Patent Application
20240115296
This disclosure relates to a scaffold material that resembles natural bone, medical devices made from this scaffold material, and related methods for bone implantation.
Spinal fusion is a commonly indicated procedure for managing fractures, instability, and common degenerative conditions, including low back pain. Fusion techniques use bone grafts and hardware, such as pedicle screws, to encourage two vertebral bodies to grow together. Prior lumbar spinal implant designs are smooth, threaded pedicle screws secured in vertebral bone with rods to hold the height and angulation of the correction until fusion is achieved.
Low back pain has been estimated to impact 60-80% of people globally. Between 1998 and 2008, annual lumbar fusion surgeries performed in the United States increased from 77,682 to 210,407. Unfortunately, the overall failure rate of lumbar spine surgery is high, around 10-46%.
In a review of spinal fusion surgeries within the PubMed database, 11,692 patients were extracted. There were 3,646 complications, the mean age at surgery was 53.3 years (range: 25-77 years), mean follow-up was 3.49 years (range: 6 weeks-9.7 years). Major perioperative complications occurred at a mean rate of 18.5%. Minor perioperative complications occurred at a mean rate of 15.7%. Long-term complications occurred at a mean rate of 20.5%.
Despite advances in technology and surgical technique, these rates have not changed substantially over the years. For example, lumbar interbody fusion (LIF) technology has advanced because of computer navigation, augmented reality, minimally invasive surgical (MIS) approaches, disc arthroplasty, bone stimulation pedicle screws, and bone void filler options. Nevertheless, the number of patients developing failed back surgery syndrome (FBSS) has increased continually because of the increased patient population and the high failure rates. (FBSS is when the outcome of the lumbar spinal surgery does not meet the patient's and surgeon's pre-surgical expectations.)
The gold standard for lumbar interbody fusions consists of inserting a smooth threaded screw into each pedicle (two per vertebral level) and placing rods into the tulip heads of the pedicle screws to stabilize the construct until fusion is achieved. However, little technological advancement has been achieved in spinal stabilization systems since 1975, and these constructs do not address key long-term stability issues related to the quality of bone mineral density and patient health. Hardware used in lumbar fusions experiences significant forces that cause hardware breakage and loosening (the so-called “Windshield Wiper Effect”). Estimates for the frequency of screw loosening during spinal fusions vary significantly, but a recent report estimated a loosening rate of over 40%, with nearly 10% being a partial pullout. This loosening due to lack of fusion can put nerves or blood vessels at risk, often requiring hardware to be removed and surgery to be repeated.
Unfortunately, revision spine surgery also suffers from poor success rates. Secondary revision cases have a success rate of 30%, third surgeries are 15%, and a fourth surgical intervention is 5%. In addition, revision adult spinal deformity patients who endured two or more previous demonstrate more coronal and sagittal imbalance and worse functional status. Other potential complications for LIF are dural tears, neurological injuries, pseudoarthrosis, infection, and wound healing issues.
Another complication of lumbar spinal fusion is infection. Surgical site infections (SSI) represent a major healthcare challenge and account for approximately 8,000 yearly deaths.21 The combined estimated direct and indirect costs stemming from SSI are between $1 and $10 billion per year. Spinal instrumented surgeries are at greater risk for SSIs, resulting in higher rates of infection relative to other orthopedic surgeries. SSIs stemming from spinal surgeries are estimated to occur between 0.2% and 16.7% of the time. A recent meta-analysis suggests instrumented spinal surgeries result in SSI 4.4% of the time. Deep incisional and organ space SSIs account for 80% of these infections and are linked to increased morbidity, longer hospital stays, and greater medical expenses.
Moreover, bone mineral density decreases after medical devices are implanted, regardless of the material used. This loss contributes to common medical device failures, including screw loosening, screw backout, and rod breakage. Though many devices promote fusion in an interbody cage, none have been developed for scaffolding and increasing bone mineral density within the vertebral body. Also, the structure of cortical bone within the vertebrae differs from the bone in other parts of the human body.
These challenges relating to long-term stability, such as bone quality and functional ability to heal, have not been satisfied. None of the prior technologies have addressed the top two reasons for implant failure revision surgery: pedicle screw backout and rod breakage before the patient achieves fusion. Smooth, threaded pedicle screws and rods do not address the quality of bone mineral density and patient health.
The present disclosure provides a scaffold for growing bone, comprising a randomized porosity pattern typical of native trabecular bone. In certain embodiments, the scaffold comprises rounded, square, and rectangular shapes and variegated patterns that align with native vertebral bone structure. In certain embodiments, the scaffold comprises one or more structural cues chosen from porosity, pore size, grain size, and surface topography. In certain embodiments, the one or more structural cues enhance at least one of multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and new bone formation. In certain embodiments, new bone formation is after MSC differentiation, osteoblast growth, ECM deposition, or combinations thereof. In certain embodiments, the scaffold is configured to house one or more biologic agents
The present disclosure also provides a medical device comprising a scaffold disclosed herein. In particular embodiments, the medical device is a pedicle screw. In certain embodiments, the pedicle screw reduces or does not exhibit screw loosening, screw backout, rod breakage, or lowered bone mineral density. In certain embodiments, the pedicle screw focuses bone growth throughout a shaft to minimize shear stresses on a distal tip and spreads micromotion throughout the screw to encourage bony ingrowth.
In certain embodiments, the pedicle screw comprises at least one trephine to harvest bone internally within the screw. In certain embodiments, the pedicle screw comprises a fluted tip. In certain embodiments, the pedicle screw is configured as a polyaxial tulip. In certain embodiments, the pedicle screw further comprises a tulip, such as a polyaxial tulip. In certain embodiments, the pedicle screw is configured in arcuate cross-section patterns varied from the proximal end to distal tip for placement into an internal cavity of a vertebral body such that upon coaxial rotation of the device autograft is harvested within the screw's scaffold. In certain embodiments, the pedicle screw further comprises at least one autologous product sprayed on or injected through the screw. In certain embodiments, the pedicle screw is configured in a double ball angulation. In certain embodiments, the pedicle screw is configured into a low profile. In certain embodiments, the pedicle screw further comprises a locking cap with reverse angle threads. In certain embodiments, the pedicle screw is cannulated. In certain embodiments, the pedicle screw is non-cannulated.
The present disclosure provides a pedicle screw comprising a cap, saddle, shaft having a core comprising a scaffold disclosed herein, and a tulip.
Additional embodiments and features are set forth in part in the following description. They will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the embodiments discussed herein. A further understanding of the nature and advantages of certain embodiments may be realized by reference to the remaining portions of the specification and the drawings, which form a part of this disclosure.
The disclosure will be readily understood by the following detailed description in conjunction with the accompanying drawings, wherein like reference numerals designate like structural elements. The drawings provide exemplary embodiments or aspects of the disclosure and do not limit the scope of the disclosure.
The present disclosure provides a scaffold for growing bone, comprising a randomized porosity pattern typical of a native trabecular bone.
The leading cause of implant failure is screw backout and/or rod breakage. Due to vertebral bone having larger pores and thinner matrices compared to other native bones, large screw stability is compromised, causing revision rates to be high. As a result, many postoperative patients endure constant pain, significant limitations in their daily activities, long-term pain management, and revision surgery.
The disclosed scaffolds, screws, and methods can prevent common failures in spinal fusion surgery. Additive manufacturing has been combined with regenerative therapies. Topography of 3D printed porous patterns has higher adhesion of stem cells to titanium. Mesenchymal and hematopoietic stem cells have therapeutic effects on bone. Combining these two modalities improves bone integrations and pullout strength over prior pedicle screws, thereby reducing the likelihood of revision lumbar fusion. Thus, in various embodiments, the porous scaffold disclosed herein corresponds to the native bone and is shaped like a traditional pedicle screw.
Surface curvature and Minkowski bone morphology curvature maps (a function that recovers a notion of distance on a linear space) demonstrate a significantly different porous matrix in trabecular bone within the vertebrae versus other areas of skeletal anatomy. A load of traditional smooth, threaded pedicle screws can be too high for vertebral bone, as bone mineral density lowers post-implantation.
