WO2011116773A1

WO2011116773A1 - Implant for treatment of skeletal deformities

Info

Publication number: WO2011116773A1
Application number: PCT/DK2011/050096
Authority: WO
Inventors: Dang Le; Morten Foss; Jens Vinge Nygaard; Flemming Besenbacher; Cody BÜNGER; Yu Wang
Original assignee: Aarhus Universitet; Region Midtjylland
Priority date: 2010-03-24
Filing date: 2011-03-23
Publication date: 2011-09-29

Abstract

The present invention relates to an implant for treatment of skeletal deformities comprising a hollow rod having at least one open end, an osmotic membrane which covers at least a part of the inner walls of said rod, a piston and a compartment delimited by said piston and said osmotic membrane. Energy for doing work, i.e. providing a distraction force, is provided by an osmotic potential across a semi-permeable membrane. Thus, the present invention relates to an implant for treatment of skeletal deformities comprising a self-contained mechanism for providing a distraction force.

Description

Implant for treatment of skeletal deformities

All patent and non-patent references cited in the application, or in the present application, are also hereby incorporated by reference in their entirety.

Field of invention

The present invention relates to an implant for treatment of skeletal deformities comprising a hollow rod having at least one open end, an osmotic membrane, which covers at least a part of the inner walls of said rod, a piston and a compartment delimited by the piston and the osmotic membrane. Energy for doing work, i.e.

providing a distraction force, is provided by an osmotic potential across a semipermeable membrane. Thus, the present invention relates to an implant for treatment of skeletal deformities comprising a self-contained mechanism for providing a distraction force.

Background of invention Scoliosis is a medical condition in which the patient's spine becomes curved and/or rotated. Normally, the spine is made up of bones that are like blocks placed on top of each other. The spine should be straight when seen from the back and a mirror-image letter 'S' from the side. The spine protects the spinal cord, and nerves coming to and from the spinal cord pass through the spine. The bones in the upper spine are connected to the ribs and help the ribs move when breathing. In scoliosis, the bones are not properly placed on top of the other causing the spine to curve sideways.

Scoliosis may worsen slowly, quickly, or not at all. The abnormal curving in the spine may limit chest movement and cause lung or heart problems. Scoliosis can be associated with neuromuscular conditions, genetic disorders and syndromes, skeletal dysplasias and connective tissue disorders as well as

miscellaneous conditions such as neurofibromatosis.

Three major types of scoliosis are congenital, idiopathic and neuromuscular scoliosis. Congenital scoliosis is defined as scoliosis resulting from the malformation of vertebrae such as hemivertebrae and unsegmented bars, which can be classified into failures of formation, segmentation or mixed anomalies. Neuromuscular scoliosis is defined as a scoliosis in a child with any known nerve or muscle disease such as cerebral palsy or muscular dystrophies as well as spinal cord injuries leading to the scoliosis. Idiopathic scoliosis has no known cause and can be subclassified on the basis of the age at onset. Infantile idiopathic scoliosis, which is the most common form of scoliosis, comprises patients from 0 to 3 years of age, juvenile idiopathic scoliosis encompasses patients from 4 to 10 years and adolescent idiopathic scoliosis patients are those greater than 10 years of age. The prevalence of idiopathic scoliosis in the pediatric population is estimated to be 0.5-3.0%.

For those persons who already have a significant curve with a significant deformity, surgery can reduce the curve and the deformity. Spinal fusion is a widely performed surgery for scoliosis, which is used to combine two or more vertebrae. This type of surgery is recommended when magnitude of curvature exceeds 40-45 degrees (Weiss et al., 2008, Scoliosis, 3:9). In this procedure, the individual bones are fused to adjacent bones. Typically 8 to 12 or more segments are included. Multiple hooks or screws are attached to the back of the individual vertebra and then these are connected to one or two metal rods, which have been pre-bent to the desired contour. Bone is grafted to the vertebrae so that when it heals they will form one solid bone mass and the vertebral column becomes rigid. This prevents worsening of the curve at the expense of some spinal mobility.

In 1962, Paul Harrington introduced a metal spinal system of instrumentation, which assisted with straightening the spine, as well as holding it rigid while fusion took place. The original, now obsolete Harrington rod operated on a ratchet system, attached by hooks to the spine at the top and bottom of the curvature that when cranked would distract, or straighten, the curve. A major shortcoming of the Harrington method was that it failed to produce a posture where the skull would be in proper alignment with the pelvis and it didn't address rotational deformity. As a result, unfused parts of the spine would try to compensate for this in the effort to stand up straight. As the person aged, there would be increased wear and tear, early onset arthritis, disc degeneration, muscular stiffness and pain with eventual reliance on painkillers and further surgery. Modern spinal systems involve a combination of rods, screws, hooks and wires fixing the spine and can apply stronger, safer forces to the spine than the Harrington rod. This technique is known as the Cotrel-Dubousset instrumentation, currently the most common technique for the procedure.

Patients who suffer from early onset scoliosis (EOS) often require stabilizing growth rod systems. As these patients are skeletally immature, repeated lengthening of the rods is required to assure sufficient height growth of the vertebral bodies. Growing rods or expandable spinal implants have been used for several decades in an attempt to control the spinal deformity and to allow for spinal growth until the child reaches an appropriate size or age for definitive fusion. Expandable segmental spinal

instrumentation techniques include insertion of a single growing rod with a claw foundation proximally and/or distally, dual growing rods with claw foundations proximally and distally, and vertical expandable prosthetic titanium rib (VEPTR) implant. These vertical expandable prosthetic titanium ribs provide the benefit of expanding the thoracic cavity and straightening the spine in all three dimensions while allowing the spine to grow. The challenges associated with the use of these systems include obtaining and maintaining deformity correction, achieving adequate spinal growth, allowing lung development, and decreasing the high incidence of complications (Thompson et al., 2007, J Pediatr Orthop.;27(3):354-61 ).

