Note: Descriptions are shown in the official language in which they were submitted.
CA 02010274 2000-OS-11
1
Biodegradable surgical implants and devices
The present invention relates to a surgical implant
and/or device.
In surgery, it is prior known to employ at least
partially biodegradable, elongated (typically tubular)
surgical implants for .supporting, connecting or
separating elongated organs, tissues or parts thereof,
such as canals, ducts, tubes, intestines, blodd
vessels, nerves etc. In this context, the biodegrad-
able (absorbable, resorbable) material refers to a
material whose decomposition and/or dissolution
products leave the system through metabolic ducts,
kidneys, lungs, intestines and/or skin by secretion.
US Patent No. 3 108 357, Liebig, discloses a tubular
device to be implanted in animals and humans, compri-
sing a resilient woven tube which contains biologically
absorbable oxidized cellulose.
US Patent No. 3 155 095, Brown, discloses hollow
cylindrical anastomosis joints which are made of an
absorbable material.
US Patent No. 3 272 204, Artandi and Bechtol, discloses
collagen-made flexible tubes which can be externally
reinforced with a plastic coil or plastic rings.
US Patent No. 3 463 158, Schmitt and Polistina,
discloses fibre-made tubular surgical devices which
are at least partially made of absorbable polyglycolic
acid (PGA).
US Patent No. 3 620 218, Schmitt and Polistina,
discloses PGA-made surgical devices, such as tubes.
2
WO 84/03035, Barrows, discloses longitudinally open-
able, porous, coarse-surfaced biodegradable tubes
used as a remedy for the nerves.
The publication Plast. Rec. Surg. 74 (1984) 329, Daniel
and Olding, discloses an absorbable anastomosis device
which comprises cylindrical, tubular, complementary
parts.
However, the prior known tubular, at least partially
biodegradable surgical implants and devices involve
several drawbacks and limitations. As for the implants
including biostable parts, such as polymeric and like
fibres, plastic or metallic coils or rings or the like,
such biostable parts or components remain in the system
even after a tissue or an organ has healed and such
components can be later harmful to a patient by causing
infections, inflammatory reactions and Tike foreign
matter reactions and/or they might release particles,
corrosion products or the like which aan wander in the
system and/or cause harmful cellular level reactions.
The prior known 'tubular biodegradable implants manu-
factured by melt working technique or a like method
are often massive and stiff creating in resilient
tissues (such as ducts, tubes, blood vessels etc.) an
undesirable stiff, non-physiological bracing effect
which can lead to harmful alterations in the properties
of a tissue to be braced. In addition, the massive,
tubular implants create a heavy local foreign matter
loading on the system at the installation site thereof
and such loading can also contribute to harmful
alterations in an operated tissue, such as canal,
tube, duct, blood vessel or the like.
On the other hand, the tubular structures constructed
from biodegradable fibres by braiding, knitting,
weaving or same other similar technique do not possess
CA 02010274 2000-OS-11
the structural rigidity and/or resilience often required of a support implant
to be fitted
inside or outside a tubular tissue.
It has been surprisingly discovered in this invention that the deficiencies
and drawbacks of
the prior known, at least partially biodegradable surgical implants and
devices used for
supporting, connecting or separating organs, tissues or parts thereof can be
substantially
eliminated with an implant, device or a part thereof which is mainly
characterized by
comprising an at least partially biodegradable elongated member which is at
least partially
wound at least once around a centre of rotation into a helical configuration
and which is at
least partially reinforced with biodegradable reinforcing elements.
According to one aspect of the present invention there is provided a surgical
implant,
device, or a part thereof made of a biodegradable material, which has been
composed of a
biodegradable matrix with biodegradable reinforcement elements therein, the
said implant
being at least partially wound at least once around a winding centre into a
helical
configuration, characterized in that the implant or device for separating
tubular tissues
and/or keeping open a tissue cavity in operated and/or damaged tissues is
formed of one
single rod.
An implant, device or a part thereof (hereinbelow "device") can be conceived
having been
formed in a manner that around a certain centre point is wound some elongated
member at
a distance of a certain winding radius from the centre point. If the winding
centre is
stationary and the winding radius increases as the winding angle increases,
the
configuration of an obtained device is a spiral configuration, especially if
the winding
radius remains in the same plane. Provided that the winding radius is constant
and the
winding centre travels during the turning of an elongated member along a
certain, e.g.
linear path, the device obtained has a circle-cylindrical screw-threaded
configuration
(helix). On the other hand, if the winding radius changes while the winding
centre travels
along a certain path, there will be produced a spiral configuration whose
external surface is
in conical shape. It is obvious that the implant, device or a part thereof can
include the
above shapes and configurations as a combination and e.g. a combination of a
spiral and a
CA 02010274 2000-OS-11
4
cylindrical screw-threaded configuration. The implant, device or a part
thereof can also be
provided with otherwise shaped members in addition to a screw-threaded
configuration,
such as plates, sleeves etc.