Porous 3D printed scaffolds promote osseointegration, fusion, and fixation within a bone. The open skeleton with a scaffold is similar to that of native bone. This similarity allows physicians to make patient-specific choices using other agents to promote bone formation and/or stabilize the device.
Triangular-shaped porosity sequences have been used in the prior art. Rounded, square/rectangular shapes and variegated patterns more closely align with native vertebral bone structure. In addition, the scaffold's structure reduces the likelihood of revision of the medical device from which it is made, for example, screw loosening, screw backout, rod breakage, and lower bone mineral density.
In certain embodiments, the disclosed scaffold and devices integrate orthopedic products with regenerative medicine to prevent the risks of delayed bone fusion to implanted devices.
In certain embodiments, the scaffold comprises one or more structural cues chosen from porosity, pore size, grain size, and surface topography. Porosity and pore size cue signal mechanical strength, cell settlement, and cell migrations. Grain size cures signal protein absorption, cell adhesion, cell proliferation, and cell adhesion. Surface topography cures signal-specific surface area, cell adhesion, and a material-tissue interface. Other scaffold features include pH and wall thickness. In certain embodiments, the one or more structural cues enhance at least one of multipotent mesenchymal stem cell (MSC) differentiation, osteoblast growth, extracellular matrix (ECM) deposition, and new bone formation. In certain embodiments, the new bone formation occurs after MSC differentiation, osteoblast growth, ECM deposition, or combinations thereof.
In certain embodiments, the scaffold's internal lattice structure mimics the geometric properties of healthy trabecular bone geometric properties. In certain embodiments, the lattice structure comprises a combination of mean, Gaussian, and net curvatures, which characterize the local shape of the trabecular bone. The mean curvature (H) represents the local convexity or concavity of the surface, while the Gaussian curvature (K) quantifies the type of surface (hyperbolic, intrinsically flat, or sphere-shaped). The net curvature (D) describes the local deviation of the surface from a planar region.
In certain embodiments, the scaffold comprises an internal lattice structure with a porous architecture characterizing the local shape of healthy trabecular bone and adapted to withstand forces of installation during surgery. That is, the scaffold is adapted to promote bone growth and having the integrity to withstand the force of surgical insertion without collapsing or breaking. In certain embodiments, the forces of installation comprise sheer force and torque.
In certain embodiments, the scaffold's lattice structure exhibits a predominantly hyperbolic geometry (K<0), consistent with the high topological complexity of trabecular bone. In such embodiments, this structure includes a combination of saddle-shaped regions, sphere-like indentations, and cylindrically-shaped rod-like elements. The distribution of curvatures throughout the scaffold is designed to reflect the spatial correlation observed in healthy trabecular bone specimens, ensuring a more biomimetic design that aids osseointegration, fusion, and fixation within the bone.
In certain embodiments, the scaffold's internal lattice structure is based on Minkowski functionals, which provide a comprehensive and robust description of the global shape of complex structures, such as trabecular bone. The Minkowski functionals include scalar measures, such as the total area of the bounding surface (W1), the area-integrated mean curvature (W2), and the area-integrated Gaussian curvature (W3). These scalar measures capture the essential geometric properties of trabecular bone, allowing for a more biomimetic design that promotes osseointegration, fusion, and fixation within the bone. Without wishing to be bound by theory, by incorporating Minkowski functionals into the scaffold's design, the lattice structure can better reflect the differences between specimens from various anatomical sites and potentially be more sensitive to subtle changes in connectivity, such as those caused by disease. Thus, this approach ensures that the scaffold's lattice structure closely mimics the natural geometry of a trabecular bone and enhances its effectiveness in bone implant applications.
In certain embodiments, Minkowski tensors (MT) capture the orientation-dependent aspects of trabecular bone morphology. Six relevant rank-two MT are defined for a 3D body, including W02,0(B), W12,0(B), W10,2, and W20,2. The tensor W10,2 describes the distribution of the surface normal vectors, W20,2 describes the distribution of the mean curvature (surface normals weighted by curvature), and W12,0 measures the mass distribution when the entire mass of B is homogeneously distributed on the surface (i.e., a “hollow” body).
The degree of anisotropy (DA) for a tensor Wvr,s is defined as DAvr,s=1−λvr,s|min|λvr,s|max, where |λvr,s|min and |λvr,s|max are the absolute values of the minimum and maximum eigenvalues of the tensor Wvr,s. In certain embodiments, different types of anisotropy of the trabecular bone samples are quantified, including the anisotropy of the interface orientation (DA10,2) and the mean curvature (DA20,2).
In certain embodiments, the ratio of the median to the maximum eigenvalue is plotted against the ratio of the minimum to the maximum eigenvalue to provide insight into the “ellipticity” of the bone specimens for a particular tensor. This allows for quantifying different sources of bone anisotropy and ellipticity by considering different Minkowski tensors (e.g., W12,0 or W20,2).
In certain embodiments, Minkowski functionals are applied to smaller substructures within trabecular bone specimens to create a Minkowski map that quantifies intra-specimen variations of integral shape indices. This spatially decomposed analysis allows for a local characterization of ellipticity for the Minkowski tensors W10,2 and W20,2. The local degree of anisotropy (DA) can vary substantially for the whole-sample value, leading to different distributions for both tensors. Distinct angle differences in the local and global principal directions can also be observed for both tensors, with wider variations detected in the L2 and L4 specimens.
In certain embodiments, higher-rank Minkowski tensors, such as the quadratic (qs) and cubic (ws) rotational invariants of the irreducible Minkowski tensors, are calculated for the spatially decomposed specimens. These scalar invariants can be used as efficient structure metrics to detect local crystalline states in disordered packings of convex shapes. In certain embodiments, significant differences between the structure metric distributions of different bone types can be detected, indicating that these higher-order structure metrics are sensitive to the structural differences between plate-like and rod-like specimens.
In certain embodiments, the surface curvature of trabecular bone is quantified using an integrated shape descriptor (ISD), which serves as an effective shape fingerprint for trabecular bone from different anatomical sites. The ISD captures morphological differences between plate-like and rod-like specimens and intermediate morphologies along the plate-rod spectrum.
In certain embodiments, scalar and tensorial Minkowski functionals are employed for global shape analysis of the trabecular bone interface. These functionals are fundamental, highly versatile, and robust indices for integral shape quantification. In certain embodiments, the Minkowski scalars correlate with traditional bone morphometric indices. In certain embodiments, the Minkowski tensors reveal different degrees of anisotropy and ellipticity depending on the morphological aspect considered.
In certain embodiments, higher-rank Minkowski metrics are applied to the shape quantification of spatially-decomposed bone specimens, showing sensitivity to morphological differences in bone from different anatomical sites. The geometric nature of these metrics offers a unifying view and geometrical foundation for traditional bone morphometric indices, which could advance the understanding of morphological changes in aging and disease, such as the plate-to-rod transition in osteoporosis.
In certain embodiments, the scaffold does not comprise planar truss units coupled to each other with a plurality of struts coupled to a plurality of nodes, wherein one or more angles defined by two struts and a node of one or more planar truss units are different than one or more corresponding angles defined by two struts and a node of one or more other planar truss units. In certain embodiments, the scaffold does not have to connect exterior surface struts that couple the nodes of the non-equivalent angle planar truss units to each other such that the implant has a varied height.
In certain embodiments, the scaffold does not include an internal space truss structure at least partially enclosed by an external frame comprising two or more planar truss units with a plurality of struts joined at nodes, wherein at least two nodes within the internal space truss structure are connected by a strut that curves or arcs between the at least two nodes, and wherein at least one of the two or more planar truss units lies in a plane that is not substantially parallel to a plane of at least one or more of the other two or more planar truss units.
