Regeneration-promoting flexible degradable nipple implant and manufacturing method thereof

Abstract

The invention relates to a regeneration-promoting flexible degradable nipple implant and a manufacturing method thereof, the regeneration-promoting flexible degradable nipple implant comprises a porous supporting structure and a directional porous structure, the porous supporting structure is located on the periphery of the degradable nipple implant, and the shape of the porous supporting structure is matched with the shape of a nipple required by a patient; the oriented porous structure is filled in the porous supporting structure and embedded with the porous supporting structure, the oriented porous structure is of a three-dimensional network structure formed by a plurality of oriented micro-nano fibers, a plurality of through oriented pore channels are formed in the oriented porous structure, and any oriented pore channel extends from the nipple root to the nipple head; a microenvironment for guiding rapid growth of cells and tissues is created through directional pore channels in the same direction, and rapid survival of nipple tissues and reconstruction of a nipple and areola complex are facilitated; the implant disclosed by the invention has the functions of structure supporting and growth guiding.

Description

Technical Field

[0001] The invention relates to the technical field of breast tissue engineering and biomanufacturing, and in particular to a regeneration-promoting flexible and degradable nipple implant and a manufacturing method thereof. Background Art

[0002] Breast cancer ranks first in the incidence of female malignant tumors and seriously threatens women's life and health. Surgical resection is the main means of treating breast cancer. Although it can effectively remove malignant tumors, patients after total mastectomy often face the problem of breast loss, which not only affects the patient's own body image, but also causes serious harm to the patient's mental health. Therefore, breast reconstruction has become an important measure to improve the physical and mental health of patients.

[0003] In the process of breast reconstruction, the reconstruction of the nipple-areola complex is particularly critical. The nipple-areola complex is one of the most important surface landmarks of the breast, and plays a vital role in restoring the natural appearance of the breast and the patient's self-identity. However, the existing clinical nipple-areola reconstruction strategies mainly rely on free transplantation of local flaps and composite tissue flaps. These methods are difficult to operate and require doctors to have superb skills to construct a replacement nipple with appropriate size, protrusion and shape; in addition, for patients, it means that they need to endure additional surgical trauma and potential complications, which undoubtedly increases the physical and mental burden of patients. Therefore, the development of a new type of nipple-areola reconstruction implant to simplify and optimize the existing surgical procedures is not only of great clinical significance, but also the key to improving the quality of life of patients after surgery.

[0004] In the prior art, a patent application entitled "Nipple Reconstruction Implant" (publication number: CN117460481A) discloses a nipple reconstruction implant composed of a polymer knitted or woven macroporous textile and a polymer microporous nonwoven or foam-like material. However, due to the lack of a controllable manufacturing process (the doctor performs suturing operations during surgery), this type of nipple reconstruction implant has low manufacturing efficiency, unstable structure, and its mechanical behavior and ability to maintain its shape after implantation cannot be guaranteed. A patent application entitled “Implant for reconstruction of nipple-areola complex and method for manufacturing the same” (publication number: CN113825470A) discloses that the implant has a cylindrical main body with a porous structure and a disc-shaped support body, which is made of biodegradable materials and manufactured by 3D printing technology; similarly, a patent application entitled “Nipple reconstruction implant” (publication number: CN117529293A) discloses an absorbable 3D printed implant having a macroporous network with an open-pore structure formed by parallel filament planes; the porous structures of the above two 3D printed degradable nipple implants are both stacked with parallel arranged fibers, lack flexibility and bending ability in the vertical direction, and cannot match the flexible nature of the natural nipple. More importantly, after the nipple implant is implanted, the patient's nipple tissue grows slowly due to the lack of a microenvironment to guide cell growth. If you want to accelerate the growth of nipple tissue, you mostly rely on the postoperative implantation of exogenous substances, such as: cells, stem cells, differentiated cells, fat cells, muscle cells, platelets, tissues, liposuction materials, extracellular fat matrix proteins, gels, hydrogels, hyaluronic acid, collagen, bioactive agents, drugs, antibiotics, etc. Secondary implantation after surgery increases the risk of secondary infection and gives patients a poor experience. Summary of the invention

[0005] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide a regenerative flexible and degradable nipple implant and a manufacturing method thereof, which has both structural support and growth guidance functions to solve the problem of slow growth of nipple tissue caused by the lack of a microenvironment to guide cell growth.

[0006] In order to achieve the above object, the technical solution of the present invention is:

[0007] A regenerative, flexible and degradable nipple implant comprising:

[0008] A porous support structure is located at the periphery of the degradable nipple implant, and the shape of the porous support structure matches the desired nipple shape of the patient;

[0009] The directional porous structure is filled inside the porous support structure and organically embedded with the porous support structure. The directional porous structure is a three-dimensional network structure formed by a number of directional micro-nano fibers. The directional porous structure includes a number of interconnected directional channels, and any directional channel extends in a directional direction from the root of the nipple toward the head of the nipple.

