Patent Description:
The present disclosure relates generally to composite biomedical implants having regions with varying porosity, and more particularly composite spinal implants having regions that are relatively porous and regions that are relatively dense, the varied porosity being selected to enhance bony ingrowth into the implant while providing mechanical support to maintain distraction of vertebrae.

Interbody spinal fusion is used to alleviate pain caused when a herniated, bulging, or flattened intervertebral disc impinges on the spinal cord or nerve root. The disc and vertebral endplates are re-moved and an interbody fusion implant is inserted in the disc space to restore vertebral height, promote fusion of bone tissue between adjacent vertebrae, and, thus, mechanically stabilize the spine. Generally, the choices for spinal implants fall largely into metallic, polymeric, carbon fiber based and ceramic. <CIT> discloses such a spinal implant know in the art. Polyaryletherketone (PAEK) and bioactive PAEK composites for biomedical devices present several advantageous properties. PAEK polymers are generally biocompatible, bioinert, and radiolucent, and they exhibit a high strength and similar compliance to bone. One example of PAEK polymers used for biological implants is polyetheretherketone (PEEK). PEEK implants have many attractive characteristics, in particular for spinal surgeons and patients. Because of the radiolucency of PAEK composites, implants formed with PEEK allow post-operative radiographic assessment of fusion, which is problematic with metallic implants due to relatively high x-ray attenuation of titanium. PEEK also exhibits a modulus of elasticity similar to bone, enhancing load transfer and osteogenic signals to tissue in the implant, and reducing the likelihood of vertebral subsidence compared to alternatives formed with metals and ceramics. Porous PEEK provides surface area and architecture to support more extensive bony tissue ingrowth into the porous implant surfaces. Of particular interest are porous PEEK materials that are reinforced with calcium phosphate, and in some examples, calcium phosphate particles selected from anisometric hydroxyapatite particles. These materials have been reported to provide bioactivity for enhanced bony ingrowth into the implant by the exposure of the anisometric hydroxyapatite particles on the surfaces of and extending within the pore voids. Despite the advantages of the foregoing described implant technologies, there remains a need in the art for implants that include the advantageous features of PAEK materials provided in an implant construct that is adapted to spinal anatomy to achieve extensive bony ingrowth into the implant and provide mechanical properties that discourage stress shielding and have strength properties to handle the physiological loads during fusion.

The implantable medical device comprises a thermoplastic composite body. The thermoplastic composite body includes an anterior surface of the thermoplastic composite body, a first lateral surface of the thermoplastic composite body, a second lateral surface of the thermoplastic composite body, a posterior surface of the thermoplastic composite body, a superior surface of the thermoplastic composite body, an inferior surface of the thermoplastic composite body, at least one dense portion, and at least one porous portion. The at least one dense portion is formed of a thermoplastic polymer matrix that is essentially non-porous, and which is continuous through a thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body. The at least one porous portion is formed of a porous thermoplastic polymer scaffold which is continuous through the thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body. In accordance with the disclosure, the composite has interconnected pores.

In another exemplary embodiment, an implantable medical device includes a thermoplastic composite body. The thermoplastic composite body includes an anterior surface of the thermoplastic composite body, a first lateral surface of the thermoplastic composite body, a second lateral surface of the thermoplastic composite body, a posterior surface of the thermoplastic composite body, a superior surface of the thermoplastic composite body, an inferior surface of the thermoplastic composite body, at least one dense portion formed of a first thermoplastic polymer matrix that is essentially non-porous, and which is continuous through a thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body, at least one porous portion formed of a porous thermoplastic polymer scaffold, the porous thermoplastic polymer scaffold being formed of a second thermoplastic polymer matrix, the at least one porous portion being continuous through the thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body, at least one reinforcement material dispersed throughout the at least one dense portion and the at least one porous portion, and at least one central through cavity extending from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body and disposed inward from the anterior surface of the thermoplastic composite body, the first lateral surface of the thermoplastic composite body, the second lateral surface of the thermoplastic composite body, and the posterior surface of the thermoplastic composite body. The at least one porous portion includes at least one porous outer wall disposed along the anterior surface of the thermoplastic composite body, the first lateral surface of the thermoplastic composite body, and the second lateral surface of the thermoplastic composite body, and at least one porous central portion defining an outer boundary of the at last one central through cavity. The at least one dense portion includes at least one dense core disposed between the at least one porous central portion and the at least one porous outer wall, the at least one dense core extending to the posterior surface of the thermoplastic composite body, forming a dense posterior edge, and a plurality of projections extending outward relative to the at least one porous portion from at least one of the superior surface of the thermoplastic composite body or the inferior surface of the thermoplastic composite body. The at least one dense portion defines a closed lateral structural support, and the thermoplastic composite body having the closed lateral structural support is more durable with respect to insertion forces than an otherwise identical comparative thermoplastic composite body lacking the closed lateral structural support. The at least one dense portion and the at least one porous portion are integrally formed such that the thermoplastic composite body is a single continuous article free of adhesive and mechanical joints between the at least one dense portion and the at least one porous portion.

The method for forming a thermoplastic composite body comprises disposing a first powder mixture in a first portion of a mold, the first powder mixture including a first thermoplastic polymer powder. The first powder mixture is compacted to densify the first powder mixture at a first pressure. A second powder mixture is disposed in a second portion of the mold, the second powder mixture including a second thermoplastic polymer powder and a porogen material. The second powder mixture is compacted to densify the second powder mixture at a second pressure. The first powder mixture and the second powder mixture are simultaneously molded at a molding temperature above room temperature and at a final molding pressure. The simultaneous molding forms at least one dense portion having a first thermoplastic polymer matrix that is essentially non-porous from the first powder mixture and forms at least one proto-porous portion having a second thermoplastic polymer matrix from the second powder mixture. The porogen material is leached from the at least one proto-porous portion, forming at least one porous portion having a porous thermoplastic polymer scaffold that is continuous from the at least one proto-porous portion. The thermoplastic polymer scaffold includes the second thermoplastic polymer matrix. The simultaneous molding and the leaching integrally form the at least one dense portion and the at least one porous portion as a single continuous article free of adhesive and mechanical joints between the at least one dense portion and the at least one porous portion. The method may involve use of more than two powder mixtures. The invention is set out in independent claims <NUM> and <NUM>, further advantageous embodiments of the invention are set forth in the appended dependent claims.

Features and advantages of the general inventive concepts will become apparent from the following description made with reference to the accompanying drawings, including drawings represented herein in the attached set of figures, of which the following is a brief description.

Wherever possible, the same reference numbers will be used throughout the drawings to represent the same parts.

The general inventive concepts will now be described with occasional reference to the exemplary embodiments of the invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art encompassing the general inventive concepts. The terminology set forth in this detailed description is for describing particular embodiments only and is not intended to be limiting of the general inventive concepts.

Provided are medical device implants which may be bioactive, particularly for use in the spine, that address the mechanical and biological requirements for maximizing integration of the implant during bony fusion between vertebrae. The implants take advantage of dense and porous reinforced polymer wherein the relative density of portions of the device may be varied to one or more of: match mechanical properties of the vertebral bodies or bone tissue which is to be contacted by the implant; provide anatomically desirable distraction between vertebrae; provide mechanical strength to support and maintain balance in the sagittal plane; minimize subsidence; and provide for optimal osteointegration.

