Interpositional patch system and method

Abstract

A patch system and method for musculoskeletal repair is provided, the patch system including a patch defining a patch thickness, the patch being fabricated in whole or in part from a composition including a citrate polymer and a bioceramic filler, the patch defining a porosity gradient across the patch thickness. The patch may be defined by multiple patch layers, e.g., multiple fibers, wherein a first fiber associated with a first patch layer is not aligned relative to a second fiber in a second, adjacent patch layer.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to U.S. provisional patent application entitled "Interpositional Patch Systems and Methods," filed December 14, 2022, and assigned application serial number 63 / 432,547, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to interpositional patch systems and methods that include physical feature(s) generated from citrate-based composite biomaterials that aid in tendon-ligament attachment regeneration. [Background technology]

[0003] Tendon-ligamentous attachments are areas of the musculoskeletal structure that have been difficult to regenerate. One of the more commonly injured areas is the rotator cuff (see, e.g., Charousset C. et al., "Arthroscopic Repair of Full-Thickness Rotator Cuff Tears: Is There Tendon Healing in Patients Aged 65 Years or Older?", Arthroscopy: J. Arthroscopic Related Surgery 2010, 26 (3), 302-309.0). Often, the rotator cuff is repaired using suture anchors alone, which has been clinically reported to have a high incidence of re-tears. This failure rate is due to the formation of fibrous tissue (scar formation) during the healing phase, which prevents the regeneration of the natural soft tissue tendon-ligamentous attachment (see, e.g., Mather et al., "The Societal and Economic Value of Rotator Cuff Repair," J. Bone Jt. Surg., Am. Vol. 10, 2010). 2013, 95(22), 1993-2000). Furthermore, current suture anchors only provide a mechanical means of constraining soft tissue, but do not provide structures or materials that support the biological healing process and regeneration of native tissue. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Charousset C. et al., “Arthroscopic Repair of Full-Thickness Rotator Cuff Tears: Is There Tendon Healing in Patients Aged 65 Years or Older?”, Arthroscopy: J. Arthroscopic Related Surgery 2010, 26 (3), 302–309.0 [Non-patent document 2] Mather et al. “The Societal and Economic Value of Rotator Cuff Repair”, J. Bone Jt. Surg., Am. Vol 2013, 95(22), 1993~2000 Summary of the Invention [Problem to be solved by the invention]

[0005] There is a need for effective systems and methods for surgical procedures / repairs that address the aforementioned challenges. [Means for solving the problem]

[0006] The present disclosure provides interposition patch systems and methods that include physical / mechanical feature(s) derived from a citrate-based composite biomaterial that supports enthesis regeneration. The disclosed systems / methods include, among other things, biodegradable citrate-based scaffolds that are effective in inducing natural healing and regeneration of tissues, particularly enthesis tissues. In exemplary embodiments, the disclosed systems utilize 3D printing equipment to facilitate the fabrication of layered, multiphase constructs that possess mechanical and biochemical characteristics more similar to those of the natural transition zone.

[0007] In embodiments, the physical / mechanical feature(s) may be advantageously arranged / deployed as a gradient architecture through the patch system via multiple layers. On the patch surface that is clinically located closer to the bone site, the physical / mechanical feature(s) are designed to create / define a porosity of approximately 300-500 microns, thereby further supporting the bone-healing side of the tendon-ligament attachment. On the side of the patch system that is located closer to the tendon, i.e., the top or tendon side of the patch, the patch system may define a pore size of approximately 100-300 microns, thereby providing an environment that is conducive to tenocyte colonization and integration between the bone and tendon.

[0008] The spacing and orientation of the various filaments defining the patch layers can be selected to optimize stimulation of the desired tissue regeneration. Similarly, the orientation of the filament direction can be selected to guide the direction of regenerating tissue. For example, the top layer (tendon side) of the patch system can be advantageously made / fabricated with longitudinal filaments to guide the tendon growth and attachment of Sharpey's fibers to bone, thereby beneficially creating a tendon-ligament attachment oriented in the direction of the resulting forces acting on the tendon.

[0009] Additional features, functions, and benefits of the disclosed patch system and associated methods will be apparent from the description that follows.

[0010] To assist those skilled in the art in making and using the disclosed systems and methods, reference is made to the accompanying figures. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 illustrates a representation of an assembled configuration of an exemplary patch system. [Figure 2] FIG. 1 illustrates a representative exploded view of an exemplary patch system. [Figure 3] FIG. 1 shows a representation of an exemplary patch system including an open / boundary-free perimeter. [Figure 4A] FIG. 10 shows a scanning electron microscope image of the patch system from top to bottom showing the porous fiber structure. [Figure 4B] FIG. 1 shows a scanning electron microscope image showing a cross section of the patch system. [Figure 4C] FIG. 10 shows a magnified section of a scanning electron microscope image of a cross section of the patch system demonstrating the submicron porous structure of the filaments. DETAILED DESCRIPTION OF THE INVENTION