In certain embodiments, the scaffold's internal lattice structure does not comprise a web structure with a plurality of struts joined at nodes to form a space truss, wherein the web structure is configured to interface with bone tissue and wherein the plurality of planar truss units are coupled to one another such that one or more planar truss units lie in a plane that is not substantially parallel to a plane of a planar truss unit that shares at least one strut with the one or more planar truss units. Moreover, the scaffold does not have a diameter and/or length of the struts and/or density of the web structure predetermined such that when the web structure is in contact with the bone, at least a portion of the struts creates a microstrain in adhered osteoblasts, bone matrix, or lamellar tissue.
Bones can generally be divided into cancellous bone and cortical bone. “Cancellous bone,” also called “trabecular bone” or “spongy bone,” is a light, porous bone enclosing numerous large spaces that give a honeycombed or spongy appearance. The bone matrix, or framework, is organized into a three-dimensional latticework of bony processes, called trabeculae, arranged along stress lines. The spaces between are often filled with marrow and blood vessels. In cross-sections, trabeculae of a cancellous bone can look like septa. But, they are topologically distinct in three dimensions, with trabeculae roughly rod or pillar-shaped and septa sheet-like.
Cancellous bone makes up about 20% of the human skeleton, providing structural support and flexibility without compact bone. It is found in most areas of bone not subject to great mechanical stress. It makes up much of the enlarged ends (epiphyses) of the long bones and is the major component of the ribs, the shoulder blades, the flat bones of the skull, and a variety of short, flat bones elsewhere in the skeleton.
Because of the increasing frequency of total joint replacements and their impact on bone remodeling, understanding the stress-related and adaptive process of trabecular bone has become a central concern for bone physiologists. To understand the role of trabecular bone in age-related bone structure and design for the bone-implant system, the mechanical properties of trabecular bone are studied as a function of the anatomic site, density, and age. So, mechanical factors, including modulus, uniaxial strength, and fatigue properties, are also studied.
High porosity makes trabecular bone compliant. Large variations in architecture lead to high heterogeneity. The modulus and strength vary inversely with porosity and highly depend on the porosity structure. Typically, the porosity percent of cancellous bone is between 75% and 95%. The density is between 0.2 and 0.8 g/cm3. Porosity can reduce the strength of the bone but also reduce its weight.
The porosity and its structure affect the strength of the material. Thus, the microstructure of trabecular bone is typically oriented. The “grain” of porosity is aligned where mechanical stiffness and strength are the greatest. Because of the microstructural directionality, the mechanical properties of trabecular bone are highly anisotropic. Young's modulus for trabecular bone, including vertebral bone, is between 800 and 14,000 Mpa. Its strength of failure is 1 to 100 MPa.
“Cortical bone” or “compact bone” is much denser than cancellous bone. It forms the hard exterior (cortex) of bones. The cortical bone gives bone its smooth, white, and solid appearance. It accounts for about 80% of the total bone mass of an adult human skeleton. Cancellous bone is usually surrounded by a shell of compact bone, which provides greater strength and rigidity. The open structure of cancellous bone enables it to dampen sudden stresses, as in load transmission through the joints. Varying proportions of space to bone are found in different bones according to the need for strength or flexibility. Cancellous bone also has a relatively high level of metabolic activity.
“Wolff's law” refers to the bone in a healthy person or animal adapting to the loads under which it is placed. For example, if loading on a particular bone increases, it will remodel itself over time to become stronger to resist that loading.
Each vertebra is an irregular bone with a complex structure composed of bone and some hyaline cartilage in the vertebrate spinal column. The proportions vary according to the segment of the backbone and vertebrate species.
The basic configuration of vertebrae varies. The large part is the body, and the central part is the centrum. The upper and lower surfaces of the vertebra body give attachment to the intervertebral discs. The posterior part forms a vertebral arch in eleven parts, consisting of two pedicles, two laminae, and seven processes. The laminae give attachment to the ligamenta flava (ligaments of the spine). There are vertebral notches formed from the shape of the pedicles, which form the intervertebral foramina when the vertebrae articulate. These foramina are the entry and exit conduits for the spinal nerves. The body of the vertebra and the vertebral arch form the vertebral foramen, the larger, central opening that accommodates the spinal canal, which encloses and protects the spinal cord.
Pedicles and laminae form the vertebral arch. Two pedicles extend from the sides of the vertebral body to join the body to the arch. The pedicles are short thick processes that extend, one from each side, posteriorly, from the junctions of the posterolateral surfaces of the centrum, on its upper surface. From each pedicle, a broad plate, called a “lamina,” projects backward and medialward to join and complete the vertebral arch and form the posterior border of the vertebral foramen, which completes the triangle of the vertebral foramen. The upper surfaces of the laminae are rough to give attachment to the ligamenta flava. These ligaments connect the laminae of the adjacent vertebra along the length of the spine from the level of the second cervical vertebra. Above and below the pedicles are shallow depressions called vertebral notches (superior and inferior). When the vertebrae articulate, the notches align with those on adjacent vertebrae, forming the intervertebral foramina openings. The foramina allow spinal nerves and associated blood vessels to enter and exit each vertebra. The articulating vertebrae provide a strong pillar of support for the body.
The present disclosure provides a device formed from a scaffold disclosed herein. In certain embodiments, the device is cannulated and fenestrated with the scaffold. In certain embodiments, the device comprises a threaded distal region, an optionally threaded central region, and an optionally threaded proximal region, depending on the compressive forces.
In certain embodiments, the device is chosen from pedicle screw, cannulated pedicle screw, fenestrated pedicle screw, large-headed screw, small-headed screw, headless screw, trauma hip fracture device, glenoid cage, screws for a glenoid cage, trauma plate, tibial stem, femoral stem, hammertoe implant, nail fusion system, Charcot foot deformity correction, radial head fracture device, high tibial osteotomy, deformity correction, corpectomy cage, oncological correction, anchor, dental implant, maxillofacial implant, and sports medicine anchor.
In some embodiments, the screw is configured with features that facilitate bone to grow through the structure of the screw from opposing sides allowing the bone to connect through the screw. In some embodiments, the structure is narrow, such as through the screw thread, thereby permitting rapid through growth. In some embodiments, the structure is deeper, such as through the minor diameter, thus bonding stronger. In some embodiments, the feature is a void in the screw or porous or structured to promote bone growth. In some embodiments, the structure collects autografts within the channels inside the device. In some embodiments, the feature is impregnated with one or more polymers.
In some embodiments, the device is configured to enhance the stabilization and fixation of bone screws within the bone and improve bone mineral density. In some embodiments, the device includes a spinal implant configured for engagement with cortical bone and cancellous bone within the vertebra. In some embodiments, the device is configured to resist and/or prevent toggling on a bone screw when the bone screw is engaged with dense cortical bone and a less dense cancellous bone resulting from a load on the bone screw. In some embodiments, the device is configured to resist and/or prevent loosening of the bone screw from the cortical bone and, in some instances, pull it out from the vertebra. In some embodiments, the device is configured to facilitate bone through-growth to improve bone attachment to the bone screw. In some embodiments, the bone screw is anchored in the bone, thereby reducing pullout. In some embodiments, the bone screw is designed to spread micromotion and reduce shearing to strengthen bone mineral density.
In some embodiments, the device includes a bone screw having bone through-growth through the shaft of the screw to reduce toggle and potential failure of the screw. In some embodiments, the bone screw includes features that allow the bone to grow through the structure of the bone screw from opposing sides allowing bone to connect through those bone screw structures. In some embodiments, the bone screw includes features that may be narrow, such as through the bone screw thread, which would allow for rapid through-growth. In some embodiments, the bone screw includes features that may be deeper, such as through the minor diameter, which would provide a larger volume of bone through-growth. In some embodiments, the bone screw includes features that may be a void or cavity through opposite sides of the bone screw and/or a void or cavity that enters and exits from the same or adjoining surfaces. In some embodiments, the void or cavity may contain a scaffold for the bone to attach or a porous structure on the surface of the void.