Implants as provided include a combination of dense and porous regions that influence the overall stiffness of the implant, wherein stiffness may be determined by the ratio of cross-sectional area (normal to direction of loading) of the portions of the implant that include porous and dense material. The ratio of cross-sectional area (normal to direction of loading) and placement of the dense and porous portions may be configured to provide an implant that can be matched to the mechanical properties of the vertebral bodies or bone tissue which it is intended to contact, both in overall implant stiffness, and in cross-sectional location of the relatively stiffer dense portions and the relatively flexible porous portions. In some embodiments, one or more of the dense and porous portions comprise one or more reinforcement particles which may be exposed on the surface of pores within at least some of the porous portions. In some particular embodiments, the implant is formed of a polymer selected from PAEK polymers, and include reinforcement particles in at least some portions, wherein the reinforcement particles comprise calcium phosphate compositions known to be bioactive.

Advantages realized according to the various embodiments of implantable devices that are adapted for use in the spine, as described herein, include the following: dense portions, for example those that comprise hydroxyapatite reinforced PEEK, provide biomechanical support only where it is needed; porous regions, for example those that comprise porous hydroxyapatite reinforced PEEK, enable bone ingrowth for osteointegration where most beneficial, for example on the inner implant surface in the graft window for graft incorporation to the implant and/or the anterior outer implant surface to support sentinel-sign bone growth; interconnected porosity provides biological pathway from vertebrae to vertebrae, through the implant to promote thorough osteo-conductivity; in some embodiments, exposed reinforcements, for example, any bioactive reinforcement, and in some specific examples, hydroxyapatite whiskers, enhance bioactivity of the implant; porous fusion anteriorly supports sentinel-sign bone growth; porous fusion laterally maximizes the breadth of bone growth stabilization as well as adds a conformable material in a region where the bony geometry is less planar; dense material on the posterior outer implant surface discourages bone growth and maximizes mechanical support to maintain foraminal height; threaded inserter hole transmits inserter impaction to a load bearing frame; keystone footprint allows for maximal endplate area contact while maintaining clearance for nerve pathways. It will be appreciated that in some embodiments, the thermoplastic polymer may be a polymer other than PEEK and other than a PAEK polymer. It will also be appreciated that in some embodiments, the thermoplastic polymer may not include any reinforcement material within any one or more of the dense and porous portions, and that in yet other embodiments, the thermoplastic polymer may contain one or a combination of reinforcement materials that may or may not comprise calcium phosphate, hydroxyapatite or hydroxyapatite whiskers. In some examples, other bioactive reinforcements that do not comprise calcium phosphate may be selected.

Human bone tissues exhibit substantial variation in mechanical properties depending on the tissue density and microstructure. The properties are highly dependent on anatomic location and apparent density of the measured specimen. For example, cortical bone, such as in a thin outer wall of a vertebral body, has a relative porosity on the order of about <NUM>-<NUM>%, and a trabecular bone, such as in the central majority or marrow cavity of a vertebral body, has a porosity on the order of about <NUM>-<NUM>%. Due to the highly significant porosity differences, trabecular bone exhibits significantly lower effective mechanical properties compared to cortical bone. Therefore, depending on the application, synthetic composite materials for use as scaffolds and/or spinal fusion implants or other implant devices should possess the mechanical properties exhibited by cortical bone or trabecular bone, but must also have effective porosity to promote bone ingrowth.

To avoid the mechanical mismatch problems, such as stress shielding, it is desirable to substantially match or mimic the mechanical properties (e.g., elastic modulus) of the adjacent and/or substituted bone tissue. Several factors may be varied during the manufacturing of the implant device, and/or composite material and scaffold of the implant device, to tailor the mechanical properties including the ratio of the cross-sectional area of dense to porous thermoplastic polymer in the implant, the reinforcement volume fraction, aspect ratio, size and orientation; the polymer; and the size, volume fraction, shape and directionality of the porosity. Tailoring the mechanical properties of the implant and/or composite materials and scaffold reduces the likelihood of mechanical mismatch leading to a decreased risk of subsidence, stress shielding, bone resorption and/or subsequent failure of adjacent vertebrae.

Porous polymer scaffolds may be tailored to mimic biological and mechanical properties of bone tissue for implant fixation, synthetic bone graft substitutes, tissue engineering scaffolds, interbody spinal fusion, or other orthopedic applications. An example porous composite material described herein reduces subsidence and/or bone resorption resulting from mechanical mismatch problems between a synthetic scaffold of an implant device and the peri-implant tissue. Additionally, porosity and/or the pore sizes of the example thermoplastic composite are tailorable to specific applications to effectively promote the vascularization and growth of bone in the pores and/or void spaces of the example scaffolds, thereby improving bonding between the scaffolds and peri-implant tissue.

Composite materials or scaffolds may be synthesized or made through a process that enables reinforcement particles to be integrally formed with or embedded within polymer matrices. In this manner, the polymer matrices embedded with the reinforcement material may provide improved material properties (e.g., elastic modulus, fatigue strength, and toughness). The reinforcement particles are also exposed on a surface of the matrices, which promotes bioactivity and/or osteointegration. Additionally, the process provides flexibility to tailor the level of reinforcement particles and porosity for a desired application. For example, a porogen material may be used to vary the porosity, while the pore size is tailored by, for example, sieving the porogen to a desired size. An additional pore tailoring method is to reshape a porogen material from it native shape to one that promotes interparticle contact between porogen particles and thus improved permeability. For example, sodium chloride particles are natively cubic. A process such as passing the particle through an energy source so that is melts and reforms to a shape other than its native cubic shape. Alternative shapes may be fibers, polyhedrals, spheres, spheroids, ellipses, ellipsoids, or any other suitable shape.

By varying the volume fraction of the reinforcement particles and the porosity of the example scaffold, the mechanical properties (e.g., elastic modulus) of the example scaffold of the implant device may be tailored to match those of the adjacent peri-implant bone tissue to reduce mechanical mismatch problems. Reducing mechanical mismatch provides a decreased risk of subsidence, stress shielding, bone resorption, and/or subsequent failure of adjacent peri-implant bone tissue. Additionally, scaffolds may include a significantly high porosity to promote bone ingrowth, while exhibiting significantly higher effective mechanical properties such as, for example, the mechanical properties of trabecular bone.

The example composite materials described herein may be used for applications such as, for example, synthetic bone graft substitutes, bone ingrowth surfaces applied to existing implants, tissue engineering scaffolds, interbody spinal fusion implants, etc. In each of the applications, bone graft materials (e.g., autograft, demineralized bone matrix, and the like) may be incorporated into the central cavity (or "graft space") of the implant to further enhance osteoinduction and/or osteoconduction to promote osteointegration. Carrier materials (e.g., collagen, hydrogels, etc.) containing growth factors, such as bone morphogenetic proteins (BMP), may also be incorporated into the pore space of the scaffold and/or the central cavity (or "graft space") of the implant to further enhance osteoinduction and/or osteoconduction to promote osteointegration.

Referring to <FIG>, in one embodiment, an implantable medical device <NUM> includes a thermoplastic composite body <NUM> having an anterior surface <NUM> of the thermoplastic composite body <NUM>, a first lateral surface <NUM> of the thermoplastic composite body <NUM>, a second lateral surface <NUM> of the thermoplastic composite body <NUM>, a posterior surface <NUM> of the thermoplastic composite body <NUM>, a superior surface <NUM> of the thermoplastic composite body <NUM>, an inferior surface <NUM> of the thermoplastic composite body <NUM>, at least one dense portion <NUM> formed of a first thermoplastic polymer matrix <NUM> that is essentially non-porous, and which is continuous through a thickness dimension <NUM> from the superior surface <NUM> of the thermoplastic composite body <NUM> to the inferior surface <NUM> of the thermoplastic composite body <NUM>, and at least one porous portion <NUM> formed of a porous thermoplastic polymer scaffold <NUM>, the porous thermoplastic polymer scaffold <NUM> being formed of a second thermoplastic polymer matrix <NUM>, the at least one porous portion <NUM> being continuous through the thickness dimension <NUM> from the superior surface <NUM> of the thermoplastic composite body <NUM> to the inferior surface <NUM> of the thermoplastic composite body <NUM>.