The invention relates also to a method for manufacturing an implant, device or
a part
thereof ("device"), as defined above, the method being characterized in that
an elongated
blank formed by a biodegradable polymer matrix and biodegradable reinforcement
elements
is wound at least partially at least once around a winding centre into a
helical
configuration.
The invention relates also to the use of an implant, device and a part
thereof.
The invention is described in more detail in the following specification with
reference made
to the accompanying drawings. In the drawings
fig. 1 shows the formation of a material micro-structure in a device of the
invention in
a perspective view schematically, an array of lamellae turning into a
fibrillated
structure,
fig. 2 shows an intra- and inter-fibrillary molecular structure,
fig. 3 shows schematically the micro-structure of a fibrillated polymer,
fig. 4 shows schematically the molecular structure of fibrillated devices of
the
invention,
~~~.~~'~~ø
figs. 5 and 6 are schematical perspective
views of spiral-shaped embodiments
of the device,
figs. 7a, b - ga, are schematical perspective views
b
of conical embodiments of the
device,
figs. l0a and lOb are schematic perspective views
of a cylindrical embodiment of
the device,
figs. lOc and lOd show some further embodiments of
a cylindrical device,
figs. lla - 111 illustrate some preferred cross-
sectional shapes and surface
patterns for the elongated member
(blank) of devices shown in
figs. 5-10,
figs. 12 and 13 illustrate one special embodiment
of the invention schematically
in a perspective view,
fig. 14 shows schematically a test
arrangement described in example
fig. 15 illustrates a surgical operation
described in example 3,
fig. l6 illustrates a surgical operation
described in example 4,
fig. 17 shows schematically an device
described in example 5, and
6
fig. 18 shows one embodiment for an
device of the invention.
In this context, the biodegradable reinforcing elements
refer to the following:
(a) orientated (aligned) structural units
included in the micro-structure (molecular
structure) of a material, such as orien-
tated parts of molecu:Les, bundles of
molecules or parts thereof or microfibrils,
fibrils or the like orientated structural
units formed thereby,
(b) biodegradable organic filaments, fibres,
membrane fibres or the like or structures
constructed thereof, such as bands, braids,
yarns, fabrics, non-woven structures or
the like; or
(c) biodegradable inorganic (ceramic) file-
ments, fibres, membrane fibres or the
like or structures constructed thereof:
A particularly preferred embodiment of the invention
is such an implant or an device which is structurally
self-reinforced. A self--reinforced biodegradable
structure is defined in the invention US Patent No. 4
743 257, Tormala, et al. In a self-reinforced struc-
ture, a biodegradable polymer matrix is reinforced
with biodegradable reinforcement elements (units)
having the same proportional elemental composition as
the matrix. The reinforcement elements are typically
ori~emta.~ed moleculesv or parts thereof or the like
obtained by orientation or fibrils, microfibrils,
fibres, filaments or the like structures constructed
thereof.
CA 02010274 1999-03-18
7
Reinforcement elements inside the microstructure of a
self-reinforced polymer material are produced e.g. by
orientating the molecular structure of a material
either in melt state or in solid state in such condi-
tions the structure-reinforcing orientation remains
at least partially permanently in material either as
a result of the rapid cooling and/or solid state of
the melt and/or as a result of the prevention of
molecular movements (relaxation) of the melt. The
self-reinforcement based on draw orientation is
described in the invention CVO 88/05312, Tormala et
al., as follows:
A partially crystalline, non-oriented piece of polymer
typically consists of crystal units i.e. spherulites
and amorphous areas thereinside and/or therebetween.
The orientation and fibrillation of a polymer system
possessing a spherulitic crystalline structure is a
process that has been extensively studied in connection
with the production of thermoplastic fibres. For
example, the invention US Patent 3 161 709 discloses
a three-step drawing process for.transforming a melt-
worked polypropene filament into a fibre having a
high tensile strength.
The mechanism of orientation and fibrillation is
basically as follows (C. L. Choy et al. Polym. Eng.
Sci. 23, 1983, p. 910). As a partially crystalline
polymer is being drawn, the molecule chains of crystal
lamellae quickly begin to parallel themselves (orien-
tate) in the drawing direction. Simultaneously the
spherulites extend in length and finally break.
Crystal blocks detach from lamellae and join together
as queues by means of tight tie-molecules which are
formed through the partial release of polymer chains
from crystal lamellae. The alternating amorphous and
s ~~1. t~~, ~~,
crystalline zones, together with tight tie-molecules,
form long, thin (appr. 100 ~ wide) microfibrils which
are paralleled in the drawing direction. Since the
intrafibrillar tie-molecules form in the phase boun-
daries between crystal blocks, they will be mainly
located on the external surface of microfibrils.
Those tie-molecules, which link various lamellae in
an isotropic material prior to drawing, serve in a
fibrillated material to link various microfibrils
together i.e. become interfibrillar tie-molecules
which are located in boundary layers between'adjacent
microfibrils.
Fig. 1 illustrates schematically the transformation of
an array of lamellae into a fibrillar structure (a
fibril consisting of a bunch of microfibrils) due to
the action of water and fig. 2 shows some of the
molecular structure inside and between miarofibrils.