[0010] The shape of the porous support structure is acquired through medical imaging data, and is formed by a number of interwoven elastic fibers. The equivalent modulus of the porous support structure ranges from 0 MPa to 1 MPa, and the line diameter of the elastic fibers ranges from 100 μm to 1000 μm.

[0011] The material of the porous support structure is a medical degradable polymer material, including polyhydroxyalkanoate (PHA), polycaprolactone (PCL), polyglycolide (PGA), polybutylene succinate (PBS) and its copolymers, as well as polyvinyl alcohol (PVA), polylactic acid (PLA) and polylactic acid-glycolic acid copolymer (PLGA); the manufacturing method includes 3D printing technology and / or mold casting technology.

[0012] The directional porous structure is formed by guiding the self-organization of micro-nano fibers through deformation, light, sound, electricity, magnetism, force, phase separation or by 3D printing.

[0013] The preparation material of the oriented porous structure includes high molecular polymer fiber, hydrogel or aerogel.

[0014] The size of the micro-nano fibers of the oriented porous structure is between 0.1 μm and 100 μm, and the pore size of the penetrating oriented channels is between 30 μm and 2000 μm.

[0015] The regeneration-promoting flexible and degradable nipple implant also includes a positioning part, one side of which is connected to one end of the porous support structure, and the other side of the positioning part is in contact with breast tissue.

[0016] The regenerative-promoting flexible and degradable nipple implant is implanted into the nipple as a carrier carrying beneficial substances, wherein the beneficial substances include drugs, active factors, exosomes, nuclides and nano fats.

[0017] The method for manufacturing the regenerative-promoting flexible and degradable nipple implant comprises the following steps:

[0018] S1: Obtain imaging data of the patient's nipple and areola through imaging methods, and use computer-aided design software for three-dimensional modeling to construct a nipple and areola appearance model;

[0019] S2: Design a porous support structure for a regenerative flexible and degradable nipple implant based on the nipple-areola appearance model, and optimize the flexibility to achieve a level close to that of autologous tissue;

[0020] S3: Using medical biodegradable polymer materials and 3D printing technology to fabricate porous support structures for regenerative flexible biodegradable nipple implants;

[0021] S4: Infuse or print hydrogel or electrospun polymer nanofibers into the porous support structure of the regenerative flexible and degradable nipple implant;

[0022] S5: A directional porous structure of a flexible and degradable nipple implant that promotes regeneration and guides the rapid growth of autologous tissue is obtained through external field guidance or phase separation.

[0023] When designing a porous supporting structure of a regenerative flexible and degradable nipple implant based on a nipple-areola appearance model and optimizing any step close to autologous tissue, beneficial substances are loaded on the degradable nipple implant. The loading methods of the beneficial substances include surface coating, injection, grafting and / or coupling.

[0024] Compared with the prior art, the present invention has the following advantages:

[0025] The present invention provides a regenerative flexible and degradable nipple implant, which creates a microenvironment guiding the rapid growth of cells and tissues through directional channels with consistent directions, and is beneficial to the rapid survival of nipple tissue and the reconstruction of the nipple-areola complex.

[0026] (1) The regenerative flexible and degradable nipple implant of the present invention has an appearance similar to that of a normal nipple-areola complex, and can reconstruct the nipple-areola complex into a shape close to nature, thereby improving the psychological satisfaction of patients.

[0027] (2) The porous support structure of the regenerative flexible and degradable nipple implant of the present invention is customized and has adjustable flexibility, which is similar to the flexibility of autologous tissue and can maintain its shape in the patient's body for a long time after implantation.

[0028] (3) The directional porous structure of the present invention is used as the internal filling of the regenerative flexible and degradable nipple implant, which solves the problem that traditional implants lack a structural microenvironment to guide rapid cell growth, and is conducive to the rapid survival of reconstructed tissue and the regeneration and reconstruction of the nipple areola complex.

[0029] (4) The regenerative flexible and degradable nipple implant of the present invention is loaded with active factors, drugs or nuclides, has certain tumor killing properties and the ability to promote the growth of autologous tissue, and further improves the reconstruction efficiency of the patient's nipple and areola. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 Schematic diagram of the structure of a flexible and degradable nipple implant that promotes regeneration according to an embodiment.

[0031] Figure 2 Schematic diagram of the porous support structure and positioning part structure of the embodiment.

[0032] Figure 3 It is a physical picture of the porous support structure and the positioning part of the embodiment.

[0033] Figure 4 Schematic diagram of the oriented porous structure of the embodiment.

[0034] Figure 5 This is a physical picture of the oriented porous structure of Example 1.