As used herein, "essentially non-porous" indicates a porosity of less than <NUM> vol. %, whereas "porous" indicates a porosity of at least <NUM> vol. In a further embodiment, the at least one dense portion <NUM> formed of a first thermoplastic polymer matrix <NUM> is substantially non-porous, and "substantially non-porous" indicates a porosity of less than <NUM> vol. The at least one porous portion <NUM> has a modulus of elasticity that is relatively less than the modulus of elasticity of the at least one dense portion <NUM>.

In a further embodiment, the at least one dense portion <NUM> and the at least one porous portion <NUM> are integrally formed such that the thermoplastic composite body <NUM> is a single continuous article free of adhesive and mechanical joints between the at least one dense portion <NUM> and the at least one porous portion <NUM>, and the first thermoplastic polymer matrix <NUM> is continuous with the second thermoplastic polymer matrix <NUM>.

The thermoplastic composite body <NUM> may have a conformation that is generally a disc or block, that may have an overall shape that ranges from generally circular to elliptical, to ovoid, to generally square to generally trapezoidal. With reference in particular to an implant intended for use in the disc space between spinal vertebrae, the thermoplastic composite body <NUM> is configured with reference to the orientation relative to the posterior, anterior, and lateral aspects of the spine. Thus, when inserted into a disc space between two vertebrae, an anterior surface <NUM> of the thermoplastic composite body <NUM> is intended to be oriented at the anterior aspect of the spine, the posterior surface <NUM> of the thermoplastic composite body <NUM> is intended to be oriented at the posterior aspect of the spine, and the first lateral surface <NUM> and the second lateral surface <NUM> of the thermoplastic composite body <NUM> is intended to be oriented at the lateral aspects of the spine.

In one example, the thermoplastic composite body <NUM> has a generally trapezoidal shape defined by a width dimension (w), a length dimension (l), and a thickness dimension <NUM>, with the periphery of the generally trapezoidal shape being defined by the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, the posterior surface <NUM> of the thermoplastic composite body <NUM>, the superior surface <NUM> of the thermoplastic composite body <NUM>, and the inferior surface <NUM> of the thermoplastic composite body <NUM>. The anterior surface <NUM> may be wider than the posterior surface <NUM> or narrower than the posterior surface <NUM>. The thickness dimension <NUM> of the thermoplastic composite body <NUM> may be continuous or varied. The thickness dimension <NUM> may uniform or varied along the length from the anterior surface <NUM> to the posterior surface <NUM>. By way of example, the thickness dimension <NUM> may vary along the length from relatively thicker at the anterior surface <NUM> to relatively thinner at the posterior surface <NUM>, providing a wedge shape for the thermoplastic composite body <NUM>, or, alternatively the thickness dimension <NUM> may vary along the length from relatively thinner at the anterior surface <NUM> to relatively thicker at the posterior surface <NUM>, providing a wedge shape for the thermoplastic composite body <NUM>. The thermoplastic composite body <NUM> may have any suitable wedge conformation, including, but not limited to a zero to twenty degree wedge shape anterior to posterior to support the lordotic curvature of the spine during the graft healing. These dimensional changes may be combined in any suitable manner to form different embodiments for particular uses.

In another example, the thermoplastic composite body <NUM> has a generally circular or elliptical shape and the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM> are designated as four quadrants of the circular or elliptical shape. The thickness dimension <NUM> may be uniform or vary along an axis bisecting each of the anterior surface <NUM> and the posterior surface <NUM>, or it may vary along the axis bisecting each of the anterior surface <NUM> and the posterior surface <NUM> from relatively thicker at the anterior surface <NUM> to relatively thinner at the posterior aspect <NUM>, or from relatively thinner at the anterior surface <NUM> to relatively thicker at the posterior aspect <NUM>.

In one embodiment, the at least one porous portion <NUM> includes at least one porous outer wall <NUM> disposed along at least one of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, or the posterior surface <NUM> of the thermoplastic composite body <NUM>. The at least one porous outer wall <NUM> may include any suitable thickness, including, but not limited to, a thickness of at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>.

The at least one porous portion <NUM> may further include at least one porous central portion <NUM>. In one embodiment, the at least one dense portion <NUM> includes at least one dense core <NUM> disposed between the at least one porous central portion <NUM> and the at least one porous outer wall <NUM>. The at least one porous central portion <NUM> may include any suitable thickness. In an embodiment, as further described below, having at least one central through cavity <NUM>, the at least one porous central portion may include, but is not limited to, a thickness of at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>. In an embodiment lacking at least one central through cavity <NUM>, the at least one porous central portion may include, but is not limited to, a thickness of at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively at least <NUM>, alternatively up to <NUM>.

In one embodiment, the at least one porous outer wall <NUM> may be disposed along one of, two of, or all three of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, and the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the at least one dense core <NUM> extends to the posterior surface <NUM> of the thermoplastic composite body <NUM>, forming a dense posterior edge <NUM>. In another embodiment, the at least one porous outer wall <NUM> may be disposed along each of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>, such that that the at least one dense core <NUM> is contained within the at least one porous outer wall <NUM>.

The thermoplastic composite body <NUM> may include at least one central through cavity <NUM> extending from the superior surface <NUM> of the thermoplastic composite body <NUM> to the inferior surface <NUM> of the thermoplastic composite body <NUM> and disposed inward from the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>. The central through cavity <NUM> may include any suitable conformation, and may be a bore, a graft space, or a graft window. In one embodiment, the at least one porous portion includes at least one porous central portion <NUM>, and the at least one porous central <NUM> portion defines an outer boundary <NUM> of the at least one central through cavity <NUM>.

In another embodiment, the thermoplastic composite body <NUM> lacks a central through cavity <NUM> extending from the superior surface <NUM> of the thermoplastic composite body <NUM> to the inferior surface <NUM> of the thermoplastic composite body <NUM> and disposed inward from the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>.

The at least one dense portion <NUM> may extend along at least one of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, or the posterior surface <NUM> of the thermoplastic composite body <NUM>, forming at least one dense edge <NUM>. In one embodiment, the at least one dense portion <NUM> extends along at least one of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>, forming at least one dense outer wall <NUM>, with the at least one porous portion <NUM> being disposed inward of the at least one dense outer wall <NUM>.

The at least one dense portion <NUM> may define a closed lateral structural support <NUM>. A thermoplastic composite body <NUM> having the closed lateral structural support <NUM> may be more durable with respect to insertion forces than an otherwise identical comparative thermoplastic composite body <NUM> lacking the closed lateral structural support <NUM>.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> is trapezoidal wedge and includes a central through cavity <NUM> with a porous central portion <NUM> defining a boundary of the central through cavity <NUM>. This thermoplastic composite body <NUM> lacks a porous outer wall <NUM> such that each of the anterior surface <NUM> the first lateral surface <NUM>, the second lateral surface <NUM>, and the posterior surface <NUM> is formed by the at least one dense portion <NUM>.