Fig. 3 illustrates schematically some of the structure
of a fibrillated polymer. The figure shows several
fibrils (one being dyed grey for the sake of clarity)
which consist of a plurality of micro.fibrils having a
length, of several microns.
Orientation is initiated right at the start of drawing
and also a fibrillated structure is formed at rather
low drawing ratios x (wherein ~ - length of piece
after drawing/length of piece prior to drawing). For
example, HD-polyethene is clearly fibrillated at a
value 8 and polyacetal (POM) at a value 3.
As the drawing of a fibrillated structure is continued
further (this stage of the process is often referred
to as ultra-orientation), the structure is further
deformed with microfibrils sliding relative to each
other to further increase the proportional volume of
straightened interfibrillar tie-molecules. If drawing
is effected at a sufficiently high temperature, the
9
oriented tie-molecules crystallize and build axial
crystalline bridges which link together crystalline
blocks.
The excellent strength and modulus of elasticity
properties of a fibrillated structure are based on the
vigorous orientation of polymer molecules and polymer
segments in the direction of drawing (in the direction
of the longitudinal axis of microfibrils) characteris
tic of the structure.
The fibrillation of macroscopic polymeric blanks, such
as rods or tubes, is prior known in the cases of
biostable polyacetal and polyethene (see e.g. K.
Nakagawa and T. iConaka, Polymer 27, 19$6, p. 1553 and
references included therein). 'What has not been
prior known, however, is the orientation and fibril
lation of at least partially helical and/or spiral or
similarly shaped members or pieces manufactured from
biodegradable polymers.
The at least partial orientation and/or fibrillation
of a biodegradable helical and/or spiral or similar
piece can be effected e.g. by rapidly chilling a
flowing state (e.g. in an injection mould) polymer w
melt into a solid state in a manner that the orienta-
tion of molecules existing in the flowing melt in
flowing direction is not allowed to discharge through
molecular movements either entirely or partially inta
a state of random orientation.
A more vigorous orientation and fibrillation and thus
also improved mechanica l qualities are generally
provided for a polymer piece by mechanically working
the material (orientation), generally drawing or
hydrostatic extrusion or die-drawing in such a physical
condition (usually in solid state), wherein it is
10
possible for the material to undergo dramatic struc-
tural deformations in its crystalline structures and
amorphous areas occurring at molecular level for
creating orientation and fibrillation. As a result
of fibrillation, e.g. a resorbable polymer material
produced by injection moulding or extrusion and
initially possessing mainly a spherolitic crystalline
structure transforms into a fibrillated structure which.
is vigorously oriented in the direction of drawing and
comprises e.g, elongated crystalline microfibrils as
well as tie-molecules linking them as well as oriented
amorphous areas. In a partially fibrillated structure,
the amorphous areas between microfibrils make up a more
substantial portion. of the material than in an ultra-
oriented material which, in the most preferred case,
only includes amorphousness as crystal defects. As a
result of orientation, fibrillation and ultra-orien
tation the values of strength and modulus of elasticity
of a material are multiplied compared to a non-fibril
lated structure.
Orientation and the resulting fibrillation can be used
for treating biodegradable polymers, copalymers and
polymer compositions so as to farm self-reinforced
composites in which nearly the entire material stock
is oriented in a desired fashion and the portion of
amorphous matrix is small, these being the reasons
why such materials have extremely high quality strength
properties in orientation direction: bending strength
e.g. up to 400-1500 MPa and modulus of elasticity 20-
50 GPa and thus the orientation and fibrillation can
be used to provide helixes or spirals or the like
devices with multiple strength values compared to
those of normal melt-processed biodegradable materials,
which are typically in the order of 30-80 MPa.
The same way as in the fibrillated structure of polymer
fibres, also in the structure of fibrillated devices
11
there can be found e.g. the following structural units
which are schematically shown in fig. 4: crystalline
blocks, the stock therebetween comprising an amorphous
material (e.g. loose polymer chains, chain ends and
molecular folds), tie-molecules which link the crystal-
line blocks together (the number and tightness of
these increases as drawing ratio a increases) as
well as possible crystalline bridges between crystal-
line blocks. Bridges can form during the drawing as
tie-molecules orientate and group themselves as bridges
(C. L. Choy et al. J. Polym. Sci., Polym. Phys. Ed.,
19, 1981, p. 335).
The oriented fibrillated structure shown in figs. 1-4
is already developed by using so-called "natural"
drawing ratios 3-8. As drawing is then continued as
ultra-orientation, the portion of crystalline bridges
can increase to be quite considerable whereby, in the
extreme case, the bridges and crystal blocks provide
a continuous crystalline structure. However, the
effects of tie-molecules and bridges are often similar
and, thus, the exact distinction thereof from each
other is not always possible.
Orientation and fibrillation can be experimentally
characterized by the application of several different
methods. Orientation function fc, which can be
determined by X-ray diffraction measurements, charac-
terizes orientation of the molecule chains of a
crystalline phase. Generally, fc already reaches a
maximum value of 1 by natural drawing ratios (a < 6).
For polymer materials having a spherolitic structure
fc » 1.
