U.S. patent application number 15/183258 was filed with the patent office on 2016-12-15 for medical device and its manufacture.
This patent application is currently assigned to BIORETEC OY. The applicant listed for this patent is BIORETEC OY. Invention is credited to Timo Allinniemi, Harri Heino, Kaarlo Paakinaho, Pertti Tormala.
Application Number | 20160361103 15/183258 |
Document ID | / |
Family ID | 38951577 |
Filed Date | 2016-12-15 |
United States Patent
Application |
20160361103 |
Kind Code |
A1 |
Paakinaho; Kaarlo ; et
al. |
December 15, 2016 |
Medical Device and Its Manufacture
Abstract
A biodegradable medical device including at least one
biodegradable material and having an initial shape and at least one
evolved shape. The evolved shape is different from the initial
shape. The initial shape is adapted to change towards the evolved
shape due to an external stimulus. The medical device has a tension
loaded to a predetermined tension level. The medical device is
adapted to resore the tension to the predetermined tension level
for at least 2 weeks in physiological conditions, or conditions
simulating the physiological conditions.
Inventors: |
Paakinaho; Kaarlo; (Tampere,
FI) ; Heino; Harri; (Tampere, FI) ; Tormala;
Pertti; (Tampere, FI) ; Allinniemi; Timo;
(Lempaala, FI) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BIORETEC OY |
Tampere |
|
FI |
|
|
Assignee: |
BIORETEC OY
Tampere
FI
|
Family ID: |
38951577 |
Appl. No.: |
15/183258 |
Filed: |
June 15, 2016 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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12329044 |
Dec 5, 2008 |
9393060 |
|
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15183258 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 2017/8655 20130101;
A61B 2017/0427 20130101; A61B 17/8605 20130101; A61B 2017/00004
20130101; A61L 31/06 20130101; A61L 31/148 20130101; A61B 17/844
20130101; A61B 2017/00871 20130101; A61L 31/06 20130101; A61B
17/866 20130101; A61B 17/7275 20130101; A61B 2017/00867 20130101;
A61B 17/7266 20130101; C08L 67/04 20130101; C08G 63/08 20130101;
A61B 17/66 20130101; A61B 17/8625 20130101; A61B 17/72 20130101;
A61B 2017/681 20130101; A61L 31/14 20130101 |
International
Class: |
A61B 17/86 20060101
A61B017/86; A61B 17/84 20060101 A61B017/84 |
Foreign Application Data
Date |
Code |
Application Number |
Dec 5, 2007 |
FI |
FI20075881 |
Claims
1. A biodegradable orthopedic device for bone fracture fixation,
said device being formed of one piece and comprising a continuous
elongated shaft made of at least one biodegradable polymer material
having an oriented polymer structure so as to have a predetermined
tension level of between 5N and 260N; the device having an initial
shape and at least one evolved shape, the at least one evolved
shape being different from the initial shape, and the initial shape
being adapted to change towards the at least one evolved shape due
to an external stimulus, wherein the change includes a full length
longitudinal shrinking and a full length radial expansion of the
continuous elongated shaft, such that the full length longitudinal
shrinkage of said device pulls bone fragments together thereby
tightening the bone fragment fixation, and wherein the external
stimulus is an aqueous environment and temperature of 35 to
42.degree. C.
2. The biodegradable orthopedic device according to claim 1,
wherein said device is adapted to restore its tension to the
predetermined tension level by change of dimensions by reducing the
tension level if the bone fragment fixation is too tight or too
loose.
3. The biodegradable orthopedic device according to claim 1,
wherein said device has a predetermined rate of changing from the
initial shape towards the at least one evolved shape.
4. The biodegradable orthopedic device according to claim 1,
wherein said device has a predetermined shape between the initial
shape and the at least one evolved shape until which it changes
towards the at least one evolved shape.
5. The biodegradable orthopedic device according to claim 1,
wherein said device comprises at least one homopolymer, copolymer,
or a polymer blend.
6. The biodegradable orthopedic device according to claim 5,
wherein said device comprises a copolymer of lactide and glycolide
or a copolymer of D-lactide and L-lactide.
7. The biodegradable orthopedic device according to claim 6,
wherein the copolymer of lactide and glycolide comprises from 5
wt.-% to 95 wt.-% of lactide and from 95 wt.-% to 5 wt.-% of
glycolide.
8. The biodegradable orthopedic device according to claim 6,
wherein the copolymer of D-lactide and L-lactide comprises from 2
wt.-% to 98 wt.-% of D-lactide and from 98 wt.-% to 2 wt.-% of
L-lactide.
9. The biodegradable orthopedic device according to claim 1,
wherein the continuous elongated shaft has grooves in the at least
one evolved shape.
10. The biodegradable orthopedic device according to claim 9,
wherein the grooves in the at least one evolved shape are
longitudinal.
11. The biodegradable orthopedic device according to claim 9,
wherein the grooves in the at least one evolved shape are in a form
of threads.
12. The biodegradable orthopedic device according to claim 9,
wherein said device comprises a head.
13. The biodegradable orthopedic device according to claim 12,
wherein said device is a screw.
14. The biodegradable orthopedic device according to claim 12,
wherein said device is a tack.
Description
PRIORITY
[0001] This is a continuation application of U.S. patent
application Ser. No. 12/329,044 filed on Dec. 5, 2008 and claiming
priority of the Finnish national application number F1200755881
filed on Dec. 5, 2007, the contents of both of which is
incorporated herein by reference.
