A guided bone regeneration composite barrier membrane based on chiral topological deformation and temperature-sensitive shape memory and a preparation method thereof

Abstract

The application relates to a guided bone regeneration composite barrier membrane based on inverse chirality topological deformation and temperature-sensitive shape memory and a preparation method thereof, and belongs to the technical field of medical devices. The barrier membrane comprises a metal framework and a base film layer completely wrapping the metal framework, wherein the metal framework comprises a plurality of rows of first circular rings and second circular rings in staggered distribution, and the first circular ring and the adjacent second circular ring are connected with a connecting rod in tangential connection. The application realizes the synergistic treatment effects of minimally invasive implantation, in-situ self-expansion, nail-free soft anchoring and full degradation through a micro-nano immersion process and reverse thermodynamic programming.

Description

Technical Field

[0001] This invention relates to a composite barrier membrane for guiding bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory, and its preparation method, belonging to the field of medical device technology. Background Technology

[0002] Guided bone regeneration (GBR) is one of the most crucial clinical techniques in dental implantology and maxillofacial bone defect repair. Its core pathophysiological principle lies in using a physical barrier membrane to isolate slower-growing osteoblasts from rapidly growing fibroblasts (soft tissue), creating a relatively closed and stable osteogenic microenvironment for the bone defect area. In this process, the barrier membrane not only needs good biocompatibility and cell-blocking capacity but also strong spatial maintenance capabilities to withstand the enormous tension generated during the suturing of the superior gingival soft tissue flap.

[0003] For the treatment of large-area or severe vertical bone defects using bone remodeling (GBR), current clinical practices primarily rely on pure titanium mesh or non-degradable polytetrafluoroethylene (d-PTFE) membranes with an embedded titanium framework. However, existing single-material technologies face intractable technical bottlenecks and efficacy limitations in clinical applications, specifically in the following aspects: First, metal supports are non-degradable, resulting in a high burden of secondary surgery. Pure titanium materials are permanent implants in the body. After bone tissue regeneration is completed (usually 6-9 months after surgery), patients must undergo a second local incision to remove the titanium mesh and fixation screws. This not only increases the patient's pain and medical costs, but the secondary incision can also easily damage the newly formed fragile periosteum, leading to the absorption of some of the newly formed bone.

[0004] Secondly, traditional metal meshes have poor conformability and a high risk of soft tissue exposure. Titanium meshes are relatively rigid at room temperature, and doctors often need to use instruments to repeatedly bend and cut them manually during surgery to fit the complex three-dimensional bone defect morphology. This manual operation is very likely to create stress concentration and sharp edges at the edges of the titanium mesh. Under the high tension of the gingival suture, the sharp metal edges can easily puncture the mucosa, leading to titanium mesh exposure (clinical exposure rate as high as 20%-30%), which in turn can cause retrograde infection and ultimately lead to bone graft surgery failure.

[0005] Third, the implantation and fixation process is complicated and invasive. Because traditional titanium mesh lacks adaptive deformation ability, doctors need to open a large area of ​​the mucoperiosteal flap to obtain a sufficient field of vision during implantation. In order to prevent the titanium mesh from shifting under the pressure of soft tissue, it must be fixed to the basal bone with miniature titanium screws (fixation screws) in an extremely narrow oral cavity. This process is difficult to operate, time-consuming, and the insertion of titanium screws may cause irreversible damage to the local cortical bone and tooth root.

[0006] Fourth, the existing biodegradable alternatives have seriously insufficient mechanical properties or uncontrollable degradation. In recent years, some studies have tried to use biodegradable magnesium (Mg) alloys to replace titanium. However, pure magnesium alloys degrade too quickly in the initial physiological environment, easily generating a large number of hydrogen bubbles, which leads to soft tissue peeling. In addition, barrier membranes made solely from biodegradable polymers such as collagen or polylactic acid (PLA) soften rapidly after being heated or soaked in blood, completely losing their ability to maintain vertical space, causing bone powder to collapse.

[0007] In summary, there is an urgent clinical need for a new generation of GBR barrier membrane systems that organically combines minimally invasive implantation, strong space maintenance, self-fixation without screws, and complete biodegradability. This system should possess the ability to drastically reduce volume before implantation, spontaneously expand in three-dimensional topological mechanical properties after implantation, have an interface with excellent tissue compliance, and a controllable degradation cycle. Summary of the Invention

[0008] To address the shortcomings of existing technologies, this invention provides a guided bone regeneration composite barrier membrane based on reverse chiral topological deformation and thermosensitive shape memory, and its preparation method. Through micro-nano impregnation technology and reverse thermodynamic programming, it achieves synergistic therapeutic effects of minimally invasive implantation, in-situ self-expansion, nail-free soft anchoring, and full degradation.