Referring to <FIG>, in one embodiment, the at least one central through cavity <NUM> includes a first central through cavity <NUM> and a second central through cavity <NUM>, and the at least one dense portion <NUM> extends along the posterior surface <NUM> of the thermoplastic composite body <NUM>, and extends from the posterior surface <NUM> of the thermoplastic composite body <NUM> between the first central through cavity <NUM> and the second central through cavity <NUM>, and toward the anterior surface <NUM> of the thermoplastic composite body <NUM> such that the at least one dense portion <NUM> is disposed between the first central through cavity <NUM> and the anterior surface <NUM> of the thermoplastic composite body <NUM>, and is further disposed between the second central through cavity <NUM> and the anterior surface <NUM> of the thermoplastic composite body <NUM>. This continuous dense linkage extending between the first central through cavity <NUM> and the second central through cavity <NUM> along a direction from the anterior surface <NUM> to the posterior surface <NUM> which connects the at least one dense portion <NUM> extending along the posterior surface <NUM> and the at least one dense portion <NUM> further extending between the first central through cavity <NUM> and the anterior surface <NUM> and between the second central through cavity <NUM> and the anterior surface <NUM>, may also provide increased durability with respect to insertion forces than an otherwise identical comparative thermoplastic composite body <NUM> lacking the extension of the at least one dense portion <NUM> between the first central through cavity <NUM> and the second central through cavity <NUM>.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> includes a central through portion <NUM> defined by a porous central portion <NUM>, a circular dense core <NUM>, and has a porous outer wall <NUM> along each of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> includes a central through portion <NUM> defined by a porous central portion <NUM>, and has a porous outer wall <NUM> along the first lateral surface <NUM> of the thermoplastic composite body <NUM> and the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and a dense edge <NUM> along the anterior surface <NUM> of the thermoplastic composite body <NUM> and the posterior surface <NUM> of the thermoplastic composite body <NUM>.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> having a cuboid block (rather that wedge) conformation includes a central through portion <NUM> defined by a porous central portion <NUM> and lacks a porous outer wall <NUM>.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> having a trapezoidal block lacks a central through portion <NUM> and includes a porous outer wall <NUM> disposed along the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body, and further includes a dense edge <NUM> along the anterior surface <NUM> of the thermoplastic composite body <NUM>.

Referring to <FIG>, in one embodiment, wherein the at least one porous portion <NUM> forms the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>, and the at least one dense portion <NUM> includes a plurality of dense cores <NUM>, each of the plurality of dense cores <NUM> is disposed at vertices <NUM> between each of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>.

Referring to <FIG>, in one embodiment, the at least one dense portion <NUM> includes a plurality of projections <NUM> extending outward relative to the at least one porous portion <NUM> from at least one of the superior surface <NUM> of the thermoplastic composite body <NUM> or the inferior surface <NUM> of the thermoplastic composite body <NUM>. Suitable projections <NUM> includes, but are not limited to, teeth, serrated teeth, ridges, bumps, and combinations thereof. Such projections <NUM> may come into direct contact with the adjacent peri-implant tissue to prevent movement relative to the peri-implant tissue after implantation. In another embodiment, the at least one dense portion <NUM> lacks any projections <NUM> extending outward relative to the at least one porous portion <NUM> from the superior surface <NUM> of the thermoplastic composite body <NUM> or the inferior surface <NUM> of the thermoplastic composite body <NUM>.

Additionally, or alternatively, although not shown, the at least one dense portion <NUM> may include holes, notches, pins, radiographic markers, or other features that may be gripped or otherwise used for positioning of the implantable medical devices <NUM> comprising the at least one dense portion <NUM> by minimally invasive surgical tools and procedures.

Referring to <FIG>, <FIG>, and <FIG>, in one embodiment, the thermoplastic composite body <NUM> includes an insertion tool engagement feature <NUM>. Suitable insertion tool engagement features <NUM> include, but are not limited to, a plurality of apertures <NUM> penetrating the anterior surface <NUM>. In a further embodiment, at least one of the plurality of apertures <NUM> penetrates through a porous outer wall <NUM>, a dense core <NUM>, a porous central portion <NUM>, and into a central through cavity <NUM>, and at least one of the plurality of apertures <NUM> penetrates only into the porous outer wall <NUM>. In yet a further embodiment, one of the plurality of apertures <NUM> penetrates through the porous outer wall <NUM>, the dense core <NUM>, the porous central portion <NUM>, and into the central through cavity <NUM>, and two of the plurality of apertures <NUM> penetrate only into the porous outer wall <NUM>. The apertures <NUM> may, independently, be threaded or unthreaded.

Referring to <FIG>, vertices <NUM> between each of the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM> may be angular or radiused corners. Additionally, the superior surface <NUM> of the thermoplastic composite body <NUM> and the inferior surface <NUM> of the thermoplastic composite body <NUM> may, independently, meet the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the posterior surface <NUM> of the thermoplastic composite body <NUM>, with angular, radiused, or chamfered corners. Further, in embodiments having at least one central through cavity <NUM>, the superior surface <NUM> of the thermoplastic composite body <NUM> and the inferior surface <NUM> of the thermoplastic composite body <NUM> may, independently, meet the outer boundary <NUM> of the at least one central through cavity <NUM>, with angular, radiused, or chamfered corners.

The first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> may be formed from any suitable thermoplastic polymer materials, including, but not limited to, polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketonekteone (PEKK), polyetherketone (PEK), polyethylene, high density polyethylene (HDPE), ultra-high molecular weight polyethylene (UHMWPE), low density polyethylene (LDPE), polyethylene oxide (PEO), polyurethane, polypropylene, polypropylene oxide (PPO), polysulfone, polyethersulfone, polyphenylsulfone, poly(DL-lactide) (PDLA), poly(L-lactide) (PLLA), poly(glycolide) (PGA), poly(ε-caprolactone) (PCL), poly(dioxanone) (PDO), poly(glyconate), poly(hydroxybutyrate) (PHB), poly(hydroxyvalerate (PHV), poly(orthoesters), poly(carboxylates), poly(propylene fumarate), poly(phosphates), poly(carbonates), poly(anhydrides), poly(iminocarbonates), poly(phosphazenes), polymethylmethacrylate (PMMA), polyacrylics from bisphenols, hydroxypropylmethacrylate (bis-GMA), tri(ethylene glycol) dimethacrylate (TEG-DMA), copolymers thereof, and blends thereof. The first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> may be formed of the same thermoplastic polymer material or the first thermoplastic polymer matrix <NUM> may be distinct from the thermoplastic polymer material of the second thermoplastic polymer matrix <NUM>.

The thermoplastic composite body <NUM> may include at least one reinforcement material dispersed throughout at least one of the at least one dense portion <NUM> and the at least one porous portion <NUM>. Suitable bioactive reinforcement materials include, but are not limited to, hydroxyapatite (HA), calcium-deficient hydroxyapatite, carbonated calcium hydroxyapatite, beta-tricalcium phosphate (beta-TCP), alpha-tricalcium phosphate (alpha-TCP), amorphous calcium phosphate (ACP), anisometric calcium phosphate, octacalcium phosphate (OCP), tetracalcium phosphate, biphasic calcium phosphate (BCP), anhydrous dicalcium phosphate (DCPA), dicalcium phosphate dihydrate (DCPD), anhydrous monocalcium phosphate (MCPA), monocalcium phosphate monohydrate (MCPM), glasses and glass-ceramics comprising SiO<NUM>, CaO, Na<NUM>O, Al<NUM>O<NUM>, and/or P<NUM>O<NUM>, and combinations thereof. Suitable non-bioactive reinforcement materials include, but are not limited to, carbon fibers, carbon nanotubes, graphene, fiberglass, barium sulfate, metallic particles, oxide particle, and combinations thereof. The thermoplastic body <NUM> may include any suitable combination of bioactive reinforcement materials and non-bioactive reinforcement materials.