BACKGROUND
[0002] H. Heino, P. Tormala, J. Ilomaki: "Influence of
Self-Reinforcing on In Vitro Stress Relaxation of 70L/30D,L PLA",
Conference abstract (oral presentation): 7.sup.th World
Biomaterials Congress 16-21 May 2004, Sydney, Australia, discloses
not self-reinforced (not oriented) samples and self-reinforced
(oriented) samples made 70L/30D,L PLA which were fixed to a sample
holder and placed in phosphate buffer solution at 37.degree. C. The
self-reinforced samples tended to keep a certain level of stress
after 7 days testing period, whereas the not oriented samples had
no significant residual stress left after 1 day.
[0003] Publication US 2005/0033295 discloses implants formed of
shape memory polymeric material for spinal fixation. The shape
memory polymeric material may be biodegradable or
non-biodegradable. The polymeric material tends to assume its
memory condition by activation of a polymer transition. The
activation can occur e.g. by adsorption of liquid by the polymer
because the polymer may be formulated to be responsive to
adsorption of a liquid by incorporating in the polymer a
hydrophilic material.
SUMMARY OF THE INVENTION
[0004] The present invention provides a biodegradable medical
device which has in physiological conditions the ability to undergo
a dimensional change with a predetermined rate and extent, being at
the same time able to exert predetermined forces on the healing
tissues for a predetermined time, e.g. the medical device can exert
compression on the healing tissues in the bone fracture or
osteotomy fixation. For example, when a fixation is too tight or
too loose, the medical device can restore the fixation tension to
the predetermined level either by increasing the fixation tension
due to the dimensional change, or by reducing the tension due to
the stress relaxation of the material. The medical device is also
adapted to change from its initial shape towards an evolved shape.
When the medical device has an elongated structure, i.e. it is, for
example, a screw, a pin, a tack or a nail, the medical device is
able to increase its diameter and therefore the fixation strength
between the medical device and the surrounding living material,
e.g. bone, increases. The medical device can be activated by a
stimulus of liquid in physiological conditions, or in conditions
which simulate the physiological conditions. The molecules of the
liquid reduce the energy level which is required for the
dimensional change of the material. Due to the above-mentioned
properties, the medical device is also insensitive to defects which
may take place during a surgical operation or after it. Such
defects can be, for example, the diameter of a drill hole in a bone
may be too large, a surgeon may tighten a medical device too much,
or parts of a fracture may move in respect of each other so that
the tension in the device joining the parts of the fracture
changes.
[0005] The importance of the compression in bone healing has been
described, for example, in the Manual of Internal Fixation,
Techniques recommended by AO-Group, 1979, p. 12. The international
Association for the Study of Internal Fixation (AO/ASIF) has
studied the effect of compression, and according to their studies,
compression greatly enhances the stability of internal fixation.
They also show that bone itself is able to maintain compression;
thus, it is feasible to expect that the compression of the fixation
device over the healing period can have a positive effect on bone
healing.
[0006] Another example of an application offering benefit over the
prior art made of the material of the present invention is a
distraction osteogenesis device, bone distractor. Distractors are
used to facilitate the modification of anatomy of bone structures
by bone growth stimulated and guided by a movement created by a
distractor device. The distractor device made using the technology
of the present invention offers continuous movement with controlled
rate, end point and force. Most often prior art distractors are
operated manually, thus the movement is rather periodical than
continuous. Manual operation requires access to the device, which
always possess an increased infection risk.
DESCRIPTION OF THE INVENTION
[0007] The present invention relates to a biodegradable medical
device which is made of at least one biodegradable material. The at
least one biodegradable material may be selected from among
homopolymers or copolymers. However, the medical device may be made
of more than one biodegradable material. The biodegradable material
may be a blend of two or more homopolymers or copolymers so that
the blends may comprise only homopolymers, only copolymers, or at
least one homopolymer and at least one copolymer. The material may
also be made of at least one polymeric component, such as a
homopolymer or copolymer, and at least one auxiliary agent. The
auxiliary agent may consist, for example, of monomers or a
hydrophilic component. The medical device may also comprise
mechanically active and non-active components, each one of them
made of biodegradable material.
[0008] The biodegradable polymeric materials may be selected, for
example, from among the following materials: polyglycolide (PGA),
copolymers of glycolide, polylactides, copolymers of polylactide,
unsymmetrically 3,6-substituted poly-1,4-dioxane-2,5 diones,
poly-.beta.-hydroxybutyrate (PHBA), PHBA/.beta.-hydroxyvalerate
copolymers (PHBA/HVA), poly-.beta.-hydroxypropionate (PHPA),
poly-p-dioxanone (PDS), poly-.delta.-valerolactone,
poly-.epsilon.-caprolactone, methylmethacrylate-N-vinyl pyrrolidine
copolymers, polyesteramides, polyesters of oxalic acid,
polydihydropyrans, polyalkyl-2-cyanoacrylates, polyurethanes (PU),
polyvinylalcohol (PVA), polypeptides, poly-.beta.-malic acid
(PMLA), poly-.beta.-alkanoic acids, polyethyleneoxide (PEO) and
chitine polymers. Copolymers of glycolide comprise, for example,
glycolide/L-lactide copolymers (PGA/PLLA) and
glycolide/trimethylene carbonate copolymers (PGA/TMC). Polylactides
comprise, for example, poly-L-lactide (PLLA), poly-D-lactide (PDLA)
and poly-DL-lactide (PDLLA). Copolymers of polylactide comprise,
for example, L-lactide/DL-lactide copolymers, L-lactide/D-lactide
copolymers, lactide/tetramethylglycolide copolymers,
lactide/trimethylene carbonate copolymers,
lactide/.delta.-valerolactone copolymer,
lactide/.epsilon.-caprolactone copolymer, polydepsipeptides
(glycine-DL-lactide copolymer), polylactide/polyethylene oxide
copolymers, glycolide/L-lactide (PGA/PLLA)/polyethylene glycol
(PEG) copolymers and polylactide/polyethylene glycol (PEG)
copolymers.