Double-refraction ( ~;,) measured with a polarization
microscope is also a quantity which represents the
orientation of molecule chains. It generally increases
at natural drawing ratios ( a < 6) vigorously and
lz
thereafter in ultra-orientation more slowly, which
indicates that the molecule chains of a crystalline
phase orientate vigorously in the drawing direction at
natural drawing ratios and orientation of the molecules
of an amorphous phase continues further at higher
drawing ratios (C.L. Choy et al. Polym Eng. Sci., 23,
1983, p. 910).
The formation of a fibrillous structure can also be
demonstrated visually by studying the fibrillated
material by means of optical and/or electronic micros-
copy (see e.g. T. Konaka et al. Polymer, 26, 1985, p.
462). Even the individual fibrils consisting of
microfibrils can be clearly distinguished in scanning
electron microscope images of a fibrillated structure.
An oriented and/or fibrillated and/or ultra-oriented
piece (blank) is then rotated at least once around a
centre of rotation into a helical configuration to form
20, "an device" of the invention by shaping it at least
partially by means of an external force or pressure
and/or external heat and/or by means of heat induceable
in the piece (e.g. by radiowave radiation). In
practice, the rotation of winding of the device is
effected in a manner that an elongated blank is wound
around a suitable, if necessary heated mould (e.g. a
mould of cylindrical shape). Such a mould is typically
round in cross-sectionso as to produce helical shapes
having a circular cross-section. The cross-sectianal
shape of a mould can also be elliptical, oval, angular
etc, to produce helical shapes having various cross-
sections. Orientation, fibrillation or ultra-orien-
tation can also be effected in a continuous action
and/or simultaneously with winding in a manner that
an elongated blank is being drawn arid the drawn section
is simultaneously wound around a cylindrical mould.
CA 02010274 1999-03-18
13
At least partially oriented and/or fibrillated and
particularly yltra-oriented biodegradable devices are
an example of an oriented, self-reinforced biodegrad-
able (US Patent 4 743 257, T~irmala et al.) composite
material, wherein the oriented reinforcement elements
(such as fibrils, microfibrils, crystal blocks, tie-
molecules or crystallized bridges) are formed and/or
grouped during a mechanical working and a phase binding
those elements consists e.g. of the following struc-
tural elements: amorphous phase, interfaces between
crystal blocks as well as interfaces between bridges
and microfibrils, a typical feature of which is also
a vigorous orientation in drawing direction.
Another method for using biodegradable reinforcement
elements in devices of the invention is the reinforce-
ment thereof with fibres manufactured from polymer,
copolymer or a polymer composition, with film fibres,
filaments or structures constructed threof, such as
braids, threads, ribbons, non-woven structures,
fabrics, knittings or the li:ke, by combining ready-
made fibres with a suitable polydmer matrix. Such
fibres can be manufactured E~.g. from biodegradable
polymers set forth in table :l. The fibres can also
be biodegradable ceramic fibres, such as calcium
phosphate fibres (see e.g. S. Vainionpaa et al.,
Progr. Polym. Sci. , Progr. Polym. Sci., 14 (1989) 679-716.
Various plastic technological methods can be applied
to manufacture devices of the invention reinforced with
biodegradable organic and/or inorganic fibres or with
structures constructed threof, said manufacturing being
carried out by binding the reinforcement structures at
least partially to each other with biodegradable
polymer, copolymer or a polymer composition (matrix)
in such conditions which serve to produce a sufficient-
ly equal quality composite from the matrix and rein-
forcement elements, said matrix being usually in
14
solution or melt state. Methods for combining rein-
forcement fibres or the like and a matrix as well as
for processing them into semi-finished products and/or
devices include e.g. injection moulding, extrusion,
pultrusion, winding, compression moulding etc.
The at least partially spirally shaped, at least
partially biodegradable device of the invention can
be used in a versatile manner for supporting, expand-
ing, joining or separating organs, tissues or parts
threof. An device of the invention offers a plurality
of benefits over the prior art implants and devices
or devices. When using an device of the invention,
the amount of foreign matter remains smaller than
with traditional implant tubes. Devices of the
invention are more flexible and resilient than the
rigid prior art tubes and, on the other hand, devices
of the invention are stronger under compression and
retain their shape better than fibre-constructed
tubular devices, whereby devices of the invention are
capable of being used for retaining open or even
expanding the medullary cavity of tubular tissues.
Devices of the invention can be manufactured from
biodegradable polymers, copolymers and polymer compo-
sitions. Table 1 shows a number of prior known
biodegradable palymers, which or mixtures of which can
be used as raw materials for devices of the invention
both as a matrix (or binder polymers) and/or reinfor
cement elements.