[0009] The technical solution of the present invention is as follows: A composite barrier membrane for guiding bone regeneration based on anti-handed topological deformation and temperature-sensitive shape memory includes a metal skeleton and a basement membrane layer that completely encloses the metal skeleton. The metal skeleton includes several rows of first and second rings arranged in an alternating pattern. The first rings and adjacent second rings are tangentially connected by connecting rods. Several first rings, second rings, and connecting rods, in their unfolded state, form a two-dimensional planar array. This array is a reciprocal topological geometric array with negative Poisson's ratio metamaterial mechanical properties. When this two-dimensional planar array is subjected to in-plane tensile stress and the entire mesh expands, the first and second rings, while undergoing relative spatial displacement as the expansion spacing increases, also undergo non-coincident spin motion around their own geometric centers. This causes the connecting rods to extend outward. Due to the physical difference between the rotational angular velocities of the rings with different diameters and the linear displacement of the released connecting rods, this in-plane asymmetric mechanical deformation can actively induce the entire metal skeleton to become unstable and warp out of the plane (Z-axis), spontaneously forming a three-dimensional raised support structure (such as a dome or saddle shape) that adapts to the anatomical morphology of the alveolar ridge in the defect area. This structure absorbs the deformation stress through the rotation of the nodes, effectively eliminating stress concentration at the microscale and preventing the brittle metal from fracturing during large-scale deformation from the material's underlying layer.

[0010] According to a preferred embodiment of the present invention, the diameter of the first ring is larger than that of the second ring. In metamaterial mechanics, rings with different diameters can induce 3D curvature. When stretched, the different rotation angles and displacements will cause them to naturally arch upwards.

[0011] According to a preferred embodiment of the present invention, the metal skeleton is made of magnesium (Mg) alloy, zinc (Zn) alloy or a composite material thereof.

[0012] According to a preferred embodiment of the present invention, the basement membrane layer is a temperature-sensitive shape memory polymer (SMP), using a medical-grade biodegradable polymer material (such as modified polyurethane, a copolymer of polycaprolactone PCL and polylactic acid PLA, etc.) whose glass transition temperature (Tg) is adjusted to be close to the physiological body temperature (approximately 35℃-38℃). The basement membrane layer completely encapsulates the metal skeleton through a coaxial micro-nano impregnation coating process. Under this impregnation process, the SMP solution not only forms a continuous coating layer on the surface of each metal wire (connecting rod and ring) of the metal skeleton, but also, at the gaps between adjacent connecting rods and the first and second rings, a smooth transition meniscus is naturally formed by the physical surface tension of the liquid, thus presenting a seamless, webbed membrane structure. Figure 3 As shown.

[0013] According to a preferred embodiment of the present invention, the non-metallic lid area on the outer side of the basement membrane layer is integrally formed with an array of multiple pure polymer microbarbs facing the bone surface through a mold hot pressing or micro-injection molding process.

[0014] According to a preferred embodiment of the present invention, the ends of the microbarbs are asymmetrical barbed. In order to adapt to the changes in bone defect morphology caused by individual differences among patients, the basement membrane layer adopts an over-coverage design in clinical applications. That is, regardless of the defect morphology, its outer skirt will naturally extend and overlap the healthy cortical bone surface around the defect area. The healthy cortical bone surface is naturally attached with a tough periosteal connective tissue. Since the microbarb array covers the entire non-metallic skirt area, when the edge skirt is stimulated by body temperature to flip outward and flatten, a large number of microbarbs at the contact edge will dynamically penetrate and wrap around the periosteal connective tissue network around the defect area, producing a micro-mechanical interlocking effect similar to Velcro.

[0015] According to a preferred embodiment of the present invention, the microbarbs are internally doped or surface-loaded with antibacterial agents (such as chlorhexidine, antimicrobial peptides) or local anesthetics (such as lidocaine). After the barbs are anchored to the soft tissue, the targeted sustained release of the drug is achieved by utilizing the in-situ hydrolysis properties of the polymer, thereby reducing the early postoperative infection rate and relieving pain in the wound area.

