование, медь,
серебро, антисептические свойства.
Introduction
The antiseptic properties of biocompatible implant materials and coatings
are considered as the most effective biomedical "tools" of successful
engraftment and functioning of modern metal implants for dental traumatology,
orthopedics, neurosurgery, and other areas of regenerative medicine [1-4]. They
allow no additional preventive therapy to reduce the duration of the course of
natural immune processes in biological tissues at early stages of healing,
minimize the occurrence of allergic and inflammatory reactions in the remote
period of implantation, as well as to provide the best conditions for the
osseointegration of implants and securely. This is due to the beneficial
effects of implant material with the properties mentioned in bioelectrochemical
and bioelektrophysical processes in nearby implantation area to maintain it
normal metabolic and cellular events, as well as the stimulation of active
biological activity of various organic structures and accelerated bone formation.
Antiseptic or bactericidal properties of materials can significantly
slow the development and proliferation of harmful microorganisms implantation
zone in the most dangerous initial postoperative period and to minimize the
risk of inflammatory processes in the later stages of implantation. Bactericidal
effect of implant materials due mainly to the presence within them of certain
chemical elements which have antimicrobial activity and contained a small
"trace" amounts. These trace elements are Ag, Cu, La, located in the
material in the form of free metal ions or bound chemical state.
Giving the
antiseptic properties of materials and coatings of implants used in
traumatology and orthopedics for external transosseous osteosynthesis, significantly
increases the efficiency of their use, creating an entirely new level of
functioning and provides a high capacity to adapt to the surrounding
biostructures implanted ware.
Antiseptic
materials or coatings can be achieved by introducing in their chemical composition
of trace elements with appropriate antimicrobial properties, that is by
modifying the implant surface with antiseptic substances, or preparations
containing the active antimicrobial components.
Implants for the
treatment of various bone pathologies of musculoskeletal system by controlled
transosseous osteosynthesis in most cases are made of titanium alloys ВT6, ВT16, and a
stainless chromium-nickel steel 12X18H9T. As the materials biocompatible
coatings of implants can be used with high efficiency non-toxic metal oxides
own, outside the chemical composition of the basics of implants. Modification
of oxidized metal surfaces with antiseptic ingredients can contribute to
improved biological adaptation implants by providing specific antimicrobial
activity of metal oxide coatings.
Therefore, the aim of work was experimental and clinical substantiation
of the effectiveness of titanium and steel orthopedic implants with
biocompatible metal-oxide coatings modified with copper and silver – the elements
with high antimicrobial activity.
Method of research
Experimental implants were screw rods for transosseous osteosynthesis
titanium alloy ВT16, and stainless steel 12X18H9T diameter of 2.5 mm
and a length of 5 cm.
The surface of
the rod implants pre-prepared by sandblasting abrasive corundum, and ultrasonic
cleaning in a washing alcoholic solution.
To create an
oxide coating implants were placed in a furnace steam-thermal oxidation, in
which the working volume of 1.2-1.3 atm pressure, superheated steam was fed,
and at 5500C and 2 h duration received a coating thickness of 40-50
microns, with a total open porosity 30-40% for the desired integration interaction
with bone tissue. Then titanium implants coated with metal oxide obtained
consisting of a mixture of phases TiO, TiO2 , Ti2O3
, Ti3O5 was placed in an electrochemical bath prepared
non-aqueous electrolyte and silver-by cathode galvanostatic implementation was
carried out covering the modification of silver. Steel oxidized implants
coverings containing in structure a mixture oxide metals (Cr, Ni, Fe, Ti),
comprising the alloy 12X18H9T, modified by the method of implementation of the
cathode copper.
To determine the
effect of silver coating of titanium implants and copper coating steel implants
in the level of the organism used biological adaptation laboratory rabbits
"Netherlands Red," which in the tibias of 50 days established
implants. Control group samples were transosseous rods with unmodified oxide
coating.
Clinical
evaluation of antimicrobial activity and ability osteoiIntegration oxidized implants
was carried out on the basis of the development of inflammation in the area of
implantation with microbiological smears of exudate, as well as
the level of coverage fusion with bone tissue using optical microscopy and by
examining histologic cuts boundaries of the «coated implant – bone».
Silver-oxide coated titanium
implants was characterized by the following ratio: a mixture of titanium
oxides: 98-99%, silver: 1-2%. Established that this component of the coating,
its thickness is 40-50 microns, and porosity, equal to 30-40%, are most
favorable for use in medical implants of titanium, as allow for the most important
functions of treatment and rehabilitation – a safe and durable engraftment accelerated
osteoiIntegration fastening of medical-technical products to the bone.
Experiments in vivo have shown that the amount of silver in the
composition of the oxide coating less than 1% does not allow to achieve high
efficiency while maintaining the bactericidal effect of microbial activity in
the area of implantation in the later stages of healing. Amount
of silver in the coating exceeds 2% is economically sensible, since silver
content in the range of 1-2% has a bactericidal effect, sufficient to
completely eliminate microbial activity on the border of the implant at all
postoperative stages.