These recurrent procedures are very invasive as they require repeated lengthening of the rod system to adjust for longitudinal growth of the spine as the patient matures. Patients treated with these techniques typically need repeated surgeries as frequently as every four to six months. They have a significantly increased risk for bleeding, infection, wound and pulmonary complications. Furthermore, as EOS patients consequently are children or adolescents, the prospect and experience of multiple procedures and stress from repeated surgery will definitely have a severe negative impact on life quality.

A second issue with current growing rod techniques relates to the timing of the expansion. Growing rods are generally left in place for a period of months before the patient is taken back to the operating room for lengthening. These interval periods allow the tissues surrounding the rods to heal, but also to scar. Scarred tissue within the telescoping connector parts is difficult and time-consuming to dissect, is more prone to infection, and complicates rod expansion. Scar tissue may also serve to further tether the growing spine, thus adding an additional deforming force. In addition, despite periodic lengthening, the interval placement of instrumentation can frequently result in cessation of spinal growth, which ultimately leads to premature fusion of the immature spine.

By using a slowly self-lengthening growth rod, the need for repeated operations is greatly reduced, possibly limited to just the initial implantation procedure and the final explanation and stiffening procedure. Expandable growth rod systems used in the treatment of scoliosis have been described in the literature. However, these systems are often dependent on electrical actuators and are thus limited by factors such as battery longevity, actuator reliability and the presence of electrical potential. Other systems are based on the properties of shape-memory metal such as nickel-titanium alloy. One concern with these shape alloy materials is that their force generation is based on inherent material property limiting the possibilities optimizing other implant properties such as surface oxide biocompatibility properties and fatigue metal life. There is no disclosure in the literature of growth rod systems taking advantage of osmotic actuators. US 2009/0204154 discloses a method for treating scoliosis comprising implanting an expandable telescoping rod under the skin and attached to selected portions of the scoliotic curve of the spine at opposing ends of the rod. A controlled force by means of expansion of the rod is produced over an extended time period until a desired spinal curve is obtained. An incremental force is generated to stretch the scoliotic curve of the spine between the selected portions where attachment of the rod is defined.

WO20051 17731 discloses an implantable apparatus for use in the correction of skeletal deformities comprising a rod, a pair of spaced apart attachment members, each of the attachment members being attachable to a bone. At least one attachment member mounts a rod being slidable along a predetermined path with respect to the rod receiving member.

WO2005074825 discloses an implant for stabilizing a bony segment including a flexible body sized and shaped to extent intravertebrally at least first and second bony portions. In use the body is attachable intravertebrally to each of the first and second bony portions to distract each of the first and second bony portions while allowing motions between said bony portions.

Takaso et al., 1998, discloses a remote-controlled growing-rod spinal instrumentation system proposed for the treatment of progressive scoliosis in young children. It can be used to stretch and correct the spinal deformities repeatedly and non-surgically, by means of a remote-controller, after the first instrumentation operation.

Summary of invention

The present invention relates to an implant for the treatment of skeletal deformities comprising a rod and a piston, wherein the energy for doing work, i.e. providing distraction force, is provided by an osmotic potential across a semi-permeable membrane. Thus, the present invention relates to an implant for treatment of skeletal deformities comprising a self-contained mechanism for providing a distraction force, which is independent of electrical actuators.

One aspect of the present invention relates to an implant for treatment of skeletal deformities comprising

a) at least one hollow rod having at least one open end

b) at least one osmotic membrane which covers at least a part of the inner walls of said rod

c) at least one piston and

d) at least one compartment delimited by said at least one piston and said at least one osmotic membrane

It is appreciated that at least a part of the piston is located within the rod and/or at least a part of the piston extends out from the open end of the hollow rod. The hollow rod and the piston are telescopically displaceable. In a preferred embodiment the hollow rod and the piston are expandable.

In one embodiment of the present invention the implant comprises at least one hollow rod having two open ends. The implant may comprise two pistons, one piston being telescopically displaceable in relation to the hollow rod. Alternatively, the implant comprises two pistons, said two pistons being telescopically displaceable in relation to the hollow rod.

In another embodiment of the present invention the hollow rod is rigid. The hollow rod and may in one preferred embodiment comprise metal or metal alloy. Thus, the hollow rod can be made of metal or metal alloy. It is preferred that the metal or metal alloy is a biological inert metal or metal alloy. In another preferred embodiment the metal is titanium and/or a titanium based alloy. In another embodiment of the present invention the piston is rigid. The piston may in one preferred embodiment comprise metal or metal alloy. Thus, the piston can be made of metal or metal alloy. It is preferred that the metal or metal alloy is a biological inert metal or metal alloy. In another preferred embodiment the metal is titanium and/or a titanium based alloy.

In a further embodiment of the present invention the implant comprises attachment means such as for example pedicle screws, hooks and/or wires. The implant may further comprise at least one breachable seal. In one embodiment of the present invention the compartment contains a hypertonic solution The hypertonic solution may comprise one or more osmotic agents and/or a combination of two or more osmotic agents. It is preferred that the osmotic agents are non-toxic. In one embodiment the osmotic agents are selected from the group consisting of sodium chloride, sorbitol, mannitol, glucose and trehalose. In another embodiment the osmotic agents are hydrolytically degradable polymers and/or combination of two or more hydrolytically degradable polymers. It is preferred that the hydrolytically degradable polymers are biodegradable and degrade into biologically inert products.

It is appreciated that the osmotic membrane is a semi-permeable membrane. An osmotic potential can be generated across the osmotic membrane thereby providing a distraction force. The distraction force may result in movement of the piston as the compartment expands. It is preferred that the concentration of osmotic agents within the compartment remains constant as the compartment expands during movement of the piston.

A second aspect of the present invention relates to a method for treatment of skeletal deformities comprising inserting at least one implant according to the present invention into an individual suffering from skeletal deformities and fastening the least one implants to at least one bone of said individual. Fastening may comprise fastening a first end of said implant at a first location of said individual and fastening a second end of said implant at a second location of said individual. The at least one implant can be fastened using at least one attachment means.

In one preferred embodiment the skeletal deformity as described herein is scoliosis. Scoliosis may comprise infantile idiopathic scoliosis, juvenile idiopathic scoliosis and adolescent idiopathic scoliosis. Thus, in one preferred embodiment the implant is fastened to the individual's spine. In another embodiment the individual is skeletally immature

Another aspect of the present invention relates to an implant according to the present invention for correction of skeletal deformities.