Reinforcement materials, for example, reinforcements in the form of calcium phosphate reinforcement particles, may be in the form of single crystals or dense polycrystals and in some embodiments may be, at least in some portion, anisometric. As used herein, "anisometric" refers to any particle morphology (shape) that is not equiaxed (e.g., spherical), such as whiskers, plates, fibers, etc. Anisometric particles are usually characterized by an aspect ratio. For example, HA single crystals are characterized by the ratio of dimensions in the c- and a-axes of the hexagonal crystal structure. Thus, the anisometric particles in the present disclosure have an aspect ratio greater than <NUM>. In one example, the mean aspect ratio of the reinforcement particles is from greater than <NUM> to about <NUM>. In accordance with the various embodiments, the mean aspect ranges from greater than <NUM>, to <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and up to and including <NUM>, including increments and ranges therein and there between.

The reinforcement particles can be provided in an amount of from about <NUM>-<NUM>% by volume of the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>, alternatively from about <NUM>-<NUM>% by volume. In accordance with the various embodiments, the volume of reinforcement particles present in the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM> can range from about <NUM>-<NUM>%, alternatively from about <NUM>-<NUM>%, alternatively from about <NUM>-<NUM>%, alternatively from about <NUM>-<NUM>%, and any suitable combination, sub-combination, range, or sub-range thereof by volume, based on the volume of the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>. Thus, the reinforcement particles may be present, by volume, based on the total volume of the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>, from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, to about <NUM> volume percent, including increments and ranges therein and there between.

Furthermore, there are no limits on the size or amount of the reinforcement particles dispersed in the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>, provided that the reinforcement particles are dispersed within and/or exposed at the surface in the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>. For example, the reinforcement particles may have a maximum dimension from about <NUM> to about <NUM>, and for example, between and including <NUM> to about <NUM>. While both nano- and micro-scale reinforcement particles improve the mechanical properties of the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>, nanoscale reinforcement particles are particularly effective for enhancing bioresorbability and cell attachment, and micro-scale particles are particularly effective for obtaining a uniform dispersion within the first thermoplastic polymer matrix <NUM> and/or the second thermoplastic polymer matrix <NUM>. Amongst suitable reinforcement particles, calcium phosphate particles are effective for increasing bioactivity. Thus, the reinforcement particles may have a size from about <NUM> to about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and to about <NUM> to about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and to about <NUM> and up to and including <NUM>, including increments and ranges therein and therebetween.

In one embodiment, the at least one porous portion <NUM> includes a second thermoplastic polymer matrix <NUM> reinforced with anisometric calcium phosphate particles. By way of example, a composite material may include a polyetheretherketone (PEEK) or a polyetherketoneketone (PEKK) matrix reinforced with various volume fractions of hydroxyapatite (HA) whiskers (e.g., <NUM> or <NUM> vol. %), wherein the second thermoplastic polymer matrix <NUM> is approximately between and including <NUM>% and <NUM>%, and in some embodiments between and including <NUM>% and <NUM>%, and in some particular embodiments between and including <NUM>% and <NUM>% porous.

In some such embodiments, the second thermoplastic polymer matrix <NUM> may also include bone morphogenetic protein (BMP) such as, for example, rhBMP-<NUM>, which can be absorbed, dispersed or accommodated by the void spaces and/or pores of the porous thermoplastic polymer scaffold <NUM> or microporous polymer matrix. Additionally, the BMP may be adsorbed to the calcium phosphate reinforcements further localizing the BMP to the surface of the porous thermoplastic polymer scaffold <NUM> or the second thermoplastic polymer matrix <NUM>.

The porous thermoplastic polymer scaffold <NUM> may include a porous thermoplastic polymer (e.g., a PEEK polymer) scaffold having anisometric calcium phosphate reinforcement particles integrally formed or embedded with the porous thermoplastic scaffold and exposed on the surface of pores in the thermoplastic polymer scaffold <NUM>. In this manner, the second thermoplastic polymer matrix <NUM> embedded with the reinforcement particles provides high material stiffness and strength, and the reinforcement particles exposed on the surface of the porous thermoplastic polymer scaffold <NUM> promote bioactivity and/or bioresorption. The reinforcement particles may further provide radiopacity (contrast for radiographic imaging). The porous thermoplastic polymer scaffold <NUM> includes a substantially continuous, interconnected porosity and a plurality of pores to promote bone ingrowth into the porous thermoplastic polymer scaffold <NUM>. In addition, the porous thermoplastic polymer scaffold <NUM> is substantially continuously interconnected via a plurality of struts. Furthermore, at least one of the plurality of struts may be a load-bearing strut.

Additionally, the first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> may optionally include other additives, if suitable. By way of non-limiting example, the first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> may include one or more surface-active agents to enhance interfacial bonding between the reinforcement particles and thermoplastic polymer. The void spaces and/or pores may accommodate and deliver one or more growth factors such as, for example, BMP-<NUM>, to enhance osteoinductivity and/or bone regeneration. Furthermore, the void spaces and/or pores may also accommodate and deliver one or more transcription factors, matrix metalloproteinases, peptides, proteins, bone cells, progenitor cells, blood plasma, bone marrow aspirate, or combinations thereof, to improve speed bone regeneration, or resorption and replacement of the biomaterial. In some examples, the void spaces and/or pores may further accommodate a carrier material that may be incorporated into the void spaces and/or pores. The carrier material may include, for example, a collagen sponge, membrane, or a hydrogel material to deliver the growth factor material such as, for example, the BMP-<NUM>. The calcium phosphate reinforcements exposed on the surface of the porous thermoplastic scaffold, along with the porosity, improve the retention and localization of the BMP-<NUM> within the porous thermoplastic scaffold and at the peri-implant interface.

In various examples, the porous thermoplastic polymer scaffold <NUM> may have pore sizes that range between and including <NUM> to about <NUM>,<NUM>, and, for example, from about <NUM> to about <NUM>. The thermoplastic polymer scaffold <NUM> may additionally contain some fraction of microporosity within scaffold struts that is less than about <NUM> in size. In accordance with the various embodiments, pores present in the thermoplastic polymer scaffold <NUM> can each have a size that ranges from about <NUM> to about <NUM>,<NUM>, including from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, and from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, and any suitable combination, sub-combination, range, or sub-range thereof. The thermoplastic polymer scaffold <NUM> may include pores having sizes that are different, wherein at least a portion of the pores has a different size than other pores, each pore having a different size within the range from about from about <NUM> to about <NUM>. Thus, the pores may have a size from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and up to and including <NUM>,<NUM>, including increments and ranges therein and there between.

In various examples the at least one porous portion <NUM> may include an amount of porosity up to <NUM>%, including from <NUM>% to about <NUM>% by volume, and, for example, between and including about <NUM>% to <NUM>% by volume. In accordance with the various embodiments, the extent of porosity in the at least one porous portion <NUM> may range from <NUM>% to about <NUM>%, from about <NUM>% to about <NUM>%, from about <NUM> to about <NUM>%, from about <NUM> to about <NUM>% from about <NUM> to about <NUM>%, from about <NUM> to about <NUM>%, and any suitable combination, sub-combination, range, or sub-range thereof by volume, based on the volume of the at least one porous portion <NUM>. Thus, the extent of pores, by volume, based on the total volume of the at least one porous portion <NUM>, can be from <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to about <NUM> volume percent, including increments and ranges therein and therebetween.

