Note: Descriptions are shown in the official language in which they were submitted.
CA 02308898 2000-OS-19
-2-
Carrier for Artificial Internal Organ
This invention relates to a medical device which forms the matrix of an
artificial internal organ and to manufacture of such a device.
A crucial new method for the radical treatment of diseases of the
internal organs is the partial or total substitution of their functions by the
transplantation of a corresponding artificial organ prepared according to
modern technologies. The resolution of the central problem - the suppression
of the recipient's immune response to the artificial organ has resulted in
remarkable progress in this area of medicine. One of the most effective
methods is the isolation of the transplanted cells by placing them into a
porous
matrix. (Medical Materials and implants with Shape Memory, Tomsk: Tomsk
University, 1998, p. 355.) The essence of this method is the isolation of the
smaller implanted cells from larger immune system entities such as
macrophages based on the size difference. The task is therefore to create a
matrix with the required distribution of pore sizes to isolate the desired
cells in
the matrix.
In nature there is no gradated transformation of any process or
relationship; this also applies to the pore size distribution within the
porous
material. It is in principle difficult to create a porous material that would
strictly exclude pores of a certain pre-defined size.
Owing to its bio-compatibility, nickel-titanium alloy or nickelide of
titanium is the most effective material for the manufacture of a matrix for
cellular-suspensions in the formation of an artificial internal organ. Its
porous
structure is created during the SHS (self propagating high-temperature
synthesis) process within a blank of a predetermined shape made of the alloy.
The fundamentals of this technology are based on the utilization of the heat
which is emitted during the exothermic interaction of the heterogeneous
metals,
nickel and titanium. Following the thermal excitation of a certain local
CA 02308898 2000-OS-19
-3-
volume, the emitted heat of the interaction heats up the adjacent layers of
the
blank, thus ensuring the self propagation of the reaction.
It is known to manufacture porous alloys of nickelide titanium by means
of SHS employing an alloy containing powders of nickel and titanium, in
certain cases with some alloying addition as in G. T. Dambaev, V. E. Gunter,
et
al, Porous Permeable Superelastic Implants in Surgery, Tomsk: Russian
Medical and Engineering Centre, Siberian State Medical University, 1996, p.
35. The nickel and titanium powders are dried, weighed, mixed and molded by
pressing them into the shape expedient for the future application. The
resulting
compact blanks are placed into a reactor, which is a container made of
stainless
steel with screwed covers, electrical current feeds, an electrical filament
for the
ignition of the powder mixture and inert gas-flow regulator, and thermocouple
vents. The reactor is filled with inert gas, for example, argon, under a
pressure
of 1-2 at.
In order to initiate the exothermic reaction, the reactor is warmed
externally, increasing the temperature in the ignition space to 423-
623°C. The
alloy is then ignited with the electrical filament. When the laminar or layer
by
layer self heating process and the sintering of the nickel and titanium
powders
has been completed, the reactor is cooled without termination of the inert gas
supply and the synthesized porous matrices are extracted from the reactor.
This alloy and the related technology are widely used in modern
medicine, especially in areas where there are no strict requirements for the
distribution of the porosity. The disadvantage of this technology for the
manufacture of material for cellular-suspension matrices is the high
percentage
of pores with a size exceeding the size of macrophages, due to the lack of
control in the pore-formation process.
An existing alloy of nickel and titanium used for the production of the
material based on nickelide titanium using the SHS method is described in
USSR Inventor's Certificate No. 662270, Class B 22 F 3/12, The Technique of
CA 02308898 2000-OS-19
-4-
Production of Materials Based on TiNi Alloy, published 15.05.1979, Bulletin
No. 18 (prototype). The SHS technology decreases the number of the larger
pores in the prototype material by raising the preheating temperatures of the
reactor containing the alloy of 0.5 - 0.9 of the fusing point of the final
product.
As a result, synthesis takes place in the liquid phase, thus providing a
higher
percentage of small-sized pores as well as a dense structure. The disadvantage
of the prior technique is the insufficient control of pore-size distribution
of the
synthesized matrix.
The technical result of the present invention is the improved regulation
of pore-size distribution during the process of self propagating high-
temperature synthesis in manufacturing porous material as a matrix for
cellular
suspensions.
In accordance with one aspect of the invention there is provided a carrier
device for an artificial internal organ comprising a matrix of an
intermetallic
material based on the elements nickel and titanium, said matrix having a
porosity effective to isolate organ cells in the matrix from immune system
entities, for example macrophages.
In another aspect of the invention there is provided an artificial internal
organ precursor comprising a carrier device of the invention, and organ cells
isolated in the pores of the matrix.
In still another aspect of the invention there is provided an artificial
internal organ comprising a Garner device of the invention, and an organ cell
growth structure extending throughout the pores of the matrix.