[0009] The medical device may also be reinforced by reinforcing the
material by using fibres manufactured of a resorbable polymer or of
a polymer alloy, or with biodegradable ceramic fibres, such as
.beta.-tricalciumphosphate fibres or bioactive glass fibres.
Ceramic powders can also be used as additives or fillers in the
medical device to promote new bone formation.
[0010] Further, the medical device may comprise various
biocompatible additives for facilitating the processability of the
material (e.g. stabilizers, antioxidants or plasticizers) or for
changing its properties (e.g. plasticizers or ceramic powder
materials or biostable fibers, such as carbon) or for facilitating
its treatment (e.g. colorants).
[0011] The medical device may also contain some other bioactive
additive(s), such as antibiotic(s) or other drug(s),
chemotherapeutic agents, agents activating the healing of wounds,
growth factor(s), bone morphogenic protein(s), anticoagulant (such
as heparin) etc. Such bioactive medical devices are particularly
advantageous in clinical use, because they have, in addition to
their mechanical effect, also biochemical, medical and other
effects to facilitate tissue healing and/or regeneration.
[0012] The medical device has an initial shape and at least one
evolved shape. The evolved shape is different from the initial
shape. The initial shape is adapted to change towards the evolved
shape in physiological conditions, physiological conditions meaning
aqueous environment and temperature at the range of 35.degree. C.
to 42.degree. C. In other words, the initial shape is the shape
which the medical device has after it has been manufactured, and
the evolved shape is the shape towards which the shape of the
medical device changes when the medical device is activated in
physiological or similar conditions. Thus, the shape-changing
behavior of the medical device can also be observed outside the
bodily conditions. It should be noted that the change from the
initial shape to the evolved shape does not take place in dry
conditions but the phenomenon requires the stimulus of the liquid
in physiological conditions, or in conditions simulating the
physiological conditions.
[0013] The medical device can be manufactured so that it has a
predetermined speed to change towards the evolved shape. The
biodegradable medical device is also programmed to change towards
the evolved shape but it does not necessarily reach the evolved
shape but there is a predetermined shape between the initial shape
and the evolved shape until which the medical device changes
towards the evolved shape.
[0014] The dimensional change which takes place during the change
from the initial shape towards the evolved shape is more than 2%
but it is often equal to or greater than 5%. For example, the
diameter of an elongated medical device, such as a nail, screw, pin
or tack, may increase so that its diameter is more than 2% and in
the preferred case more than 5% larger than in its initial
shape.
[0015] The medical device is also loaded to have a predetermined
tension. The method how the medical device may be loaded with the
predetermined tension will be explained below. The medical device
is adapted to restore its tension to the predetermined tension
level for at least 2 weeks under physiological conditions, i.e. for
at least 2 weeks after implantation or for at least two weeks in a
simulated body fluid at a temperature of 37.degree. C. The
simulated body fluid is a phosphate buffer solution or other liquid
simulating the conditions of human tissues. In order to observe
this tension-restoring ability of the medical device in vitro, the
medical device must be rigidly fixed (locked) in its place and it
must be immersed in a liquid at physiological temperature. It
should be noted that the medical device is adapted to restore its
tension regardless of external loads exerted on it provided that
the loads are reasonable in regard to the load carrying capacity of
the medical device.
[0016] Due to the predetermined tension which has been loaded in
the medical device, the medical device tends to restore its tension
to the predetermined tension level. When the tension of the medical
device is below the predetermined tension, the medical device
contracts and restores the predetermined tension. This may happen,
for example, when the fixation is too loose. The speed of
contraction can also be adjusted in advance during the manufacture
of the medical device. When the tension of the medical device is
above the predetermined tension, the medical device reduces the
tension through a controlled stress relaxation so that the
predetermined tension is achieved. This may happen, for instance,
when a surgeon has tightened the medical device over the
predetermined tension.
[0017] As one can readily understand, the time range during which
the medical device is able to restore its tension level is
adjustable. The time range should be adjusted so that it is
sensible in respect of the healing period of an injury. It is
natural that the ability to restore the predetermined tension
weakens when the medical device has achieved a certain point in
degrading. However, periods that are significant in regard to the
healing of the injury are easily achievable. For example, two weeks
may be an adequate period for the initial consolidation of a bone
fracture or a growth plate fracture of a small baby, but four to
six weeks may be required to achieve the consolidation of
cancellous bone fracture in the case of adults.
[0018] The method of the invention for manufacturing a
biodegradable medical device starts by the selection of at least
one biodegradable material. After the material selection, a preform
is formed via melt processing of at least one biodegradable
material. In the melt processing step, granular raw materials are
molten, mixed and subsequently given the desired form. The
preferred methods for forming the preform are extrusion, injection
moulding and compression moulding. The extrusion process yields a
continuous preform profile, whereas the injection moulding and
compression moulding can be used to manufacture preform parts. Twin
screw extrusion is a preferable melt processing method due to its
mixing efficiency, which enables the production of good quality
preforms with one or more auxiliary components. Depending on the
raw materials, the processing temperatures in the melt processing
may vary between 50.degree. C. and 300.degree. C.
[0019] After the melt processing, the preform possesses a
non-oriented original shape. A deformation process follows the melt
processing step. The deformation process actually creates the
mechanical activity properties of the material. In the deformation
process, the preform is deformed at a temperature which is adequate
to cause a temporary change in its shape so that the deformed
preform achieves the initial shape of the medical device. The
deformation process may be, for example, die drawing, free drawing,
twisting, ring enlargement, compression, or bending. Practically
any deformation made in the material can be recovered as mechanical
activity in physiological conditions. The deformation takes place
at a temperature which is above the glass transition temperature
and below the melting temperature of the material. The direction
and the maximal extent of movement are defined in this processing
step. In practice, the theoretical maximum mechanical activity
movement is equal to the deformation applied in this processing
step.
