Scaffolds based on continuous folded sheets

Abstract

Provided herein are various embodiments related to the design, creation, and use of a folded sheet scaffold for medical devices. The scaffold comprises a shellular porous pseudorandom orientable architecture composed of a continuous folded sheet of topological genus-n. Methods for designing the scaffold involve driving noise from an infinite 3D noise field to define a field with real space, tuning field values based on user input, and subtracting to create thin wall geometry. The methods can be computer-implemented or executed by a processor following instructions stored on a non-transitory computer-readable medium. A computer system for designing the scaffold includes modules for noise-driving, tuning, and subtracting. The disclosure also includes a folded sheet scaffold formed by these methods and a medical device comprising the folded sheet scaffold.

Description

SCAFFOLDS BASED ON CONTINUOUS FOLDED SHEETS

[0001] This application claims the benefit of priority of the United States Provisional Patent Application Serial No. 63 / 605,404 filed on December 1, 2023, the disclosure of which is incorporated by reference in its entirety for all purposes.

[0002] This disclosure relates to a scaffold material that resembles natural bone, medical devices made from this scaffold material, and related methods for bone implantation.

[0003] 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.

[0004] 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%, depending on bone quality and osteoporosis. In all cases, screw loosening is a concern.

[0005] 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%.

[0006] Despite advances in technology and surgical technique, these rates have remained the same. 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.)

[0007] 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. Otherpotential complications for LTF are dural tears, neurological injuries, pseudoarthrosis, infection, and wound healing issues.

[0008] 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.

[0009] These challenges relating to long-term stability, such as bone quality and functional ability to heal, have yet to be 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.SUMMARY

[0010] The present disclosure provides a folded sheet scaffold for use in medical devices. The scaffold comprises a pseudorandom architecture comprising a continuous folded sheet of topological genus-n, wherein real 3 -dimensional space is divided into sub-volumes.

[0011] The disclosure also provides a method for designing a folded sheet scaffold for use in medical devices. The method comprises driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, tuning the upper and lower bounds of the field values based on user input, and subtracting to create thin wall geometry.

[0012] Further, the disclosure provides a computer-implemented method for designing a folded sheet scaffold for use in medical devices. The method comprises implementing a processor to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, using the processor to tune the upper and lower bounds of the field values based on user input, and implementing the processor to subtract and create thin wall geometry.

[0013] The disclosure also provides a computer system for designing a folded sheet scaffold for use in medical devices. The system comprises a noise-driving module configured to drive noise from an infinite 3D noise field to define a field with real space, the field having field values eachcomprising an upper bound and a lower bound, a tuning module configured to tune the upper and lower bounds of the field values based on user input, and a subtracting module configured to subtract and create thin wall geometry.

[0014] Additionally, the disclosure provides a non-transitory computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform a method for designing a folded sheet scaffold for use in medical devices. The method comprises driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, tuning the upper and lower bounds of the field values based on user input, and subtracting to create thin wall geometry.

[0015] The disclosure also provides a folded sheet scaffold formed by a method disclosed herein.

[0016] The disclosure further provides a medical device comprising the folded sheet scaffold disclosed herein or produced by a method disclosed herein.

[0017] 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.BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG. 1 shows a flowchart illustrating the workflow and variable inputs for producing a folded sheet scaffold.

[0019] FIG. 2 shows a cross-section of a folded sheet scaffold produced from the workflow of FIG. 1.

[0020] FIG. 3 shows a plan view of a side of the folded sheet scaffold of FIG. 2.

[0021] FIG. 4 shows a perspective orthogonal view of the folded sheet scaffold of FIG. 2.

[0022] FIG. 5 shows the top view of a pedicle screw presenting a folded sheet scaffold disclosed herein.

[0023] FIG. 6 shows the bottom view of the pedicle screw of FIG. 5.

[0024] FIG. 7 shows a perspective view of the pedicle screw of FIG. 5.

[0025] FIG. 8 shows the back view of the pedicle screw of FIG. 5.

[0026] FIG. 9 shows the front view of the pedicle screw of FIG. 5.

[0027] FIG. 10 shows a magnified inset of the front view of the porous pedicle screw of FIG. 5, highlighting the scaffold.

[0028] FIG. 11 shows the top view of a pedicle screw presenting a folded sheet lattice disclosed herein and textured threads having substantially the same topography as the folded sheet lattice.

[0029] FIG. 12 shows the bottom view of the pedicle screw of FIG. 11.

[0030] FIG. 13 shows a perspective view of the pedicle screw of FIG. 11.

[0031] FIG. 14 shows the back view of the pedicle screw of FIG. 11.

[0032] FIG. 15 shows the front view of the pedicle screw of FIG. 11.

[0033] FIG. 16 shows a magnified inset of the front view of the pedicle screw of FIG. 11, highlighting the scaffold.

[0034] FIG. 17 shows the top view of a headless screw presenting a folded sheet lattice disclosed herein.

[0035] FIG. 18 shows the bottom view of the headless screw of FIG. 17.

[0036] FIG. 19 shows a perspective view of the headless screw of FIG. 17.

[0037] FIG. 20 shows the back view of the headless screw of FIG. 17.

[0038] FIG. 21 shows the front view of the headless screw of FIG. 17.

[0039] FIG. 22 shows a magnified inset of the front view of the headless screw of FIG. 17, highlighting the scaffold.

[0040] FIG. 23 shows the top view of a headless screw presenting a folded sheet lattice disclosed herein and textured threads having substantially the same topography as the folded sheet lattice.

[0041] FIG. 24 shows the bottom view of the headless screw of FIG. 23.

[0042] FIG. 25 shows a perspective view of a headless screw of FIG. 23.

[0043] FIG. 26 shows the back view of the headless screw of FIG. 23.

[0044] FIG. 27 shows the front view of the headless screw of FIG. 23.

[0045] FIG. 28 shows a magnified inset of the front view of the headless screw of FIG. 23, highlighting the scaffold.

[0046] FIG. 29 is a plot of load (N) over a logarithmic scale of cycles for test samples 7, 8 and 9.

[0047] FIG. 30 is a plot of the runout moment (Nm) for the tested implant compared to the measured run-out moments for 98 comparative implants tested.

[0048] The disclosure will be readily understood by the following detailed description in conjunction with the accompanying drawings, wherein like reference numerals designate likestructural elements. The drawings provide exemplary embodiments or aspects of the disclosure and do not limit the scope of the disclosure.DETAILED DESCRIPTION

[0049] The present disclosure provides a scaffold for growing bone, comprising a randomized porosity pattern typical of a native trabecular bone.

[0050] 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.

[0051] 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 integration 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.

[0052] 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.Scaffold

[0053] As used herein, “scaffold” or “lattice” refers to a three-dimensional structure or framework used in the field of medical devices, particularly in tissue engineering and regenerative medicine. In certain embodiments, a scaffold is designed to provide structural support and guide the growth of new tissue, such as bone, into the device. For example, in orthopedic implants, a scaffold might be constructed from biocompatible and bioresorbable materials, providing a template for bone tissue to grow into and gradually replace as the bodyresorbs the scaffold material. The scaffold’s architecture, including its porosity, mechanical strength, and degradation rate, can be tailored to match the specific requirements of the bone tissue regeneration process.

[0054] FIG. 1 shows a flowchart illustrating the workflow 100 steps 130 and type 140 and variable inputs 150 for producing a folded sheet scaffold 600. Main workflow 100 steps are connected with a solid arrow. Optional workflow 100 steps are connected with a hatched arrow.

[0055] As used herein, “folded sheet scaffold” 600 refers to a shellular porous structure with a pseudorandom orientable architecture derived from a continuous folded sheet of a topological genus-n. This architecture divides the three-dimensional space into two distinct, non-intersecting sub-volumes, or labyrinths, which, in certain embodiments, are incongruent. A dimensionless three-dimensional noise field influences the pseudorandom orientation of this structure, the characteristics of which — including type, frequencyjitter, and magnitude — are adjustable. In certain embodiments, the folded sheet scaffold exhibits a continuous, perforated, or functionally graded sheet architecture. In various embodiments, the architecture is semi-regular or determined by specific modulating algorithms that control spatially-varying features.

[0056] In certain embodiments, “folded sheet scaffold” 600 is formed by manipulating a flat sheet into a three-dimensional structure through noise driving, subtraction, multiplication, voxelization, smoothening, and insertion. In certain embodiments, a folded sheet scaffold is characterized by its high strength-to-weight ratio, adaptability, and ease of assembly.

[0057] “ Dimensionless” refers to a characteristic, quantity, or property that does not have an associated physical or spatial dimension. It is a purely numerical measure and independent of any unit of measurement. In the case of a “dimensionless 3-dimensional noise field,” the term “dimensionless” refers to the noise field being defined or characterized by numerical values that do not correspond to a specific physical dimension but rather serve to influence the properties or characteristics of the folded sheet scaffold.

[0058] “Functionally graded” refers to a characteristic of the sheet architecture where its properties vary gradually over volume due to a continuous change in structure or composition. This grading can be designed to meet specific requirements of different parts of the scaffold.

[0059] The term “genus-n” is a topological concept referring to the number of “holes” or “handles” in a given surface. In the context of a “continuous folded sheet of topological genus- n,” it denotes the complexity of its structure, with n indicating the number of such features.

[0060] “Labyrinth” refers to the complex network-like structure formed within the divided subvolumes of the three-dimensional space. These labyrinths result from the pseudorandom orientation of the folded sheet scaffold, creating intricate pathways or channels.

[0061] “Perforated” refers to the presence of a series of holes or openings in the sheet architecture of the scaffold. These perforations range in size and arrangement. They contribute to the porous nature of the scaffold, influencing its functional properties.

[0062] “ Semi-regular” refers to a characteristic of the sheet architecture where there is a degree of regularity or consistency in the structure but not absolute uniformity. In certain embodiments, “semi-regular” refers to patterns or features that repeat with some variation.

[0063] “ Shellular” refers to a specific type of porous structure that resembles a shell or a series of shells. This structure is characteristic of the folded sheet scaffold, contributing to its overall architecture and functional properties.

[0064] “Spatially-varying feature” refers to characteristics or properties of the folded sheet scaffold that change or vary across different points or regions in space. These features include, but are not limited to, variations in the structure, composition, or functional properties of the scaffold.

[0065] “ Statistical variation” in the context of a “dimensionless 3-dimensional noise field” refers to the fluctuations or changes in the noise field that follow a certain statistical distribution. This variation influences the pseudorandom orientation of the folded sheet scaffold.

[0066] “ Sub-volume” refers to separate or distinct portions of a three-dimensional space that do not share common points or intersect. These sub-volumes are created by dividing the three- dimensional space by the continuous folded sheet of topological genus-n.

[0067] The present disclosure provides a method for designing a folded sheet scaffold 600. The method comprises driving noise 131 from an infinite 3D noise field to define a field with real space having field values, each comprising an upper bound and a lower bound, tuning 132 the upper and lower bounds of the field values to user input, subtracting 135 to create thin wall geometry.

[0068] In certain embodiments, after the tuning step, the method further comprises adding 133 biases 177 to the field values to offset geometry.

[0069] In certain embodiments, after the tuning step, converting 134 negative field values are converted into positive field values.

[0070] Tn certain embodiments, after the subtracting step, the method further comprises multiplying 136 to add units to the field.

[0071] In certain embodiments, after the subtracting step, the method further comprises voxelizing 137 the field to form sized voxels defining a voxel grid in the field’s real space. In certain embodiments, the method further comprises smoothening 138 the voxel grid after the subtracting step. In certain embodiments, after the subtracting step, the method further comprises intersecting 139 the smoothened voxel grid with a desired design space.