In some embodiments, the bone screw includes features or structures that may be disposed along a shaft portion of the bone screw. In some embodiments, the bone screw includes features or structures that may be disposed continuously along a surface of the bone screw, such as, for example, along a distal end. In some embodiments, the bone screw includes features or structures that may be disposed discontinuously along a portion of the bone screw. In some embodiments, the bone screw includes features or structures that may include a scaffold or polymers.
In some embodiments, the device comprises a spinal implant having a hybrid configuration that combines a manufacturing method, such as, for example, one or more prior manufacturing features and materials, and a manufacturing method, such as, for example, one or more additive manufacturing features and materials. In some embodiments, additive manufacturing includes 3-D printing. In some embodiments, additive manufacturing includes fused deposition modeling, selective laser sintering, direct metal laser sintering, selective laser melting, electron beam melting, layered object manufacturing, and stereolithography. In some embodiments, additive manufacturing comprises one or more chosen from rapid prototyping, desktop, direct, digital, instant, and on-demand manufacturing. In some embodiments, the device comprises a spinal implant manufactured by a fully additive process and grown or otherwise printed.
In certain embodiments, the devices comprises one or more chosen from demineralized bone matrix (DBM), pre-packed DBM, pre-packed synthetic DBM, unpacked DBM, and magnesium-infused titanium.
In some embodiments, the device comprises a spinal implant, such as, for example, a bone screw manufactured by combining traditional manufacturing methods and additive manufacturing methods. In some embodiments, the bone screw is manufactured by applying additive manufacturing material where the bone screw can benefit from the materials and properties of additive manufacturing. In some embodiments, traditional materials are used where the benefits, such as physical properties and cost, are superior to those resulting from additive manufacturing features and materials.
In some embodiments, the device treats a spinal disorder chosen from degenerative disc disease, disc herniation, osteoporosis, spondylolisthesis, stenosis, scoliosis, other curvature abnormalities, kyphosis, tumor, and fractures.
“Treating” or “treatment” of a disease or condition refers to performing a procedure that may include administering one or more drugs to a patient, employing implantable devices, and/or employing instruments that treat the disease, such as microdiscectomy instruments to remove portions bulging or herniated discs, and/or bone spurs, to alleviate signs or symptoms of the disease or condition. Treating or treatment does not require complete alleviation of signs or symptoms, does not require a cure, and specifically includes procedures that have a marginal effect on the patient. For example, treatment can include inhibiting the disease, e.g., arresting its development, or relieving the disease, e.g., causing regression.
“Prevention” refers to alleviation before signs or symptoms of a disease or condition appear. Thus, prevention includes preventing the disease from occurring in a patient who may be predisposed to the disease but has not yet been diagnosed as having it.
“Tissue” includes soft tissue, ligaments, tendons, cartilage, and/or bone. In certain embodiments, the tissue is cancellous bone, cortical bone, or corticocancellous bone.
In some embodiments, devices are used with other osteal and bone-related applications, including diagnostics and therapeutics. In some embodiments, devices are alternatively employed in surgical treatment with a patient in a prone or supine position and/or employ various surgical approaches to the spine, including anterior, posterior, posterior mid-line, lateral, posterolateral, and/or anterolateral approaches, and in other body regions such as maxillofacial and extremities. The devices may also be alternatively employed with procedures for treating the lumbar, cervical, thoracic, sacral, and pelvic regions of a spinal column. The devices may also be used on animals, bone models, and other non-living substrates, for example, in training, testing, and demonstration.
In certain embodiments, the device is a custom medical device. In certain embodiments, the device is adapted for sports medicine.
In certain embodiments, the device is temperature-sensing. In certain embodiments, the device is pH-balancing.
In certain embodiments, the devices are fabricated having a porosity with a porogen that is spheroidal, cuboidal, rectangular, elongated, tubular, fibrous, disc-shaped, platelet-shaped, polygonal, or a mixture thereof. In some embodiments, the porosity is based on a plurality of macropores, micropores, nanopores structures, and/or a combination thereof.
In certain embodiments, the device is fabricated from biologically acceptable materials suitable for medical applications, including metals, synthetic polymers, ceramics, bone material, and composites thereof. In certain embodiments, the device comprises one or more chosen from a metal, ceramic, rubber, hydrogel, rigid polymer, fabric, bone material, and composites thereof.
In certain embodiments, the device comprises a metal chosen from stainless steel alloys, aluminum, commercially pure titanium, titanium alloys, Grade 5 titanium, superelastic titanium alloys, magnesium-infused titanium, cobalt-chrome alloys, superelastic metallic alloys such as nitinol, super elastoplastic metals such as Gum Metal®. In certain embodiments, the device comprises a ceramic and composites thereof, such as calcium phosphate (e.g., Skelite™) In certain embodiments, the device comprises a rubber chosen from polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO4 rubber, polyethylene terephthalate (PET), silicone, polyurethane, silicone-polyurethane copolymer, and polyolefin rubber. In certain embodiments, the device comprises a hydrogel. In certain embodiments, the device comprises fabric. In certain embodiments, the device comprises a rigid polymer chosen from polyphenylene, polyimide, polyetherimide, polyethylene, and epoxy. In certain embodiments, the device comprises bone material chosen from autograft, allograft, xenograft, or transgenic cortical and/or corticocancellous bone. In certain embodiments, the device comprises tissue growth or differentiation factors. In certain embodiments, the device comprises resorbable materials, such as composites of metals and calcium-based ceramics, composites of PEEK and calcium-based ceramics, composites of PEEK with resorbable polymers, totally resorbable materials, such as calcium-based ceramics, for example, calcium phosphate, tri-calcium phosphate (TCP), hydroxyapatite (HA)-TCP, calcium sulfate, or other resorbable polymers, such as polyketide, polyglycolide, polytyrosine carbonate, polycaprolactone, and other combinations.
In certain embodiments, the device comprises a rubber chosen from polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSO4 rubber, polyethylene terephthalate (PET), silicone, polyurethane, silicone-polyurethane copolymer, polyolefin rubber, synthetic collagen, and collagen matrix. In certain embodiments, the device comprises synthetic collagen. In certain embodiments, the device comprises collagen matrix.
In certain embodiments, the device comprises magnesium, vitamins, and minerals. “Vitamin” refers to an organic molecule (or a set of molecules closely related chemically, i.e. vitamers) that is an essential micronutrient that an organism needs in small quantities for the proper functioning of its metabolism. Some sources list fourteen vitamins, by including choline, but major health organizations typically list thirteen: vitamin A (as all-trans-retinol, all-trans-retinyl-esters, as well as all-trans-beta-carotene and other provitamin A carotenoids), vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B7 (biotin), vitamin B9 (folic acid or folate), vitamin B12 (cobalamins), vitamin C (ascorbic acid), vitamin D (calciferols), vitamin E (tocopherols and tocotrienols), and vitamin K (phylloquinone and menaquinones). In the context of nutrition, a “mineral” refers to a chemical element required as an essential nutrient by organisms to perform functions necessary for life, including potassium, chlorine, sodium, calcium, phosphorous, magnesium, iron, zinc, manganese, copper, iodine, chromium, molybdenum, selenium, and cobalt.
In certain embodiments, the device comprises a metal chosen from iron, stainless steel alloys, aluminum, commercially pure titanium, titanium alloys, Grade 5 titanium, superelastic titanium alloys, magnesium-infused titanium, cobalt-chrome alloys, superelastic metallic alloys such as nitinol, super elastoplastic metals such as Gum Metal®. In certain embodiments, the device comprises titanium. In certain embodiments, the device comprises iron.
In certain embodiments, the device is manufactured or 3D-printed from materials such as titanium, titanium alloy, cobalt chrome, carbon fiber, magnesium infused titanium, iron, or stainless steel. In certain embodiments, the device is manufactured from a shape memory alloy or shape memory polymer, allowing the device to conform to an anatomical shape of the patient's body.
In certain embodiments, the device comprises magnesium-infused titanium. In certain embodiments, the device comprises an angiotensin receptor blocker coating. In certain embodiments, the device comprises a type-1 cartilage collagen coating. In certain embodiments, the device is infused with an antibiotic.