[0035] Figure 6 Schematic diagram of constructing a directional porous structure in Example 2.

[0036] Figure 7 This is a physical picture of the oriented porous structure of Example 2. DETAILED DESCRIPTION

[0037] The present invention is further described in detail below in conjunction with the examples and accompanying drawings. It should be noted that the following detailed descriptions are exemplary and are intended to provide further explanation of the present invention. Unless otherwise specified, all technical and scientific terms used have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs.

[0038] Example 1, a regenerative flexible and degradable nipple implant, comprising a porous support structure 101 for supporting the external shape and a directional porous structure 102 filled inside for guiding the growth of vascularized tissue, such as Figure 1 As shown; the shape of the porous support structure 101 matches the natural nipple, providing suitable mechanical support and shape retention capabilities for nipple reconstruction, such as Figure 2 , Figure 3 As shown; the directional porous structure 102 is located inside the porous support structure 101 and is interlocked with it. The directional channels that penetrate each other can guide the rapid growth of vascularized tissue, such as Figure 1 , Figure 4 shown.

[0039] The shape of the porous support structure 101 is consistent with the actual nipple contour of the implanted patient, which is obtained by extracting the patient's medical imaging data; the porous support structure 101 is custom-designed according to mechanical properties, the fiber type used is a spiral elastic structure, the fiber size is 500μm, and the equivalent modulus of the porous support structure is 20-500kPa.

[0040] The porous support structure 101 is printed by laser powder bed melting technology, and the medical degradable polymer material used is polycaprolactone.

[0041] The regenerative flexible and degradable nipple implant further comprises a positioning portion 103, one side of the positioning portion 103 is connected to one end of the porous support structure 101, and the other side of the positioning portion 103 is in contact with the breast tissue. Figure 1 , Figure 3 shown.

[0042] like Figure 4 As shown, the directional porous structure 102 includes a plurality of directional channels that are interconnected, and any directional channel extends from the nipple root toward the nipple head.

[0043] like Figure 5 As shown, the micro-nano fibers obtained by electrospinning are resuspended and then unidirectionally freeze-casted, followed by freeze-drying. The micro-nano fibers are squeezed to the interface between ice crystals by ice crystals that grow directionally along the temperature gradient, forming a directional porous structure 102 that extends directionally from the nipple root toward the nipple head.

[0044] The method for manufacturing the above-mentioned regenerative flexible and degradable nipple implant comprises the following steps:

[0045] S1. Obtain imaging data of the patient's nipple and areola by imaging methods, and use computer-aided design software to perform three-dimensional modeling to construct a nipple and areola appearance model;

[0046] S2. Design of a porous support structure 101 of a flexible and degradable nipple implant for promoting regeneration based on a nipple-areola appearance model, such as Figure 2 As shown; the flexibility close to that of autologous tissue is optimized, and the shape of the porous support structure 101 in the figure is formed by spiral fibers winding, and its mechanical behavior can be regulated by adjusting the pitch, fiber size and spiral radius of the spiral fibers;

[0047] S3. Using medical degradable polymer materials and 3D printing technology to produce a porous support structure of a regenerative flexible degradable nipple implant 101, such as Figure 3 As shown;

[0048] S4, infusing the electrospun chopped fibers into the porous support structure 101 of the regenerative flexible and degradable nipple implant;

[0049] Prepare 10% polycaprolactone-hexafluoroisopropanol solution; use a 20G needle, voltage 15kV, flow rate 0.6mLh -1 and receiving distance of 15 cm to prepare micro-nano fibers; after drying, using a freezing slicer and an ultrasonic disperser to cut the electrospun chopped fibers into pieces and disperse them into a chopped fiber suspension in ultrapure water; injecting the chopped fiber suspension into the porous support structure 101 for unidirectional freeze casting;

[0050] S5, obtaining a directional porous structure 102 of a regenerative flexible degradable nipple implant that guides rapid growth of autologous tissue by freeze-drying phase separation;

[0051] In this embodiment, a directional porous structure 102 inside a regenerative flexible and degradable nipple implant is obtained by unidirectional freeze casting followed by freeze drying. Figure 5 As shown, the cross section in the figure shows that the oriented porous structure 102 has interlaced pores, the pore size is between 30-200μm, and the longitudinal interface shows its single orientation method. The wall of the pore structure is also a porous structure composed of micro-nano fibers with a wall thickness of about 1μm. The micro-nano fibers can load radionuclides to kill the surrounding residual cancer tissue cells in a controlled manner in time and space, thereby promoting the growth of normal tissues; when the regenerative flexible and degradable nipple implant is implanted in the body, part of the autologous tissue such as skin flaps or fat can be migrated to embed and fix it, and the oriented porous structure 102 will guide the autologous tissue to grow rapidly to achieve nipple reconstruction.