Another aspect of the present invention relates to the use of the implant according to the present invention for correction of skeletal deformities.

A further aspect of the present invention relates to the use of the implant according to the present invention for leg and/or limb extension.

Yet another aspect of the present invention relates to a kit of parts for correction of skeletal deformities comprising at least one implant according to the present invention and at least one attachment means.

The skeletal deformity as described herein is in one preferred embodiment scoliosis. Detailed description

In the following, the invention is described in detail with reference to the drawings, in which:

Fig. 1 is a first embodiment of the present invention. Fig. 1 a and 1 b are side perspective cross-sectional views of the implant. Fig. 1 a is a detailed side perspective cross-sectional view of the implant indicated by the circle B in Fig. 1 b. Fig. 1 c is a top view of the implant. The line A indicates the cross-section shown in Fig. 1 b.

Fig. 2a and 2b illustrate a first embodiment showing perspective cross-sectional views of the implant according to the present invention.

Fig. 3 is a second embodiment of the present invention. Fig. 3a and 3b are side perspective cross-sectional views of the implant. Fig. 3a is a detailed side perspective cross-sectional view of the implant indicated by the circle B in Fig. 3b. showing a side perspective view of the implant. Fig. 1 c is a top view of the implant. The line A indicates the cross-section shown in Fig. 1 b.

Fig. 4 is a second embodiment showing a perspective cross-sectional view of the implant according to the present invention. Fig. 1 a and 1 b illustrates a first embodiment of the present invention, which is an implant comprising a hollow rod (1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of said rod (1 ), a first piston (4) and a first compartment (5) delimited by the first piston (4) and the first osmotic membrane (3). Three O-rings (10) are situated around the first piston (4). The hollow rod (1 ) comprises openings (6), which expose the membrane (3) to fluids such as for example body fluids. The implant may further comprise a second open end (7) and a solid rod (8) located at the second open end (7). The solid rod (8) has been fastened to the hollow rod (1 ) by an Allen bolt (9). Fig. 1 a is a detailed view of the implant indicated by the circle B in Fig. 1 b. Fig. 1 c illustrates a top view of the implant. The line A indicates the cross-section shown in Fig. 1 b. The first piston (4) as shown in Fig. 1 b has a hexagonal cross-section. The cross-section of the first piston (4) can also be circular.

Fig. 2a and 2b illustrate the first embodiment showing perspective cross-sectional views of the implant according to the present invention. The implant comprises a hollow rod (1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of said rod (1 ), a first piston (4) located at the first open end (2) and a compartment (5) delimited by the first piston (4) and the first osmotic membrane (3). Three O-rings (10) are situated around the piston (4). The hollow rod (1 ) comprises openings (6), which expose the membrane to fluids such as for example body fluids. The implant may further comprise a second open end (7) and a solid rod (8) located at the second open end (7). The solid rod (8) has been fastened to the hollow rod (1 ) by an Allen bolt (9). Fig. 3a and 3b illustrate a second embodiment of the implant comprising a hollow rod

(1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of said rod (1 ) and a first piston (4) located at the first open end

(2) and a first compartment (5) delimited by the first piston (4) and the first osmotic membrane (3). The hollow rod (1 ) comprises openings (6), which expose the membrane to fluids such as for example body fluids. The implant further comprises a second open end (7) and a second piston (1 1 ) located at the second open end (7), a second osmotic membrane (12), which covers at least a part of the inner walls of said rod (1 ) and a second compartment (13) is delimited by the second piston (1 1 ) and the second osmotic membrane (12). Three O-rings (10) are situated around the first piston (4) and the second piston (1 1 ). Fig. 3a is a detailed view of the implant indicated by the circle B in Fig. 3b. Fig. 3c illustrates a top view of the implant. The line A indicates the cross-section shown in Fig. 3b.

Fig. 4 illustrates the second embodiment showing perspective cross-sectional views of the implant according to the present invention. The implant comprises a hollow rod (1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of said rod (1 ) and a first piston (4) located at the first open end (2) and a first compartment (5) delimited by the first piston (4) and the first osmotic membrane

(3) . The hollow rod (1 ) comprises openings (6), which expose the membrane to fluids such as for example body fluids. The implant further comprises a second open end (7) and a second piston (1 1 ) located at the second open end (7), a second osmotic membrane (12), which covers at least a part of the inner walls of said rod (1 ) and a second compartment (13) is delimited by the second piston (1 1 ) and the second osmotic membrane (12). The present invention relates to an implant for treatment of skeletal deformities comprising

a) at least one hollow rod having at least one open end

c) at least one piston and

d) at least one compartment delimited by said at least one piston and said at least one osmotic membrane Thus, in a first embodiment of the present invention, the implant comprises at least one hollow rod having at least one open end. The implant further comprises at least one piston being telescopically displaceable in relation to the hollow rod. Accordingly, referring to Fig. 1 a and 1 b, the implant comprises at least one hollow rod (1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of the hollow rod (1 ), a first piston (4) and a first compartment (5) delimited by the first piston (4) and the first osmotic membrane (3). The hollow rod (1 ) comprises openings (6), which expose the membrane (3) to fluids such as for example body fluids. The implant may further comprises a second open end (7) and a solid rod (8) located at the second open end (7). The solid rod (8) has been fastened to the hollow rod (1 ) by an Allen bolt (9).

In a second embodiment of the present invention the implant has two open ends and comprises two pistons, which are telescopically displaceable in relation to the hollow rod. Referring to Fig. 3a and 3b, the implant comprises a hollow rod (1 ) having a first open end (2), a first osmotic membrane (3), which covers at least a part of the inner walls of the hollow rod (1 ), a first piston (4) and a first compartment (5) delimited by the first piston (4) and the first osmotic membrane (3). The implant further comprises a second open end (7) and a second piston (1 1 ) located at the second open end (7), a second osmotic membrane (12) and a second compartment (13) delimited by the second piston (1 1 ) and the second osmotic membrane (12). The hollow rod (1 ) comprises openings (6), which expose the first osmotic membrane (3) and the second osmotic membrane (12) to fluids such as for example body fluids.