~'~~.~~
5
Table 1. Biodegradable polymers
1. Polyglycolide (PGA)
Copolymers of alycolide
10 2. Glycolide/lactide copolymers (PGA/PLA)
3. Glycolide/trimethylene carbonate copolymers
(PGA/TMC)
Polylactides (PLA)
Stereoisomers and copolymers of PLA
4. Poly-L-lactide (PLLA)
5. Poly-D-lactide (PDLA)
6. Poly-DL-lactide (PDLLA)
7. L-lactide/DL-lactide copolymers
L-lactide/D-lactide copolymers
Copolymers of PLA
8. Lactide/tetramethylene glycolide copolymers
9. Lactide/trimethylene carbonate copolymers
10. Lactide/6-valerolactone copolymers ,
11. Lactide/E-caprolactone copolymers
12. Polydepsipeptides (glycine-DL-lactide copolymer)
13. PLA/ethylene oxide copolymers
14. Asymmetrically 3,6-substituted poly-1,4-dioxane-
2,5-diones
15. Poly=J3-hydroxybutyrate (PHBA)
16. PHBA/J3-hydroxyvalerate copolymers (PHBA/PHVA) ,
17. Poly-J3-hydroxypropionate (PHPA)
18. Poly-(i-dioxanone (PDS)
19. Poly-8-valerolactone
20. Poly-E-caprolactone
21. Methylmethacrylate-N-vinylpyrrolidone copolymers
22. Polyesteramides
23. Polyesters of oxalic acid
24. Polydihydropyranes
25. Polyalkyl-2-cyanoaarylates
26. Polyuretanes (PU)
27. Polyvinyl alcohol (PVA)
28. Polypeptides
29. Poly-j3-malefic acid (PMLA)
30. Poly-~3-alkanoic acids
31. Polyethylene oxide (PEO)
32. Chitin polymers
Reference: S. Vainionpaa, P. Rokkanen and P. Tormala,
Progr. Polym. Sci., in printing
16
It is obvious that other biodegradable polymers than
those set forth in table 1 can also be used as raw
materials for implants, devices or parts thereof. For
example, the biodegradable (absorbable) polymers
described in the following publications can be used for
the above purposes: US Patent No. 4 700 704 (Jamiolkows
and Shalaby), US Patent No. 4 655 497 (Bezwada, Shalaby
and Newman), US Patent No. 4 649 921 (Koelmel, Jamiol-
kows and Bezwada), US Patent No. 4 559 945 (Koelmel
and Shalaby), US Patent No. 4 532 928 (Rezada, Shalaby
and Jamiolkows), US Patent No. 4 605 730 (Shalaby and
Jamiolkows), US Patent No. 4 441 496 (Shalaby and
Koelmel), US Patent No. 4 435 590 (Shalaby and Jamiol-
kows), US Patent No. 4 559 945 (Koelmel and Shalaby).
It is also natural that devices of the invention may
contain various additives and adjuvants for facilita-
ting the processability of the material (e. g. stabili-
zers, antioxidants or plasticizers) or for modifying
the properties thereof (e. g. plastzcizers or powdered
ceramic materials or biostable fibres, such as carbon
fibres) or for facilitating the manipulation thereof
(e. g. colourants).
According to one preferred embodiment, devices of the
invention contain some bioactive agent or agents, such
as antibiotics, chemotherapeutic agents, wound-healing
agents, growth hormone, contraceptive agent, anticoa-
gulant (such as heparin) etc. Such bioactive devices
or devices are particularly preferred in clinical
application since, in addition to mechanical effect,
they have biochemical, medical and the like effects
in various tissues.
Devices of the invention can also be advantageously
combined with other types of biodegradable implants and
devices. For example, by inserting a helical device
17
as shown in figs. 7-10 into a tube woven or knitted
from biodegradable and/or biostable thread there is
obtained a firm and resilient tube which has a variety
of applications in surgery for replacing or supporting
tissues and/or for keeping open the cavities within or
between tissues.
A device of the invention can also be fitted with long
biodegradable rods which extend parallel to the
longitudinal axis of e.g. a helical-shaped device.
Thus, if necessary, the device can be braced to form
a tubular structure.
The device can also be fitted with various other
accessories, such as flat perforated plates at the ends
of a device for securing the ends of a device firmly
to the surrounding tissues by means of surgical
stitches.
Devices of the invention can have various geometrical
configurations. Fig. 5 illustrates a flat or planar
(in imaginary plane l) spiral 2 that can be used as a
resilient separating material between tissues. The
helixes of spiral 2 can also be connected with each
other by means of biodegradable radial wires, rods 3
or the like as shown in fig. 6, the spiral having a
high strength in the direction of plane 1 but being
resilient in the direction perpendicular to that plane .
A device of the invention can also vary in its dimen-
sions in various sections threof. For example, figs.
7a-l0a and 7b-lOb illustrate thematically a few such
devices. These can be used for providing external
and/or internal support for organs or their parts of
various shapes (such as liver, spleen, kidneys,
intestines etc.).
18
A device shown in fig. 7a is wound into a conical
body. The conical body can have a side face outline
which is either straight or arched or a combination
thereof according to intended application. Devices
shown in figs. 8a and 9a include two conical bodies
joined to each other either at the base of conical
bodies (fig. 8a) or at the apex threof (fig. 9a).
Fig. 10a illustrates a device having its outer face
wound into a cylindrical configuration.