[0020] In the deformation process, the preform is loaded with a
predetermined tension. The level of the predetermined tension
depends on the temperature and the deformation ratio, e.g. the draw
ratio. The predetermined tension, i.e. the force level, is adjusted
in the deformation process by changing the deformation temperature.
At low temperatures, high forces are required to create the
deformation, and therefore, the medical device is able to produce
high forces when it is in use in physiological conditions or
conditions simulating the physiological conditions. At high
temperatures, only low forces are required to cause the deformation
and therefore, the medical device is able to produce only low
forces in use in physiological conditions or conditions simulating
the physiological conditions.
[0021] In the following step, the deformed preform is cooled while
still maintaining the predetermined level of stress, and the
initial shape and the predetermined tension is fixed. In order to
create certain features in the medical device, a finishing step may
be required. However, the finishing step may be omitted. The
finishing step may include at least one of machining or
thermoforming. In the finishing step after the deformation, care
must be taken to preserve the mechanical activity in the desired
areas. For example, thermoforming of the head for a contraction
nail removes the mechanical activity properties of the head due to
the deformation towards the direction in which the mechanical
activity would drive the material. This is, however, beneficial in
this case, because the head of the nail is preferably dimensionally
stable and the activity comes from the shaft. Mechanical activity
properties can also be modified by treating the material thermally
or mechanically after the deformation process. A tubular rod which
would decrease in length and increase in diameter can e.g. be
thermally treated on one side to partially release the stresses
created in the deformation process, whereby a rod is created which
will curve strongly when the mechanical activity properties are
activated. A similar effect can be achieved with asymmetrical
machining of the material. Finally, the ready-made medical device
is sterilized, for example, by gamma irradiation.
[0022] The raw material selection defines a frame for the strength
and for the strength retention time but also sets some limits on
the mechanical activity. The properties of the medical device are
mainly adjusted by the raw material selection and the manufacturing
method. As stated before, there is a vast selection of raw
materials available. By selecting the raw materials and determining
their amounts, it is possible to obtain the desired properties for
the medical device. As also stated before, the material selection
can be made from among homopolymers, copolymers, or blends. A
polymeric component or polymeric components may be accompanied by
at least one auxiliary agent. The auxiliary agent may consist of
monomers. The monomers may be fed, for example, into an extruder
and mixed with the polymeric component. However, the monomer can
also be generated in the material by increasing the processing
temperature to a level which enables spontaneous monomer generation
through thermal degradation of the polymer. For example, a
copolymer of glycolide and lactide may have an L-lactide monomer as
an auxiliary agent.
[0023] The biodegradable medical device may also consist of a
copolymer of D-lactide and L-lactide. The copolymer of D-lactide
and L-lactide may comprise D-lactide from 98 wt.-% to 2 wt.-%, and
L-lactide from 2 wt.-% to 98 wt.-%. For example, the material may
be PLA 50D/50L.
[0024] The biodegradable medical device may also comprise a
copolymer of L-lactide and DL-lactide. The copolymer of L-lactide
and DL-lactide may comprise L-lactide from 96 wt.-% to 4 wt.-% and
DL-lactide from 4 wt.-% to 96 wt.-%. For example, the material may
be PLA 70L/30DL. In addition to the copolymer of L-lactide and
DL-lactide, the medical device may comprise L-lactide monomers.
Their content may range from 0.1 wt.-% to 10 wt.-%.
[0025] The biodegradable medical device may also comprise a blend
of a copolymer of lactide and glycolide and a copolymer of
D-lactide and L-lactide. The copolymer of lactide and glycolide may
comprise from 5 wt.-% to 95 wt.-% of lactide and from 95 wt.-% to 5
wt.-% of glycolide. The copolymer of D-lactide and L-lactide may
comprise from 98 wt.-% to 2 wt.-% of D-lactide and from 2 wt.-% to
98 wt.-% of L-lactide.
DETAILED DESCRIPTION OF THE INVENTION
[0026] In the following, the invention will be described by
referring to the appended drawings in which
[0027] FIG. 1 shows a diagram on combined stress relaxation and
force generation test data for a mechanically active material
according to the present invention,
[0028] FIGS. 2a and 2b show a preform of a medical device in which
the mechanical shape memory is programmed to open a closed
fork,
[0029] FIGS. 3a and 3b show a preform of a medical device in which
the mechanical shape memory is programmed to bend one of the two
halves of a fork,
[0030] FIGS. 4a and 4b show a preform of a medical device in which
the mechanical shape memory is programmed to bend the initial rod
or other shape according to predefined programming,
[0031] FIGS. 5a and 5b show a preform of a medical device in which
the mechanical shape memory is programmed to bend the initial rod
or other shape according to predefined programming,
[0032] FIGS. 6a and 6b show a preform of a medical device in which
the mechanical shape memory is programmed to bend the initial rod
or other shape according to predefined programming,
[0033] FIGS. 7a, 7b and 7c show the cross-section of a preform of a
medical device,
[0034] FIGS. 8a, 8b and 8c show a perspective view of the preform
of the medical device of FIG. 7,
[0035] FIGS. 9a, 9b and 9c show the cross-section of a preform of a
medical device,
[0036] FIGS. 10a, 10b and 10c show a perspective view of the
preform of the medical device of FIG. 9,
[0037] FIGS. 11a, 11b and 11c show the cross-section of a preform
of a medical device,
[0038] FIGS. 12a, 12b and 12c show a perspective view of the
preform of the medical device of FIGS. 11a, 11b and 11c,
[0039] FIGS. 13a, 13b and 13c show the cross-section of a preform
of a medical device,
[0040] FIGS. 14a, 14b and 14c show a perspective view of a preform