In a third embodiment of the present invention the implant comprises a hollow rod (1 ) having a first open end (2), a first osmotic membrane (3) which covers at least a part of the inner walls of said rod, a piston (4) and a compartment (5) delimited by the piston

(4) and the osmotic membrane (3).

The invention allows for surgical treatment of skeletal deformities, especially the spine, and can be used in paediatric orthopaedics and for leg and limb lengthening.

In one embodiment of the present invention, at least a part of the piston (4) is located within the hollow rod (1 ) and telescopes in a linear fashion relative to the inner walls of the hollow rod (1 ). The part of the piston (4), which is located within the rod (1 ), is in contact with the osmotic membrane (3), which is located on the inner walls of the hollow rod (1 ) (Fig. 1 ). The piston (4) is a mobile tight-sealing piston, which prevents diffusion of fluid from the compartment (5). In one embodiment at least one O-ring (10) is situated around the piston (4) to prevent diffusion of fluid from the compartment (5). In another embodiment at least 2, such as at least 3, such as for example at least 4 or such as at least 5 O-rings (10) are situated around the piston (4). In one preferred embodiment 3 O-rings are situated around the piston (4) (Fig. 1 a). The O-rings (10) are preferably located at the distal end of the piston (4), which is inside the compartment

(5) .

The piston (4) and the hollow rod (1 ) are telescopically displaceable along their longitudinal axes. In one preferred embodiment the piston (4) and the hollow rod (1 ) are expandable. Thus, when the piston (4) moves relative to the hollow rod (1 ), the compartment (5) expands. The hollow rod (1 ) comprises openings (6), which exposes the membrane (3) to fluids such as for example body fluids. The hollow rod may comprise at least one, such as at least two, such as for example at least three, such as at least four, such as for example at least five, such as at least six, such as for example at least seven, such as at least eight or such as for example at least ten or even more openings.

The implant of the present invention can be used either alone or in combination with conventional implants or growing rods, which are known to the skilled artisan. It is preferred that the implant is compatible with conventional implants or growing rods used for the treatment of skeletal deformities and/or scoliosis.

The piston (4), (1 1 ), the hollow rod (1 ) and the solid rod (8) can be sized and shaped similarly to conventional growing rod systems. In addition, the piston (4), (1 1 ), the hollow rod (1 ) and/or the solid rod (8) can have a combined length, in retracted and extended positions that is similar to that of conventional growing rods used in orthopaedic surgery. The cross section of the rod (1 ) and/or the piston (4), (1 1 ) may assume any shape. In one embodiment the cross section of the rod (1 ) and/or the piston (4), (1 1 ) can be rectangular, square, pentagonal, hexagonal, heptagonal, octagonal, polygonal or other regular or irregular cross sectional shape. In another embodiment the cross section of the rod (1 ) and/or the piston (4), (1 1 ) can be elliptical. In a preferred embodiment the cross section of the rod (1 ) and/or the piston (4), (1 1 ) is circular. In another preferred embodiment the rod (1 ) and/or the piston (4), (1 1 ) takes form of a cylinder.

In one embodiment of the present invention the rod (1 ) and/or the piston (4), (1 1 ) is rigid. The rod (1 ) and/or the piston (4), (1 1 ) can be made from any bio-compatible or biologically inert material. The term biologically inert, as used herein refers to a material, compound and/or substance, which shows no reaction with the human body and does not cause allergic reactions. In one embodiment the rod (1 ) and/or piston (4), (1 1 ) is made of ceramic materials such as for example alumina or zirconia, or polymeric materials or a combination thereof, for example polymer-ceramic or polymer- carbon derivative composites. In another embodiment the rod (1 ) and/or the piston (4), (1 1 ) is made of metal or metal alloy as for example stainless steel, chromium-cobalt based alloys, magnesium and/or magnesium based alloys or surface modified materials as for example surface-coated stainless steel. In a preferred embodiment the metal is a biologically inert metal. In another preferred embodiment the metal is titanium and/or a titanium based alloy. In another preferred embodiment the metal is stainless steel coated with tantalum by e.g. Chemical Vapor Deposition (CVD) or Physical Vapor Deposition (PVD) . The rod (1 ) and/or the piston (4), (1 1 ) may also be made of a combination of two or more of the above mentioned materials or any biocompatible or biologically inert material.

The inner surfaces of the hollow rod and/or the surface of the piston is coated with an abrasion resistant biologically inert compound such as for example titanium nitride, chromium nitride, titanium aluminium nitride, silicon nitride, zirconium nitride. This is done to improve tribological properties during the relative motion of the components and improve corrosion resistance. The coating can be done via e.g. PVD, cathodic arc, anodizing and/or plasma spraying techniques.

The sealing of the osmotic compartment with the piston can be facilitated by a gasket of a wear resistant elastomeric or non-elastomeric material. In one embodiment, the osmotic membrane is integrated with a polymer, metal, or ceramic lining that results in a smooth surface. The lining can be of the same or different material from the porous membrane. The range of lining polymers can comprise but are not limited to FEP, PSU, Cellulose, PTFE, PEEK or POM.