[0072] In certain embodiments, the method comprises driving noise 131 from an infinite 3D noise field to define a field with real space having field values, each comprising an upper bound and a lower bound, tuning 132 the upper and lower bounds of the field values to user input, adding 133 biases to the field values to offset geometry, converting 134 negative field values into positive field values, subtracting 135 to create thin wall geometry, multiplying 136 to add units to the field, voxelizing 137 the field to form sized voxels defining a voxel grid in the field’s real space, smoothening 138 the voxel grid, and intersecting 139 the smoothened voxel grid with a desired design space.

[0073] In certain embodiments, a base field is established, which forms the initial sheet, the method provides the capability for further manipulation of this base field. The further manipulations included, but are not limited to, remapping the curvature of the base field, warping the base field cylindrically, and functionally grading the base field.

[0074] In certain embodiments, the method comprises driving noise 131 from an infinite 3D noise field to define a field with real space having field values, each comprising an upper bound and a lower bound. The variable inputs 150 are chosen from cubic noise 101, value noise 102, gradient noise 103, Perlin noise 104, cellular noise 105, simplex noise 106, and white noise 107. The type inputs 140 are chosen from frequency 108, random seed 109, jitter 110, distance 111, and return type 112. In certain embodiments, the variable input is cellular noise 105.

[0075] As used herein, “cubic noise” 101 refers to noise generation used in computer graphics and digital art to create texture or randomness. Cubic noise is a simple alternative to Perlin and simplex noise, taking a low-resolution white noise and scales it up using cubic interpolation. This approach means that cubic noise is smooth but much more random than Perlin and simplex noise.

[0076] As used herein, “value noise” 102 refers to a technique in computer graphics for generating procedural textures and patterns. Value noise is a type of noise commonly used as a procedural texture primitive in computer graphics. This approach creates a lattice of points, each assigned random values. The noise function then returns an interpolated number derived from the values of the surrounding lattice points. In certain embodiments, value noise produces visually diverse and naturalistic textures.

[0077] As used herein, “gradient noise” 103 refers to a technique used in computer graphics to generate a low -pass filtered stochastic function, often used for procedural texturing and modeling. Gradient noise offers an alternative method of generating this function by using the pseudorandom numbers (PRNs) at each lattice point to derive gradient vectors, which are used instead of the values themselves.

[0078] As used herein, “pseudorandom numbers” refer to sequences of numbers that, while not truly random, simulate randomness to such a degree that they can be used in place of truly random numbers in various computational applications. In certain embodiments, pseudorandom numbers are generated by deterministic processes, such as specific mathematical algorithms. Hence, given the same initial state or “seed,” these processes will produce the same sequence of numbers. Despite the deterministic nature of their generation, pseudorandom numbers are designed to satisfy certain statistical properties of randomness, making them practically indistinguishable from true random sequences in many applications.

[0079] As used herein, “Perlin noise” 104 refers to gradient noise. Perlin noise is a primitive procedural texture characterized by its pseudorandom appearance, yet all its visual details are the same size. However, despite its pseudorandom appearance, the output of the Perlin noise function is deterministic and repeatable.

[0080] As used herein, “cellular noise” 105, also known as “Worley noise,” refers to a noise function used in computer graphics to generate procedural textures and patterns. Cellular noise is an extension of the Voronoi diagram that outputs a real value at a given coordinate corresponding to the distance of the nth nearest seed, usually the nearest seed. The seeds are distributed evenly through the region.

[0081] As used herein, “Voronoi diagram” refers to partitioning a plane into regions based on the distance to a specific set of points, known as seeds or sites. In certain embodiments, each region in a Voronoi diagram consists of all points closer to a particular seed than any other.

[0082] As used herein, “simplex noise” 106 refers to an n-dimensional noise function comparable to Perlin noise, but it exhibits fewer directional artifacts and, in higher dimensions, offers lower computational overhead. However, like Perlin noise, the output of the simplex noise function is deterministic and repeatable.

[0083] As used herein, “white noise” 107 refers to a random signal having equal intensity at different frequencies, giving it a constant power spectral density. In certain embodiments, white noise is a basis for generating more complex noise types for procedural texture creation. The term “white” is used in analogy with white light, which contains all visible wavelengths of light at equal intensity.

[0084] As used herein, “frequency” 108 refers to a characteristic of a signal or pattern that defines its density or rate of repetition over a certain unit area or period. It typically represents the number of plus / minus noise features per unit area, thereby defining the density of the noise field pattern. Frequency refers to the density of a texture or noise pattern, influencing the level of detail in the resulting image or model. The specific value of the frequency can be adjusted to control the properties of the signal or pattern.

[0085] As used herein, “random seed” 109 or “seed” refers to a number or vector used to initialize a pseudorandom number generator. This initialization allows noise algorithms to generate a unique pattern for every scalar input seed. Despite the randomness of the output, using a specific seed ensures the reproducibility of the results, as the same seed will always generate the same sequence of pseudorandom numbers in a given algorithm.

[0086] As used herein, “jitter” 110 refers to a signal’s timing variation from its nominal value, affecting how regular the noise cells are. In the context of noise generation, jitter introduces irregularity into the pattern of noise cells, enhancing the natural appearance of the resulting texture or pattern.

[0087] As used herein, “noise cell” refers to a component of a larger noise field containing a specific value or set of values contributing to the overall pattern or texture. Each noise cell contributes to the visual detail of the texture, with variations in the values of the noise cells creating the perceived randomness or organic quality of the texture.

[0088] As used herein, “distance” 111 refers to the algorithm type used to evaluate the noise borders from each center “seed,” either Euclidian, Manhattan, or Natural. The type of distance can affect the appearance of the resulting noise pattern. “Euclidean distance” measures thestraight-line distance between two points, “Manhattan distance” measures the sum of the absolute differences of their coordinates, and “Natural distance” uses a combination of both.

[0089] As used herein, “return type” 112 tells the algorithm how to return the noise field distance to n points. In certain embodiments, the return type specifies whether the algorithm should return the minimum, maximum, or average distance to a set of points in a noise field.

[0090] In certain embodiments, the method comprises tuning 132 the upper and lower bounds of the field values to user input. The type inputs 140 are chosen from coarse resolution 113, fine resolution 114, min tune 115, and max tune 116.

[0091] As used herein, “coarse resolution” 113 describes the initial sampling of the tuning function. In certain embodiments, when a texture or model is initially created at a coarse resolution to quickly establish its overall shape or pattern, subsequent refinements add finer details to this initial representation.

[0092] As used herein, “fine resolution” 114 refers to the heightened precision and granularity in generating or manipulating noise patterns. Fine resolution describes the refined sampling of the tuning function.

[0093] As used herein, “min tune” 115 refers to the lowest permissible limit, or the “infimum,” of a tuned field, thereby defining the lower boundary for the range of possible values that a particular parameter or set of parameters can assume. In certain embodiments, min tune dictates the minimum level of detail or resolution that can be applied to a rendered object.

[0094] As used herein, “max tune” 116 refers to the highest permissible limit, or the “supremum.” of a tuned field, thereby defining the upper boundary for the range of possible values that a particular parameter or set of parameters can assume. In certain embodiments, max tune dictates the maximum level of detail or resolution that can be applied to a rendered object.

[0095] In certain embodiments, the method comprises adding 133 biases 117 to the field values to offset geometry.

[0096] As used herein, “bias” or “additional bias” 117 refers to an adjustable parameter or factor for offsetting the isosurface of the noise field to a user-specified value in a given system or method. Additional bias may shift, adjust, or otherwise modify the baseline or reference point of a particular parameter or set of parameters. In certain embodiments, additional bias adjusts the perceived depth or intensity of a texture or pattern generated through noise fields. Therefore,additional bias is a means for fine-tuning system outputs or behaviors according to a user-defined value.

[0097] As used herein, “isosurface” refers to a three-dimensional surface representing points of a constant value, or “isovalue,” within a volume of space in a given system or method. An isosurface represents areas of a texture or pattern where a particular attribute — such as color intensity or noise value — remains constant.

[0098] In certain embodiments, the method comprises converting 134 negative field values into positive field values.

[0099] In certain embodiments, the method comprises subtracting 135 to create thin wall geometry.

[0100] As used herein, “thicken” or “thickening” 118 refers to augmenting an isosurface of a noise field to a user-specified value, thereby enhancing its perceptual weight or prominence. In certain embodiments, thickening 118 increases the visual density or complexity of a texture or pattern generated through noise fields. In a three-dimensional modeling system, thickening 118 increases the thickness or depth of a modeled object or shape.

[0101] In certain embodiments, the method comprises multiplying 136 to add units to the field.

[0102] As used herein, “unit” 119 refers to a value or measure added to the field via multiplication to adjust its properties or characteristics, such as its scale, density, or distribution.

[0103] In certain embodiments, the method comprises voxelizing 137 the field to form sized voxels defining a voxel grid in the field’s real space.

[0104] As used herein, “voxel” refers to a unit of graphic information that defines a point in three-dimensional (3D) space. Similar to a pixel representing 2D image data, a voxel represents volume in 3D space. In certain embodiments, a voxel is characterized by its position and other attributes, such as color and density. Each voxel may carry information about lighting, color, and material properties.

[0105] In certain embodiments, the resolution of a voxel-based representation depends on the size of the voxel. As used herein, “voxel size” 120 refers to the spatial dimensions of a voxel, such as the measure of the length, width, and depth of a voxel, and can be used to determine the resolution and detail of a 3D model or structure. For instance, a smaller voxel size would typically correspond to a higher level of detail and resolution. A larger voxel size would typicallycorrespond to a lower level of detail and resolution. Accordingly, in certain embodiments, the desired voxel size for a final smoothening algorithm is selected.

[0106] As used herein, “voxelize,” “voxelizing,” and “voxelization” refer to converting a continuous geometric shape or object into a discrete set of voxels. In certain embodiments, voxelization represents a 3D object as an assembly of cubic or rectangular parallelepiped elements in a 3D grid space. In certain embodiments, voxelization transforms a polygonal 3D model into a voxel dataset. In certain embodiments, the granularity of the voxel representation varies, allowing for different levels of detail in a voxelized object. In the context of designing a folded sheet scaffold for use in medical devices, the folded sheet algorithm creates an initial canvas that, when subjected to a voxel grid and subsequent smoothening, refines the scaffold to more closely approximate the topology of bone. This refined scaffold is then functionally tunable, providing a more accurate and adaptable representation of the bone structure.

[0107] As used herein, “voxel grid” refers to a spatial partitioning data structure used in three- dimensional (3D) space, where the 3D space is divided into discrete blocks, each represented by a voxel. In certain embodiments, a voxel grid is a 3D array of voxels, where each voxel corresponds to a specific location in the 3D space and contains information pertinent to that location.

[0108] In certain embodiments, the method comprises smoothening 138 the voxel grid. The variable input 150 is chosen from a dilate operation 121, Gaussian filter 122, eikonal equation 123, discrete Laplace operator 124, mean filter 125, mean curvature filter 126, and median filter 127. The type input is chosen from width 128 and iterations 129.