In certain embodiments, the device is employed to treat an affected section of vertebrae. A medical practitioner obtains access to a surgical site, including the vertebrae, in any appropriate manner, such as through incision and retraction of tissues. In certain embodiments, the device comprises a bone screw to augment a surgical treatment. In certain embodiments, the device can be pre-assembled for delivery to a surgical site or assembled in situ. In certain embodiments, the device is entirely or partially revised, removed, or replaced.
In certain embodiments, the device is used with surgical methods or techniques, including, but not limited to, open surgery, mini-open surgery, minimally invasive surgery (MIS), and percutaneous surgical implantation, whereby the vertebra is accessed through a mini-incision or a sleeve provides a protected passageway to the area. Once access to the surgical site is obtained, a surgical treatment, such as a corpectomy or discectomy, can be performed to treat a disease or disorder.
In certain embodiments, the surface of the devices comprises a non-solid configuration, such as a lattice. In some embodiments, the non-solid configuration comprises a porous structure or a trabecular configuration.
In various embodiments, the non-solid configuration is configured to provide one or a plurality of pathways to aid bone growth within and through from one surface to an opposite surface of the device. In some embodiments, the lattice comprises one or more portions, layers, or substrates. In some embodiments, one or more portions, layers, or substrates of the lattice are disposed side by side, offset, staggered, stepped, tapered, end to end, spaced apart, in series, or parallel. In some embodiments, the lattice defines a thickness, which may be uniform, undulating, tapered, increasing, decreasing, variable, offset, stepped, arcuate, angled, and/or staggered. In some embodiments, one or more lattice layers are disposed in a side-by-side, parallel orientation within a wall. In certain embodiments, the lattice comprises one or more layers of a material matrix.
In some embodiments, the lattice comprises a plurality of nodes and openings disposed in rows and columns or randomly. In some embodiments, the plurality of nodes and openings are disposed in series. In some embodiments, the plurality of nodes and openings are disposed in parallel.
In some embodiments, the lattice forms a rasp-like configuration. In some embodiments, the lattice is configured to engage tissue. In certain embodiments, the engagement of the lattice is to cut, shave, shear, incise or disrupt the tissue. In some embodiments, the lattice comprises a configuration chosen from cylindrical, round, oval, oblong, triangular, polygonal having planar or arcuate side portions, irregular, uniform, non-uniform, consistent, variable, horseshoe shape, U-shape, or kidney bean shape. In some embodiments, the lattice is rough, textured, porous, semi-porous, dimpled, knurled, toothed, grooved, or polished, for example, to engage and cut the tissue. In some embodiments, the lattice forms a tunnel configured to guide, drive, or direct the cut tissue into an opening, such as fusing the device to the tissue.
In certain embodiments, the device is a screw. In some embodiments, the screw is chosen from a posted screw, a pedicle screw, a bolt, a bone screw for a lateral plate, an interbody screw, a uniaxial screw, a fixed angle screw, a multi-axial screw, a side-loading screw, a sagittal adjusting screw, a transverse sagittal adjusting screw, an awl tip, a dual rod multi-axial screw, midline lumbar fusion screw, and/or a sacral bone screw.
In certain embodiments, the device is a bone screw. In certain embodiments, the device is a pedicle screw. Referring to
In certain embodiments, the internal core of the screw is a trephine to collect and harvest autograft upon and/or during insertion of the screw.
In certain embodiments, post-implantation options prevent revision surgery through polymer injection through the screw.
In certain embodiments, the pedicle screw does not exhibit screw loosening, screw backout, rod breakage, or lowered bone mineral density.
In certain embodiments, the pedicle screw comprises a neck that is thicker than the shank, thereby strengthening the point where rod breakage most frequently occurs during screw installation.
In certain embodiments, the pedicle screw has reduced one or more screw loosening, screw backout, rod breakage, and lowered bone mineral density.
The disclosed screws focus on bone growth throughout the shaft to minimize shear stresses on the distal tip and spread micromotion evenly throughout the screw to encourage bony ingrowth.
In certain embodiments, the scaffold of pedicle screw provides options for simple to complex bone mineral densities and immunocompromised patients. In certain embodiments, the scaffold is impregnated with one or more biologics, antibiotics, demineralized bone matrices, nanotechnology, or regenerative medicine therapies.
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In some embodiments, the distal tip 220 of the pedicle screw 200,300,400,500 has a surface configuration chosen from angled, irregular, uniform, non-uniform, offset, staggered, tapered, arcuate, undulating, mesh, porous, semi-porous, dimpled, pointed, textured, or combinations thereof. In some embodiments, the distal tip 220 includes a nail configuration, barbs, expanding elements, raised elements, ribs, and/or spikes to provide a fabrication platform for forming a portion thereon via additive manufacturing. In some embodiments, the distal tip 220 has a cross-section configuration chosen from oval, oblong triangular, square, polygonal, irregular, uniform, non-uniform, offset, staggered, tapered, or combinations thereof.
In certain embodiments, the pedicle screw 200,300,400,500 comprises a thread 230 that extends between the proximal end 210 and distal tip 220. In certain embodiments, the thread 230 comprises an external thread form. In certain embodiments, the thread form comprises a leading edge 231 having a leading surface 235 and a trailing edge 232 having a trailing surface 236. The leading surface 235 defines a first opening 251. The trailing surface 236 defines a second opening 252. In some embodiments, the first and second openings 251,252 are axially aligned. In some embodiments, the first and second openings 251,252 are disposed circumferentially about the thread form. In some embodiments, the leading surface 235 and/or the trailing surface 236 comprises at least one tissue-gathering member. In some embodiments, the tissue gathering member comprises a cutting edge. In some embodiments, the cutting edge is configured to be rasp-like. In some embodiments, the cutting edge is configured to engage tissue, for example, to cut, shave, shear, incise, or disrupt the tissue. In some embodiments, the cutting edge is configured to be cylindrical, round, oval, oblong, triangular, polygonal, having planar or arcuate side portions, irregular, uniform, non-uniform, consistent, variable, horseshoe shape, U-shape, or kidney bean shape. In some embodiments, the cutting edge is rough, textured, porous, semi-porous, dimpled, knurled, toothed, grooved, or polished to engage and cut the tissue. In some embodiments, the cutting edge forms a tunnel configured to guide, drive, or direct the cut tissue into the void, such as fusing the screw with the tissue.
For example, manipulating the pedicle screw 200,300,400,500 by rotation or translation causes the cutting edge 271 of the screw to cut and guide the tissue or bone into the core 260, thereby promoting bone growth and fusion to the pedicle screw 200,300,400,500. In some embodiments, the tissue is embedded into the core 260 to promote bone growth and fusion to the pedicle screw 200,300,400,500. In some embodiments, the lattice is disposed within the core 260 to form a scaffold 280 for bone growth.
In some embodiments, the thread 230 is configured as fine, closely spaced, or shallow to engage with the tissue. In some embodiments, the thread 230 comprises an increased pitch and an equal lead between thread turns. In some embodiments, the thread 230 comprises a smaller pitch or more thread turns per the axial distance to fixate stronger fixation with the tissue or resist loosening from the tissue. In some embodiments, the thread 230 is configured to be continuous along a portion. In some embodiments, the thread 230 is configured to be intermittent, staggered, or discontinuous. In certain embodiments, the thread 230 comprises a single thread turn.
In certain embodiments, the thread comprises a plurality of discrete threads. In certain embodiments, the thread has a concave profile.
In some embodiments, the thread 230 comprises a penetrating element, for example, chosen from a nail configuration, barb, expanding element, raised elements, rib, or spike. In some embodiments, the thread 230 is configured as self-tapping or intermittent at the distal tip 220. In some embodiments, the distal tip 220 is rounded. In some embodiments, the distal tip 220 is self-drilling. In some embodiments, the distal tip 220 comprises a solid outer surface.