of a medical device,
[0041] FIGS. 15a, 15b and 15c show the cross-section of a preform
of a medical device,
[0042] FIGS. 16 and 17 show a perspective view of a medical device
for distraction osteogenesis,
[0043] FIGS. 18 and 19 show a perspective view of a medical device
for bone fracture fixation,
[0044] FIGS. 20 and 21 show a schematic view of a medical device
when it is used for bone fracture fixation,
[0045] FIGS. 22a and 22b show a perspective view of a medical
device; in this case the medical device is a medical fastener,
[0046] FIGS. 23a, 23b and 23c shows a perspective view of a medical
device; in this case the medical device is a fastening band,
[0047] FIGS. 24a and 24b shows a perspective view of a medical
device for fracture fixation of soft tissue fixation to the
bone,
[0048] FIGS. 25a and 25b show the cross-section of a medical
device, FIGS. 26a and 26b show a perspective view of the medical
device of FIGS. 25a and 25b,
[0049] FIGS. 27a and 27b show a perspective view of a medical
device,
[0050] FIG. 28 shows a perspective view of a medical device, in
this case a screw,
[0051] FIG. 29 shows a diagram on the effect of L-lactide monomer
(auxiliary component) content on the dimensional changes in
physiological conditions,
[0052] FIG. 30 shows a diagram on the effect of blending of
dimensionally stable and dimensionally unstable polymers on the
dimensional changes in physiological conditions,
[0053] FIG. 31 shows a diagram on the dimensional changes of PLA
50L/50D and PLGA 85L/15G blends,
[0054] FIG. 32 shows a diagram on the effect of the deformation
force on the residual force in stress relaxation testing, and
[0055] FIG. 33 shows dimensional changes of P(L/D)LA 50/50 in
37.degree. C. dry environment and in 21.degree. C. and 37.degree.
C. aqueous environment.
THE MATERIAL PROPERTIES
[0056] The material of the present invention shows controllable
mechanical activity properties. The material has the ability to
contract at a predetermined contraction speed to a predetermined
extent, being able to produce a predetermined force in a
predetermined direction. On the other hand, when excess stress is
applied to the material, the material reduces the stress due to the
controlled stress relaxation to a predetermined level. The FIG. 1
shows a diagram on the test results of a combined stress relaxation
and contraction test.
[0057] The predetermined tension of the medical device was adjusted
to be 100 N.
[0058] The test is made by first attaching a 3 mm thick rod at both
ends in the test system. The test is carried out in a phosphate
buffer solution at 37.degree. C. The composition of the buffer
solution is: 0.0546 mol/l of Na.sub.2HPO.sub.4 and 0.0121 mol/l of
KH.sub.2PO.sub.4. The pH of the solution is 7.4.+-.0.2. The
contraction force which the sample is able to generate is measured,
but no contraction is allowed. The sample gradually generates a
force of about 100 N. In the next step, the sample is mechanically
stressed up to 250 N and the system is locked in position. The
sample starts to gradually decrease the stress down to slightly
above 100 N, although no contraction of the sample is allowed. The
sample tends to keep this achieved stress level. The stress of the
sample is again mechanically relieved and the position is locked.
The sample is again capable of generating a force of about 100 N in
the test system. One more tensioning to 250 N yields similar
gradual decrease down to 100 N as noted previously. In a summary,
the stress level is programmed to the material and it tends to keep
it in spite of the disturbances from the environment.
[0059] In general, the above described test method may be used to
test the medical device in regard to its ability to maintain the
predetermined tension level.
The Medical Device Solutions
[0060] There are various ways to utilize the mechanical activity in
bioabsorbable medical devices. Some examples of medical devices
based on mechanically active shape memory polymers are presented
below.
[0061] FIGS. 2a and 2b show a preform of a medical device in which
the mechanical shape memory is programmed to open a closed fork.
FIG. 2a shows the preform of the medical device in its initial
condition and FIG. 2b shows the preform of the medical device when
it has been changed towards the evolved shape.
[0062] The mechanical shape memory is based on the fact that the
oriented and stressed polymer chains contract towards the initial
non-oriented state. When the orientation is removed from the inner
side of the fork spikes 1, the oriented and stressed polymer chains
contract towards the original non-oriented state thus the sides of
the fork tend to bend outwards. The bending will continue until the
stress between the inner and the outer side of the fork spikes 1
are in the same level of stress or until an external stress exerted
on the article is as great as the stress generated by the
contracting polymer chains. The degree of bending can be adjusted
by adjusting the temperature and time, which are to deorient the
selected parts of the preform.
[0063] FIGS. 3a and 3b show a preform of a medical device in which
the mechanical shape memory is programmed to bend one of the two
halves of a fork. FIG. 3a shows the preform of the medical device
in its initial condition and FIG. 3b shows the preform of the
medical device when it has been changed towards the evolved
shape.
[0064] When the orientation is removed from the inner side of one
of the fork spikes 1, the oriented and stressed polymer chains
contract towards the initial non-oriented state; thus, the spike of
the fork is bent. The bending will continue until the stress
between the inner and the outer sides of the fork spikes 1 are in
the same level of stress or until an external stress exerted on the
article is as great as the stress generated by the contracting
polymer chains. Spikes 1 which are not thermally treated will not
tend to bend due to the homogeneity of the internal stress of the
polymer spike.
[0065] FIGS. 4a and 4b show a preform of a medical device in which
the mechanical shape memory is programmed to bend the initial rod
or other shape according to predefined programming. FIG. 4a shows
the preform of the medical device in its initial condition and FIG.
4b shows the preform of the medical device when it has been changed
towards the evolved shape.