[0109] As used herein, “dilate” or “dilating” or “dilation” 121 refers to a fundamental operation in mathematical morphology that expands or enlarges the shapes present in an input image using a structuring element. In certain embodiments, dilation 121 can be applied to binary images, grayscale images, and complete lattices. For binary morphology, the dilation 121 of a binary image A by a structuring element B is defined as the union of the translation of A by each element in B, resulting in an expanded or enlarged version of A. In grayscale morphology, dilation 121 involves mapping images into a set that includes real numbers and infinite elements, with the grayscale dilation 121 of an image f by a structuring function b given by the supremum of the sum of f(y) and b(x-y) for all y in E. Dilation 121 can also operate on complete lattices, partially ordered sets where every subset has an infimum and a supremum.

[0110] As used herein, “Gaussian filter” 122 refers to a filter characterized by an impulse response that is a Gaussian function or an approximation. A Gaussian filter 122 suppresses high frequencies while minimizing spatial spread. The filter 122 operates by modifying the input signal through convolution with a Gaussian function, a transformation also known as the Weierstrass transform. The digital implementation of a Gaussian filter 122 involves convolution, with the filter function serving as the kernel of an integral transform. The two-dimensional application of this filter produces a Gaussian surface with concentric circular contours. While the Gaussian filter 122 is non-causal, meaning the filter window is symmetric about the origin in the time domain, a causal approximation can achieve any tolerance with a modest delay.

[0111] As used herein, “eikonal function” 123 refers to the solution to the eikonal equation, which calculates the minimal time required to travel from a point x to 5 , where the speed of travel is defined by a function f and an exit-time penalty is defined by a function q. In certain embodiments, the eikonal function 123 solves the shortest path problems on graphs with nonnegative edge lengths. It is also connected with the time-optimal control problem via Bellman’s optimality principle and a Taylor expansion. Different algorithms, such as Sethian’s fast marching method (FMM), label-correcting methods like the Bellman-Ford algorithm, sweeping algorithms, and hybrid methods, have been developed to solve the eikonal equation efficiently. The numerical approximation of the eikonal equation involves discretization into a uniform grid with spacings in the x and y directions, and the approximation can be solved as a quadratic under certain conditions.

[0112] As used herein, “discrete Laplace operator” 124 refers to a mathematical tool analogous to the continuous Laplace operator, specifically designed for application on discrete structures such as three-dimensional graphs or grids. In certain embodiments, this operator is employed in the design and analysis of 3D objects, where it considers the connectivity of nodes and edges in a graph and the geometry of a surface, such as the angles at the nodes. For instance, in a two- dimensional manifold triangle mesh, an integral component of 3D object design, the Laplace- Beltrami operator of a scalar function at a vertex can be approximated. If the grid size is 1, the result is the negative discrete Laplacian on the graph, corresponding to the square lattice grid. Moreover, in certain embodiments, multidimensional discrete Laplacians on rectangular cuboid regular grids, a common structure in 3D object design, possess unique properties, such as Kronecker sums of one-dimensional discrete Laplacians. This operator is also frequently used inimage processing applications related to 3D object design, such as edge detection and motion estimation.

[0113] As used herein, “mean filtering” 125 refers to a method of image smoothing that reduces the intensity variation between adjacent pixels, often employed to decrease image noise. In certain embodiments, mean filtering 125 replaces each pixel value in an image with the mean value of its neighbors, including the pixel itself, thereby eliminating pixel values uncharacteristic of their surroundings. This process is typically implemented as a convolution filter centered around a kernel that defines the shape and size of the neighborhood to be sampled when calculating the mean. In certain embodiments, mean filtering 125 functions as a lowpass frequency filter, reducing the spatial intensity derivatives present in the image. Variations on the mean smoothing filter, such as Threshold Averaging, apply smoothing only if the difference between the original pixel value and the average value exceeds a preset threshold, thus smoothing noise with less dramatic loss in image detail.

[0114] As used herein, “mean curvature” 136 refers to an extrinsic measure of curvature, denoted as H, that characterizes the curvature of a surface, S, embedded in an ambient space, such as a Euclidean space. In certain embodiments, the mean curvature is calculated as the average of the signed curvature over all angles, typically derived using Euler’s theorem as the average of the principal curvatures (K1 and K2). It can also be defined as the trace of the second fundamental form divided by n, equivalent to the shape operator, or expressed in terms of the covariant derivative as Hn = gijViVjX, where X(x) is a smoothly embedded hypersurface, n is a unit normal vector, and gij is the metric tensor. Surfaces with a mean curvature of zero are classified as minimal surfaces and are often utilized in 3D object design due to their unique properties. The mean curvature is also related to a unit normal of the surface. It can be expressed using the first and second fundamental forms for a surface parametrization S(x,y) and two linearly independent vectors (u,v) in parameter space. For an axisymmetric 3D object defined as z = S(r), the mean curvature can be calculated using the derivative of S(r) = S(sqrt(xA2 + yA2)).

[0115] As used herein, “median filter” 137 refers to a non-linear digital filtering technique for removing noise from an image or signal. In certain embodiments, this noise reduction acts as an initial pre-processing step to enhance the results of later processing, such as edge detection on an image. The technique is characterized by its edge preservation capabilities during noise removal, making it widely used in digital image processing and signal processing. The process involvestraversing the signal entry by entry, replacing each entry with the median of neighboring entries within a “window” that slides over the entire signal. In implementing a median filter 137, signal boundaries are handled carefully due to the potential insufficiency of entries to fill an entire window, with various schemes employed depending on specific circumstances. Most computational effort in implementing the median filter is spent on calculating the median of each window. For small to moderate levels of Gaussian noise, the median filter 137 is demonstrably superior to Gaussian blur at removing noise while preserving edges for a given, fixed window size. It is particularly effective for speckle noise and salt-and-pepper noise.

[0116] As used herein, “width” or “width value” 128 refers to a scalar value that, in certain embodiments, is a multiple of the voxel size. This scalar value is associated with the filter used for smoothening processes. The width value 128 may range from a single voxel size to multiple n voxel sizes, where ‘n’ is an integer. For example, if the voxel size is 1 unit, the width 128 of the filter could be anywhere from 1 unit (i.e., the same size as the voxel) to n units, depending on the level of smoothening required. In certain embodiments, a larger width value 128 corresponds to a higher degree of smoothening, while a smaller width value 128 corresponds to a lower degree of smoothening.

[0117] As used herein, “iteration” 129 refers to the discrete number of times the filter for smoothening is passed over the data. In certain embodiments, the iteration 129 is represented by a discrete integer value, ranging from 1 to n, where ‘n’ is an integer. For instance, an iteration value of 1 signifies a single pass of the filter over the data. In contrast, an iteration value of 5 indicates that the filter is passed over the data five times. The degree of smoothening generally increases with the number of iterations 129, with a higher iteration value resulting in more smoothening and a lower iteration value resulting in less smoothening.

[0118] In certain embodiments, the method comprises intersecting 139 the smoothened voxel grid with a desired design space.

[0119] FIG. 2 shows a cross-section of a folded sheet scaffold 600 produced from workflow 100 of FIG. 1. FIG. 3 shows a plan view of a side of the folded sheet scaffold 600 of FIG. 2. FIG. 4 shows a perspective orthogonal view of the folded sheet scaffold 600 of FIG. 2. The folded sheet scaffold 600 presents vugs 610, pockets 630, and surface topography 650. These features 610,630,650 are also seen in cross-sections 620 of the scaffold 600.

[0120] 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.

[0121] 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 cues signal protein absorption, cell adhesion, cell proliferation, and cell adhesion. Surface topography cues signalspecific 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.

[0122] 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 ( ) describes the local deviation of the surface from a planar region.

[0123] 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.

[0124] 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 from 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.

[0125] 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.

[0126] 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.Bone

[0127] 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.

[0128] 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 and is 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.

[0129] 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 becomea 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.

[0130] 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.

[0131] 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.

[0132] ‘ ‘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.

[0133] “Wolffs 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.Computerized method, system, and media

[0134] The disclosure provides a computer-implemented method for designing a folded sheet scaffold for use in medical devices. The method comprises implementing a processor to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, using the processor to tune the upperand lower bounds of the field values based on user input, and implementing the processor to subtract and create thin wall geometry.

[0135] In certain embodiments, the processor-driven noise comprises a variable input. These inputs may be chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise. In certain embodiments, the processor-driven noise further comprises type inputs. These inputs may be chosen from frequency, random seed, jitter, distance, and return type. In certain embodiments, the variable input is cellular noise. This cellular noise may have a frequency of 2000 peaks / mm2, a random seed of 1, a jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply],

[0136] In certain embodiments, the subtraction is non-dimensional. In certain embodiments, the subtraction is set at 0.1.

[0137] In certain embodiments, the computer-implemented method further comprises the processor adding biases to the field values to offset geometry after the tuning step.

[0138] In certain embodiments, the computer-implemented method further comprises the processor converting negative field values into positive field values after the tuning step. In certain embodiments, the tuning comprises type inputs. These inputs may be chosen from coarse resolution, fine resolution, min tune, and max tune. In certain embodiments, the tuning comprises a min tune of -0.3 and a max tune of 2.0.

[0139] In certain embodiments, the computer-implemented method further comprises the processor multiplying and adding units to the field after the driving noise step and before the converting step, when present. In certain embodiments, a multiply units parameter is set at 1 mm.

[0140] In certain embodiments, the computer-implemented method further comprises the processor voxelizing the field to form sized voxels, defining a voxel grid in the field’s real space after the subtracting step. In certain embodiments, the voxel size is set at 0.075 mm.

[0141] In certain embodiments, the computer- implemented method further comprises the processor smoothening the voxel grid after the voxelizing step. In certain embodiments, the smoothening comprises a variable input. These inputs may be chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean filter, mean curvature filter, and median filter. In certain embodiments, the smoothening further comprises type input. This input may be chosen from width and iterations. In certain embodiments, the smoothening comprises a mean curvature with 1 iteration and a width of 1.

[0142] In certain embodiments, the computer-implemented method further comprises the processor intersecting the smoothened voxel grid with a desired design space after the smoothening step.

[0143] In certain embodiments, the computer-implemented method comprises, in order, implementing a processor to drive noise from an infinite 3D noise field to define a field with real space, using the processor to tune the upper and lower bounds of the field values based on user input, adding biases to the field values to offset geometry, converting negative field values into positive field values, subtracting to create thin wall geometry, multiplying to add units to the field, voxelizing the field to form sized voxels defining a voxel grid in the field’s real space, smoothening the voxel grid, and intersecting the smoothened voxel grid with a desired design space.

[0144] The disclosure also provides a computer system for designing a folded sheet scaffold for use in medical devices. The system comprises a noise-driving module configured to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, a tuning module configured to tune the upper and lower bounds of the field values based on user input, and a subtracting module configured to subtract and create thin wall geometry.

[0145] In certain embodiments, the noise-driving module comprises a variable input. These inputs may be chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise. In certain embodiments, the noise-driving module further comprises type inputs. These inputs may be chosen from frequency, random seed, jitter, distance, and return type. In certain embodiments, the variable input is cellular noise. This cellular noise may have a frequency of 2000 peaks / mm2, a random seed of 1, a jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply].

[0146] In certain embodiments, the subtracting module is configured to perform non- dimensional subtraction. In certain embodiments, the subtracting module is configured to subtract set at 0.1.

[0147] In certain embodiments, the computer system further comprises a bias-adding module. This module is configured to add biases to the field values to offset geometry after the tuning step.

[0148] Tn certain embodiments, the computer system further comprises a converting module. This module is configured to convert negative field values into positive field values after the tuning step. In certain embodiments, the tuning module comprises type inputs. These inputs may be chosen from coarse resolution, fine resolution, min tune, and max tune. In certain embodiments, the tuning module comprises a min tune of -0.3 and a max tune of 2.0.