In clinical trials it was found that rod implants with an oxide coating
without silver content and silver content less than 1% are not contributing to
the prevention of inflammation of surrounding tissue and showed no signs of
bactericidal activity a surface (Table 1). In the area of
installation of the implants occurred inflammatory phenomena
associated with the development of pathogenic micro-organisms already on the
2nd day test.
Table
1
|
Material rod implants |
Oxide cover |
Clinical and biological characteristics of
the test |
||
|
Morphological analysis histologic cuts of а bone on the border with implants |
Microbiological swabs of exudate |
Visual and optical analysis of the implant surface
after testing |
||
|
titanic alloy ВT16 |
without silver content |
presence of a thin layer of newly formed bone |
mikroflora activity at the initial stage of
implantation (2-7 days), the resulting tissue tumorogenesis |
presence of fragments of bone, which is integrated
with an oxide coating |
|
with silver content less than 1% |
presence of microbial flora and the
appearance of inflammation at 2 days after implantation with tumor tissue at
4 days |
|||
|
with silver content of 1-2% |
the presence of a significant amount of bone
regenerate |
absence of pathogens and inflammation
biostructures throughout the test period |
||
Titanium implants coated with silver-oxide showed high osteointegration
ability the coating in the absence of tissue inflammation throughout the test
period. Microbiological smears obtained at the boundary of the implants and
soft tissues did not reveal the presence of pathogenic organisms, which
indicates that the effective antimicrobial action of silver in the composition
of the oxide coating.
Oxide copper-coated steel
implants was characterized by a following parity of
components: a mixture of metal oxides (Cr, Ni, Fe, Ti), comprising the alloy:
from 95 to 98%, copper: from 2 to 5%.
Effective antimicrobial activity copper-containing oxide coating that
promotes improved biological adaptation steel implants without the risk of
occurrence of inflammatory processes in the surrounding tissues was determined
by clinical trials.
As a result of carrying out of tests it is
established that in a zone of injection rod implants made of stainless
chromium-nickel steel with an oxide-coated copper-free (control samples) for 20
days operation proceeded inflammation associated with increased microbial
activity in the surrounding tissues. The process of healing implants was difficult
and was accompanied by intense purulent formation early healing (3-8 days).
Because of this high-coverage fusion with bone tissue has not occurred (Table
2).
Rod implants with an oxide coating containing
copper in an amount less than 2%, did not show high antibacterial activity of
the surface. In the area of introduction of these rods on the 10th
day of the experiment occurred tumorogenesis tissues due to inflammatory
processes associated with the development of microbial flora around the
implants.
Results for steel implants with an oxide coating containing copper in
the range 2-5%, showed that throughout the period of operation in the area of
implantation was no pathogenic microbial flora without
inflammation biostructures flow (Table 2). In addition, morphological analysis
histologic cuts bone on the border with implants showed that the copper-oxide
coating firmly grown together with the surrounding bone, which indicates a high
osteointegration ability to apply the coating.
|
Oxide cover |
Clinical and biological characteristics of
the test |
||
|
Morphological analysis histologic cuts of а bone on the border with implants |
Microbiological swabs of exudate |
Visual and optical analysis of the implant
surface after testing |
|
|
without the copper content |
presence of a thin layer of newly formed bone |
presence of microbial flora and inflammation
in the area of implantation for 20 days |
presence of fragments of bone, which is
integrated with an oxide coating |
|
with a copper content of less than 2% |
the emergence of microbial flora with
inflammation and tumor tissues at 10 days |
||
|
with a copper content at the level of 2-5% |
the presence of a significant amount of bone
regenerate |
absence of microbial flora and inflammation
biostructures throughout the test period |
|
It was found that the engraftment of steel implants with an oxide
coating containing copper in the range from 2 to 5% by 2 times faster compared
to steel implants having oxide coating without the copper content and copper
content of less than 2%.
Thus, laboratory and
clinical trials using the silver-oxide coatings on titanium implants and copper-oxide
coatings on steel implants have shown that the applied coatings have a high
level of biocompatibility, the ability strongly to grow together with bone
structures at full suppression of activity of harmful microorganisms on the border «biological tissue
– implant». In addition, medical and biological experiments indicate that the
process of healing implants with oxide coatings containing antiseptic modifying
components is carried out much faster than with implants having oxide coatings,
antibacterial unmodified components (copper or silver). In turn, this contributes
to a significant reduction in postoperative rehabilitation period and accelerate
the treatment of patients in general.
Clinical trials had shown that the use of silver-oxide
coatings on implants made of titanium alloy ВT16 and copper-oxide
coatings on implants made of stainless steel provides high engraftment 12X18H9T
products in the body due to osteointegration ability and antimicrobial activity
of the surface.
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