In yet another aspect of the invention there is provided a method of
producing a Garner device for an artificial internal organ comprising: forming
a
shaped pressed article simulating an artificial internal organ, of nickel and
titanium powders and nickel titanium alloy powder, subjecting said pressed
article to a self propagating high temperature synthesis to produce nickel
titanium alloy from said nickel and titanium powders with formation of a
CA 02308898 2000-OS-19
-5-
porous matrix corresponding to said shaped article, said porous matrix having
a
porosity effective to isolate organ cells in the matrix from immune system
entities, for example macrophages.
In still another aspect of the invention there is provided a method of
forming an artificial internal organ comprising: implanting a precursor of the
invention in a recipient in need of an artificial internal organ, said cells
being
cells which form the needed organ and allowing cell growth to establish
throughout the matrix.
In yet another aspect of the invention there is provided use of a carrier
device of the invention for the formation of an artificial internal organ.
The carrier device of the invention serves to isolate within it, organ cells
which will grow throughout the matrix of the device, from larger immune
system entities such as macrophages which would otherwise attack the organ
cells. The organ cells are isolated within the matrix and the immune system
entities are unable to penetrate the matrix to attack the organ cells because
of
their larger size.
In particular embodiments, the matrix is derived from a powder
composition composed of 45 to 55%, by weight, of nickel powder and 55 to
45%, by weight, titanium powder, to a total of 100%; and titanium nickel alloy
powder in an amount of 5 to 30%, by weight, based on the total weight of
nickel and titanium powders.
Preferably the powder composition contains 47 to 53%, by weight of
said nickel powder and 53 to 47%, by weight of said titanium powder to a total
of 100%.
Suitably at least 30%, and preferably at least 50%, of the porosity of the
matrix is defined by pores having a pore size of less than 100 microns.
An analysis of the kinetics of the self propagating high-temperature
synthesis demonstrates complicated multifunctional relationships of the final
structure of the synthesized intermetallic compound to the initial conditions
of
CA 02308898 2000-OS-19
-6-
the synthesis: the proportions of the original components, the degree of their
dispersion and compactness, the inert gas pressure and other factors. These
parameters condition the propagation velocity of the combustion wave, the
maximal temperature of the synthesis and the intensity of gas release. All of
these attributes determine the final structure of the synthesized material in
its
variations from highly porous to dense.
The addition of 'TiNi powder, the inert element in the reaction, changes
the SHS kinetics and provides the required pore-size distribution, so as to
create a required porosity and to ensure the isolation of the cells of an
artificial
organ from macrophages; it was found that the proportion of the inert TiNi
component should be 5-30%, by weight, based on the total weight of the
mixture of nickel and titanium powders. When the percentage of the TiNi
powder is less than 5%, the synthesis can not be efficiently controlled; when
the percentage of the TiNi powder is higher than 30%, the synthesis does not
take place.
An additional technical benefit of the proposed invention is the
improvement of the mechanical workability of the synthesized material.
The invention is illustrated by reference to the drawings in which:
Fig. 1 is a photomicrograph of a conventional porous structure of TiNi
alloy; and
Fig. 2 is a photomicrography of the porous structure of TiNi alloy in
accordance with the invention.
EXAMPLE
The alloy used to produce the porous material contained a mixture of
titanium (brand PTOM) and nickel (brand PNK-lOT2) powders in a
stoichiometric proportion, by weight, of 50:50 each, and TiNi powder in an
amount of 15%, by weight, based on the total weight of the mixture of nickel
and titanium powders.
CA 02308898 2000-OS-19
') _
The mixture obtained after 8 hours of blending in a laboratory blender
was loaded into a cylindrical closed mould with a diameter of 30 mm and a
length of 250 mm; the mould was placed into a reactor. A flow or argon was
directed through the reactor to prevent the access of ambient air. The reactor
was heated to a temperature of 600°C. and the formed alloy was ignited
with
the electrical filament. Self propagating high-temperature synthesis developed
in a layered regime of combustion and lasted for 15 seconds.
The technical result of the present solution becomes clear in a
comparison of the structure of the synthesized porous material of the
invention
(Fig. 2) with the structure of the material obtained using similar technology
in
the prior art (Inventor's Certificate 662270). The percentage of pore sizes
ranging from 0 to 100 microns was evaluated in both samples. In the prior art
of Fig. 1, S% of the pores were of this size, the remainder of the pores being
larger; in the present technical solution, 50% of the pores were of this size.
Visual evaluation gave evidence of an abrupt decrease in pore-sizes ranging
from microns to fractions of a micron. The material synthesized using the
present technology was successfully employed in a clinical trial in treatment
of
parenchymatous organs involving their partial or total substitution by
transplants.