[0149] In certain embodiments, the computer system further comprises a multiplying module. This module is configured to multiply and add units to the field after the driving noise step and before the converting step, when present. In certain embodiments, a multiply units parameter is set at 1 mm.

[0150] In certain embodiments, the computer system further comprises a voxelizing module. This module is configured to voxelize the field to form sized voxels, defining a voxel grid in the field’s real space after the subtracting step. In certain embodiments, the voxel size is set at 0.075 mm.

[0151] In certain embodiments, the computer system further comprises a smoothening module. This module is configured to smoothen the voxel grid after the voxelizing step. In certain embodiments, the smoothening module comprises a variable input. These inputs may be chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean filter, mean curvature filter, and median filter. In certain embodiments, the smoothening module further comprises type input. This input may be chosen from width and iterations. In certain embodiments, the smoothening module comprises a mean curvature with 1 iteration and a width of 1.

[0152] In certain embodiments, the computer system further comprises an intersecting module. This module is configured to intersect the smoothened voxel grid with a desired design space after the smoothening step.

[0153] In certain embodiments, the computer system comprises a noise-driving module configured to drive noise from an infinite 3D noise field to define a field with real space, a tuning module configured to tune the upper and lower bounds of the field values based on user input, a bias-adding module configured to add biases to the field values to offset geometry, a converting module configured to convert negative field values into positive field values, a subtracting module configured to subtract and create thin wall geometry, a multiplying module configured to multiply and add units to the field, a voxelizing module configured to voxelize thefield to form sized voxels defining a voxel grid in the field’s real space, a smoothening module configured to smoothen the voxel grid, and an intersecting module configured to intersect the smoothened voxel grid with a desired design space.

[0154] Additionally, the disclosure provides a non- transitory computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform a method for designing a folded sheet scaffold for use in medical devices. The method comprises driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound, tuning the upper and lower bounds of the field values based on user input, and subtracting to create thin wall geometry.

[0155] The disclosed computer system is configured to design a folded sheet scaffold for use in medical devices per one or more embodiments. In some cases, the system may include one or more computing platforms. The computing platforms may be communicab ly coupled with one or more remote platforms. Users may access the system via these remote platforms.

[0156] The computing platforms may be configured by machine-readable instructions. These instructions may include modules implemented as functional logic, hardware logic, electronic circuitry, software modules, etc. The modules may include a noise-driving module, a tuning module, a subtracting module, and / or other modules.

[0157] The noise-driving module may be configured to drive noise from an infinite 3D noise field to define a field with real space. The tuning module may be configured to tune the upper and lower bounds of the field values based on user input. The subtracting module may be configured to subtract and create thin wall geometry.

[0158] The computing platforms may be communicatively coupled to the remote platforms. This communicative coupling may include coupling through a networked environment. The networked environment may be a radio access network, a local area network, a wide area network such as the Internet, or wireless LAN, for example.

[0159] The computing platforms may include one or more processors for processing information and executing instructions or operations. The processors may perform functions associated with the operation of the system, which may include, for example, driving noise, tuning field values, subtracting to create thin wall geometry, and overall control of the computing platforms, including processes related to the management of design resources.

[0160] The computing platforms may further include or be coupled to a memory (internal or external), which may be coupled to the processors for storing information and instructions that the processors may execute. The memory may be any type suitable to the local application environment and may be implemented using any suitable volatile or nonvolatile data storage technology. The instructions stored in memory may include program instructions or computer program code that, when executed by the processors, enable the computing platforms to perform tasks as described herein.

[0161] In some embodiments, the computing platforms may also include or be coupled to one or more interfaces for transmitting and receiving signals and / or data to and from the computing platforms. The interfaces may be configured to communicate via a plurality of interfaces that may be coupled to the interfaces.

[0162] According to one embodiment, an example flow diagram of a method may include driving noise from an infinite 3D noise field to define a field with real space, tuning the upper and lower bounds of the field values based on user input, and subtracting to create thin wall geometry. One or more hardware processors may perform the method, configured by machine- readable instructions.

[0163] The exemplary system for implementing the disclosure includes a general-purpose computing device in the form of a conventional computer, including a processing unit, a system memory, and a system bus that couples various system components, including the system memory to the processing unit. The system memory includes read-only memory (ROM) and random-access memory (RAM). A basic input / output system (BIOS) containing the basic routines that help transfer information between elements within the computer, such as during startup, may be stored in ROM.

[0164] The computer may also include various drives for reading from and writing to different types of media, providing nonvolatile storage of computer-executable instructions, data structures, program modules, and other data for the computer

[0165] Program code comprising one or more program modules may be stored in the memory, including an operating system, one or more application programs, other program modules, and program data. A user may enter commands and information into the computer through various input devices. These input devices are often connected to the processing unit through an interfacecoupled to the system bus. Alternatively, the input devices may be connected by other interfaces. A display device is also connected to a system bus via an interface.

[0166] The computer may operate in a networked environment using logical connections to one or more remote computers. These remote computers may each be another personal computer, a server, a router, a network PC, a peer device, or another common network node. These typically include many or all the elements described above relative to the computer. However, only memory storage devices and their associated application programs have been illustrated in the context of this system. The logical connections include a local area network (LAN) and a wide area network (WAN).

[0167] When used in a LAN networking environment, the computer is connected to the local network through a network interface or adapter. When used in a WAN networking environment, the computer may include a modem, a wireless link, or other means for establishing communications over the wide area network, such as the Internet. The modem, internal or external, is connected to the system bus via the interface. In a networked environment, program modules depicted relative to the computer or portions thereof may be stored in the remote memory storage device.

[0168] One or more aspects of the disclosure may be embodied in computer-executable instructions (i.e., software), such as a software object, routine, or function stored in system memory or nonvolatile memory as application programs, program modules, and / or program data. The software may alternatively be stored remotely. Generally, program modules include routines, programs, objects, components, data structures, etc., that perform particular tasks or implement particular abstract data types when executed by a processor in a computer or other device. The computer-executable instructions may be stored on a computer-readable medium. As will be appreciated by one of skill in the art, the functionality of the program modules may be combined or distributed as desired in various embodiments. In addition, the functionality may be embodied in whole or in part in firmware or hardware equivalents such as integrated circuits, field programmable gate arrays (FPGA), and the like.

[0169] A programming interface (or, more simply, interface) may be viewed as any mechanism, process, or protocol for enabling one or more segment(s) of code to communicate with or access the functionality provided by one or more other segment(s) of code. Alternatively, a programming interface may be viewed as one or more mechanism(s), method(s), function call(s),module(s), object(s), etc., of a component of a system capable of communicative coupling to one or more mechanism(s), method(s), function call(s), module(s), etc. of another component (s). The term “segment of code” in the preceding sentence is intended to include one or more instructions or lines of code. It includes, e.g., code modules, objects, subroutines, functions, and so on, regardless of the terminology applied, whether the code segments are separately compiled, or whether the code segments are provided as a source, intermediate or object code, whether the code segments are used in a run-time system or process, or whether they are located on the same or different machines or distributed across multiple machines, or whether the functionality represented by the segments of code are implemented wholly in software, wholly in hardware, or a combination of hardware and software. By way of example, and not limitation, terms such as application programming interface (API), entry point, method, function, subroutine, remote procedure call, and component object model (COM) interface are encompassed within the definition programming interface.

[0170] Aspects of such a programming interface may include the method whereby the first code segment transmits information (where “information” is used in its broadest sense and includes data, commands, requests, etc.) to the second code segment; the method whereby the second code segment receives the information; and the structure, sequence, syntax, organization, schema, timing, and content of the information. In this regard, the underlying transport medium itself may be unimportant to the operation of the interface, whether the medium is wired or wireless, or a combination of both, as long as the information is transported in the manner defined by the interface. In certain situations, information may not be passed in one or both directions in the conventional sense, as the information transfer may be either via another mechanism (e.g., information placed in a buffer, file, etc., separate from information flow between the code segments) or non-existent, as when one code segment accesses functionality performed by a second code segment. An aspect applies based on the situation, such as whether the code segments are part of a system in a loosely coupled or tightly coupled configuration. So, this list should be considered illustrative and non-limiting.

[0171] This notion of a programming interface is known to those skilled in the art and is clear from the provided detailed description. Some illustrative implementations of a programming interface may also include factoring, redefinition, inline coding, divorce, and rewriting, to name a few. There are, however, other ways to implement a programming interface. Unless expresslyexcluded, these, too, are intended to be encompassed by the claims set forth at the end of this specification.

[0172] “Computing device” refers to any mobile device, such as a smartphone, a cell phone, a pager, a personal digital assistant (PDA, e.g., with GPRS NIC), a mobile computer with a cellular radio, or the like. A typical mobile device is a wireless data access-enabled device (e.g., an iPhone® smartphone, a Blackberry® smartphone, a Nexus One™ smartphone, an iPad™ device, or the like) capable of sending and wirelessly receiving data using protocols like the Internet Protocol (IP) and the wireless application protocol (WAP). This allows users to access information via wireless devices, such as smartphones, mobile phones, pagers, two-way radios, communicators, etc. Many wireless networks support wireless data access, including, but not limited to, CDPD, CDMA, GSM, PDC, PHS, TDMA, FLEX, ReFLEX, iDEN, TETRA, DECT, DataTAC, Mobitex, EDGE, and other 2G, 3G, 4G, and LTE technologies. It operates with many handheld device operating systems, such as PalmOS, EPOC, Windows CE, FLEXOS, OS / 9, JavaOS, iOS, and Android.

[0173] Typically, these devices use graphical displays and can access the Internet (or other communications network) on so-called mini- or micro-browsers, web browsers with small file sizes that can accommodate the reduced memory constraints of wireless networks. In a representative embodiment, the mobile device is a cellular telephone or smartphone that operates over General Packet Radio Services (GPRS), a data technology for GSM networks. In addition to conventional voice communication, a given mobile device can communicate with another such device via many different types of message transfer techniques, including short message service (SMS), enhanced SMS (EMS), multimedia message (MMS), email WAP, paging, or other known or later-developed wireless data formats. Although many of the examples provided herein are implemented on a mobile device, the examples may similarly be implemented on any suitable “computing device.”

[0174] Embodiments within the scope of the present disclosure also include computer-readable media and computer-readable storage media for carrying or storing computer-executable instructions or data structures. Such computer-readable media can be any available media accessed by a general-purpose or special-purpose computer. By way of example, and not limitation, such computer-readable media can comprise RAM, ROM, EEPROM, CD-ROM or other optical disk storage, magnetic disk storage, or other magnetic storage devices, or any othermedium that can be used to carry or store desired program code means in the form of computerexecutable instructions or data structures, and a general-purpose or special-purpose computer can access that, when information is transferred or provided over a network or another communications connection (either hardwired, wireless, or a combination of hardwired or wireless) to a computer, the computer properly views the connection as a computer-readable medium. Thus, any such connection is properly termed a computer-readable medium. Combinations of the above should also be included within the scope of computer-readable media. Computer-executable instructions comprise, for example, instructions and data that cause a general-purpose computer, particular-purpose computer, or special-purpose processing device to perform a certain function or group of functions.

[0175] ‘ ‘Communication media” typically embodies computer-readable instructions, data structures, program modules, or other data in a modulated data signal such as a carrier wave or other transport mechanism and includes any information delivery media.