In one embodiment, the thermoplastic composite body <NUM> includes a ratio of cross-sectional area of the at least one porous portion <NUM> to the at least one dense portion <NUM> normal to loading that provides an overall stiffness for the thermoplastic composite body within <NUM>% of adjacent vertebral bodies between which the implantable medical device <NUM> is inserted. This ratio may be tailored with respect to the adjacent vertebral body composition, such as, by way of example, cancellous bone tissue or cortical bone tissue. In one embodiment, the at least one porous portion <NUM> includes an elastic modulus within <NUM>% of cancellous bone, and the at least one dense portion <NUM> includes an elastic modulus within <NUM>% of cortical bone. In one embodiment overall stiffness in axial (superior-inferior) compression is within <NUM>% of that for adjacent cervical, thoracic and/or lumbar vertebral bodies which are known to exhibit a stiffness in axial compression in the range of about <NUM> to about <NUM> kN/mm, and more commonly from about <NUM> to about <NUM> kN/mm. The at least one dense portion <NUM> may include an elastic modulus within <NUM>% of that for cortical bone which is known to exbibit an elastic modulus in the range of about <NUM> to about <NUM> GPa. The at least one porous portion <NUM> may include a compressive elastic modulus within <NUM>% of that for cancellous bone, which is known to exhibit a compressive elastic modulus in the range of about <NUM> to about <NUM>,<NUM> MPa.

The implantable medical device according to claim <NUM>, wherein the thermoplastic composite body includes a stiffness in axial (superior-inferior) compression less than about <NUM> kN/mm and a block stiffness in axial compression greater than about <NUM> N/mm. As used herein, "block stiffness" is a measure of how readily an implant subsides into adjacent bone superior and inferior to the implant upon loading in axial compression, as set forth in ASTM F2267. As known by one skilled in the art, a higher block stiffness indicates a greater resistance to subsidence, whereas a lower block stiffness indicates a lesser resistance to subsidence.

The thermoplastic composite body <NUM> may be manufactured by methods common to reinforced thermoplastic and thermosetting polymers, including but not limited to injection molding, reaction injection molding, compression molding, transfer molding, extrusion, blow molding, pultrusion, casting/potting, solvent casting, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, or any other suitable processes or combinations thereof.

Referring to <FIG>, in one embodiment the thermoplastic composite body <NUM> is non-destructively compressible in the direction of loading by at least about <NUM>% of the thickness dimension <NUM>, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%, alternatively by at least about <NUM>%. As used herein, "non-destructively compressible" indicates elastic or non-elastic compression without fracture of the thermoplastic composite body <NUM>.

Referring to <FIG>, in one embodiment, a method that may be used to prepare a thermoplastic composite body <NUM> is provided. While an exemplary manner of synthesizing the thermoplastic composite body <NUM> has been illustrated in <FIG>, one or more of the steps and/or processes illustrated in <FIG> may be combined, divided, re-arranged, omitted, eliminated and/or implemented in any other way. Further still, the exemplary method of <FIG> may include one, or more processes and/or steps in addition to, or instead of, those illustrated in <FIG>, and/or may include more than one of any or all of the illustrated processes and/or steps. Further, although the exemplary method is described with reference to the flow chart illustrated in <FIG>, persons of ordinary skill in the art will readily appreciate that many other methods of synthesizing the example composite material may alternatively be used.

Referring to <FIG>, the thermoplastic composite body <NUM> may be processed using a powder processing approach in conjunction with compression molding and particle leaching techniques and is particularly suited for achieving a relatively high concentration (e.g., ><NUM> vol%) of well-dispersed (and aligned, if desired) anisometric calcium phosphate reinforcements (e.g., HA whiskers) in a thermoplastic matrix (e.g., PEEK) with minimal degradation of the calcium phosphate size/shape during processing. In this manner, the calcium phosphate reinforcement volume fraction, aspect ratio, size and orientation; the polymer; and the size, volume fraction, shape and directionality of the void space and/or porosity may be tailored to vary the mechanical properties of the composite material.

A polymer such as, for example, PEEK, and reinforcements, such as HA whiskers, are provided in powder form. The PEEK polymer powder may have, for example, a mean particle size of about <NUM>. The HA whiskers may be synthesized using, for example, molten salt synthesis, hydrothermal synthesis, the chelate decomposition method, precipitation, solvothermal synthesis, precursor pyrolysis, solid state reactions, and the like.

The polymer powder, for example, a PAEK polymer powder such as PEEK, and reinforcement, such as, for example, synthesized HA whiskers, optionally together with a porogen, as further described herein below, are co-dispersed, either in a fluid such as, for example ethanol, and mixed using, for example, ultrasonication under constant stirring - forming a viscous suspension, or as a dry mixture using powder blending methods known to the industry. The amount of each component may be varied to obtain the desired mixture by the percentage of HA relative to the polymer powder and the percentage of HA and polymer blend relative to the porogen. Of course, depending on the polymer selected, where for example the polymer is not a PAEK polymer, other forms of mixing may be employed for inclusion of a porogen, such as for example, solvent mixing.

In one example, after the polymer powder and the reinforcement are mixed, the porosity of the composite material is selectively varied and/or tailored by any one of a variety of methods, for example as described below.

In one such example, the porosity may be formed and tailored by the addition of a suitable porogen material such as, for example, NaCl, wax, polysaccharides (sugars), cellulose, polymer or glass beads, and the like. The extent of the porosity can be controlled by varying the amount of porogen used, and the pore size could be tailored by sieving the porogen to a desired size prior to mixing the porogen with the polymer mixture, or by selecting a porogen having a specified controlled size, or by blending one or more porogens of different sizes, or combinations of these. In various examples, one or more porogen employed for the formation of pores may have a size that ranges from between and including <NUM> to about <NUM>,<NUM>, and, for example, from about <NUM> to about <NUM>. It is contemplated that while the ranges contemplate average porogen size, there may be some porogen particles that are larger or smaller than the average, and thus, there may be porogen particles that have a size below <NUM>, and thus some porogen particles may have a size in the range from <NUM> to <NUM>. Likewise, there may be particles that have a size that is greater than <NUM>,<NUM>. In accordance with the various embodiments, porogens employed for forming pores in the composite material can have a size that ranges from about <NUM> to about <NUM>,<NUM> or greater than <NUM>,<NUM>, including from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, and from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, from about <NUM> to about <NUM>, and any suitable combination, sub-combination, range, or sub-range thereof. The disclosure contemplates the use of one or more porogen that includes sizes that are different, wherein the porogen comprises a blend of sizes within the range from about from about <NUM> to about <NUM>. Thus, the any one or more porogen may have a size from about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, and up to and including <NUM>,<NUM>, including increments and ranges therein and there between.

In various examples, one or more porogen employed for the formation of pores may have any shape, which may be irregular or regular, for example, but not limited to, spheres, cubes, fibers, polyhedra, and the like. Indeed, a plurality of porogens may be used each having a different shape. In some particular examples, a porogen is select that has generally rounded surfaces.

In another such example, the porosity and/or the pore size of the polymer matrix may be selectively varied using any other suitable methods and/or process(es) such as, for example, microsphere sintering, fiber weaving, solvent casting, electrospinning, freeze drying (lyophilization), thermally induced phase separation, gas foaming, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (aka, robocasting), selective laser sintering, fused deposition modeling, three- dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable process(es) or combination(s) thereof. The viscous suspension may be wet-consolidated by, for example, vacuum filtration, and drying to remove any residual fluid (i.e., ethanol or other solvents). In other embodiments that do not include fluid, the powder components may be arranged such that the material to be porous (the dry mixture containing the porogen) are in the regions of a preform which is desired to be porous; and the regions that are to be more dense, are filled with the dry mixture that has less porogen in it. The composite mixture is densified by, for example, uniaxial compression, to form a composite preform. In one embodiment each region of material is densified before the next region of a different density is added. At completion, each region will be densified with the relatively equal compression.