[0012] As discussed above, the present disclosure provides interpositional patch systems and related methods that include physical / mechanical feature(s) derived from citrate-based composite biomaterials that support tendon-ligament attachment regeneration. The physical / mechanical feature(s) are typically arranged / deployed as a gradient structure through the patch system via multiple layers. On the surface of the patch that is clinically located closer to the bone site, the physical / mechanical feature(s) create / define a porous structure of approximately 300-500 microns, thereby designed to further support the bone-healing side of the tendon-ligament attachment. On the side of the patch system that is located closer to the tendon, i.e., the top or tendon side of the patch, the patch system defines a pore size of approximately 100-300 microns, thereby providing an environment conducive to tenocyte colonization and integration between the bone and tendon. The spacing and orientation of the various filaments defining the patch layers can be selected to optimize stimulation of the desired tissue regeneration. Similarly, the orientation of the filament direction can be selected to guide the direction of regenerating tissue.

[0013] A first exemplary embodiment of the disclosed patch system is depicted generally in FIG. 1 (assembled) and FIG. 2 (exploded view).

[0014] As shown in FIGS. 1 and 2, the patch system 100 includes multiple patch layers 102, 104, 106, 108, 110, 112, and 114 that, in the assembled configuration shown in FIG. 1, define a stacked configuration having a substantially common outer edge. The patch system 100 defines a substantially elliptical outer geometry. Adjacent layers are in a contiguous relationship. At least one opening / pathway is defined in the surface of each patch layer (openings 102a-114a), and when assembled, the openings / pathways 102a-114a are arranged to define substantially adjacent paths through the patch system 100. The disclosed adjacent paths provide locations / spaces for the formation of natural host tissue (i.e., bone-tendon-ligament attachment-tendon). Multiple paths are typically provided within the patch, and the dimensions of the paths are typically designed with a size and shape to facilitate / accommodate the formation and ingress of desired tissue. For example, large channel spacing generally favors the formation of bone tissue, while small channel spacing generally favors tendon tissue (enthesis) with a gradient between bone to tendon morphology transition.

[0015] In the depicted embodiment of Figures 1 and 2, each of the layers 102-114 defines a solid perimeter formed, for example, by an extruded polymer, although in alternative embodiments, the perimeter of the layer(s) may be open, i.e., borderless, to facilitate cellular diffusion of the patch material and bodily fluids (see Figure 3).

[0016] As best seen in Figure 2, the filaments defining each layer are generally oriented with unaligned axes such that there is crossover of fibers between adjacent layers. Note that the alignment of the filaments is not necessarily different in each layer relative to other layers in exemplary embodiments of the present disclosure; adjacent layers are defined only by the fibers of the adjacent layer(s) and the fibers that are unaligned. Typical fiber diameters range from 1 micron to 5 microns, although the present disclosure is not limited by or in any way limited to such exemplary fiber dimensions.

[0017] The patch system 100 thus defines a gradient structure across layers 102-114. The patch surface / layer clinically located closer to the bone site typically defines a porous structure (porosity) of approximately 300-500 microns, thereby providing additional support to the bone-healing side of the tendon-ligament attachment, while the patch's top or tendon side typically defines a layer / surface located closer to the tendon with a pore size of approximately 100-300 microns, thereby providing an environment conducive to tenocyte colonization and integration between the bone and tendon. The spacing and orientation of the various filaments defining the patch layers can be selected to optimize stimulation of desired tissue regeneration, and the orientation of the filament direction can be selected to guide the direction of regenerating tissue.

[0018] In alternative embodiments of the disclosed patch system, alternative outer geometries / profiles may be selected, i.e., geometries / profiles other than the elliptical design of patch system 100. For example, a square or triangular geometry / profile may be selected, although the present disclosure is not limited by or to any particular outer geometry / profile.

[0019] The exemplary patch system 100 includes seven layers (102-114). However, the disclosed patch system is not limited to or by such exemplary implementations, and patch systems may be fabricated / practiced in accordance with the present disclosure including more or less than seven layers. It is also contemplated that the present disclosure does not require fabrication of the individual layers assembled in the manner shown in Figures 1 and 2, but instead, alternative fabrication methods may be used through alternative manufacturing techniques that provide a gradient effect across the thickness of the patch system.

[0020] As noted above, alternative embodiments of the present disclosure may include a layer(s) that define an open / unbounded perimeter. Figure 3 schematically depicts an exemplary patch system 200 that includes an open / unbounded perimeter.

[0021] The beneficial clinical properties of the disclosed patch system are further enhanced by the chemical nature of the materials used to fabricate the patch system. Specifically, the disclosed patch system is made primarily of a citrate-based polymer, a metabolite important in the production of energy in the Krebs cycle. In exemplary embodiments, the disclosed patch system is fabricated in whole or in part from a biocomposite composed of a citrate polymer and a bioceramic filler.