[0176] “Modulated data signal” refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in the signal. By way of example, and not limitation, communication media includes wired media such as a wired network or direct- wired connection, and wireless media such as acoustic, radio frequency (RF), infrared, and other wireless medium. In addition, combinations of those mentioned above are included within the scope of computer-readable media.

[0177] When the subject matter is embodied in the general context of computer-executable instructions, the embodiment may comprise program modules executed by one or more systems, computers, or other devices. Generally, program modules include routines, programs, objects, components, data structures, and the like, which perform particular tasks or implement abstract data types. Typically, the functionality of the program modules may be combined or distributed as desired in various embodiments.

[0178] Operating environments in which embodiments of the present disclosure may be implemented are well-known. In a representative embodiment, a computing device, such as a mobile device, is connectable to a transmission functionality that varies depending on implementation. Thus, for example, where the operating environment is a wide-area wireless network (e.g., a 2.5G network, a 3G network, or a 4G network), the transmission functionality comprises one or more components such as a mobile switching center (MSC) (an enhancedISDN switch that is responsible for call handling of mobile subscribers), a visitor location register (VLR) (an intelligent database that stores temporarily data required to handle calls set up or received by mobile devices registered with the VLR), a home location register (HLR) (an intelligent database responsible for the management of each subscriber's records), one or more base stations (which provide radio coverage with a cell), a base station controller (BSC) (a switch that acts as a local concentrator of traffic and provides local switching to effect handover between base stations), and a packet control unit (PCU) (a device that separates data traffic coming from a mobile device). The HLR also controls certain services for incoming calls. Of course, the present disclosure may be implemented in other and next-generation mobile networks and devices.

[0179] The “mobile device” is the physical equipment the end-user uses, typically a subscriber to the wireless network. Typically, a mobile device is a 2.5G-compliant device, 3G-compliant device, or a 4G-compliant device that includes a subscriber identity module (SIM), which is a smart card that carries subscriber-specific information, mobile equipment (e.g., radio and associated signal processing devices), a user interface or a man-machine interface (MMI), and one or more interfaces to external devices (e.g., computers, PDAs, and the like). The mobile device may also include a memory or data store. The presently disclosed subject matter is now described in more detail.

[0180] When elements are referred to as being “connected” or “coupled,” the elements can be directly connected or coupled, or one or more intervening elements may also be present. In contrast, when elements are referred to as being “directly connected” or “directly coupled,” no intervening elements are present.Devices

[0181] 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.

[0182] 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 headfracture device, high tibial osteotomy, deformity correction, corpectomy cage, oncological correction, anchor, dental implant, maxillofacial implant, and sports medicine anchor.

[0183] 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.

[0184] In certain embodiments, the surface of the thread is rough, having a surface topography mimicking the topography of a scaffold disclosed herein. In certain embodiments, the leading edge of the thread is rough. In certain embodiments, a proximal portion of the thread is rough, wherein the shaft is solid and, for a few seconds, turns over the portion of the shaft comprising the scaffold.

[0185] 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 the 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.

[0186] 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 screwstructures. 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.

[0187] In some embodiments, the bone screw includes features or structures that may be disposed of 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.

[0188] 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, grown or otherwise printed.

[0189] In certain embodiments, the devices comprise one or more chosen from a demineralized bone matrix (DBM), pre-packed DBM, pre-packed synthetic DBM, unpacked DBM, and magnesium-infused titanium.

[0190] 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 applyingadditive 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.

[0191] In some embodiments, the device treats a spinal disorder chosen from degenerative disc disease, disc herniation, osteoporosis, spondylolisthesis, stenosis, scoliosis, other curvature abnormalities, kyphosis, tumors, and fractures.

[0192] “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 it, e.g., causing regression.

[0193] “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.

[0194] “Tissue” includes soft tissue, ligaments, tendons, cartilage, and / or bone. In certain embodiments, the tissue is cancellous bone, cortical bone, or corticocancellous bone.

[0195] 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.

[0196] In certain embodiments, the device is a custom medical device. In certain embodiments, the device is adapted for sports medicine.

[0197] Tn certain embodiments, the device is temperature-sensing. In certain embodiments, the device is pH-balancing.

[0198] 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.

[0199] 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.

[0200] 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), poly etherketoneketone (PEKK), po lye therke tone (PEK), carbon- PEEK composites, PEEK-BaSCU 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.

[0201] Tn certain embodiments, the device comprises a rubber chosen from polyaryletherketone (PAEK), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), polyetherketone (PEK), carbon-PEEK composites, PEEK-BaSC 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 a collagen matrix.

[0202] 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 to properly function its metabolism. Some sources list fourteen vitamins, by including choline, but major health organizations typically list thirteen: vitamin A (as all-trans-retinol, all-zra / z.s'-rctinyl-cstcrs, as well as aW-trans -beta-carotene and other provitamin A carotenoids), vitamin Bi (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), vitamin Bs (pantothenic acid), vitamin Be (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.

[0203] 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.

[0204] 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.

[0205] 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.

[0206] 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 treat a disease or disorder.Screw

[0207] 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.

[0208] In certain embodiments, the device is a bone screw. In certain embodiments, the device is a pedicle screw.

[0209] FIG. 5 shows the top view of a pedicle screw 200 presenting a folded sheet scaffold 600 disclosed herein. Drive 215 and cannula 260 can be seen from this view. FIG. 6 shows the bottom view of the pedicle screw 200 of FIG. 5, including a cutting member 270. FIG. 7 shows a perspective view, FIG. 8 shows the back view, and FIG. 9 shows the front view of the pedicle screw 200 of FIG. 5. FIG. 10 shows a magnified inset of the front view of the pedicle screw 200 of FIG. 5, highlighting the scaffold 600.

[0210] In these embodiments, the pedicle screw 200 comprises a thread 230 disposed around a shaft 240 that extends between the proximal end 210 and distal tip 220. The thread 230 comprises an external thread form with 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. The first and second openings 251,252 are axially aligned. The pedicle screw 200 has a core 240 extending through the center of the pedicle screw 200 from the proximal end 210 to the distal tip 220. The distal tip 220 comprises at least one cutting member 270, each having a cutting edge 271.

[0211] FIG. 11 shows the top view of another embodiment of a pedicle screw 200 presenting a folded sheet scaffold 600 disclosed herein and textured threads 237 having substantially the same topography as the folded sheet scaffold 600. Drive 215 and cannula 260 can be seen from this view. FIG. 12 shows the bottom view of the pedicle screw 200 of FIG. 11, including a cutting member 270. FIG. 13 shows a perspective view, FIG. 14 shows the back view, and FIG. 15 shows the front view of the pedicle screw 200 of FIG. 11. FIG. 16 shows a magnified inset of the front view of the pedicle screw 200 of FIG. 11, highlighting the scaffold 600.

[0212] In these embodiments, the pedicle screw 200 comprises a thread 230 disposed around a shaft 240 that extends between the proximal end 210 and distal tip 220. The thread 230 comprises an external thread form with 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. The first and second openings 251,252 are axially aligned. The threads 230 near the proximal end 210 are textured 237 to have a surface topography substantially the same as the surface topography of scaffold 600. The pedicle screw 200 has a core 240 extending through the center of the pedicle screw 200 from the proximal end 210 to the distal tip 220. The distal tip 220 comprises at least one cutting member 270, each having a cutting edge 271.

[0213] In certain embodiments, the device is a headless screw. FIG. 17 shows a top plan view of the headless screw 300 presenting a folded sheet scaffold 600. Drive 215 and cannula 260 can be seen from this view. FIG. 18 shows a bottom plan view of the headless screw 300 of FIG. 17, including two cutting members 270. FIG. 19 shows a perspective view, FIG. 20 shows a back plan view, and FIG. 21 shows a front plan view of the headless screw 300 of FIG. 17. FIG. 22 shows a magnified inset of the front view of the headless screw 300 of FIG. 18, highlighting the folded sheet scaffold 600, as described herein.

[0214] In this embodiment, the headless screw 300 comprises a thread 230 disposed around a core 240 that extends between the proximal end 210 and distal tip 220, and narrow threads 290 disposed on the shaft 295 adapted for receiving a reduction cap 500 at the proximal end 210. The core 240 comprises a scaffold 600 exposed to the outer surface of the headless screw 300. The thread 230 comprises an external thread form with 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 firstopening 251. The trailing surface 236 defines a second opening 252. The first and second openings 251,252 are axially aligned.

[0215] The headless screw 300 has a core 240 filled with scaffold 600 extending through the center of the headless screw 300 from the proximal end 210 to the distal tip 220. The core 240 is the stem of screw 200 from which the threads 230 protrude. The distal tip 220 comprises two cutting members 270 disposed on opposite sides of the distal tip 220, each cutting member 270 having a cutting edge 271.

[0216] FIG. 23 shows a top plan view of the headless screw 300 presenting a folded sheet scaffold 600. Drive 215 and cannula 260 can be seen from this view. FIG. 24 shows a bottom plan view of the headless screw 300 of FIG. 23, including two cutting members 270. FIG. 25 shows a perspective view, FIG. 26 shows a back plan view, and FIG. 27 shows a front plan view of the headless screw 300 of FIG. 23. FIG. 28 shows a magnified inset of the front view of the headless screw 300 of FIG. 23, highlighting the folded sheet scaffold 600, as described herein.

[0217] In this embodiment, the headless screw 300 comprises a thread 230 disposed around a core 240 that extends between the proximal end 210 and distal tip 220, and narrow threads 290 disposed on the shaft 295 adapted for receiving a reduction cap 500 at the proximal end 210. The core 240 comprises a scaffold 600 exposed to the outer surface of the headless screw 300. The thread 230 comprises an external thread form with 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. The first and second openings 251,252 are axially aligned. The threads 230 near the proximal end 210 are textured 237 to have a surface topography substantially the same as the surface topography of scaffold 600.

[0218] The headless screw 300 has a core 240 filled with scaffold 600 extending through the center of the headless screw 300 from the proximal end 210 to the distal tip 220. The core 240 is the stem of headless screw 300 from which the threads 230 protrude. The distal tip 220 comprises two cutting members 270 disposed on opposite sides of the distal tip 220, each cutting member 270 having a cutting edge 271.

[0219] In some embodiments, the distal tip 220 of the screw 200,300 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. Insome 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.

[0220] In certain embodiments, the pedicle screw 200 comprises a thread 230 that extends between the proximal end 210 and distal tip 220. In certain embodiments, thread 230 comprises an external thread form. In certain embodiments, the thread form comprises a leading edge 231 with a leading surface 235 and a trailing edge 232 with 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.

[0221] 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.

[0222] For example, manipulating the screw 200,300 by rotation or translation causes the cutting edge 271 of the screw to cut and guide the tissue or bone into the core 240, thereby promoting bone growth and fusion to the screw 200,300. In some embodiments, the tissue is embedded into the core 240 to promote bone growth and fusion to the screw 200,300. In some embodiments, the lattice is disposed within the core 240 to form a scaffold 600 for bone growth.

[0223] In some embodiments, thread 230 is configured as fine, closely spaced, or shallow to engage with the tissue. In some embodiments, thread 230 comprises an increased pitch, and anequal lead between thread turns. Tn some embodiments, 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, thread 230 is configured to be continuous along a portion. In some embodiments, thread 230 is configured to be intermittent, staggered, or discontinuous. In certain embodiments, thread 230 comprises a single thread turn. In certain embodiments, the thread comprises a plurality of discrete threads.

[0224] In certain embodiments, thread 230 is textured 237 with a rough surface to mimic the topography of the scaffold 600.