[0016] The preparation method of the above-mentioned composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory includes the following steps: (1) At the in vitro manufacturing end, the metal skeleton is completely immersed in the viscous flow state of the temperature-sensitive shape memory polymer solution under the 3D raised shape of mechanical stretching and is pulled up at a uniform speed. The physical surface tension of the liquid is used to form a liquid film in the gap of the skeleton. The coaxial impregnation and curing of the temperature-sensitive shape memory polymer is completed by solvent evaporation or cross-linking drying to form a base film layer. This shape is physically fixed as the permanent memory shape of the composite material. (2) At an ambient temperature higher than the glass transition temperature, the three-dimensional structure of step (1) is forcibly compressed and folded into a long tube or a compact roll, and then rapidly cooled to room temperature (e.g., 25°C) to freeze the polymer chain segments and lock them into an extremely small temporary compressed form as the final delivery form of the medical device.

[0017] In the clinical setting, when the product in step (2) is placed under the periosteum and reaches the glass transition temperature, the SMP releases extremely strong shape recovery stress, actively and evenly pulling the internal anti-handed metal skeleton to unfold synchronously, spontaneously supporting the preset 3D osteogenic space under the periosteal flap.

[0018] The beneficial effects of this invention are as follows: 1. This invention establishes a dual mechanism of minimally invasive implantation and self-expanding expansion, significantly reducing surgical trauma compared to traditional titanium mesh implantation which relies on extensive incisions and flap creation. This invention utilizes the thermosensitive phase transition properties of shape memory polymers, causing the barrier membrane to exhibit an extremely contracted, tubular shape before implantation, allowing surgeons to insert it subperiosteally through a minimally invasive tunneling approach. Upon stimulation by body temperature, the polymer's restoring force forcibly drives the internal anti-chiral metal framework to precisely expand under dark-field conditions. Due to the synergistic extensional properties of the toroidal-tangential topology, the membrane generates a strong and uniform radial tenting force on the bone surface, successfully resisting the suture retraction tension of the gingival soft tissue and creating an undisturbed, optimal three-dimensional osteogenic microenvironment for bone particles.

[0019] 2. This invention designs a coaxial impregnation and continuous membrane process in an unfolded state, substantially solving the problems of material deformation interference and excessively rapid degradation of magnesium alloys. Traditional pressing processes easily lead to delamination and detachment of the metal and polymer during folding. This invention creatively enables SMP to grow in situ on unfolded metal wires, forming an extremely thin, webbed, continuous membrane. Its smooth transition meniscus not only effectively dissipates the stress during folding, preventing membrane tearing caused by repeated deformation; more importantly, this 100% dense coating without dead angles not only completely blocks the infiltration of fibroblasts, but also acts as a slow-release physical coating for the reactive magnesium alloy. Body fluids can only slowly permeate through the polymer matrix, ensuring that the mechanical strength of the metal skeleton does not drop sharply or suddenly generate gas to detach tissue during the critical period of bone regeneration (the first 12 weeks after surgery), and then both are safely degraded and absorbed synchronously.

[0020] 3. This invention constructs a drug-loaded, all-polymer Velcro soft anchoring system, completely eliminating the clinical risks associated with metal retainers and sharp edges. This invention abandons the hard-on-hard metal barbs, creatively utilizing pure polymer integrated microbarbs combined with the edge-turning stress generated by the heating of the SMP itself. When the skirt expands upon heating, it automatically anchors the flexible barbs into the periosteal collagen fibers, like pressing a thumbtack. This biomimetic soft gripping provides sufficient membrane retention force to counteract clinical suture tension, completely eliminating the extremely high surgical risks of titanium screws and the possibility of hard metal puncturing the gums; simultaneously, the microbarbs' built-in antibacterial / analgesic sustained-release function provides a pioneering local biochemical protective barrier for oral GBR surgery, which is highly susceptible to infection. Attached Figure Description

[0021] Figure 1 This is a schematic planar view of the metal skeleton of the present invention; Figure 2 This is a schematic diagram of the metal skeleton protrusion of the present invention; Figure 3 This is a microscopic schematic diagram of the basement membrane layer of the present invention; Figure 4 This is a schematic diagram illustrating the compression to expansion process of the present invention; Figure 5 This is a schematic diagram of the microbarb structure of the present invention; Figure 6 This is a schematic diagram illustrating the usage state of the present invention; Among them: 10, two-dimensional planar array; 11, first ring; 12, connecting rod; 13, in-plane tensile stress; 14, second ring; 15, three-dimensional raised support shape; 20. Cross-section of a metal wire; 21. Basement membrane layer; 22. Webbed membrane structure; 23. Concave meniscus; 30. Permanent memory form; 31. Temporary compressed form; 32. Thermally activated shape recovery process; 33. Forced compression and cooling locking process; 40. Skirt edge; 41. Micro-barbs; 42. Periosteal connective tissue; 50. Natural teeth; 51. Alveolar bone base; 52. Gingival soft tissue flap; 53. Composite barrier membrane; 54. Radial support force; 55. Independent osteogenesis three-dimensional space; 56. Bone graft particles. Detailed Implementation

[0022] The present invention will be further described below with reference to the embodiments and accompanying drawings, but is not limited thereto.