In certain embodiments, the screw is a 3D-printed porous pedicle screw. Its porosity mimics native vertebral bone to attach and keep stem cells, growth factors, and other proteins within the structure of the pedicle screw and encourage bone growth through the screw, stabilizing the overall construct. During insertion into vertebral bone, the built-in trephines collect autograft and regenerative cells within the porous matrix. The disclosed topography attracts bone-forming stem cells within and around the device, reducing overall construct macromotion. In certain embodiments, this device enables surgeons to meet patient-specific needs, such as, but not limited to, spraying/injecting regenerative products to stimulate the bone-forming osteogenic cascade, proactively injecting the screw scaffold with antibiotics for diabetic prone infections, and the option to inject bone cement to further stabilize the construct in severely osteoporotic bone.
In certain embodiments, the screw reduces revision rates, improves bone mineral density, and/or addresses patient-specific needs during spine fusions. In certain embodiments, bone mineral density improves, constructs are stabilized, and the likelihood of revision is reduced.
In certain embodiments, the screw is a 3D-printed titanium porous pedicle screw with a porous pattern throughout the screw similar to native bone. Without wishing to be bound by theory, the function of the porous pattern is to attach to the surrounding bone, keeping osteogenic stem cells in place and collecting autograft bone within its porous structure. An advantage of the porous structure is the ability to inject polymers and regenerative therapies through the screw. In certain embodiments, stem cell therapies are injected through the screw implant. In such embodiments, failure likelihood is reduced.
In certain embodiments, the surgeon can inject or spray the screw with autologous concentrated stem cells. Without wishing to be bound by theory, as the screw turns during insertion into the vertebrae, the screw's pores collect an autograft/stem cell mixture internally using its built-in trephines. The osteogenic stem cells then bind with the concentrated blood stem cells and signal the process of mutation and replication, forming more osteogenic cells within the screw, followed by a healing cascade of bone directed within and around the screw. In these embodiments, the combination of (a) osteoconductive (bone grows on the surface), (b) osteoinductive (recruiter of cells for bone healing), and (c) osteogenic (development and formation of bone) healing cascade of the stem cells improve bone mineral density and support superior bone integration and pullout strength.
In certain embodiments, the patient is diabetic and prone to infection. In these embodiments, the surgeon can inject a mixture comprising a calcium sulfate product and antibiotics through the screw before or after insertion or on the screw within the pedicle to provide antibiotic delivery in the area. In certain embodiments, the antibiotics are delivered for between two and six weeks. As such, the likelihood of revision due to infection is reduced.
The devices disclosed herein can be manufactured using various methods. In some embodiments, manufacturing comprises machining, such as subtractive, deformative, or transformative manufacturing. In some embodiments, manufacturing includes cutting, grinding, rolling, forming, molding, casting, forging, extruding, whirling, grinding, cold working, or combinations thereof. In some embodiments, manufacturing includes a portion of the device formed by a medical machining process. In some embodiments, machining uses computer numerical control (CNC) high-speed milling machines, Swiss machining devices, CNC turning with living tooling, wire EDM 4th axis, and combinations thereof. In some embodiments, the manufacturing for fabricating a portion of the devices includes a finishing process, such as laser marking, tumble blasting, bead blasting, micro blasting, powder blasting, or combinations thereof.
In certain embodiments, the device is fabricated per instructions from a computer and processor based on the digital rendering and/or data of a selected configuration via additive manufacturing.
In some embodiments, additive manufacturing comprises 3-D printing. In some embodiments, additive manufacturing is chosen from fused deposition modeling, selective laser sintering, direct metal laser sintering, selective laser melting, electron beam melting, layered object manufacturing, stereolithography, and combinations thereof. In some embodiments, additive manufacturing comprises rapid prototyping, desktop manufacturing, direct manufacturing, direct digital manufacturing, digital fabrication, instant manufacturing, on-demand manufacturing, or combinations thereof.
In some embodiments, a portion of the device is manufactured by additive manufacturing and then mechanically attached to a surface of the device, for example, by welding, threading, adhesives, or staking.
In one embodiment, the device is configured based on imaging from patient anatomy. Suitable imaging techniques include, but are not limited to, X-ray, fluoroscopy, computed tomography (CT), magnetic resonance imaging (MRI), surgical navigation, bone density (DEXA), or acquirable 2-D or 3-D images of patient anatomy. Selected configuration parameters for the device are collected, calculated, or determined. Examples of configuration parameters include, but are not limited to, patient anatomy imaging, surgical treatment, historical patient data, statistical data, treatment algorithms, implant material, implant dimensions, porosity, and manufacturing method. In some embodiments, the configuration parameters comprise implant material and device porosity based on patient anatomy and surgical treatment. In some embodiments, porosity is selected. In some embodiments, the configuration parameter of the device is patient specific. In some embodiments, the configuration parameter of the device is based on a generic configuration and is not patient specific.
For example, a digital rendering or data of a device is generated for display from a graphical user interface or storage on a database attached to a computer and a processor. In some embodiments, the computer display via a monitor saves, digitally manipulates, or prints a hard copy of the digital rendering or data. In some embodiments, the device is designed virtually with a CAD/CAM program on a computer display. In some embodiments, the processor executes code stored in a computer-readable memory medium to execute one or more computer instructions, for example, transmitting instructions to an additive manufacturing device. In some embodiments, the database or computer-readable medium comprises RAM, ROM, EPROM, magnetic, optical, digital, electromagnetic, flash drive, semiconductor technology, or combinations thereof. In some embodiments, the processor instructs motors to control the movement and rotation of device components.
“Regenerative medicine” refers to a branch of translational research in tissue engineering and molecular biology, which deals with replacing, engineering, or regenerating human cells, tissues, or organs to restore or establish normal function. This field holds the promise of engineering damaged tissues and organs by stimulating the repair mechanisms within the patient's body to functionally heal previously irreparable tissues or organs. For example, during bone regeneration, new bone formation is primarily affected by physicochemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment.
In certain embodiments, regenerative medicine is incorporated with the scaffolds or devices disclosed herein. Autogenous graft incorporation occurs in five stages: inflammation, vascularization, osteoinduction, osteoconduction, and remodeling.
Inflammation lasts for about 7 to 14 days. Initial insult to the local blood supply and decortications results in hematoma around the bone graft, in which inflammatory cells invade. The fibroblast-like cells in the inflammatory tissue transform into the fibrovascular stroma. Perioperative anti-inflammatory medications decrease fusion rates because of the inflammatory process.
Vascular buds appear in the fibrovascular stroma, resembling scar tissue formation during vascularization. Primary membranous bone forms near the decorticated bone. Next, minimal cartilage and endochondral ossification occur.
During osteoinduction at weeks 4 to 5, reparation comprises increased vascularization, necrotic tissue resorption, osteoblasts, and chondroblasts differentiation. In particular, stem cells differentiate into osteoblasts. New bone extends towards the central zone of the fusion mass. The cortical portion of the graft continues to resorb.
Osteoconduction is characterized by ingrowth into the host bone and creeping substitution. Osteoblasts create new bone while osteoclasts simultaneously resorb graft bone. A central zone of the endochondral interface is observed at the center of fusion mass, uniting the lower and upper halves of fusion. Pluripotent cells in this central zone differentiate into cartilaginous tissue with less vascularization.
During remodeling at weeks 6-10, a peripheral cortical rim forms around fusion. Bone marrow activity increases, forming secondary spongiosa. The cortical rim thickens. The trabecular process extends to the center of fusion. Remodeling typically completes one year after device implantation.
Pseudarthrosis (nonunion) was a leading cause of pain postoperatively and accounted for 45%-56% of revisions. Boney fusion directly correlates to successful clinical outcomes. Patients with pseudarthrosis were asymptomatic in about 30% of cases. Younger age has a significantly increased symptomatic pseudarthrosis rate (43.8 years vs. 52.1 years, p<0.01).