The thickness of the rod (1 ) and/or the piston (4), (1 1 ) may be in the range of 1 mm to at least 30 mm or even thicker. In one embodiment the thickness of the rod is preferably in the range of from 1 mm to preferably less than 30 mm, such as in the range of 1 mm to preferably less than 25 mm, for example in the range of from 1 mm to preferably less than 20 mm, such as in the range of from 1 mm to preferably less than 15, for example in the range of from 1 mm to preferably less than 10 mm, such as in the range of from 1 mm to preferably less than 5 mm, for example in the range of from 10 mm to preferably less than 30 mm, such as in the range of from 10 mm to preferably less than 25 mm, for example in the range of from 10 mm to preferably less than 20 mm, such as in the range of from 10 mm to preferably less than 15 mm, for example in the range of from 20 mm to preferably less than 30 mm, such as in the range of from 20 mm to preferably less than 25 mm, for example in the range of from 25 mm to preferably less than 30 mm. The length of the rod (1 ) may be in the range of 5 mm to at least 200 mm or even longer. In one embodiment the length of the rod (1 ) is preferably in the range of from 5 mm to preferably less than 200 mm, such as in the range of 5 mm to preferably less than 160 mm, for example in the range of from 5 mm to preferably less than 120 mm, such as in the range of from 5 mm to preferably less than 80, for example in the range of from 5 mm to preferably less than 40 mm, such as in the range of from 5 mm to preferably less than 20 mm, for example in the range of from 10 mm to preferably less than 200 mm, such as in the range of 10 mm to preferably less than 160 mm, for example in the range of from 10 mm to preferably less than 120 mm, such as in the range of from 10 mm to preferably less than 80, for example in the range of from 10 mm to preferably less than 50 mm, such as in the range of from 10 mm to preferably less than 30 mm, for example in the range of from 100 mm to preferably less than 200 mm, such as in the range of from 100 mm to preferably less than 180 mm, for example in the range of from 100 mm to preferably less than 160 mm, such as in the range of from 100 mm to preferably less than 140 mm, for example in the range of from 100 mm to preferably less than 120 mm.

The length of the piston (4), (1 1 ) may be in the range of 5 mm to at least 300 mm or even longer. In one embodiment the length of the piston (4) is preferably in the range of from 5 mm to preferably less than 300 mm, such as in the range of 5 mm to preferably less than 250 mm, for example in the range of from 5 mm to preferably less than 200 mm, such as in the range of from 5 mm to preferably less than 150, for example in the range of from 5 mm to preferably less than 100 mm, such as in the range of from 5 mm to preferably less than 50 mm, for example in the range of from 10 mm to preferably less than 300 mm, such as in the range of 10 mm to preferably less than 250 mm, for example in the range of from 10 mm to preferably less than 200 mm, such as in the range of from 10 mm to preferably less than 150, for example in the range of from 10 mm to preferably less than 100 mm, such as in the range of from 10 mm to preferably less than 50 mm, for example in the range of from 100 mm to preferably less than 300 mm, such as in the range of from 100 mm to preferably less than 250 mm, for example in the range of from 100 mm to preferably less than 200 mm, such as in the range of from 100 mm to preferably less than 150 mm, for example in the range of from 200 mm to preferably less than 300 mm, such as in the range of from 200 mm to preferably less than 250 mm, for example in the range of from 250 mm to preferably less than 300 mm.

In another embodiment the implant includes an anti-rotation mechanism to prevent relative rotational motion between the piston (4), (1 1 ) and the rod (1 ). For example, the anti-rotation mechanism may include mating keyed elements of the piston (4), (1 1 ) and the rod (1 ) to prevent relative rotation (described in WO 2009/146377). Alternatively, a non-circular cross section of the hollow rod (1 ) and the piston (4), (1 1 ) can be employed to avoid relative rotational motion between the piston (4), (1 1 ) and the rod (1 )-

To prevent the unintentional collapse of the piston (4), (1 1 ) and the rod (1 ) in case of loss of osmotic potential or fluid leakage, the implant can include an anti-retraction mechanism that incrementally blocks the piston from retracting into the rod (1 ). For example, the anti-retraction mechanism can include at least one mechanical catch on the piston and at least one mechanical catch on the rod (1 ) that selectively engages the piston (4), (1 1 ) to prevent collapse while permitting their expansion.

In a further embodiment of the present invention the implant comprises attachment means. The word "attachment means" used herein refers to means, which is/are used to fasten the implant to one or more bones of an individual. The implant can be fastened to the patient's spine in a conventional fashion using commercially available fastening means. Fastening means may include screws, pedicle screws, hooks, lamina hooks, pedicle hooks, universal clamp ®, wires and/or other devices known to the skilled artisan. The term "pedicle screw", as used herein refers to a particular type of bone screw designed for implantation into the pedicle part of vertebra. Pedicle screws provide a means of gripping a spinal segment. The pedicle screws themselves do not fixate the spinal segments, but provide firm anchor points. Only if the pedicle screws are connected with a rod or the implant according to the present invention, fixation of the spinal segments will be obtained.

In order to achieve additional distraction force, multiple implants according to the present invention can be fastened along the bone(s). The implants may be fastened end to end and/or spaced along the bone(s). In the case of scoliosis multiple implants can be fastened end to end and/or spaced along the spine.

The osmotic system

The term "osmosis" as used herein refers to the natural movement of a solvent through a semi-permeable membrane into a solution of higher solute concentration. Osmotic systems imbibe water from the surroundings through a semi-permeable membrane into a solution of higher solute concentration.

In the present invention, the first compartment (5) is delimited by the first piston (4) and the first osmotic membrane (3) and the second compartment (13) is delimited by the second piston (1 1 ) and the second osmotic membrane (12). The term "osmotic membrane" as used herein refers to a semi-permeable membrane, which is defined as a membrane that is permeable to a solvent, e.g. water and biological fluids, but impermeable to ionic compounds or other higher molecular weight compounds. The semi-permeable membrane is permeable to water outside the compartment but impermeable to solute within the compartment. The semi-permeable membrane may comprise polymeric materials, which may include, but are not limited to, plasticized cellulosic materials, enhanced polymethylmethacrylate such as

hydroxyethylamethacrylate (HEMA) and elastomeric materials such as polyurethanes and polyamides, polyetherpolyamide copolymers and thermoplastic copolyesters and/or blends thereof. In one embodiment the membrane is made of regenerated cellulose and/or blends thereof. Regenerated cellulose as referred to herein is cellulose fibers such as for example rayon, cellophane and /or cellulose acetate. In another embodiment the membrane comprises polysulfone and/or derivates thereof. The membrane may for example be made from polysulfone blends. In a further embodiment the membrane comprises ceramic materials and/or blends thereof. The membrane may for example comprise ceramic or polymer-ceramic osmotic membranes as well as carbon nanotube osmotic membranes

The membrane may comprise at least two, at least three, at least four, at least five or even more of the above mentioned materials. The membrane may comprise any combination or blend of the above mentioned materials.