Following the initial densification, the preform is compression molded and/or sintered at elevated temperatures (e.g., approximately <NUM> to <NUM>) sufficient to fuse the polymer particles with minimal damage to the reinforcement particles. The process or composite material may be heated to a desired processing temperature and the implant may be shaped or formed. Densifying and molding the composite material may include aligning the reinforcement particles (e.g., HA whiskers) morphologically and/or crystallographically within the scaffold struts. Thus, in accordance with the various embodiments, the temperature for molding is in the range (°C) from and including <NUM> to about <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, <NUM> to <NUM> including increments and ranges therein and there between.

The porous thermoplastic polymer scaffold <NUM> may have any shape and/or size (e.g., any polygonal shape), and may be formed by methods common to reinforced thermoplastic and thermosetting polymers, including but not limited to injection molding, reaction injection molding, compression molding, transfer molding, extrusion, blow molding, pultrusion, casting/potting, solvent casting, and rapid prototyping processes such as solid freeform fabrication, robotic deposition (also known as robocasting), selective laser sintering, fused deposition modeling, three-dimensional printing, laminated object manufacturing, stereolithography, etc., or any other suitable processes. The thermoplastic composite body <NUM> may be formed by the mold walls and/or machining after molding. The porous thermoplastic polymer scaffold <NUM> undergoes a leaching process to remove, for example, the porogen used during synthesis of the porous thermoplastic polymer scaffold <NUM>. The leaching may occur, for example, via a dissolution method, heating method, and/or any other suitable methods and/or process(es). More specifically, dissolution may include immersing the porous thermoplastic polymer scaffold <NUM> in a fluid, such as, for example, deionized water. Furthermore, viscous flow of the polymer/reinforcement mixture during molding can be designed to tailor the preferred orientation of the anisometric reinforcements in the implant. Additionally, surface-active agents may be added during the mixing process and/or to the surface of the porous thermoplastic polymer scaffold <NUM> to enhance interfacial bonding between reinforcement particles and the second thermoplastic polymer matrix <NUM>.

Referring to <FIG>, in one embodiment, a method for forming a thermoplastic composite body <NUM> includes disposing a first powder mixture in a first portion of a mold, the first powder mixture including a first thermoplastic polymer powder. The first powder mixture is compacted to densify the first powder mixture at a first pressure. A second powder mixture is disposed in a second portion of the mold, the second powder mixture including a second thermoplastic polymer powder and a porogen material. The second powder mixture is compacted to densify the second powder mixture at a second pressure. The first powder mixture and the second powder mixture are simultaneously molded at a molding temperature above room temperature and at a final molding pressure. The simultaneous molding forms at least one dense portion <NUM> having a first thermoplastic polymer matrix <NUM> that is essentially non-porous from the first powder mixture and at least one proto-porous portion having a second thermoplastic polymer matrix <NUM> from the second powder mixture. The porogen material is leached from the at least one proto-porous portion, forming at least one porous portion <NUM> having a porous thermoplastic polymer scaffold <NUM> that is continuous from the at least one proto-porous portion. The thermoplastic polymer scaffold <NUM> includes the second thermoplastic polymer matrix <NUM>. The simultaneous molding and the leaching integrally form the at least one dense portion <NUM> and the at least one porous portion <NUM> as a single continuous article free of adhesive and mechanical joints between the at least one dense portion <NUM> and the at least one porous portion <NUM>. In a further embodiment, either or both of the first powder mixture and the second powder mixture may include reinforcement particles.

In one embodiment, the first powder mixture and the second powder mixture are compacted below the molding temperature. In a further embodiment, the first powder mixture and the second powder mixture are compacted at room temperature. The molding temperature may be any suitable temperature, including, but not limited to between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>, alternatively between <NUM> to about <NUM>. Of course, it will be appreciated by one of ordinary skill that thermoplastic polymers will be molded at a temperature above the glass transition temperature and below the thermal decomposition temperature.

In one embodiment, following simultaneously molding the first powder mixture and the second powder mixture, subtractive manufacturing (i.e., material removal) is utilized to form the net shape of the thermoplastic composite body <NUM> prior to leaching the porogen material from the at least one proto-porous portion.

The first pressure may be below, at, or above, the final molding pressure. The second pressure may be below, at, or above, the final molding pressure. The second pressure may be lower, the same as, or higher than the first pressure. The final molding pressure may be any suitable pressure, including, but not limited to, at least <NUM> MPa, or alternatively at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, alternative at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa, or at least <NUM> MPa.

Referring to <FIG>, an exemplary cervical interbody fusion cage was prepared following the specifications and methods disclosed herein with overall dimensions measuring <NUM> by <NUM> by <NUM>. This thermoplastic composite body <NUM> includes a porous outer wall <NUM> disposed along the anterior surface <NUM> of the thermoplastic composite body <NUM>, the first lateral surface <NUM> of the thermoplastic composite body <NUM>, and the second lateral surface <NUM> of the thermoplastic composite body <NUM>, and the dense core <NUM> is disposed between the at least one porous central portion <NUM> and the porous outer wall <NUM>, and extends to the posterior surface <NUM> of the thermoplastic composite body <NUM> forming a dense posterior edge <NUM>. The porous central portion <NUM> is <NUM> thick and defines the outer boundary <NUM> of the central through cavity <NUM>. The central through cavity <NUM> contains <NUM> of volume. The dense core <NUM> is <NUM> to <NUM> thick at all points along the closed structural support <NUM>. The superior surface <NUM> area of the at least one porous portion <NUM> is about <NUM><NUM>, and the superior surface <NUM> area of the at least one dense portion <NUM> is about <NUM><NUM>, indicating a cross-sectional surface ratio of at least one porous portion <NUM> to the at least one dense portion <NUM> normal to loading of about <NUM>. The first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> is comprised of polyetheretherketone (PEEK) with <NUM> vol. % hydroxyapatite whisker reinforcements. The at least one porous portion <NUM> includes about <NUM>-<NUM> vol. % porosity, and the pores thereof are about <NUM>-<NUM> in size. Hydroxyapatite whiskers are both embedded within the first thermoplastic polymer matrix <NUM> and the second thermoplastic polymer matrix <NUM> and are also exposed on scaffold struts surfaces within pore spaces of the porous thermoplastic polymer scaffold <NUM>.

Exemplary implantable medical devices <NUM> were prepared in accordance with <FIG> a PEEK powder, about <NUM> in size, hydroxyapatite whisker reinforcements, about <NUM> in diameter and with a length-to-diameter aspect ratio ranging from about <NUM> to about <NUM>, and a spherical sodium chloride porogen, about <NUM>-<NUM> in diameter. A first powder mixture, including a PEEK powder, HA whisker reinforcements, and sodium chloride porogen, was dispensed into a mold in locations corresponding proto-porous regions of the implant, wherein for the medical device <NUM> described herein above, this corresponds to the proto-porous regions of the outer porous wall. The first powder mixture was compacted by uniaxial compression at a pressure of <NUM> MPa at ambient temperature into a specific region of a cylindrical mold. A second powder mixture, including a PEEK powder and HA whisker reinforcements, was then dispensed into the same mold in specific regions corresponding to the location of dense regions of the implant. The second powder mixture was compacted by uniaxial compression at a pressure of <NUM> MPa at ambient temperature. A third dispensing was performed, filling the remainder of proto-porous regions of the implant, wherein for the medical device <NUM> described herein above, this corresponds to the proto-porous regions of the porous central portion, using the first powder mixture with porogen, polymer and HA whisker reinforcements, and compacted by itself to <NUM> MPa. Each entire exemplary implantable medical device <NUM>, including both porous portions <NUM> and dense portions <NUM> simultaneously, was then compression molded at a temperature of <NUM> and a pressure of <NUM> MPa. After molding, the consolidated round billet was cooled and ejected from the mold. Exterior implant surfaces and a central cavity were created by material removal using a high-speed end mill. Holes were drilled into the dense material region to accommodate the insertion of tantalum pins <NUM> serving as radiographic markers. The exemplary implantable medical devices <NUM> were then cleaned in Alconox (TM) to remove any contamination from the machining process. The porogen was subsequently removed by soaking the exemplary implantable medical devices <NUM> in deionized water for <NUM> hours at <NUM>, under ultrasonication and vacuum. The exemplary implantable medical devices <NUM> were dried in a drying oven at <NUM>.