Figs. 7b, 8b, 9b and 10b illustrate device configurat-
ions matching those of figs. 7a, 8a, 9a and 10a and
fitted with rods 3 connecting the turns of a helical
body.
Furthermore, fig. lOc shows an embodiment in which the
device is comprised of two nested device elements V01
and V02 wound into a helical configuration preferably
in opposite directions. Each has cylindrical helical
configuration. Fig. lOd shows an embodiment of a
device, wherein a number of device olements wound
into a helical configuration have been twined together.
The device elements are adapted to run alternately
over and under each other to form a tubular structure.
Figs. lla-111 illustrate same types of cross-section
for a blank. A blank for manufacturing devices of the
invention can have a cross-section which is e.g.
circular (lla), elliptical (llb, llc), flat (lld,
lle), angular (llf, llg, 11h), asteroid (lli) etc.
By varying the cross-section of a blank it is possible
to effect e.g: on the mechanical properties of a
device, the growth of tissues on the surface of a
blank and the growth of tissues through the device.
The thickness of a blank can also vary in different
sections of a blank or it can be provided with holes
19
R (llj) or similar structures, such as recesses L
(llk) or slots (111) for facilitating the fastening
or securing threof to tissues.
According to one preferred embodiment, a device of the
invention is manufactured by winding or rolling a flat
blank having a cross-section shown in fig. 12 into a
tube as shown in fig. 13. Since the longitudinal edges
of a blank (see figs. l2a and 13a) are provided with
folded or otherwise designed gripping means T which
engage each other, during the winding there will be
formed a flexibletube that can be used in the treat-
ment of a . g . a windpipe or the like flexible tissue
channels as a temporary prothesis.
According to one preferred embodiment, devices of the
invention can be used join together tissues, organs or
parts thereof, such as muscular tissue or the like soft
tissues. Such embodiment is illustrated in fig. 18.
Fig. 18a shows a cross-section of a tissue K1 and a
tissue K2 which should be joined with each other. The
joining can be effected by using a sharp-pointed spiral
S which is driven the same way as a corkscrew through
the tissues {fig. 18b). By locking the top portion
of a spiral in position after the turning (e.g. by
stitching the spiral firmly to surrounding tissues by
means of surgical stitches disssolving through the
holes made in the spiral blank) said spiral serves to
secure tissues K1 and K2 to each other preventing the
separation or sliding 'thereof relative to each other.
The invention and its applicability is described in
more detail by means of the following examples.
EXAMPLE 1.
Some polymers set forth in table 1 were used to prepare
helical devices of the invention, such as that shown
20
in fig. 10 (blank thickness 1 mm, outer diameter of
helix 6 mm, inner diameter 4 mm, pitch angle 15 degrees
and length of device 20-50 mm), by subjecting the
polymeric melt to injection moulding to produce blanks
having a diameter (~) of 1.5 - 2.0 mm by drawing
(orientation and self-reinforcement) them at a tempe-
rature of Tm > T > Tg (wherein Tg is polymer glazing
temperature and Tm is polymer (possibly) melting
temperature) to the QS reading of 1 mm and by winding
them in hot state around a metal pipe (diameter 4 mm)
as well as by cooling the device and by removing the
finished device from the surface of the metal pipe.
Reference materials were made by using similar polymers
to prepare tubular pieces (tube length 10 mm, outer
diameter 6 mm and inner diameter 4 mm) by injection
moulding polydmer melt into a Gaoled tubular mould.
The compression strength of the devices and that of the
corresponding tubes were compared to each other by
squeezing a device (fig. 14b) or a tube (fig. 14a)
placed between two steel plates with an external
force in the direction orthogonal to its longitudinal
axis. The bending of a device in lateral direction
was prevented by prepressing the device into a compact
bundle between two vertical plates (fig. 14b).
The compression load strengths of a tube (fig. 14a) and
a device (fig. 14b) made of the same polymer and having
equal weights were compared to each other. This was
followed by the determination of the relative compres-
sion load strength (SP) of the device - a force
required to fracture the device/a force required to
fracture the tube. Devices and tubes were manufactured
by using the following biodegradable polydmers,
copolymers and polymer compositions: polyglycolide
(Mw 60 000), glycolide/lactide copolymer (Mw 40 000),
21
glycolide/trimethylenecarbonate copolymer (Mw 60000),
PLLA (Mw 260 000), PDLLA (Mw 100 000), lactide/8-
valerolactone copolymer (Mw 60 000), lactide/E-capro-
lactone copolymer (Mw 60 000), PHBA (Mw 700 000),
PHPA (Mw 50 000) and PDS (Mw 40 000). Resulting
values for SP were ranging between 1.8 - 12.
EXAMPLE 2.