In one embodiment the compartment (5), (13) contains a hypotonic solution. The term "hypotonic solution", as used herein, refers to a solution, which contains a lower concentration of impermeable solutes or osmotic agents than the solution on the other side of the osmotic membrane. In this scenario, fluid or water will escape from the hypotonic compartment across the osmotic membrane and the piston will consequently retract into the compartment.

The compartment (5) may also contain a saturated solution at equilibrium with the undissolved solid phase of the solute.

In a preferred embodiment the compartment (5), (13) contains a hypertonic solution. The term "hypertonic solution", as used herein, refers to a solution, which contains a greater concentration of impermeable solutes or osmotic agents than the solution on the other side of the osmotic membrane. In this scenario, fluid, such as for example water or body fluid will be drawn across the osmotic membrane and into the hypertonic compartment. The resulting increased pressure will consequently lead to movement of the piston (4), (1 1 ) out of the rod (1 ) as the compartment (5), (13) expands. The hypertonic solution may comprise one or more osmotic agents and/or a combination of two or more osmotic agents. The term "osmotic agents" as used herein refers to compounds affecting the osmotic potential as described herein. It is preferred that the osmotic agents are non-toxic and/or biodegradable, i.e. degrades into biological inert products.

In one embodiment, the osmotic agents are hydrophilic polymers and/or a combination of two or more hydrophilic polymers. The term "hydrophilic polymers" as used herein refers to hydrophilic polymers, which interact with water and biological fluids and swell or expand to an equilibrium state. The hydrophilic polymers exhibit the ability to retain a significant portion of the imbibed fluid within the polymer structure. The hydrophilic polymers swell or expand to a very high degree, usually exhibiting a 2 to 50 fold volume increase. The hydrophilic polymers can be non-cross-linked or cross-linked. The swellable, hydrophilic polymers are in one embodiment lightly cross-linked, such cross-links being formed by covalent or ionic bonds or residue crystalline regions after swelling. The hydrophilic polymers can be of plant, animal or synthetic origin.

Hydrophilic polymers include poly (hydroxy-alkyl methacrylate); poly (vinylpyrrolidone); anionic and cationic hydrogels; polyelectrolytes complexes; poly (vinyl alcohol) having a low acetate residual, cross-linked with glyoxal, formaldehyde, or glutaraldehyde; a mixture of methyl cellulose, cross-linked agar and carboxymethyl cellulose; a mixture of hydroxypropyl methylcellulose and sodium carboxymethylcellulose; a mixture of hydroxypropyl ethylcellulose and sodium carboxymethyl cellulose; sodium

carboxymethylcellulose; potassium carboxymethylcellulose; gelatin and cross-linked gelatin, a water insoluble, water swellable copolymer formed from a dispersion of finely divided copolymer of maleic anhydride with styrene, ethylene, propylene, butylene or isobutylene cross-linked with from 0.001 to about 0.5 moles of saturated cross-linking agent per mole of maleic anhydride per copolymer; water swellable polymers of N-vinyl lactams; polyoxyethylene-polyoxypropylene gel; polyoxybutylene-polyethylene block copolymer gel; carob gum; polyacrylic gel; polyester gel; polyuria gel; polyether gel; polyamide gel; polycellulosic gel; polygum gel; initially dry hydrogels that imbibe and absorb water which penetrates the glassy hydrogel and lowers its glass temperature; and the like.

Representative of other hydrophilic polymers comprise polymers that form hydrogels are Carbopol® acidic carboxypolymer, a polymer of acrylic and cross-linked with a polyallyl sucrose, also known as carboxypolymethylene and carboxyvinyl polymer; Cyanamer® polyacrylamides; cross-linked water swellable indene-maleic anhydride polymers; Good-rite® polyacrylic acid; Polyox® polyethylene oxide polymer; starch graft copolymers; Aqua-Keeps® acrylate polymer polysaccharides composed of condensed glucose units such as diester cross-linked polygluran; and the like.

In another embodiment the osmotic agents are hydrolytically degradable polymers and/or a combination of two or more hydrolytically degradable polymers. The term "hydrolytically degradable polymers" as used herein refers to polymers, which degrade by hydrolysis. The hypertonic solution may comprise at least one hydrolytically degradable polymer or a combination of two or more hydrolytically degradable polymers. The hydrolytically degradable polymers are preferably biodegradable and degrade into osmotically active biologically inert products.

In one embodiment, the hydrolytically degradable polymer is a fatty-acid containing polyester. These polyesters are prepared by the condensation of an aliphatic diol, an aliphatic or unsaturated dicarboxylic acid, and one or more fatty acids and/or fatty acid containing molecules to form a prepolymer. Fatty acids are suitable for the preparation of biodegradable polymers as they are natural body components. Most fatty acids, however, are monofunctional and cannot serve as monomers for polymerization.

Bifunctional fatty acids such as ricinoleic acid can be polymerized to form polyesters without modification. Unsaturated fatty acids such as oleic acid, linoleic acid, and erucic acid can be modified to introduce a hydroxyl group or can be further polymerized through the double bond.

In another preferred embodiment of the present invention the hydrolytically degradable polymers are selected from the group consisting of polylysine, poly (lactic acid) (PLA), poly (glycolic acid) (PGA), copolymers and mixtures of PLA and PGA, e.g., poly (lactide-co-glycolide) (PLG), poly (caprolactone) (PCL), poly (lactide-co-caprolactone) (PLC), and poly (glycolide-co-caprolactone) (PGC).

Depending on the erosion mechanism of the polymer, bulk erosion or surface erosion, the degradation rate of the polymer will be more or less determined by the geometry and shape of the polymer construct. The degradation of polymer and thus the concentration of solute in the compartment (5), (13) can be controlled by shaping the polymer to e.g. a starlike cross section to provide a larger area for surface erosion thereby increasing the rate of polymer degradation with a resulting bi-phasic or multiphasic pressure generation progression. The shaped polymer may also be a

combination of two or more polymers with different degradation rates to produce a multiphasic pressure.