[0225] In some embodiments, the thread 230 comprises a penetrating element, for example, chosen from a nail configuration, barb, expanding element, raised element, rib, or spike. In some embodiments, 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 selfdrilling. In some embodiments, the distal tip 220 comprises a solid outer surface.

[0226] In certain embodiments, the pores of the scaffold 600 promote boney in-growth through the screw. In certain embodiments, other materials for fabricating the pedicle screw include but are not limited to, pre-packed demineralized bone matrix (DBM), pre-packed synthetic DBM, unpacked DBM, and magnesium-infused titanium. In certain embodiments, built-in channels capture autograft during insertion. In certain embodiments, the screw has double-ball angulation and a low profile. In certain embodiments, the screw comprises a locking cap with reverse-angle threads. The screw can be cannulated or non-cannulated.

[0227] In certain embodiments, the screws are between 35 mm and 65 mm long and between 4.5 mm and 8.5 mm in diameter. In certain embodiments, the rod acceptance is 5.5 mm.

[0228] In certain embodiments, the device is tested in cobalt chrome and meets American Society for Testing and Materials (ASTM) standards F543-17, 1798, and 1717.

[0229] The ASTM Standard F543-17 evaluates metallic bone screws for their resistance to various conditions, including the application of torsional forces, axial pullout forces, and insertion torques. Three procedures are presented: one under Practice A (Torsional Properties Test), and two under Practice B (Driving Torque and Axial Pullout Strength Tests). These practices report changes in weight, dimensions, appearance, color, strength, and other mechanical properties. Standard test methods are specified to establish results on a comparable basis, without precluding other pertinent tests specific to the mechanical properties requirements.Provisions are made for various exposure times, stress conditions, and exposure to tests at elevated temperatures. The type of testing (torsional or axial pullout strength method) depends upon the screw's end-use.

[0230] ASTM standard 1798 measures 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 the performance levels of spinal implants.

[0231] 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 the 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.

[0232] In certain embodiments, the screw is individually packaged in a double Tyvek™ peel tray.

[0233] In certain embodiments, the screw 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.

[0234] 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.

[0235] In certain embodiments, post-implantation options prevent revision surgery through polymer injection through the screw.

[0236] In certain embodiments, the screw does not exhibit screw loosening, screw backout, rod breakage, or lowered bone mineral density.

[0237] In certain embodiments, the screw comprises a neck that is thicker than the shank, thereby strengthening the point where rod breakage most frequently occurs during screw installation.

[0238] In certain embodiments, the screw has reduced one or more screw loosening, screw backout, rod breakage, and lowered bone mineral density.

[0239] 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.

[0240] In certain embodiments, the screws disclosed herein overcome the many failures of the prior art pedicle screws. In certain embodiments, the screw lacks a windshield wiper effect. In certain embodiments, the screw resists backout. In certain embodiments, the screw does not exhibit excessive micromotion. In certain embodiments, the screw has a low frequency of low- virulent microorganisms detected by sonication, for example, due to individual screw sterilization and packaging. In certain embodiments, the head and shaft of the screw resist failure. In certain embodiments, the screw is adapted for each type of bone quality. In certain embodiments, the screw has adequate thread depth. In certain embodiments, the screw withstands insertion torque, particularly at the head-to-screw coupling. In certain embodiments, the fatigue lifespan of the pedicle screw does not decrease when the screw is fully inserted. In certain embodiments, the screw has good instrumentation. In certain embodiments, the screw achieves angulation for rod acceptance. In certain embodiments, the screw does not have cyclic loading based on physiological conditions during walking. In certain embodiments, the screw does not fail in long-segment posterior cervical fusion, not requiring concomitant C6 or T1 buttress pedicles. In certain embodiments, the screw distributes stress. In certain embodiments, the screw does not immunocompromise the patient. In certain embodiments, the screw does not comprise PEEK. In certain embodiments, the screw does not have tulip or locking cap stresses.

[0241] 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 constructmacromotion. Tn certain embodiments, this device enables surgeons to meet patient-specific needs, such as, but not limited to, spraying / injecting regenerative products to stimulate the boneforming 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.

[0242] 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.

[0243] 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, the likelihood of failure is reduced.

[0244] 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.

[0245] 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.Man ufacturing

[0246] 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 fomied 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.

[0247] 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.

[0248] 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.

[0249] 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.

[0250] In one embodiment, the device is configured based on imaging from the patient's 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, historicalpatient 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.

[0251] 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

[0252] “Regenerative medicine” refers to a branch of translational research in tissue engineering and molecular biology that 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 physico-chemical cues in the surrounding microenvironment. Tissue cells reside in a complex scaffold physiological microenvironment.

[0253] 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.

[0254] 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.

[0255] 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.

[0256] During osteoinduction, reparation at weeks 4 to 5 comprises increased vascularization, necrotic tissue resorption, osteoblasts, and chondroblast 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.

[0257] 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.

[0258] 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 is typically completed one year after device implantation.

[0259] 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).

[0260] 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.

[0261] 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.

[0262] 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.

[0263] 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.EXAMPLES

[0264] 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.Table 1 - Reference numeralsExample 1 - Folded sheet scaffold

[0265] A method for designing a folded sheet scaffold for use in medical devices was perfomied.The method involved several stages, each incorporating specific experimental parameters.

[0266] Noise driving: Noise was driven from an infinite 3D noise field to define a field with real space, using FastNoise™ by Jordan Peck, an open-source tool provided under license from the Massachusetts Institute of Technology (MIT). The field had field values, each comprising an upper and lower bound. The 3D Cellular Noise had 2000 peaks / mm2frequency, a random seed of 1, a jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply],

[0267] Tuning: The upper and lower bounds of the field values were tuned based on user input. The tuning parameters included a Min Tune of -0.3 and a Max Tune of 2.0.

[0268] Geometry subtraction: Subtraction was performed to create thin wall geometry. The subtract parameter was set at 0.1 (non-dimensional).

[0269] Additional steps were also conducted to refine the scaffold further.

[0270] Unit multiplication: Multiplication was performed to add units to the field after the subtracting step. The Multiply Units parameter was set at 1 mm.

[0271] Voxelization: The field was voxelized to form sized voxels, defining a voxel grid in the field’s real space after the subtracting step. The voxel size was set at 0.075 mm.

[0272] Grid smoothening: The voxel grid was smoothened after the voxelizing step. The smoothening parameters included using Mean Curvature with 1 iteration and a width of 1.

[0273] Intersection: The smoothened voxel grid intersected with the desired design space after the smoothening step to produce 3D models to print pedicle screws.Example 2 - Diamond scaffold structure

[0274] Bone screws were 3D-printed and tested with the diamond scaffold structure. In certain embodiments, scoop features are located along a helical pattern, for example, corresponding to the helical pattern of the openings into the internal scaffold structure.

[0275] The design was based on a triply periodic minimal surface (TPMS), a minimal surface in R3that is invariant under a rank-3 scaffold of translations. These surfaces have the symmetries of a crystallographic group. Numerous examples of cubic, tetragonal, rhombohedral, and orthorhombic symmetries are known.

[0276] Specifically, a Schwartz Diamond TPMS was used for the scaffold, formed from symmetry arguments, remapped from Cartesian coordinates to spherical polar coordinates about the central axis of the screw shaft, sheared to form a helical wrap, thickened, subtracted, and as intersected with the 3D geometry space for the scaffold.

[0277] The surfaces were generated using symmetry arguments: Given a solution to Plateau's problem for a polygon, reflections of the surface across the boundary lines also produce valid minimal surfaces that can be continuously joined to the original solution. If a minimal surface meets a plane at right angles, then the mirror image in the plane can also be joined to the surface. Hence, periodic surfaces can be constructed given a suitable initial polygon inscribed in a unit cell.

[0278] The equation 1 approximates the TPMS for these bone screws: cos(x) cos(y) cos(z) - sin(x) sin(y) sin(z) = 0 (1) which is the specific base equation for this embodiment of the bone screw. The x, y, and z variables define the periodicity (i.e., pattern) in X / Y / Z, similar to how cubic scaffolds are defined. This surface is called a “diamond” because it has two intertwined congruent labyrinths, each having the shape of an inflated tubular version of the diamond bond structure. For the sake of discussion, a regularly repeating cell has been assumed, although TPMS geometry is influenced topologically to be pseudo-random.

[0279] An exact expression exists regarding elliptic integrals based on the Weierstrass-Ennepar parameterization. It defines the Schwarz D surface through infinite real space as an equation. Such a surface splits real space into two identical volumes — Positive space passes into negative space defines the iso- or mid-surface. FIG. 22 illustrates the 2-dimensional slice through the Schwarz Diamond mathematical field, where teal space is “positive” and purple space is “negative.” FIG. 23 illustrates a 3-dimensional cross-section of the non-thickened surface from FIG. 22, where light gray represents the positive side of the surface and dark gray represents the negative side, as defined by surface normal vectors. In certain embodiments, the cubic repeating pattern is 1.8 mm in X / Y / Z.

[0280] After creating the Schwarz equation, it was remapped helically (i.e., twisted) to create the base of the final shape. The equation was mapped from Cartesian space to polar space using conventional methods to do this. The periodicity was mapped cylindrically. The number of “spokes” radially remained a multiple of the selected cell size. FIG. 24 shows the cylindrical remap after conversion to polar space. The remap was about the central axis of the screw shaft.

[0281] After being remapped, the space was sheared to create the helical wrap, similar to how an inclined plane is wrapped around a cylinder to create a screw. To create the shear, the Schwarz Dequation is remapped from X / Y / Z coordinate space by shearing one (or multiple of the coordinates): x -> x, y -> y, and z -> z + x, where the Schwarz Diamond was sheared in the XZ plane. Such a shear operation maintained a continuous field.

[0282] After the field was sheared and remapped cylindrically, it was thickened using an absolute value operation, which converted the negative space of the equation into positive in three dimensions (FIG. 25). The helical wrap of the medical device is defined with a period three times the size of the cubic repeating pattern (5.4 mm), forming a single helix with a circumferential count of three for three radial spokes. After this, a subtract mathematical operation offset the central geometry to create a sheet-like structure, as seen in FIG. 26, wherein thin- wall geometry is represented by the thin pink wall radiating cylindrically. In certain embodiments, the walls are about 0.50 mm thick. The thin-walled scaffold field was intersected with the 3D geometry space to define where the scaffold exists and to model for the scaffold was produced (FIG. 29).Example 3 - Dynamic assessment of pedicle screws

[0283] The smallest diameter of a pedicle screw was tested to run out to 5,000,000 cycles per ASTM F1717-21.

[0284] The materials used in this experiment included components for sixteen constructs, with various types of screws with two types of scaffolds (Gaussian or diamond), different topography and dimensions. The “Gaussian” (“G”) samples comprised the folded sheet scaffold of Example 1. The “diamond” (“D”) samples comprised the Schwarz diamond TPMS of Example 2. All components were assembled using the parameters defined in the protocol, with any deviations or observations documented and reported.Table 2 - Components for testing

[0285] The testing environment was maintained at room temperature with all testing performed in laboratory ambient air. The test methods followed the guidelines of ASTM F1717-21, focusing on Dynamic Compression Bending.

[0286] Each construct comprised two rods, four screws, and set screws. Left and right pin-to-pin measurements were recorded pre-test, while post-test measurements were recorded for run-outs only. A minimum of one construct per screw type was tested in dynamic compression bending, set up per ASTM Fl 717-21 Figure 12.