Devices of the invention such as that shown in fig. 10
were prepared by using a biodegradable polymer matrix
as well as biodegradable reinforcing fibres included
threin as reinforcements by compression moulding a
bundle of parallel fibres and fine particulate polymer
powder (particle size 1-10 Vim) mixed therein (thermo
plastic polymers) in a rod-shaped mould (length 8 cm,
1.5 mm) above the melting point (partially crystal
line polymers) or glazing point (amorphous polymers)
of the matrix polymer: The amount of reinforcing
fibres was 40-60 ~ by volume. The rod blanks were
wound in a heated condition helically around a hot
cylindrica l mould (outer diameter of helix 8 mm) and
the mould was cooled. When using a reaction polymer
(n-butylcyano acrylate) as a matrix, the bundle of
reinforcing fibres was rapidly impregnated with
cyanoacrylate and the uncured wetted bundle of threads
was wound helically around a teflon-coated steel pipe
followed by wetting and removing the device. A
corresponding device was made by using just cyano
acrylate.
Impregnation technique was also applied when using a
matrix containing segmented polyurethane (S. Gogolewski
and A. Pennings, Makromol. Chem. Rapid Comm. 4, 1983,
p. 213) which was dissolved in N,N°'-dimethylformamide-
/tetrahydrofurane solution (weight ratio 3/2). Then,
the bundle of fibres helically wound on the surface
of a teflon-coated pipe was impregnated at 80 degrees
22
with a polyurethane solution and the pipe was immersed
in a mixture of ethanol/distilled water (1:1). This
process was repeated several times for preparing the
device. A corresponding device was made by using
just polyurethane.
Devices corresponding to such reinforced devices were
also manufactured from mere thermoplastic matrix
polymers by the application of melt working technique.
Table 2 illustrates the matrix polymers and fibrous
reinforcements for the devices prepared.
23
Table 2. Structural components
for fibre-reinforced
biodegradable devices.
Matrix polymer Fibre reinforcement
PDS PGA
-"- PGA/TMC
-"- PGA/PLLA
-"- PLLA
_"_ PHBA
-"- PHBA/HVA
-"- Chitin fibre
-"- PDS
PDLLA PGA
_"_ PGA/TMC
_ PGA/PLLA
_ PLLA
_"_ pHBA
-"- PHBA/HVA
_"_ PDS'
-"- PALLA
PLLA PGA
-"- PGA/TMC
'
_"- PLLA
PVA PGA
-" PGA/TMC
"_ PGA/PLLA
_"_ ~LLA
" pHBA
" pHBA/HVA
-"- pDS
-"- Chitin fibres
PGA/TMC PGA
- PGA/TMC
PHBA PGA
-"- PGA/TMC
-"- pHBA
Poly-E-caprolactone PGA
-"- PGA/TMC
4 _ " -- PHBA
5
Methylmetacrylate- PGA
N-vinylpyrrolidone
Polyurethane PGA
Collagen (catgut)
PEO PGA
_ - PGA/TMC
"- PGA/PLA
"_ PLLA
n-Butylcyano- Collagen (catgut)
acrylate PGA
~~~.~~'7~
24
The devices were secured by their ends to a tension
apparatus and were drawn until broken in the direction
of the longitudinal axis of the device (winding axis
of the blank). This was followed by the determination
of the relative tensile load-bearing strength (SV) of
a reinforced device = a force required to fracture a
reinforced device/a force required to fracture a
corresponding non-reinforced device. The SV values
were ranging between 1.5 - 8.
EXAMPLE 3.
Preparation of a self-reinforced polylactide device as
shown in fig. 10 (hereinb~low "heli:x" (KR) (raw
material poly-L-lactide/poly-DL-lactide copolymer
(PLLA/PDLLA molar ratio 80/20), Mw = 60 000). Helix
(KR) was manufactured from a thick, extrusion-made
PLLA/PDLLA rod which was drawn to a drawing ratio of
a = 7 at a temperature of 90 degrees for self-rein
forcing the material. A thus prepared self-reinforced
rod having a thickness of l mm was then wound to form
"a helix" as described in example 1. The helix was
cut into lengths of 12 mm for the following examina
tion.
The gastric cavity of a dog was opened in general
anaesthesia, the rotes roes were set aside and the bile
duct (ST) was exposed by preparation (see fig. 15).
A roughly 6 mm long incision (AK1) was made threin.
As shown in fig. 15a, a distance of 5 mm of this
incision was provided with non-resorbable stitches
(KO) (which pucker up the duct and narrow it permanent-
ly together with a cica~rical tissue formed on incision
(AK1). This was followed by closing the gastric
cavity, stitching the skin and, after waking up from
anaesthesia, the dog was allowed to move freely in
its cage. After one month the dog was re-anesthetized,
25
the gastric cavity was incised and the blocked bile '
duct was prepared to re-expose it. The duct was
opened with a longitudinal incision (AK2) at the
region of cicatricial pucker, a helix having an inner
diameter of 2 mm and an outer diameter of 3 mm was
inserted in the bile duct in a manner that both of
its ends were located in healthy bile duct and its
central portion within the incised pucker region.
The bile duct was closed with a stitch (0), whereby
its walls extended around the spiral. The situation
is schematically illustrated in the cross-sectional
figure 15c. After the operation, the bile duct was
normal in volume. The gastric cavity and skin were
closed the same way as in the first operation. The
dog was put away after 14 months by~which time the
helix had nearly disappeared and the bile duct had a
normal extent and volume and the pucker was no longer
macroscopically observable.