In a further preferred embodiment one or more osmotic agents are selected from a group comprising sodium chloride, magnesium sulfate, magnesium chloride, potassium sulfate, sodium sulfate, lithium sulfate, potassium acid phosphate, mannitol,

magnesium succinate, tartaric acid, urea, sugars such as inositol, sorbitol, mannitol, glucose raffinose, sucrose, lactose and/or trehalose.

The hypertonic compartment may comprise any combination of one or more osmotic agents as described herein and above. Thus, the hypertonic compartment may comprise any combination of one or more polymers and/or sugars and/or salts.

When the implant according to the present invention is embedded in a solution containing a lower concentration of impermeable solutes than the hypertonic solution, an osmotic potential will be generated across the osmotic membrane, and fluid will be drawn across the osmotic membrane and into the compartment. Thus, the osmotic potential provides a distraction force, which results in movement of the piston as the compartment expands.

The fluid flux into the hypertonic compartment is simplistically described as: ύ=Κ^χΑ^χ(Δττ-ΔΡ) where J is the fluid flow rate, K is the membrane's water permeability, A is the effective membrane surface area, Δπ is the trans-membrane osmotic pressure and ΔΡ is the trans-membrane hydrostatic pressure. At equilibrium, i.e. J=0, ΔΡ=ρττ, where p is the osmotic reflection coefficient. As the compartment (5), (13) expands with the movement of the piston (4), (1 1 ), the trans-membrane pressure and hence the distraction force will decline. To counter this, it is advantageous to have a critical or supersaturated solution with an excess of osmotic agents in the compartment (5), (1 3). In one embodiment, the concentration of osmotic agents within the compartment (5), (13) remains constant as the compartment (5), (13) expands during movement of the piston. One method to preserve and control the distraction force is to utilize the degradation products from the hydrolytically cleavable polymers to provide the concentration gradient and thereby the osmotic potential across the semi-permeable membrane. Thereby, one can chose from a wide variety of hydrolytically cleavable polymers on the basis of well-described degradation rates to create an inclining force profile. The force profile can also be regulated by properties of the osmotic membrane.

In one embodiment of the present invention the implant comprises a breachable seal, which breaches when a specific high pressure is reached inside the compartment (5), for example in cases where the piston (4), (1 1 ) retracts into the hollow rod (1 ). The breachable seal can be located anywhere on the walls of the rod (1 ). The breachable seal also provides a mechanism for interrupting the movement or expansion of the piston, for example in cases where no further expansion is needed. Breaching of the breachable seal will lead to equalisation between the concentrations of osmotic agents outside and inside the hypertonic compartment and the osmotic pressure will consequently disappear.

Based on the above disclosure, it will be understood that the exact design of the implant of the present invention is not critical as long as the implant is suitable for being accurately fixed to the intended position of the spine, bone and/or limb of the individual to be treated.

Methods for treatment of skeletal deformities

The present invention is also directed to methods for treatment of an individual suffering from skeletal deformities.

One aspect of the present invention provides a method for the treatment of skeletal deformities comprising inserting at least one implant according to the present invention into an individual, such as an animal or a human being, suffering from skeletal deformities and fastening at least one implant to at least one bone of the individual. In one embodiment of the present method the skeletal deformity is scoliosis. Scoliosis may comprise infantile idiopathic scoliosis, juvenile idiopathic scoliosis and adolescent idiopathic scoliosis. In another embodiment the individual suffering from skeletal deformities is skeletal immature.

The implant can be fastened to one, two or more bones. In one embodiment the implant is fastened to the individual's spine. Fastening may comprise fastening a first end of said implant at a first location of said individual and fastening a second end of said implant at a second location of said individual. The implant is fastened using at least one fastening means, at least two fastening means, at least three fastening means, at least four fastening means, at least five fastening means, at least six fastening means, at least seven fastening means, at least eight fastening means or even more fastening means.

The implant as described herein can be used for the correction of the skeletal deformities such as for example scoliosis. The implant can be used for the correction of spinal deformities by correcting or straighten a curved portion of the spinal column. Furthermore, the implant can stabilize the spinal curve while allowing growth of the spine. This is important as patients suffering from scoliosis are often children or adolescents and consequently skeletally immature. It is contemplated that the implant according to the present invention also can be used for bone and limb lengthening. Bone and limb lengthening can be performed both in children and adults with limb length discrepancy and deformity. In children, limb shortening may give rise to limping, secondary scoliosis, increased energy expenditure and psychological problems. When the condition is not treated and continues to adulthood, arthritis of the opposite knee and hip and chronic back pain can develop. In children, indication for limb lengthening may include proximal focal femoral deficiency, fibular hemimelia and congenital hemiatrophy. Growth plate defects or damage due to trauma or infection can cause shortening with deformity requiring treatment. In adults indication for limb lengthening may include achondroplasia fibular, hemimelia, post-trauma shortening and poliomyelitis. Indications for limb lengthening may also include neglected club foot, complex foot deformities, equinus, ankle arthrodesis, metatarsal lengthening and acute unstable fractures with substantial bone loss. Of special motion is lengthening for constitutional short stature. These patients are a special group where careful psychological assessment is required prior to surgery. It is further contemplated that the implant according to the present invention can be used for the correction of paediatric skeletal deformities. Such deformities may include Congenital Hip Disorders such as Painful and Painless Limping, Developmental Dysplasia of the Hip (DDH), Perthes' disease, Slipped capital femoral epiphysis and In- toeing and Out-toeing. Knee and foot disorders such as Common Digital Deformities, Kohler's Disease, Freiberg's Disease, Metatarsus Adductus, Flatfoot, Tarsal Coalition, Club Foot, Bowleg and Knock-Knee and Blount's Disease and Trauma Surgery. The implant according to the present invention may further be used for the correction of Spina bifida, which is a spinal defect that is present at birth. In spina bifida, the spinal cord does not form properly and the vertebrae and skin cannot form around it. Spina bifida results from an error in the development of the embryo that occurs about a month after a woman becomes pregnant.