[0023] Example 1: like Figure 1-6As shown, this embodiment provides a guide bone regeneration composite barrier membrane based on anti-handed topological deformation and temperature-sensitive shape memory, including a metal skeleton and a basement membrane layer 21 that completely encloses the metal skeleton. The metal skeleton includes several rows of first rings 11 and second rings 14 that are staggered. The first rings 11 and adjacent second rings 14 are tangentially connected by connecting rods 12. Several first rings, second rings, and connecting rods, in their planar unfolded state, form a two-dimensional planar array 10, which is a reciprocal topological geometric array with negative Poisson's ratio metamaterial mechanical properties. When this two-dimensional planar array is subjected to in-plane tensile stress 13 and the mesh expands as a whole, the first and second rings, while undergoing relative spatial displacement as the expansion spacing increases, will also undergo non-coincident spin motion around their own geometric center, thereby driving the connecting rods to extend outward. Due to the physical difference between the rotational angular velocity of the rings with different diameters and the linear displacement of the released connecting rods, this in-plane asymmetric mechanical deformation can actively induce the metal skeleton to become unstable and warp out of the plane (Z-axis), spontaneously forming a three-dimensional raised support structure (such as a dome or saddle shape) that adapts to the anatomical morphology of the alveolar ridge in the defect area. This structure absorbs deformation stress through the rotation of the nodes, essentially eliminating the stress concentration phenomenon at the acute angle dead connection, and endowing the brittle magnesium alloy with excellent three-dimensional deformation compliance and vertical compressive stiffness.

[0024] The diameter of the first ring 11 is larger than that of the second ring 14. In metamaterial mechanics, rings with different diameters can induce 3D curvature. When stretched, the different rotation angles and displacements will cause them to arch upwards naturally.

[0025] The metal skeleton is made of medical-grade biodegradable magnesium alloy (such as Mg-Nd-Zn-Zr alloy) foil, which is prepared by femtosecond laser cutting process.

[0026] The basement membrane layer 21 is a temperature-sensitive shape memory polymer (SMP), made of medical-grade biodegradable polymer materials (such as modified polyurethane, copolymers of polycaprolactone PCL and polylactic acid PLA, etc.) with a glass transition temperature (Tg) adjusted to near human physiological body temperature (approximately 35℃-38℃). The basement membrane layer completely encapsulates the metal skeleton through a coaxial micro-nano impregnation coating process. Under this impregnation process, the SMP solution not only forms a continuous coating layer on the surface of each metal wire (connecting rod and ring) of the metal skeleton, but also, at the gaps between adjacent connecting rods 12 and the first ring 11 and the second ring 14, a smooth transition meniscus 23 is naturally formed by the physical surface tension of the liquid, thus presenting a seamless, webbed membrane structure 22. Figure 3 As shown, this ensures sufficient stress buffer space during subsequent compression-re-expansion cycles, completely preventing membrane tearing and establishing a perfect physical barrier against soft tissue and body fluids.

[0027] The non-metallic lid area of ​​the outer skirt 40 of the basement membrane layer is integrally set with an array of multiple pure polymer microbarbs 41 facing the bone surface through mold hot pressing or micro injection molding process. The height of the microbarbs 41 is 300-600 micrometers.

[0028] The ends of the microbarbs 41 are asymmetrical barbed. To accommodate the changes in bone defect morphology caused by individual differences among patients, the basement membrane layer adopts an over-coverage design in clinical applications. That is, regardless of the defect morphology, its outer skirt will naturally extend and overlap the healthy cortical bone surface around the defect area. The healthy cortical bone surface is naturally attached with a tough periosteal connective tissue 42. Since the microbarb array covers the entire non-metallic skirt area, when the edge skirt is stimulated by body temperature to flip outward and flatten, a large number of microbarbs at the contact edge will dynamically penetrate and wrap around the periosteal connective tissue network around the defect area, producing a micro-mechanical interlocking effect similar to Velcro.