The exemplary implantable medical devices <NUM> were tested according to the methods outlined in ASTM F2077 and F2267, which are well-known in the art. An exemplary implantable medical device <NUM> tested in static axial compression exhibited a stiffness of <NUM> kN/mm, a yield force of <NUM> kN, and an ultimate force of <NUM> kN. An exemplary implantable medical device <NUM> tested in static compressive shear exhibited a stiffness of <NUM> kN/mm, a yield force of <NUM> kN and an ultimate force of <NUM> kN. An exemplary implantable medical device <NUM> tested in dynamic axial compression in phosphate buffered saline at <NUM> at <NUM> with a maximum applied force of <NUM>,<NUM> N and minimum applied force of <NUM> N, exhibited runout at <NUM> million cycles. An exemplary implantable medical device <NUM> tested in static axial compression in between two polyurethane foam test blocks, which mimic adjacent cancellous bone, exhibited a test block stiffness (Kp) of <NUM>,<NUM> N/mm.

Referring to <FIG>, exemplary implantable medical devices <NUM> show that the thermoplastic composite body <NUM> is integrally formed as a single continuous article free of adhesive and mechanical joints between the at least one dense portion <NUM> and the at least one porous portion <NUM>. The interface between the at least one porous portion <NUM> and the at least one dense portion <NUM>, as shown in <FIG> is free of any discernible mechanical or adhesive joint. Thus, as exemplified in the drawings, the thermoplastic polymer matrix is continuous between a porous portion and a dense portion of an implantable medical device, according to an embodiment of the disclosure.

Referring to <FIG>, scanning electron micrographs are shown of a porous portion <NUM> of an implantable medical device <NUM> at a lower magnification (a), a higher magnification (b), and at the higher magnification with backscattered electron imaging, according to an embodiment of the disclosure.

Referring to <FIG>, two implantable medical devices <NUM> prepared by the methods described herein are shown in a photograph, each implantable medical device <NUM> having different ratios of the cross-sectional area of the porous <NUM> and dense <NUM> portions.

Referring to <FIG> a photograph of an exemplary implantable medical device <NUM> shows the implantable medical device <NUM> resting in colored aqueous solution, with the aqueous solution being drawn into the porous portion by capillary action and hydrophilicity, emphasizing the distinction between the porous <NUM> and dense <NUM> portions, and provides a high-contrast view of the clear transitions between the at least one porous portion <NUM> and the at least one dense portion <NUM>.

The exemplified embodiments of implantable medical devices <NUM> described herein are representative of implantable medical devices <NUM> that include polymeric materials, for example, PAEK materials, that may include one or more of reinforcement particles and porosity. It will be appreciated that these materials may be used in accordance with the teachings herein for other bony implant applications, such as for implant fixation, fraction fixation, synthetic bone graft substitutes, interbody spinal fusion, tissue engineering scaffolds, and other applications, and the implants may be tailored to provide specific mechanical, biological, and surgical functions by varying the distribution and proportions of dense and porous polymer, and by varying one or more of the polymer composition and molecular orientation, porosity and pore size of the porous thermoplastic scaffold, or the reinforcement, for example, HA, content, morphology, preferred orientation, and size.

While various inventive aspects, concepts and features of the general inventive concepts are described and illustrated herein in the context of various exemplary embodiments, these various aspects, concepts and features may be used in many alternative embodiments, either individually or in various combinations and sub-combinations thereof. Unless expressly excluded herein all such combinations and sub-combinations are intended to be within the scope of the general inventive concepts. Still further, while various alternative embodiments as to the various aspects, concepts and features of the inventions (such as alternative materials, structures, configurations, methods, devices and components, alternatives as to form, fit and function, and so on) may be described herein, such descriptions are not intended to be a complete or exhaustive list of available alternative embodiments, whether presently known or later developed.

Those skilled in the art may readily adopt one or more of the inventive aspects, concepts or features into additional embodiments and uses within the scope of the general inventive concepts even if such embodiments are not expressly disclosed herein. Additionally, even though some features, concepts or aspects of the inventions may be described herein as being a preferred arrangement or method, such description is not intended to suggest that such feature is required or necessary unless expressly so stated.

Unless otherwise indicated, all numbers expressing quantities, properties, and so forth as used in the specification and claims are to be understood as being modified in all instances by the term "about. " Accordingly, unless otherwise indicated, the numerical properties set forth in the specification and claims are approximations that may vary depending on the suitable properties desired in embodiments of the present invention.

All ranges and amounts given herein are intended to include subranges and amounts using any disclosed point as an end point. Similarly, a range given of "about <NUM> to <NUM> percent" is intended to have the term "about" modifying both the <NUM> and the <NUM> percent endpoints, and meaning within <NUM> percent of the indicated number (e.g. "about <NUM> percent" means <NUM> - <NUM> percent and "about <NUM> percent" means <NUM> - <NUM> percent). Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the general inventive concepts are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical values, however, inherently contain certain errors necessarily resulting from error found in their respective measurements. Thus, while exemplary or representative values and ranges may be included to assist in understanding the present disclosure; however, such values and ranges are not to be construed in a limiting sense and are intended to be critical values or ranges only if so expressly stated. Moreover, while various aspects, features and concepts may be expressly identified herein as being inventive or forming part of an invention, such identification is not intended to be exclusive, but rather there may be inventive aspects, concepts and features that are fully described herein without being expressly identified as such or as part of a specific invention. Descriptions of exemplary methods or processes are not limited to inclusion of all steps as being required in all cases, nor is the order that the steps are presented to be construed as required or necessary unless expressly so stated. Further, while disclosed benefits, advantages, and solutions to problems have been described with reference to specific embodiments, these are not intended to be construed as essential or necessary to the invention.

Claim 1:
An implantable medical device (<NUM>), comprising:
a thermoplastic composite body including:
an anterior surface of the thermoplastic composite body;
a first lateral surface of the thermoplastic composite body;
a second lateral surface of the thermoplastic composite body;
a posterior surface of the thermoplastic composite body;
a superior surface of the thermoplastic composite body;
an inferior surface of the thermoplastic composite body;
at least one dense portion (<NUM>) formed of a first thermoplastic polymer matrix that is essentially non-porous, and which is continuous through a thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body; and
at least one porous portion (<NUM>) formed of a porous thermoplastic polymer scaffold, the porous thermoplastic polymer scaffold being formed of a second thermoplastic polymer matrix, the at least one porous portion being continuous through the thickness dimension from the superior surface of the thermoplastic composite body to the inferior surface of the thermoplastic composite body,
wherein the at least one dense portion and the at least one porous portion are integrally formed such that the thermoplastic composite body is a single continuous article free of adhesive and mechanical joints between the at least one dense portion and the at least one porous portion.