The implant according to the present invention may also be used for the correction of Kyphosis, also called hunchback is a forward bending of the spine. Kyphosis is caused by any condition that deforms the bones of the upper part of the spine so that the person is bent forward. Diseases that cause kyphosis include tuberculosis, syphilis, and rheumatoid arthritis.

The implant according to the present invention may further be used for treatment of hemithorax (fused ribs) by expanding thoracic cavity gradually.

Kit-of-parts

The present invention also provides a kit of parts comprising at least one implant according to the present invention and at least one attachment means, at least two attachments means, at least three attachments means, at least four attachment means, at least five attachment means, at least six attachment means or even more

attachment means. The kit-of-parts is preferably a sterile, pre-packaged kit-of-parts. The contents of the kit-of-parts will be separated from an external environment by a sterile barrier seal which is broken prior to the contents of the kit-of-parts being used in a surgical procedure. The kit-of-parts may comprise implants according to the present invention of different sizes and/or one or more implants known to the skilled artisan and/or fastening means such as pedicle screws all capable of being used with said implants of different sizes.

The implant of the present invention provides a number of advantages over the prior art designs. For example, growing rods, known from the prior art, require frequent operative procedures, are expensive, require excessive resources, and place the patient at unnecessary risk. A number of the growing rod systems allow for a single operative procedure for placement followed by periodic rod expansion performed with a less invasive procedure. However, the recurrent procedures still leave the patient at risks of bleeding, infection, pulmonary complications, and frequent anaesthetic exposure.

Claims

1 . Implant for treatment of skeletal deformities comprising

at least one hollow rod having at least one open end

a. at least one osmotic membrane which covers at least a part of the inner walls of said rod

b. at least one piston and

c. at least one compartment delimited by said at least one piston and said d. at least one osmotic membrane

2. The implant according to claim 1 , wherein at least a part of said piston is located within said hollow rod.

3. The implant according to any of the preceding claims, wherein said hollow rod and said piston are telescopically displaceable.

4. The implant according to any of the preceding claims, wherein said hollow rod and said piston are expandable.

5. The implant according to any of the preceding claims, wherein at least a part of said piston extends out from the open end.

6. The implant according to any of the preceding claims wherein said implant comprises at least one hollow rod having two open ends.

7. The implant according to claim 6, wherein said implant comprises two pistons, one piston being telescopically displaceable in relation to the at least one hollow rod.

8. The implant according to claim 6, wherein said implant comprises two pistons, said two pistons being telescopically displaceable in relation to the at least one hollow rod.

9. The implant according to any of the preceding claims, wherein said hollow rod is rigid.

10. The implant according to claim 9, wherein said hollow rod comprises metal or metal alloy.

1 1 . The implant according to claim 10, wherein said metal or metal alloy is a

biologically inert metal or metal alloy.

12. The implant according to any of claims 10-1 1 , wherein said metal is titanium and/or a titanium based alloy.

13. The implant according to any of the preceding claims, wherein said piston is rigid.

14. The implant according to claim 13, wherein said piston comprises metal or metal alloy.

15. The implant according to claim 14, wherein said metal or metal alloy is a

biologically inert metal or metal alloy.

16. The implant according to claims 14-15, wherein said metal is titanium and/or a titanium based alloy.

17. The implant according to any of the preceding claims, further comprising

attachment means such as for example pedicle screws, hooks and/or wires.

18. The implant according to any of the preceding claims, wherein said implant further comprises at least one breachable seal.

19. The implant according to any of the preceding claims, wherein said compartment contains a hypertonic solution.

20. The implant according to claim 19, wherein said hypertonic solution is comprised of one or more osmotic agents and/or combination of two or more osmotic agents.

21 . The implant according to claim 20, wherein said osmotic agents are non-toxic.

22. The implant according to any of claims 20-21 , wherein said osmotic agents are selected from the group consisting of sodium chloride, sorbitol, mannitol, glucose and trehalose

23. The implant according to any of claims 20-21 , wherein said osmotic agents are hydrolytically degradable polymers and/or combination of two or more hydrolytically degradable polymers.

24. The implant according to claim 23, wherein said hydrolytically degradable polymers are biodegradable and degrade into biologically inert products.

25. The implant according to claim 1 , wherein said osmotic membrane is a semipermeable membrane.

26. The implant of claim 25, wherein said osmotic membrane comprises polysulfone and/or regenerated cellulose.

27. The implant according to any of the preceding claims, wherein an osmotic potential is generated across said osmotic membrane.

28. The implant according to claim 27, wherein said osmotic potential provides a distraction force.

29. The implant according to claim 28, wherein said distraction force results in movement of the piston as the compartment expands.

30. The implant according to claims 20-29, wherein the concentration of osmotic agents within the compartment remains constant as the compartment expands during movement of the piston.

31 . A method for treatment of skeletal deformities comprising inserting at least one implant according to any of the preceding claims into an individual suffering from skeletal deformities and fastening the least one implants to at least one bone of said individual.

32. The method according to claim 31 , wherein fastening comprises fastening a first end of said implant at a first location of said individual and fastening a second end of said implant at a second location of said individual.

33. The methods according to any of claims 31 -32, wherein the at least one implant is fastened using at least one attachment means.

34. The method according to claim 31 , wherein said skeletal deformity is scoliosis.

35. The method according to claim 34, wherein scoliosis comprises infantile idiopathic scoliosis, juvenile idiopathic scoliosis and adolescent idiopathic scoliosis.

36. The method according to any of claims 34-35, wherein said implant is fastened to the individual's spine.

37. The methods according to any of claims 31 -36, wherein the individual is skeletally immature.

38. An implant as defined in any of the preceding claims for correction of skeletal deformities.

39. The implant according to claim 38, wherein said skeletal deformity is scoliosis.

40. Use of implant as defined in any of the preceding claims for correction of skeletal deformities.

41 . The use according to claim 40, wherein said skeletal deformity is scoliosis.

42. Use of implant according to any of the preceding claims for leg and/or limb extension.

43. Kit of parts for correction of skeletal deformities comprising at least one implant as defined in any of the preceding claims and at least one attachment means.