[0052] Example 2: This example uses structural deformation / mechanics to guide the orientation of hydrogel fibers to obtain another oriented porous structure 102 inside a flexible and degradable nipple implant that promotes regeneration. Its manufacturing steps S1-S3 are consistent with those of Example 1.

[0053] like Figure 6 As shown, in order to construct its directional porous structure 102, a 0.6 mg / mL bovine fibrinogen aqueous solution is prepared and the active factors are uniformly mixed therewith; then, the porous support structure 101 is compressed to a strain of 20%, and the bovine fibrin solution is mixed with thrombin and then poured into the compressed and deformed porous support structure 101. After the bovine fibrin is cross-linked, a bovine fibrin hydrogel-porous support structure complex is formed. At this time, the directions of the bovine fibrin fibers are random and disordered, as shown in FIG. Figure 7 As shown; then release its external constraints, the porous support structure 101 restores its original height, in this process the bovine fibrin is stretched and deformed, and the bovine fibrin micro-nano fibers inside are oriented along the stretching deformation direction to form a directional porous structure 102 inside the flexible and degradable nipple implant that promotes regeneration, as shown Figure 7 shown.

Claims

1. A regenerative, flexible, degradable nipple implant, characterized in that: include: A porous support structure is located at the periphery of the degradable nipple implant, and the shape of the porous support structure matches the desired nipple shape of the patient; The directional porous structure is filled inside the porous support structure and organically embedded with the porous support structure. The directional porous structure is a three-dimensional network structure formed by a number of directional micro-nano fibers. The directional porous structure includes a number of interconnected directional channels, and any directional channel extends in a directional direction from the root of the nipple toward the head of the nipple.

2. A regenerative, flexible and degradable nipple implant according to claim 1, characterized in that: The shape of the porous support structure is acquired through medical imaging data, and is formed by a number of interwoven elastic fibers. The equivalent modulus of the porous support structure ranges from 0 MPa to 1 MPa, and the line diameter of the elastic fibers ranges from 100 μm to 1000 μm.

3. A regenerative, flexible and degradable nipple implant according to claim 1, characterized in that: The material of the porous support structure is a medical degradable polymer material, including polyhydroxyalkanoate (PHA), polycaprolactone (PCL), polyglycolide (PGA), polybutylene succinate (PBS) and its copolymers, as well as polyvinyl alcohol (PVA), polylactic acid (PLA) and polylactic acid-glycolic acid copolymer (PLGA); the manufacturing method includes 3D printing technology and / or mold casting technology.

4. A regenerative and flexible degradable nipple implant according to claim 1, characterized in that: The oriented porous structure is formed by guiding the self-organization of micro-nano fibers through deformation, light, sound, electricity, magnetism, force, phase separation or by 3D printing.

5. The regenerative flexible and degradable nipple implant according to claim 1, characterized in that: The preparation material of the oriented porous structure includes high molecular polymer fiber, hydrogel or aerogel.

6. A regenerative, flexible and degradable nipple implant according to claim 1, characterized in that: The size of the micro-nano fibers of the oriented porous structure is between 0.1 μm and 100 μm, and the pore size of the penetrating oriented channels is between 30 μm and 2000 μm.

7. A regenerative, flexible and degradable nipple implant according to claim 1, characterized in that: It also includes a positioning part, one side of which is connected to one end of the porous support structure, and the other side of the positioning part is in contact with the breast tissue.

8. The regenerative flexible and degradable nipple implant according to claim 1, characterized in that: Beneficial substances are implanted into the nipple as carriers, including drugs, active factors, exosomes, radionuclides and nano-fats.

9. A method for manufacturing a regenerative flexible and degradable nipple implant according to any one of claims 1 to 8, characterized in that: The following steps are involved: S1: Obtain imaging data of the patient's nipple and areola through imaging methods, and use computer-aided design software for three-dimensional modeling to construct a nipple and areola appearance model; S2: Design a porous support structure for a regenerative flexible and degradable nipple implant based on the nipple-areola appearance model, and optimize the flexibility to achieve a level close to that of autologous tissue; S3: Using medical biodegradable polymer materials and 3D printing technology to fabricate porous support structures for regenerative flexible biodegradable nipple implants; S4: Infuse or print hydrogel or electrospun polymer nanofibers into the porous support structure of the regenerative flexible and degradable nipple implant; S5: A directional porous structure of a flexible and degradable nipple implant that promotes regeneration and guides the rapid growth of autologous tissue is obtained through external field guidance or phase separation.

10. The manufacturing method according to claim 9, characterized in that: When designing a porous supporting structure of a regenerative flexible and degradable nipple implant based on a nipple-areola appearance model and optimizing any step close to autologous tissue, beneficial substances are loaded on the degradable nipple implant. The loading methods of the beneficial substances include surface coating, injection, grafting and / or coupling.

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