[0066] The programming is based on the controlled removal of the
oriented polymer structure. The rod or other shape will tend to
bend to the opposite side from which the orientation has been
removed. The degree of shape change can be adjusted according to
thermal treatment of the polymer article or by controlling the
oriented polymer structure itself.
[0067] FIGS. 5a, 5b, 6a and 6b show a preform of a medical device
in which the mechanical shape memory is programmed to bend the
initial rod or other shape according to predefined programming.
FIGS. 5a and 6a show the preform of the medical device in its
initial condition, and FIGS. 5b and 6b show the preform of the
medical device when it has been changed towards the evolved shape.
The thermal treatment is performed on opposite sides of the halves
of the rod. Thus the shape tends to shift towards the S-shape.
[0068] FIGS. 7a, 7b and 7c show the cross-section of a preform of a
medical device and FIGS. 8a, 8b and 8c show a perspective view of
the preform of the medical device of FIG. 7. The medical device in
these drawings is a preform of a medical device in which the
mechanical shape memory is programmed to deform from a spherical
temporary shape to a spherical permanent shape. The shape change is
due to the mechanical activity of the material which has been
oriented for example in a die drawing process. The original and
permanent shape, which is shown is FIGS. 7a and 8a, is due to the
melt processing of the polymer. The polymer structure after melt
processing is non-oriented. After the die drawing, the polymer
structure is oriented (see FIGS. 7b and 8b) and this enables the
dimensional change towards the evolved and permanent structure,
which is shown in FIGS. 7c and 8c. As one can see from FIGS. 7a,
8a, 7c and 8c, the original shape of the preform of the medical
device corresponds to the evolved shape of the preform of medical
device. The diameter of the article expands as the length of the
article shortens. The contraction-expansion behavior can be
adjusted by the degree of the orientation.
[0069] FIGS. 9a, 9b and 9c show the cross-section of a preform of a
medical device, FIGS. 10a, 10b and 10c show a perspective view of
the preform of the medical device of FIG. 9. The preform of the
medical device in these drawings is a preform of a medical device
in which the mechanical shape memory is programmed to deform from a
spherical temporary shape to an ellipsoidal permanent shape. As in
above mentioned example, the original and permanent shape is in
non-oriented state. The article tends to change its shape towards
the evolved and permanent shape which is the ellipsoidal shape.
[0070] FIGS. 11a, 11b and 11c show the cross-section of a preform
of a medical device, FIGS. 12a, 12b and 12c show a perspective view
of the preform of a medical device of FIGS. 11a, 11b and 11c. The
preform of the medical device in these drawings is a preform of a
medical device in which the mechanical shape memory is programmed
to deform from a spherical temporary shape to an angular permanent
shape. As in the above mentioned example, the original and
permanent shape is in non-oriented state. The article tends to
change its shape towards the evolved and permanent shape which is
the angular shape, and which corresponds to the original permanent
shape.
[0071] FIGS. 13a, 13b and 13c show the cross-section of a preform
of a medical device, FIGS. 14a, 14b and 14c show a perspective view
of a preform of a medical device. The preform of the medical device
in these drawings is a preform of a medical device in which the
mechanical shape memory is programmed to deform from a spherical
temporary shape to a grooved spherical permanent shape. As in the
above mentioned examples, the original and permanent shape is in
non-oriented state. The article tends to change its shape towards
the evolved and permanent shape which is the grooved spherical
shape and corresponds to the original permanent shape.
[0072] The preform of the medical device may be useful in the
manufacture of a bioabsorbable, sterilizable polymeric or composite
bone fracture or osteotomy fixation device, such as a pin
comprising a shaft. The surface of the shaft is smooth in its
initial state but comprises longitudinal grooves in its evolved
state. Between the grooves there are naturally ridges. The fixation
device can also be a bioabsorbable tack (a pin with a widening
head) comprising a shaft. The surface of the shaft is also provided
with longitudinal grooves and ridges in its evolved state. The
fixation device may comprise a copolymer of L-lactide and
glycolide, the content of L-lactide ranging from 5 wt.-% to 95
wt.-% and the amount of glycolide ranging from 95 wt.-% to 5 wt.-%.
The fixation device may comprise L-lactide monomers as an auxiliary
agent. The content of L-lactide monomers may vary between 0.1 wt.-%
and 4 wt.-%. The predetermined tension of the medical device may
vary between e.g. 5 N and 250 N. For example, the pins having the
predetermined tension of 100 N are useful in the fixation of
cancellous bone fractures of foot and hand.
[0073] FIGS. 15a, 15b and 15c show the cross-section of a preform
of a medical device. The medical device in these drawings is a
medical device in which the mechanical shape memory is programmed
to deform from a ring or a tubular temporary shape to a ring or a
tubular permanent shape. As in the above mentioned examples, the
original and permanent shape is in non-oriented state. The article
tends to deform towards the evolved and permanent shape which
corresponds to the original permanent shape.
[0074] FIGS. 16 and 17 show a perspective view of a medical device
for distraction osteogenesis. The distraction device comprises
dimensionally stabile frame structure and a mechanically active
element 2. The mechanically active shape memory element of the
distraction device generates an expulsive force on the
dimensionally stable frame. As the mechanically active shape memory
element contracts, the contraction force is converted to an
expulsive force on the frame structure. As the frame structure is
fastened to bone tissue, the force generated by the mechanically
active element is transmitted to the bone tissue. The extrinsic
force transmitted to the bone tissue enforces the bone tissue to
grow in the direction of the applied force. The distraction device
can be composed of one or multiple contracting or expanding
elements which enable the movement of the fastened edges of the
device.