In certain embodiments, bone marrow aspirate (BMA) with allograft substitutes autogenous bone graft in single-level revision posterolateral lumbar fusion (PLF). In certain embodiments, bone marrow aspirate with allograft is more cost-effective than recombinant human bone morphogenetic protein-2 (rhBMP). In certain embodiments, bone marrow-derived cell-enriched allografts compare to autografts in bone grafting and spinal fusion procedures. In certain embodiments, BMA increases the regenerative potential of corticocancellous allogeneic bone grafts. When treating unicameral bone cysts, healing rates were high (98.7%) for bone marrow with demineralized bone matrix injection.
When introducing elements of the present disclosure or the embodiments(s) thereof, the articles “a,” “an,” “the,” and “said” are intended to mean that there are one or more of the elements. The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.
Having described the disclosure in detail, it will be apparent that modifications and variations are possible without departing from the scope of the disclosure defined in the appended claims.
Although the disclosure described herein is susceptible to various modifications and alternative iterations, specific embodiments thereof have been described in greater detail above. It should be understood, however, that the detailed description of the composition is not intended to limit the disclosure to the specific embodiments disclosed. Rather, it should be understood that the disclosure is intended to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure as defined by the claim language.
The following examples are included to demonstrate certain embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples represent techniques discovered by the inventors to function well in the practice of the disclosure. Those of skill in the art should, however, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. Therefore, all matter is interpreted as illustrative and not in a limiting sense.
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The pedicle screw 500 comprises a thread 230 disposed around a shaft 240 that extends between the proximal end 210 and distal tip 220. The shaft 240 comprises regions of scaffold 280 exposed to the outer surface of the pedicle screw 500 between the middle thirteen turns of the thread 230. The thread 230 comprises an external thread form with a leading edge having a leading surface and a trailing edge having a trailing surface. The pedicle screw 500 had a core filled with scaffold 280 extending through the center of the pedicle screw 500 from the proximal end 210 to the distal tip 220. The distal tip 220 comprised cutting members 270.
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When present, the pores of the scaffold 280 promoted boney in-growth through the screw. Other materials fabricating the pedicle screw included pre-packed demineralized bone matrix (DBM), pre-packed synthetic DBM, unpacked DBM, and magnesium-infused titanium. Built-in channels captured autograft during insertion. The screw had double ball angulation and a low profile. The screw comprised a locking cap with reverse-angle threads. The screw can be cannulated or non-cannulated.
The screws were between 35 mm and 65 mm long and between 4.5 mm and 8.5 mm in diameter. The rod acceptance was 5.5 mm.
Built-in channels for autograft collection enhance the structural integrity of the implantation. These superiorly resisted bone mineral density loss and reduced micromotion. The randomized porosity pattern of the scaffold 280 was typical of native trabecular bone. In addition, built-in struts provided structural integrity. The pedicle screws 200,300,400,500 were manufactured in cobalt chrome, titanium, and magnesium-infused titanium.
The device was tested in cobalt chrome and met American Society for Testing and Materials (ASTM) standards 543, 1798, and 1717.
ASTM standard 543 evaluates plastic materials for resistance to chemical reagents, including cast, hot-molded, cold-molded, laminated resinous products, and sheet materials. Three procedures are presented, two under practice A (Immersion Test) and one under practice B (Mechanical Stress and Reagent Exposure under Standardized Conditions of Applied Strain). These practices report changes in weight, dimensions, appearance, color, strength, and other mechanical properties. Standard reagents are specified to establish results on a comparable basis without precluding other chemical reagents pertinent to specific chemical resistance requirements. Provisions are made for various exposure times, stress conditions, and exposure to reagents at elevated temperatures. The type of conditioning (immersion or wet patch/wipe method) depends upon the material's end-use.
ASTM standard 1798 covers the measurement of uniaxial static, fatigue strength, and resistance to loosening the component interconnection mechanisms of spinal arthrodesis implants. This test method provides a means of mechanically characterizing different designs of spinal implant interconnections. The various components and interconnections may be combined for static and fatigue testing of the spinal implant construct. This test method does not address the analysis of spinal implant constructs or subconstructs or define levels of performance of spinal implants.
ASTM standard 1717 covers the materials and methods for the static and fatigue testing of spinal implant assemblies in a vertebrectomy model. The test materials for combinations of spinal implant components can be specific, depending on the spinal location and intended application method to the spine. These test methods provide a basis for the mechanical comparison among past, present, and future spinal implant assemblies. They allow comparison of spinal implant constructs with different intended spinal locations and application methods to the spine. These test methods are not intended to define levels of performance. Instead, these test methods set out guidelines for load types and methods of applying loads, measuring displacements, determining the yield load, and evaluating the stiffness and strength of the spinal implant assembly. Methods for three static load types and one fatigue test are defined for the comparative evaluation of spinal implant assemblies.
In certain embodiments, the pedicle screw 200,300,400,500 is individually packaged in a double Tyvek™ peel tray.
In certain embodiments, the pedicle screw 200,300,400,500 is injected or sprayed with a material, such as BMA concentrate, calcium phosphate, biologic, and/or antibiotics. The filled or coated screw rested for 10-15 minutes before insertion for the material to absorb.
A 3D Voronoi surface lattice structure was applied at the minor diameter of the screw with at least one different lattice size and random shape patterns and sizes. See
In certain embodiments, the minor diameter can be constant or variable. In certain embodiments, a plurality of surface lattice structures is superimposed, with each surface lattice structure providing random pore sizes and a different dimensional and/or cross-sectional value for the connecting elements. In certain embodiments, structures of the plurality of surfaces lattice structures are merged and connected, then the interfaces between each structure are rounded and/or blended.
In certain embodiments, the internal lattice structure has a randomized pattern similar to healthy trabecular bone, such as that found in the lumbar vertebrae. This natural lattice structure has been described, for example, in Callens et al., “The local and global geometry of trabecular bone” Acta Biomaterialia 130 (2021): 343-361, incorporated herein by reference in its entirety.
In certain embodiments, the average Gaussian curvature distributions of the pores in the scaffold are on hyperbolic (K<0). This prevalence of negative Gaussian curvature is consistent with the high topological complexity (i.e., high genus) of trabecular bone, according to the Gauss-Bonnet theorem. The net curvature captures regions where the trabecular surface is strongly bent, without distinguishing between the saddle- or sphere-like nature of these bends. In certain embodiments, the pores comprises arc-like transitions between plate-like elements. In certain embodiments, high net curvature in pores is concentrated in cylindrically-shaped rod-like elements.
The pedicle screw has passed all the benchtop and simulation testing and validation necessary for large animal testing. The device was tested in titanium and met ASTM standards 543, 1798, and 1717 in an engineering laboratory. In a simulation pipeline, overall analysis of the current worst-case device (5.5 mm diameter) shows a very small percentage of points over the fatigue limit of titanium.
A second simulation was conducted with a screw with a 6 mm diameter. No points were found above the fatigue limit of titanium. These data provided an acceptable alternative design.
In-vivo assessments, ex-vivo assessments, and data from this six sheep study will determine how this treatment modality affects bone mineral density, polymorphonuclear cells (PMNs), lymphocytes, plasma cells, macrophages (Mφ), giant cells, necrosis, osteoblastic cells, signs of bone remodeling by osteoclasts, neovascularization, fibrosis, signs of implant degradation, and particulate debris.
The first specific aim is to determine whether the porous pedicle screw promotes bone integration and pullout strength compared to the gold-standard pedicle screw/rod constructs in a posterior lumbar interbody fusion sheep model. The topography of 3D printed porous patterns has higher adhesion of stem cells to titanium. In addition, mesenchymal and hematopoietic stem cells have therapeutic effects on bone. By combining these two modalities, superior results can be achieved in the disclosed porous pedicle screws concerning bone integration and pullout strength over current pedicle screws.
To this end, the bone mineral densities (BMD) of 84 vertebral bodies (L1-L6) will be measured from six sheep one week preoperatively and postoperatively at 24 and 36 weeks. Each subject will receive two separate lumbar interbody fusions (LIF) at the L2-L3 and L4-L5 joints. L1 and L6 will be naïve controls to compare changes with and without hardware.