[0287] Dynamic testing was performed per ASTM F1717-21 section 8.2, with loading applied at a sinusoidal waveform at a frequency of 5 Hz at an R-Ratio of 10. Testing continued until device failure, a maximum displacement of 10 mm was exceeded from initial displacement at minimum desired load level, or a run-out of 5,000,000 cycles was achieved.

[0288] Force levels were selected to establish the highest maximum run-out force, with the difference between the lowest force resulting in a failure and the maximum run-out force being no greater than 1.25X the highest established runout force.

[0289] Displacement and force data were recorded at regular intervals and saved for further analysis. Failure modes, observations, and any deviations were detailed in the final report. The construct mounting clevis was not free to rotate about the Z-axis (test frame load axis), which was a noted deviation from the protocol.

[0290] The results of this experimental example were reported per ASTM F 1717-21 section 9.

[0291] Test results for compression bending are shown in Table 3. Screws on the top were labeled as locations A and B and on the bottom were labeled as locations C and D. Specimens 4, 5, and 6 had different designs on the top and bottom. For Specimen 4, A and B had scaffold G and C and D had scaffold D. In these pairs, the screws with scaffold D failed and the screws with scaffold G did not. Elsewhere, the rods fractured, but failure was not observed for the screws with scaffold G.Table 3 - Compression bending test results

[0292] Further mechanical tests were completed on samples of Specimen 7 (05.5 x 30 mm porous pedicle screws with a folded sheet scaffold of Example 1):• Static Axial Compression per ASTM Fl 717-21• Dynamic Axial Compression per ASTM Fl 717-21• Static Torsion per ASTM Fl 717-21• Torsional Properties per ASTM F543• Driving Torque per ASTM F543• Screw Pullout per ASTM F543Worst-case Size Determination

[0293] For F1717 static and dynamic compression and static torsion, the worst-case screw construct contains the smallest diameter cross-section. Since the screws are inserted into ultra- high molecular weight polyethylene (UHMWPE) blocks for the testing, the smallest exposed cross-sectional area is located at the screw neck just below the head of the screw. This cross section increases as screw diameter increases, meaning the smallest diameter screw will present the weakest area.

[0294] The worst-case rod is the smallest diameter due to the smaller cross-sectional area. Ti- 6A1-4V has lower mechanical properties than CoCrMo. Based on this justification, the smallest diameter not shielded by the test block for the system is 5.3 mm in diameter (05.5 mm screw) and a Ti-6A1-4V 05.5 rod were used as the worst case.

[0295] For ASTM F543 Torque-to-Failure / Driving Torque, the worst-case screw shank is the smallest diameter screw since the cross-sectional area contains the smallest polar moment of inertia, meaning it is least resistant to torsional loads. Worst-case length is the longest screw, since longer shafts can have lower torsional rigidity, leading to larger angular deflections for a given torque. In very long shafts, issues such as lateral-torsional buckling can become a concern, which may not be evident in shorter shafts. Thus, the longest available screw should be used for torsional assessments. Therefore, the worst-case for the subject system in this test mode was determined to be a 05.5 x 60 mm screw.

[0296] For ASTM F543 Pullout, the worst-case screw shank is the smallest diameter screw because it has the smallest cross-section resulting in the least amount of contact and engagement with the bone. Worst-case length is the shortest screw, as it exhibits the least amount of engagement (i.e. , surface area contact) with the bone. Therefore, the worst-case for the subject system in this test mode was determined to be a 05.5 x 30 mm screw.

[0297] The subject device must perform at a minimum of the fifth percentile of the ASTM F 1717 testing thoracolumbosacral pedicle screw systems evaluated by the FDA and reported in Tables 3 and 4 of “Mechanical performance of thoracolumbosacral pedicle screw systems; An analysis of data submitted to the Food and Drug Administration” by Peck, et al. (2021) incorporated herein by reference.• ASTM F1717 Static compression bending yield force of 203 N or stiffness of 18.9 N / mm• ASTM Fl 717 Dynamic compression bending runout force of 120 N• ASTM Fl 717 Static torsion yield of 5.3 N-m or stiffness of 1.2 N-m / deg• ASTM F543 Ultimate Pullout Strength of 291 (N)• ASTM F543 Screw Torsion equivalent to or greater than cleared predicateStatic Axial Compression

[0298] Six specimens were tested in static axial compression. UHMWPE blocks were used for assembling the vertebrectomy model. Pilot holes were drilled into the UHMWPE blocks per subject device surgical technique. Tests were performed in dry air at room temperature. An axial rate of 20 mm / min was used. The results of the static axial compression testing are listed in Table 4. All samples failed due to slippage of the screw heads.Table 4 - Results of Static Axial Compression TestingDynamic Axial Compression

[0299] Six specimens were tested in dynamic axial compression. UHMWPE blocks were used for assembling the vertebrectomy model. Pilot holes were drilled into the UHMWPE blocks per subject device surgical technique. Tests were performed in dry air at room temperature. A maximum test frequency of 5 Hz was used. Testing was stopped after 5 million cycles or at implant failure. The results of the dynamic axial compression testing are listed in Table 5.Table 5 - Results of dynamic axial compression testingStatic Torsion

[0300] Six specimens were tested in static torsion. UHMWPE blocks were used for assembling the vertebrectomy model. Pilot holes were drilled into the UHMWPE blocks per subject device surgical technique. Aluminum blocks were used to prevent rotation in the X-Z direction. Tests were performed in dry air at room temperature. The implant was rotated clockwise to achieve the worst case in torsion at a rate of 20° / min. Torque and displacement data were recorded.

[0301] The results of the static torsion testing are displayed in Table 6. All samples failed because of loosening of the pedicle screw within the load blocks. Ultimate torque and angular displacement could not be determined except for specimens 2.3 and 2.6 because the machine displacement limit was reached.Table 6 - Static Torsion Testing Results*The results of specimen 2.1 were excluded from the mean and SD calculations due to a setup piece slipping.Torsional Properties per ASTM F543

[0302] Five screws were tested in torsion. Screws were embedded into a test block with five threads exposed and placed between a screwdriver and a torque sensor. Testing was performed in ambient air at room temperature at a rate of five rotations per minute. Testing was terminated after failure of the screw. Results from testing are in Table 7.Table 7 - Results from Torsion TestingDriving Torque per AST M F543

[0303] Five specimens were placed between a screwdriver and Grade 20 foam test block. The test blocks included a pilot hole. Specimens were driven into the test block at a rate of 30 revolutions per minute for the full threaded length of the screw. Removal torque was measured by changing the driving direction of the screwdriver at a rate of 30 revolutions per minute. Results are displayed in Table 8.Table 8 - Results from Driving and Removal Torque TestingScrew Pullout per ASTM F543

[0304] Five specimens were driven into Grade 20 foam test blocks at a rate of 30 revolutions per minute for the complete length of the threads. The test block was placed in a clamp while the head of the screw was pulled at a rate of 5 mm / min. Testing was terminated once the screw was removed from the foam block. Results from testing are displayed in Table 9.Table 9 - Results from Pullout Testing

[0305] In conclusion, the subject devices met all the acceptance criteria established for static and dynamic axial compression per ASTM F 1717. The subject device was substantially equivalent to the predicate devices from a mechanical perspective. The testing results are summarized in Table 10 below and in FIGS. 29 and 30:• ASTM F 1717 Static compression bending yield force of 203 N or stiffness of 18.9 N / mm• ASTM F 1717 Dynamic compression bending runout force of 120 N• ASTM F1717 Static torsion yield of 5.3 N-m or stiffness of 1.2 N-m / deg• ASTM F543 Ultimate Pullout Strength of 291 N• ASTM F543 Screw Torsion equivalent to or greater than cleared predicateTable 10 - Comparison of acceptance criteria to resultsExample 4 - Sheep study

[0306] 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 (Mcp), giant cells, necrosis, osteoblastic cells, signs of bone remodeling by osteoclasts, neovascularization, fibrosis, signs of implant degradation, and particulate debris.

[0307] 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.

[0308] To this end, the bone mineral densities (BMD) of 84 vertebral bodies (Li-Le) 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. Li and Lt, will be naive controls to compare changes with and without hardware.Table 11 - Animal subjects

[0309] 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 Ls 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.

[0310] 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.

[0311] 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.).

[0312] 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).

[0313] 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.

[0314] 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 12. After scoring all the slides for data post-processing, the pathologist will be unblinded so they can compare data to the control samples.Table 12 - Scoring system for histological evaluation of bone sections for cell type and responseReference: ISO 10993-6 Annex E (Biological evaluation of medical devices - Part 6: Tests for local effects after implantation)

[0315] 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 (a) 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.

[0316] 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.

[0317] After sacrifice, histology will be compared with prior studies to determine the differences and similarities of polymorphonuclear cells (PMNs), lymphocytes, plasma cells, macrophages (Mcp), 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 between the control, naive, and treatment sites. An unpaired t-test with an alpha (a) 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, naive screws, and prior studies.

[0318] 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.

[0319] 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.

[0320] 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 naive subjects, as well as similar adhesion rates to prior studies.Example 5 - Sheep study for infection

[0321] 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.

[0322] 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.

[0323] 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.

[0324] 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.

[0325] The experimental design and methods will be substantially the same as the sheep study above in Example 4, including Tables 3 and 4.

[0326] 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.

[0327] 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.

Claims

CLAIMSWhat is claimed is:

1. A folded sheet scaffold for use in medical devices, the scaffold comprising a shellular porous pseudorandom orientable architecture comprising of a continuous folded sheet of topological genus-n, wherein real 3 -dimensional space is divided into sub-volumes.

2. The folded sheet scaffold of claim 1, wherein the sub-volumes are incongruent and nonintersecting.

3. The folded sheet scaffold of claim 1 or 2, wherein the pseudorandom architecture is driven by a dimensionless 3 -dimensional noise field.

4. The folded sheet scaffold of any one of claims 1 to 3, wherein the sheet architecture has one or more characteristics chosen from continuous, perforated, functionally graded, semi-regular, and driven by modulating algorithms that control spatially-varying features.

5. The folded sheet scaffold of any one of claims 1 to 4, wherein the scaffold is adapted to be incorporated into a pedicle screw.

6. The folded sheet scaffold of any one of claims 1 to 4, wherein the scaffold is adapted to be incorporated into a headless screw of a reduction trauma screw system.

7. The folded sheet scaffold of any one of claims 1 to 6, configured to house one or more biologic agents.

8. The folded sheet scaffold of any one of claims 1 to 7, not comprising vertices or struts.

9. A method for designing a folded sheet scaffold for use in medical devices, the method comprising: driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; tuning the upper and lower bounds of the field values based on user input; and subtracting to create thin wall geometry.

10. The method of claim 9, wherein the driving noise comprises a variable input chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise.

11. The method of claim 9 or 10, wherein the driving noise further comprises type inputs chosen from frequency, random seed, jitter, distance, and return type.

12. The method of claim 11, wherein the variable input is cellular noise.

13. The method of claim 12, wherein the cellular noise has a frequency of 2000 peaks / mm2, a random seed of 1, jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply].

14. The method of any one of claims 9 to 13, wherein the subtracting is non-dimensional.

15. The method of any one of claims 9 to 14, wherein the subtracting is set at 0.1.

16. The method of any one of claims 9 to 15, further comprising adding biases to the field values to offset geometry after the tuning step.

17. The method of any one of claims 9 to 16, further comprising converting negative field values into positive field values after the tuning step.

18. The method of any one of claims 9 to 17, wherein the tuning comprises type inputs chosen from coarse resolution, fine resolution, min tune, and max tune.