[0075] FIGS. 18 and 19 show a perspective view of a medical device
for bone fracture fixation. The mechanically active shape memory
device is comprised of a grooved head which enables the tight
initial fixation in the bone tissue and a contracting shaft which
generates a predefined compression on the fracture site. The
grooved part of the device tends to expand as the whole device
tends to contract according to the predefined material
programming.
[0076] FIGS. 20 and 21 show a schematic view of a medical device
when it is used for bone fracture fixation. In these drawings, the
medical device is an orthopedic nail for bone fracture fixation.
The orthopedic nail comprises a head 6, an elongated shaft 7 and a
tapering tip 8. On the shaft 7 there is a length which comprises
ridges 9 and, naturally, grooves therebetween. The head 6 comprises
a recess (not shown) for an implanting tool. The shape change is
shown in FIGS. 18 and 19. The initial mechanism of locking to bone
is achieved by the grooved shape near the tip of the nail. The
attachment to the bone is enhanced by the dimensional change of the
device. The oriented structure of the medical device tends to
contract, and at the same time, the diameter of the round device
tends to expand, thus enhancing the fixation to the bone. On the
other hand, the contraction, which occurs on the longitudinal axis
of the device, pulls the fixed bone fragments together and thus
tightens the fixation of the fracture site. As shown in FIG. 1, the
device is also capable of adjusting the stress level of the
fracture surface to a predefined level if the manual fixation is
too tight or too loose.
[0077] FIGS. 22a and 22b show a perspective view of a medical
device; in this case the medical device is a medical fastener. The
medical fastener comprises a dimensionally stable body 3 and a
mechanically active shape memory element 4. The grip of the
fastener is tightened as the mechanically active shape memory
element contracts and opens the structure. The edges of the body
are compressed against the walls of the drill hole, thus enabling a
tighter fastening over time.
[0078] FIG. 23 shows a perspective view of a medical device; in
this case the medical device is a fastening band. The band is
manufactured from a mechanically active shape memory material. The
heads of the band are fastened together by a nail or another
method. The band contracts according to the material programming
towards the evolved shape which corresponds to the original
non-oriented shape.
[0079] FIGS. 24a and 24b show a perspective view of a medical
device for fracture fixation of soft tissue fixation to the bone.
FIG. 24a shows the medical device in its initial shape before
implantation. After implantation, the scales 5 of the implant are
raised due to the mechanical shape memory, thus enhancing the
fixation of the device as shown in FIG. 24b.
[0080] FIGS. 25a and 25b show the cross-section of a medical
device, and FIGS. 26a and 26b show a perspective view of the
medical device of FIGS. 25a and 25b. In these drawings, the medical
device is a medical stent device having mechanically active shape
memory properties. The mechanically active shape memory stent is
delivered to a blood vessel or to another tubular structure that is
to be kept open, for example the gall duct, by an endoscopic
instrument. When the stent is released from the instrument, it will
expand to its normal dimensions. This is the normal case of the
delivery process of biodegradable stents. However, the stents
manufactured from biodegradable dimensionally stable polymers might
have poor expanding properties after longer storage times. When
components manufactured from mechanically active shape memory
polymers are incorporated in the stent structure, the stent will be
able to expand more than the stents manufactured from dimensionally
stable polymers. The stents are able to maintain the expanded shape
due to the mechanically active shape memory components which are
incorporated in the stent structure. The stent is also able to
generate a predefined force of expansion due to the predetermined
tension applied to at least part of the filaments of the stent in
the manufacturing process and is thus capable of opening the
tubular structure even more after the mechanical shape memory
effect has been initiated in the implantation site.
[0081] FIGS. 27a and 27b show a suture anchor having a mechanical
shape memory. The mechanical shape memory is activated in
physiological environment. The diameter of the suture anchor
expands as the length decreases (see FIG. 27b). The grooved shape
provides the initial locking to the bone and the expansion of the
diameter provides a permanent locking effect on the bone.
[0082] The suture anchor comprises an elongated shaft 12 and a
tapering tip 11. The shaft 12 may be provided with ridges 10. In
the shaft 12 near the tip 11 there is at least one hole 14 for a
yarn 13.
[0083] FIG. 28 shows a screw comprising a head 15 and an elongated
shaft 16 provided with threads. As in the case of the
above-mentioned suture anchor, the shaft of the screw also has a
mechanical shape memory and the shaft of the screw expands as the
length decreases.
[0084] FIG. 29 shows a diagram on the effect of L-lactide monomer
(auxiliary component) content on the dimensional changes in
physiological conditions. The content of auxiliary component can be
used to adjust the rate and extent of the mechanical activity. The
tests are carried out by placing the samples freely in a phosphate
buffer solution at 37.degree. C. and periodically measuring the
dimensions manually using a slide gauge.
[0085] The basic material is PLGA 85L/15G. The auxiliary agent in
this case is L-lactide monomer. It can be clearly seen that
increasing the monomer content yields an increasing speed and an
increasing extent of dimensional changes. The materials are melt
processed varying parameters between the samples but the
deformation process of different samples is similar. Thus, the
differences between the samples are due to the differences in the
melt processing. The monomer can be fed into the extruder and mixed
with the polymer, or the monomer can be generated in the material
by increasing the processing temperature to a level which enables
spontaneous monomer generation through thermal degradation of the
polymer.
[0086] FIG. 30 shows a diagram on the effect of blending of
dimensionally stable and dimensionally unstable polymers on the
dimensional changes in physiological conditions. The PLA 50L/50D
acts as a dimensionally unstable material and PLGA 85L/15G as a
dimensionally stable material in this test. Pure PLA 50L/50D shows
a fast dimensional change and a large extent of dimensional change.
Melt mixing (blending) PLGA 85L/15G with PLA 50L/50D impedes both
the rate and extent of the dimensional change. Increasing the
content of PLGA 85L/15G yields a dimensional change that is slower
and has a smaller extent.