[0029] The barbs are internally doped or surface-loaded with antibacterial agents (such as chlorhexidine, antimicrobial peptides) or local anesthetics (such as lidocaine). After the barbs are anchored to the soft tissue, the in-situ hydrolysis properties of the polymer enable targeted and sustained release of the drug, thereby reducing the early postoperative infection rate and relieving pain in the wound area.

[0030] The preparation method of the above-mentioned composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory includes the following steps: (1) At the in vitro manufacturing end, the metal skeleton is fully immersed in the viscous flow state of the temperature-sensitive shape memory polymer solution under the 3D raised shape of mechanical stretching and is pulled at a uniform speed. The physical surface tension of the liquid is used to form a liquid film in the gap of the skeleton. The coaxial impregnation and curing of the temperature-sensitive shape memory polymer is completed by solvent evaporation or cross-linking drying to form a base film layer. The shape is physically fixed as the permanent memory shape 30 of the composite material. (2) At an ambient temperature above the glass transition temperature (37°C), the three-dimensional structure of step (1) is forcibly compressed and folded into a long tube or a compact roll, and then rapidly cooled to room temperature (e.g., 25°C) to freeze the polymer chain segments and lock them into an extremely small temporary compressed form 31 as the final delivery form of the medical device.

[0031] After being placed in the affected area, the barrier membrane quickly absorbs heat from the human blood to reach Tg (37°C). The frozen stress inside the SMP material is released instantly, generating a strong shape recovery force. This actively drives the embedded metal skeleton to expand synchronously. Under the periosteum, the barrier membrane spontaneously expands and recovers to a permanent memory shape that fits the alveolar ridge morphology.

[0032] This self-expansion process generates an upward supporting force sufficient to counteract the tension of the gingival flap suture, constructing a robust, closed three-dimensional cavity. At this point, the surrounding microbarbs have automatically grasped the periosteum to complete anchoring. Subsequently, the dentist injects bone graft particles into this independent cavity through a microchannel. The dense SMP layer on the outside prevents the invasion of fibroblasts, while the internal bone particles gradually transform into mature autologous bone in a static, undisturbed microenvironment, thus achieving a closed-loop, highly efficient, minimally invasive, and fully degradable bone regeneration treatment.

Claims

1. A composite barrier membrane for guiding bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory, characterized in that, It includes a metal skeleton and a base film layer that completely encloses the metal skeleton. The metal skeleton includes several rows of first and second rings arranged in an alternating pattern. The first rings and adjacent second rings are tangentially connected by connecting rods.

2. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 1, characterized in that, The diameter of the first ring is larger than the diameter of the second ring.

3. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 1, characterized in that, The metal frame is made of magnesium alloy, zinc alloy or their composite materials.

4. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 1, characterized in that, The base film is a temperature-sensitive shape memory polymer. The base film completely encapsulates the metal skeleton through a coaxial micro-nano immersion coating process. At the gaps between adjacent connecting rods and the first and second rings, a smooth transition concave meniscus is naturally formed by the physical surface tension of the liquid, thus presenting a seamless webbed membrane structure.

5. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 1, characterized in that, The non-metallic lid area on the outer side of the basement membrane layer is integrally set with an array of multiple micro-barbs facing the bone surface through mold hot pressing or micro-injection molding processes.

6. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 5, characterized in that, The ends of the microbarbs have an asymmetrical barb shape.

7. The composite barrier membrane for guided bone regeneration based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 5, characterized in that, The microbarbs are internally doped or surface-loaded with antibacterial agents or local anesthetics.

8. The preparation method of the guided bone regeneration composite barrier membrane based on anti-chiral topological deformation and thermosensitive shape memory as described in claim 4, comprising the following steps: (1) At the in vitro manufacturing end, the metal skeleton is completely immersed in the viscous flow state of the temperature-sensitive shape memory polymer solution under the 3D raised shape of mechanical stretching and is pulled at a uniform speed. The physical surface tension of the liquid is used to form a liquid film in the gap of the skeleton. The coaxial impregnation and curing of the temperature-sensitive shape memory polymer is completed by solvent evaporation or cross-linking drying to form a base film layer. This shape is physically fixed as the permanent memory shape of the composite material. (2) At an ambient temperature higher than the glass transition temperature, the three-dimensional structure of step (1) is forcibly compressed, folded into a long tube or a compact roll, and cooled to room temperature to freeze the polymer chain segments and lock them into a temporary compressed form as the final delivery form of the medical device.

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