In each subject, a titanium interbody cage and bone void filler packed into the interbody cage will be placed between the L2-L3 and L4-L5 segments. Then, 4.5, 5.5, or 6.5-mm diameter and 45±10 mm screws will be inserted into the right and left pedicles within the L2, L3, L4, and L5 vertebral bodies. This configuration represents traditional fusion devices and surgical techniques. Before insertion, the porous pedicle screws (treatment) will be sprayed with autologous stem cell concentrate along the length of the porous portion screw.
In-life lumbar spine radiographs will be performed on all animals immediately post-op (PO) and at sacrifice. Animals will be visually assessed at least once daily throughout the study. Abnormalities, such as signs of infection at the surgical site, will be recorded. A total of 6 animals will be sacrificed 36 weeks after surgery.
Following euthanasia, lumbar spine sections (L1-L5) will be freshly dissected to a single functional spinal unit (FSU) (i.e., L4-L5) for post-sacrifice assessments. High-resolution biplanar digital radiographs and photos will be taken at sacrifice following fine dissection in the sagittal and coronal planes. Non-destructive range of motion (ROM) biomechanics will be measured on all samples, including ROM biomechanics under pure moment loading in flexion-extension, lateral bending, and axial rotation to 6.0 N-m, yielding range of motion (Degrees), construct stiffness (Deg./N-m), and neutral zone (Deg.).
Destructive pedicle screw pullout will be tested. Quasi-static ramp to failure testing will yield construct stiffness (N/mm), yield force (N), ultimate failure force (N), and mode of failure (MOD) observed visually. Destructive pedicle screw torque-out will be tested for N=1 of 4 screws from each, and quasi-static torque counterclockwise to loosen the screw will yield ultimate torque (Nm).
Other tests will include micro-computed tomography (MicroCT) of each FSU and associated pedicle screws, quantitative assessment of the posterior lumbar fusion (PLF) region (bone volume and bone density), qualitative assessment of bone ingrowth around pedicle screws, pedicle screw histology, organ histology, and static histomorphometry of screw regions of interest (ROIs), including the percentage of the bone area within ROI, percentage of fibrous tissue within ROI, percentage of void space with ROI, percentage of the screw within ROI, and percentage of bone on-growth to the device.
Slides will be delivered to a certified pathologist for histopathology analysis. The pathologist will be initially blinded to the treatment parameters of each site. Then, when applicable, the sections will be analyzed and graded per cell type and responses following the grading scheme in Table 3. After scoring all the slides for data post-processing, the pathologist will be unblinded so they can compare data to the control samples.
+Osteoblastic cells-severe suggests numerous OB Cells
#Signs of bone remodeling by osteoclasts-severe suggests abundant bone remodeling present
&Neovascularization-severe suggests numerous neovascular vessels
The histopathology report will include, but will not be limited to, a summary of methods and materials, tabulated and qualitative data through the last time point and conclusions, low-power images, and representative photomicrographs to illustrate the findings. An unpaired t-test with an alpha (α) value of 0.05 will be performed to determine statistical significance for biomechanical and histomorphometric outcome parameters. Then, the data will be compared with similar retrospective studies.
This study's second specific aim is to show that injecting and spraying autologous concentrated stem cells within and around pedicle screws is safe. Porous 3D-printed titanium interbody cages are commonly impregnated intraoperatively with autologous stem cells. They have been proven safe and are the gold standard to aid fusion between the vertebrae after removing the disc. This study aims to prove the same can be performed within the vertebral bone in sheep to provide confidence of safety for a human clinical trial.
After sacrifice, histology will be compared with prior studies to determine the differences and similarities of polymorphonuclear cells (PMNs), lymphocytes, plasma cells, macrophages (Mφ), giant cells, necrosis, osteoblastic cells+, signs of bone remodeling by osteoclasts, neovascularization, fibrosis, signs of implant degradation, and particulate debris. Histology reports will also be compared and contrasted between the control, naïve, and treatment sites. An unpaired t-test with an alpha (α) value of 0.05 will be performed to determine statistical significance for biomechanical and histomorphometric outcome parameters. Injecting autologous stem cells within and around the porous pedicle screws is expected to be safe compared to the control screws, naïve screws, and prior studies.
This study's third specific aim is to show that porous pedicle screws have a topography and porous pattern for promoting stem cell adhesion. Human mesenchymal stem cells have the strongest adhesive affinity for titanium surfaces with porosities between 50% and 70%, a more robust and dense internal cellular migration pattern, and high cell viability. Therefore, the porous pattern and topography of porous pedicle screws should have a similar adhesion to stem cells.
After the sheep have been sacrificed, the screws will be removed from the vertebrae and studied for stem cell adhesion. Cell viability on the implant surface will be performed with a LIVE/DEAD assay. A conditioned media assay will be used to study bone morphogenic protein 2 (BMP2) expression levels, vascular endothelial growth factor (VEGF), osteocalcin, osteoprotegerin expression, DNA, and alkaline phosphatase activity.
The correlation between cell adhesion with 3D printed titanium patterns and porous pedicle screws will be shown. Porous pedicle screws demonstrate better stem cell adhesion than the control and naïve subjects, as well as similar adhesion rates to prior studies.
A separate sheep study demonstrated the safety of injecting autologous stem cells within and around the disclosed pedicle screws and testing the efficacy of the screws in allowing for stem cell adhesion to aid in osteo-integration and pullout strength.
Another six-animal study will focus on testing the feasibility of injecting calcium sulfate with antibiotic mixtures as a means of reducing rates of infection following spinal fusions. The main objectives of this project are to confirm whether (1) the tested pedicle screw aids superior bone integration and pullout strength compared to the gold-standard pedicle screw/rod constructs in a posterior lumbar interbody fusion sheep model; (2) injecting calcium sulfate with antibiotic mixtures can reduce the rate of infection following spinal fusions; and (3) the tested pedicle screws have topography and porous pattern for supporting injection of the above goals.
For the first aim, the rationale is that, if a patient has an infected bone, surgeons can protect the hardware by injecting an antibiotic mixture through the device. Through the proposed animal study, we will confirm that, in an infected and contained area (e.g., vertebral bone), the pedicle screw will (1) protect surgical hardware (i.e., confirm infection has not spread into hardware) compared to controls and (2) reduce infection in the bone.
An ovine model was chosen because sheep have the spinal column most similar to the human spine. Sheep vertebrae are large enough to accommodate a pedicle screw disclosed herein. Smaller animals are not viable because the screws are too large for their bones.
This sample size was chosen to realistically assess feasibility and achieve proof-of-concept within a Phase I scope and timeline. In alignment with program objectives, Phase I results will be interpreted as preliminary and tentative conclusions will be used to inform an anticipated Phase II where we can propose a large, controlled, well-powered animal study that evaluates efficacy endpoints in a scientifically rigorous manner.
The experimental design and methods will be substantially the same as the sheep study above in example 3, including Tables 2 and 3.
All references, patents, or applications, US or foreign, cited in the application are because of this incorporated by reference as if written herein in their entireties. Where any inconsistencies arise, the material disclosed herein controls.
From the preceding description, one skilled in the art can easily ascertain the essential characteristics of this invention and, without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.
This application is Continuation-in-Part of and claims the benefit of the International Application No. PCT/US2022/077245, filed Sep. 29, 2022, and claims the benefit of priority of U.S. Provisional Patent Application Ser. No. 63/249,945 filed Sep. 29, 2021, and also claims the benefit of priority of the U.S. Provisional Patent Application Ser. No. 63/422,628 filed Nov. 4, 2022, the disclosures of which are incorporated by reference in their entireties for all purposes.
| Number | Date | Country | |
|---|---|---|---|
| 63422628 | Nov 2022 | US | |
| 63249945 | Sep 2021 | US |
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/US2022/077245 | Sep 2022 | US |
| Child | 18502005 | US |