[0087] FIG. 31 shows a diagram on the dimensional changes of PLA
50L/50D and PLGA 85L/15G blends. Thus, FIG. 29 represents a closer
view of the two blends with 50% and 75% PLA 50L/50D content.
[0088] The data in FIG. 31 suggests that increasing the PLA 50L/50D
content yields increasingly aggressive dimensional changes in
physiological conditions. The process steps following the melt
process have been similar in all samples, which shows that the
effect is truly due to the composition of the mixture.
[0089] FIG. 32 shows a diagram on the effect of the deformation
force on the residual force in stress relaxation testing. The
samples are produced by using the free drawing method. The samples
are fastened at both ends, heated for a specific time to a
temperature above the glass transition temperature and drawn along
the longitudinal axis to about 4 times the original length. The
drawing force is measured during the deformation process, and the
maximum value is represented in the graph for each sample. It can
clearly be seen that the residual stress level nicely follows the
deformation force level. After 7 days at 37.degree. C. in phosphate
buffer saline, drawing forces of 140 N, 93 N and 54 N yield
residual relaxation forces of 125 N, 99 N and 67 N, whereas the
used temperature ranges in the drawing process were from 57 to
62.degree. C., from 68 to 73.degree. C. and from 85 to 90.degree.
C., respectively.
[0090] FIG. 33 presents the mechanical shape memory effect and the
factors which have an effect on it. The results of the tests show
that the mechanical shape memory is activated in a physiological
environment. If the tests are performed in dry conditions but at a
physiological temperature (37.degree. C.), no mechanical shape
memory effect is detected. If the tests are performed in an aqueous
environment but at room temperature (21.degree. C.), no mechanical
shape memory effect is detected. Thus, the stimulus for the
mechanical shape memory effect is not the effect of liquid as such
or the effect of the temperature as such but the synergy of
temperature and liquid in the physiological conditions.
Example 1
[0091] PLA 50D/50L is melt extruded to a round profile having a
diameter of 6.45 mm using a 20 mm twin screw extruder. The
extrusion temperatures are between 50.degree. C. and 280.degree. C.
The throughput is 700 g/h. The 6.45 mm rod is then die drawn at
80.degree. C. to a 3.40 mm rod having a grooved surface and
subsequently cooled down to room temperature. The resulting draw
ratio is 4. The billet has now the mechanical activity properties
described in FIG. 1. A medical device represented in FIG. 18 and
FIG. 19 is made out of this billet. First, a 30 mm long piece is
cut out of this billet and one end is machined to form a sharp
angle. The thinner section is made by machining. The head is
compression molded at 110.degree. C. and subsequently coo led down
to room temperature. The function of this medical device in bone
fixation application is represented in FIGS. 20 and 21.
Example 2
[0092] A blend of PLGA 85L/15G and PLA 50D/50L is injection molded
to a predefined shape for a biodegradable band for closure of
sternotomy. The pre-shape is then free drawn at 78.degree. C.,
wherein this temperature lies between the glass transition
temperature and the melting temperature of the material. The final
shape and details are machined after the orientation process. The
oriented band is implanted around the sternum to close the
sternotomy. The compression of the polymer band generates a
predefined compression force in the sternotomy as shown in FIG. 1.
Five to seven such bands are used in one sternotomy closure. The
mechanism for the contraction of the band is shown in FIG. 23.
Example 3
[0093] A device for distraction osteogenesis is shown in FIG. 16
and in FIG. 17. The frame structure is extruded and machined or
injection molded from PLA 96L/4D and a contractile and expandable
active component having mechanical activity shown in FIG. 1 is
extruded and drawn from PLA 70L/30DL with L-lactide auxiliary
component. The device is implanted to the distraction site and
fixed to the bone using bioabsorbable screws. The device generates
a predefined force level as described in FIG. 1 and a predefined
contraction-expansion behavior as described in FIG. 28, FIG. 29 and
FIG. 30.
Example 4
[0094] A drillable pin for bone fracture fixation is shown in FIG.
13 and FIG. 14. A preform is extruded from a blend of PLGA 85L/15G
and PLA 50D/50L to a grooved continuous form following die drawing
to a round continuous form. The temperatures used in the extrusion
process are between 50.degree. C. and 260.degree. C. The
orientation temperature in the die drawing process lies between the
glass transition temperature and the melting temperature of the
blend. The pin is machined to the final product form and is gamma
sterilized. The pin is drilled into the cancellous bone or compact
bone using a predrilled hole. The round and smooth surfaced pin
will initiate the shape transformation after implantation. The
locking of the device to the bone is enhanced as the diameter of
the device expands due to the device contracting and pulling the
bone fragments tighter together as shown in FIG. 20 and FIG. 21.
The grooved shape to which the device changes its shape in the
drill hole generates a better torque resistance than round shaped
devices. This stabilizes the fracture site, still enabling the
surgeon to drill the device into the bone.
Example 5
[0095] A medical fastener for bone fracture fixation of soft tissue
attachment is shown in FIG. 22a. The device comprises of a fastener
made of PLGA 85L/15G by extrusion and orientation, and a
mechanically active component extruded and drawn from PLA 50D/50L.
The fastener is machined to its final form before use, and the
drawn and machined mechanically active part is attached to the bulk
part. For both of the components, the extrusion temperatures are
between 50.degree. C. and 260.degree. C. and the drawing
temperatures are between the glass transition temperature and the
melting temperature of each material. The fastener is gamma
sterilized. After implantation, the fastener is activated due to
the physiological environment. After the activation the
mechanically active shape memory component starts to contract and
the dimensionally stable component starts to open, due to the
opening force generated by the contracting active component, thus
enhancing the stability of the fixation as shown in FIG. 22b.
* * * * *