19. The method of claim 18, wherein the tuning comprises a min tune of -0.3 and a max tune of 2.0.

20. The method of any one of claims 9 to 19, further comprising multiplying to add units to the field after the driving noise step and before the converting step, when present.

21. The method of claim 20, wherein a multiply units parameter is set at 1 mm.

22. The method of any one of claims 9 to 21, further comprising voxelizing the field to form sized voxels defining a voxel grid in the field’s real space after the subtracting step.

23. The method of claim 22, wherein the voxel size is set at 0.075 mm.

24. The method of any one of claims 9 to 23, further comprising smoothening the voxel grid after the voxelizing step.

25. The method of claim 24, wherein the smoothening comprises a variable input chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean fdter, mean curvature fdter, and median fdter.

26. The method of claim 24 or 25, wherein the smoothening further comprises type input chosen from width and iterations.

27. The method of claim 26, wherein the smoothening comprises a mean curvature with 1 iteration and a width of 1.

28. The method of any one of claims 22 to 27, further comprising intersecting the smoothened voxel grid with a desired design space after the smoothening step.

29. The method of claim 9, comprising, in order: driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; tuning the upper and lower bounds of the field values based on user input, adding biases to the field values to offset geometry; converting negative field values into positive field values; subtracting to create thin wall geometry, multiplying to add units to the field; voxelizing the field to form sized voxels defining a voxel grid in the field’s real space; smoothening the voxel grid; and intersecting the smoothened voxel grid with a desired design space.

30. A computer- implemented method for designing a folded sheet scaffold for use in medical devices, the method comprising: implementing a processor to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; using the processor to tune the upper and lower bounds of the field values based on user input; andimplementing the processor to subtract and create thin wall geometry.

31. The computer-implemented method of claim 30, wherein the processor-driven noise comprises a variable input chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise.

32. The computer-implemented method of claim 30 or 31, wherein the processor-driven noise further comprises type inputs chosen from frequency, random seed, jitter, distance, and return type.

33. The computer-implemented method of claim 32, wherein the variable input is cellular noise.

34. The computer-implemented method of claim 33, wherein the cellular noise has a frequency of 2000 peaks / mm2, a random seed of 1 , jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply],35. The computer-implemented method of any one of claims 30 to 34, wherein the subtraction is non-dimensional.

36. The computer- implemented method of any one of claims 30 to 35, wherein the subtraction is set at 0.1.

37. The computer- implemented method of any one of claims 30 to 36, further comprising the processor to add biases to the field values to offset geometry after the tuning step.

38. The computer- implemented method of any one of claims 30 to 37, further comprising the processor to convert negative field values into positive field values after the tuning step.

39. The computer-implemented method of any one of claims 30 to 38, wherein the tuning comprises type inputs chosen from coarse resolution, fine resolution, min tune, and max tune.

40. The computer-implemented method of claim 39, wherein the tuning comprises a min tune of -0.3 and a max tune of 2.0.41 . The computer-implemented method of any one of claims 30 to 40, further comprising the processor to multiply and add units to the field after the driving noise step and before the converting step, when present.

42. The computer-implemented method of claim 41, wherein a multiply units parameter is set at 1 mm.

43. The computer-implemented method of any one of claims 30 to 42, further comprising the processor to voxelize the field to form sized voxels defining a voxel grid in the field’s real space after the subtracting step.

44. The computer-implemented method of claim 43, wherein the voxel size is set at 0.075 mm.

45. The computer- implemented method of any one of claims 30 to 44, further comprising the processor to smoothen the voxel grid after the voxelizing step.

46. The computer- implemented method of claim 45, wherein the smoothening comprises a variable input chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean filter, mean curvature filter, and median filter.

47. The computer-implemented method of claim 45 or 46, wherein the smoothening further comprises type input chosen from width and iterations.

48. The computer-implemented method of claim 47, wherein the smoothening comprises a mean curvature with 1 iteration and a width of 1.

49. The computer-implemented method of any one of claims 43 to 48, further comprising the processor to intersect the smoothened voxel grid with a desired design space after the smoothening step.

50. The computer-implemented method of claim 30, comprising, in order: implementing a processor to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound;using the processor to tune the upper and lower bounds of the field values based on user input, adding biases to the field values to offset geometry; implementing the processor to convert negative field values into positive field values; subtracting to create thin wall geometry, multiplying to add units to the field; voxelizing the field to form sized voxels defining a voxel grid in the field’s real space; smoothening the voxel grid; and intersecting the smoothened voxel grid with a desired design space.

51. A computer system for designing a folded sheet scaffold for use in medical devices, the system comprising: a noise-driving module configured to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; a tuning module configured to tune the upper and lower bounds of the field values based on user input; and a subtracting module configured to subtract and create thin wall geometry.

52. The computer system of claim 51, wherein the noise-driving module is further configured to comprise a variable input chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise.

53. The computer system of claim 51 or 52, wherein the noise-driving module is further configured to comprise type inputs chosen from frequency, random seed, jitter, distance, and return type.

54. The computer system of claim 53, wherein the variable input is cellular noise.

55. The computer system of claim 54, wherein the cellular noise has a frequency of 2000 peaks / mm2, a random seed of 1, jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply],56. The computer system of any one of claims 51 to 55, wherein the subtracting module is further configured to perform non-dimensional subtraction.

57. The computer system of any one of claims 1 to 56, wherein the subtracting module is further configured to subtract set at 0.1.

58. The computer system of any one of claims 51 to 57, further comprising a bias-adding module configured to add biases to the field values to offset geometry after the tuning step.

59. The computer system of any one of claims 51 to 58, further comprising a converting module configured to convert negative field values into positive field values after the tuning step.

60. The computer system of any one of claims 51 to 59, wherein the tuning module is further configured to comprise type inputs chosen from coarse resolution, fine resolution, min tune, and max tune.

61. The computer system of claim 60, wherein the tuning module is further configured to comprise a min tune of -0.3 and a max tune of 2.0.

62. The computer system of any one of claims 51 to 61, further comprising a multiplying module configured to multiply and add units to the field after the driving noise step and before the converting step, when present.

63. The computer system of claim 62, wherein a multiply units parameter is set at 1 mm.

64. The computer system of any one of claims 51 to 63, further comprising a voxelizing module configured to voxelize the field to form sized voxels defining a voxel grid in the field’s real space after the subtracting step.

65. The computer system of claim 64, wherein the voxel size is set at 0.075 mm.

66. The computer system of any one of claims 51 to 65, further comprising a smoothening module configured to smoothen the voxel grid after the voxelizing step.

67. The computer system of claim 66, wherein the smoothening module is further configured to comprise variable inputs chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean filter, mean curvature filter, and median filter.

68. The computer system of claim 66 or 67, wherein the smoothening module is further configured to comprise type input chosen from width and iterations.

69. The computer system of claim 68, wherein the smoothening module is further configured to comprise a mean curvature with 1 iteration and a width of 1.

70. The computer system of any one of claims 64 to 69, further comprising an intersecting module configured to intersect the smoothened voxel grid with a desired design space after the smoothening step.

71. The computer system of claim 51, comprising: a noise-driving module configured to drive noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; a tuning module configured to tune the upper and lower bounds of the field values based on user input, adding biases to the field values to offset geometry; a converting module configured to convert negative field values into positive field values; a subtracting module configured to subtract and create thin wall geometry, multiplying to add units to the field; a voxelizing module configured to voxelize the field to form sized voxels defining a voxel grid in the field’s real space; a smoothening module configured to smoothen the voxel grid; and an intersecting module configured to intersect the smoothened voxel grid with a desired design space.

72. Anon-transitory computer-readable medium storing instructions that, when executed by a processor, cause the processor to perform a method for designing a folded sheet scaffold for use in medical devices, the method comprising: driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound; tuning the upper and lower bounds of the field values based on user input; and subtracting to create thin wall geometry.

73. The non-transitory computer-readable medium of claim 72, wherein the driving noise comprises a variable input chosen from cubic noise, value noise, gradient noise, Perlin noise, cellular noise, simplex noise, and white noise.

74. The non-transitory computer-readable medium of claim 72 or 73, wherein the driving noise further comprises type inputs chosen from frequency, random seed, jitter, distance, and return type-75. The non-transitory computer-readable medium of claim 74, wherein the variable input is cellular noise.

76. The non-transitory computer-readable medium of claim 75, wherein the cellular noise has a frequency of 2000 peaks / mm2, a random seed of 1, jitter of 0.5, Euclidean distance, and a return type of Distance2[Multiply].

77. The non-transitory computer-readable medium of any one of claims 72 to 76, wherein the subtracting is non-dimensional.

78. The non-transitory computer-readable medium of any one of claims 72 to 77, wherein the subtracting is set at 0.1 .

79. The non-transitory computer-readable medium of any one of claims 72 to 78, further comprising instructions for adding biases to the field values to offset geometry after the tuning step.

80. The non-transitory computer-readable medium of any one of claims 72 to 79, further comprising instructions for converting negative field values into positive field values after the tuning step.

81. The non-transitory computer-readable medium of any one of claims 72 to 80, wherein the tuning comprises type inputs chosen from coarse resolution, fine resolution, min tune, and max tune.

82. The non-transitory computer-readable medium of claim 81, wherein the tuning comprises a min tune of -0.3 and a max tune of 2.0.

83. The non-transitory computer-readable medium of any one of claims 72 to 82, further comprising instructions for multiplying to add units to the field after the driving noise step and before the converting step, when present.

84. The non-transitory computer-readable medium of claim 83, wherein a multiply units parameter is set at 1 mm.

85. The non-transitory computer-readable medium of any one of claims 72 to 84, further comprising instructions for voxelizing the field to form sized voxels defining a voxel grid in the field’s real space after the subtracting step.

86. The non-transitory computer-readable medium of claim 85, wherein the voxel size is set at 0.075 mm.

87. The non-transitory computer-readable medium of any one of claims 72 to 86, further comprising instructions for smoothening the voxel grid after the voxelizing step.

88. The non-transitory computer-readable medium of claim 87, wherein the smoothening comprises a variable input chosen from a dilate operation, Gaussian filter, eikonal equation, discrete Laplace operator, mean filter, mean curvature filter, and median filter.

89. The non-transitory computer-readable medium of claim 87 or 88, wherein the smoothening further comprises type input chosen from width and iterations.

90. The non-transitory computer-readable medium of claim 89, wherein the smoothening comprises a mean curvature with 1 iteration and a width of 1.

91. The non-transitory computer-readable medium of any one of claims 85 to 90, further comprising instructions for intersecting the smoothened voxel grid with a desired design space after the smoothening step.

92. The non-transitory computer-readable medium of claim 72, comprising: instructions for driving noise from an infinite 3D noise field to define a field with real space, the field having field values each comprising an upper bound and a lower bound;instructions for tuning the upper and lower bounds of the field values based on user input, adding biases to the field values to offset geometry; instructions for converting negative field values into positive field values; instructions for subtracting to create thin wall geometry, multiplying to add units to the field; instructions for voxelizing the field to form sized voxels defining a voxel grid in the field’s real space; instructions for smoothening the voxel grid; and instructions for intersecting the smoothened voxel grid with a desired design space.

93. A folded sheet scaffold formed by a method of any one of claims 9 to 29.

94. A medical device comprising the folded sheet scaffold of any one of claims 1 to 8 or 30.

95. The medical device of claim 94, wherein the medical device is a bone screw.

96. The medical device of claim 95, wherein the bone screw is a pedicle screw.

97. The medical device of claim 95, wherein the bone screw is a headless screw.

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