EXAMPLE 4.
The femoral vein (RL in fig. l6a) of a dog was cut in
general anaesthesia in the right hind leg. The base
portion of the more distal vein wasthreaded into the
interior of a biodegradable, reinforced device ("hel-
ix") having an inner diameter of 8 mm and an outer
diameter of 9 mm and a length of 2 am, said device
being like the one shown in fig. 10 (reinforcing
fibres: Ca/P-fibres; matrix polymer PLLA, Mw - 100
000; fibre/polymer weight ratio - 30/70 (w/w) and
vein (LO) was stitched with end-to-end technique by
using a resorbable 6-0 yarn to make a tight seam with
no bleeding. After the operation, due to the flabbi-
ness of the walls, the vein tended to collapse within
the region of the stitched seam and this leads to a
poorer circulation in the vein resulting easily in
the development of a coagulation or a clot formed by
blood particles within the region of the seam and
26
thus the vein will be blocked. The situation is
illustrated in the schematic view of fig. 16a from the
side of stitched seam and in fig. 16b from above a
stitched seam. Therefore, a biodegradable helix (KR)
was pulled over the seam portion with the stitched seam
remaining at the half-way point of helix (KR) . The
wall of a vein was attached at the stitched seam over
its entire circumference to the helix by means of non-
resorbable support stitches (TO) (fig. l6c). ,This way
the vein was tensioned to its normal extent with the
help of a support provided by the device. After the
seam had healed, especially after the inner surface
of a blood vessel or endothelium had healed, there is
no longer a risk of developing a clot and the helix can
resorb away with no harm done. After 6 months the dog
was put away and the femoral vein had healed without
a pucker or a clot.
EXAMPLE 5.
The test animals were male rabbits weighing 3'kg. The
animals were anesthetized for the operation with im.
ketamin and iv. pentobarbital preparations: A poly-
lactide blank (~ 1 mm) was used to prepare a helix
having an outer diameter of 8'mm and a length of 15
mm and an extension formed by athin tubular neck
section, 10 mm, followed by two helical coils (fig:
17).
The anesthetized test animals were subjected to a
surgical incision of the urinary bladder through
abdominal covers. Thxough the opened bladder the
prothesis was threaded into position with the narrow
neck section remaining within the region of closure
muscle and the helical coil ends on the side of the
urinary bladder.
27
The prothesis was fitted in 15 test animals which were
under observation for 3 months . The study verified
that an implant of the invention can be used for
preventing a lower urethra obstruction caused by the
enlargement of forebland.
EXAMPLE 6.
The test animals were male rabbits weighing appr. 3
kg. The animals were anesthetized for the operation
with im. ketamin and iv. pentobarbital preparations.
The implants employed were PLLA helixes as described
in example 1 (cross-section of blank circular, thick-
ness of blank l mm, outer diameter of helix 6 mm
and length 15 mm).
On the anesthetized test animals was performed scission
of the blind urethra to the extent suf f icient for a
prothesis . The prothesis was placed on the distal side
of closure muscle. In connection with the operation
an antibiotic as a single dose: ampicillin 100 mg/kg.
The prothesis was fitted in l5 animals which were put
away with iv overdose of anesthetic 2 weeks, 3 months,
6 months, 1 year and 2 years after the implantation.
The urethra was dissected and tissue samples were
taken for histological and electron microscopic
analysis.
Histological studies indicatedd that PLLA had caused
only slight foreign matter reaction in tissues. 2
years after the implantation the helix hadnearly
completely biodegraded and the urethra was almost
normal in its dimensions.
2 s ~r~.~~'''J~
EXAMPLE 7.
Cloggings in the ureters leading from kidney to bladder
will become more common as a result of the increased
observation surgery of upper urethras. The ureter
has a good regeneration ability when subjected lon-
gitudinal incision but its healing requires an internal
support. Transverse incision or short deficiency
always leads to the development of a clogging.
The purpose of this example was to examine the app
licability of a helix made of a biodegradable material
both to the healing of a longitudinal dissection of
the urethra and to the healing of a transverse de
ficiency.
The test animals were female rabbits weighing appr. 3
kg. The animals were anesthetized. Incision of the
abdominal cavity was performed on the flank without
opening, however, the actual abdominal cavity.
a) the urethra having a diameter of ca. 9 mm was
dissected lengthwise over'a distance of ca. 2, cm
followed by threading a self-reinforced PGA-helix
(blank thickness l mm) inside the urethra, said
helix having an outer diameter of 4 mm and a length
of 20 mm. The region of dissection was co~rered
with fat.
b) a length of ca. 1 cm was cut off the urethra, the
remaining ends were dissected over a distance of 0.5
cm and the above-described prothesis was threaded
in, so that the remaining defect zone of the tissue
was l cm. The defect zone was covered with sur-
rounding fat. After l month, 3 months and Z year
from the operation a tracer imaging of the kidneys
29
was performed for observing the healing of urethra.
The operated urethras had healed to almost normal
condition over the period of 1 year (on the basi s
of tracer imaging).