[0022] Fabrication of the disclosed patch system can be addressed, for example, by 3D printing modalities that utilize the extrusion of biocomposite materials in a process known as fused deposition modeling (FDM). In FDM, biocomposite materials are extruded through a nozzle, patterned, and layered to create a 3D object. FDM allows for the creation of multiple filaments with varying diameters and interfilament spacing to create pockets (pores) that can vary as the spacing or filament diameter changes. The filaments themselves can be solid or semi-porous, using various methods to create microporous structures within the filaments, including the addition of solvents or sacrificial elements that can be subsequently removed. The microporous structure of the filaments can be modified to help control degradation rates and provide additional mechanical features for cell attachment (see, e.g., Figures 4A-4C).

[0023] The FDM method allows for the generation of multiple patterns that can be varied layer by layer to create features that allow for optimized biological integrity and cell signaling. Although the fabrication of the implant is described using FDM 3D printing, this layering method can also be created using casting techniques or other additive manufacturing processes, such as laser printing, or with binder jetting techniques.

[0024] The citrate polymer may possess various types of bioceramic fillers, such as bioglass, hydroxyapatite (HA), tricalcium phosphate (TCP), calcium sulfate, or various other ceramic fillers, either in particle or fiber form. The bioceramic filler may take the form of a blend or mix of bioceramic materials, specifically including the exemplary bioceramic filler materials identified herein. The bioceramic materials referenced above may be used at various concentrations to best address clinical requirements. For example, the bioceramic filler may be incorporated into the fibers / layers at levels ranging from 0% to 50% by weight. For example, the bioceramic may be included at lower levels in the "tendon" layer, e.g., 25% by weight, at higher levels in the middle layer(s), e.g., 35% by weight, and at the highest levels in the "bone" layer, e.g., 45% by weight. Variable bioceramic levels may vary based on clinical requirements, including, but not limited to, such exemplary weight percentages, as noted above. The biomaterials can also be enriched with and / or conjugated with various proteins or peptides to increase cellular responses.

[0025] In exemplary embodiments of the present disclosure, the disclosed patch system may be used for rotator cuff repair. Exemplary patch system design parameters for rotator cuff repair may include: Patch Thickness: 2mm to 5mm Patch dimensions: 5mm x 5mm Fiber / strut diameter: 1 micron or more Porous structure: 300-500 microns on the bone side, 100-300 microns on the tendon side Degradation profile: 12-18 months Bioceramics HA, TCP, calcium sulfate and their mixtures Gradient layering: tendon side - lower ceramic content, bone side - higher ceramic content

[0026] Although the present disclosure has been described with reference to exemplary embodiments and performances of the disclosed patch system / method, the present disclosure is not limited by or to such exemplary embodiments / performances.

Claims

1. 1. A patch system for use in musculoskeletal repair, comprising: a patch defining a patch thickness, the patch being made in whole or in part from a composition comprising a citrate polymer and a bioceramic filler; A patch system in which the patch defines a porosity gradient across the thickness of the patch.

2. The patch system of claim 1 , wherein the patch is defined by multiple patch layers.

3. The patch system of claim 2 , wherein the patch layer is formed from a plurality of fibers.

4. The patch system of claim 3 , wherein a first fiber in a first patch layer is not aligned with a second fiber in a second, adjacent patch layer.

5. 10. The patch system of claim 1, wherein each of the patch layers defines an opening, and wherein the openings of the patch layers are substantially aligned when the patch is assembled.

6. The patch system of claim 1 , wherein the patch defines a perimeter that is tight.

7. 10. The patch system of claim 1, wherein the patch defines an open or borderless perimeter.

8. 2. The patch system of claim 1, wherein the bioceramic filler is selected from the group consisting of bioglass, hydroxyapatite (HA), tricalcium phosphate (TCP), calcium sulfate, and combinations thereof.

9. 10. The patch system of claim 1, wherein the patch is formed from multiple patch layers and the level of bioceramic filler varies across the patch layers.

10. 2. The patch system of claim 1, wherein the patch defines a first patch layer configured to be positioned adjacent to a bone and a second patch layer configured to be positioned adjacent to a tendon, and wherein the bioceramic filler is at a higher level in the first patch layer compared to the second patch layer.

11. 2. The patch system of claim 1, wherein the patch defines a first patch layer configured to be positioned adjacent to a bone and a second patch layer configured to be positioned adjacent to a tendon, and wherein the porous structure is larger in the first patch layer compared to the second patch layer.

12. 12. The patch system according to claim 11, wherein the pore structure of the first patch layer is 300 to 500 microns, and the pore structure of the second patch layer is 100 to 300 microns.

13. 10. The patch system of claim 1, wherein the degradation profile of the patch is 12 to 18 months.

14. 10. The patch system of claim 1, wherein the patch is made from a plurality of fibers, the fibers having a diameter of 1 micron to 5 microns.

15. 10. The patch system of claim 1, wherein the patch has a thickness of 2 mm to 5 mm.

16. 10. The patch system of claim 1, wherein the patch dimensions are approximately 5 mm x 5 mm.

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