A facial implant

Abstract

The application discloses a facial implant, which comprises an outer nose prosthesis, a nose column prosthesis and a nasal septum prosthesis, one side of the nasal septum prosthesis is connected with the inner arc side of the outer nose prosthesis, and adjacent sides of the nasal septum prosthesis are connected with the nose column prosthesis, and the facial implant is symmetrically arranged about the plane where the nasal septum prosthesis is located; the facial implant is prepared based on silk fibroin. The facial implant is prepared by using silk fibroin, has good mechanical properties and biocompatibility, can be effectively plasticized, and can promote tissue repair and regeneration.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical devices, in particular to a facial implant. BACKGROUND

[0002] At present, the mainstream material of facial implants is still silicone, and the application of some biodegradable materials and composite materials, such as polylactic acid, titanium alloy and bioceramics combination, is also gradually increasing; however, silicone has low hardness, has the risk of displacement, and long-term implantation can easily cause inflammation; titanium alloy is difficult to process, and needs to be removed by secondary surgery, which is inconvenient to operate; and the degradation rate of polylactic acid is too fast, and the degradation product is prone to inflammatory reaction. SUMMARY

[0003] In view of the problems existing in the prior art, the present application provides a facial implant, and the technical solution is as follows:

[0004] The present application provides a facial implant, comprising an external nose prosthesis, a nasal column prosthesis and a nasal septum prosthesis, one side of the nasal septum prosthesis is connected with the inner arc side of the external nose prosthesis, the adjacent side of the nasal septum prosthesis is connected with the nasal column prosthesis, and the facial implant is symmetrically arranged about the plane where the nasal septum prosthesis is located.

[0005] The facial implant is made of silk fibroin.

[0006] Further, the external nose prosthesis, the nasal septum prosthesis and the nasal column prosthesis are connected with each other through a mortise and tenon structure.

[0007] Further, the nasal septum prosthesis is in a trapezoidal structure, the nasal septum prosthesis comprises a first tenon and a second tenon, the first tenon is located on the inclined side of the nasal septum prosthesis, and the second tenon is located on the bottom side of the nasal septum prosthesis.

[0008] The inner arc side of the external nose prosthesis is provided with a first mortise hole, and the first mortise hole is connected with the first tenon.

[0009] The nasal column prosthesis is provided with a second mortise hole on one side facing the nasal septum prosthesis, and the second mortise hole is connected with the second tenon.

[0010] Further, the nasal column prosthesis is provided with a mortise groove on the nasal columella prosthesis, and the second mortise hole is located in the mortise groove.

[0011] One end of the external nose prosthesis is provided with a third tenon, the mortise groove is at least partially connected with the third tenon, and the mortise groove is at least partially connected with the bottom side of the nasal septum prosthesis through the mortise and tenon structure.

[0012] Further, the first tenon and the second tenon satisfy at least one of the following characteristics:

[0013] The width of at least one of the first tenon and the second tenon is 1.5mm-2.0mm;

[0014] The length of at least one of the first tenon and the second tenon is 1.0mm-5.0mm;

[0015] The interval between two adjacent first tenons in the direction of the bevel of the nasal septum prosthesis is 0.1mm-10.0mm;

[0016] The interval between two adjacent second tenons in the direction of the bottom edge of the nasal septum prosthesis is 0.1mm-10.0mm;

[0017] The number of at least one of the first tenon and the second tenon is 1-6.

[0018] Further, the cooperation tolerance between the outer nose prosthesis, the nasal septum prosthesis and the nasal column prosthesis is-0.1mm-+0.1mm.

[0019] Further, the outer nose prosthesis comprises a nasal ridge prosthesis and a nasal back prosthesis, the nasal ridge prosthesis is arranged opposite to the inner arc side, and the nasal back prosthesis is symmetrically arranged on both sides of the nasal ridge prosthesis.

[0020] The nasal column prosthesis comprises a nasal columella prosthesis and a nasal ala prosthesis, the nasal columella prosthesis is connected with the nasal septum prosthesis, and the nasal ala prosthesis is symmetrically arranged on both sides of the nasal columella prosthesis.

[0021] Further, the cross-sectional area of one end of the outer nose prosthesis close to the nasal column prosthesis is smaller than the cross-sectional area of the other end of the outer nose prosthesis away from the nasal column prosthesis.

[0022] Further, the face implant satisfies at least one of the following characteristics:

[0023] The tensile modulus of the face implant is 28.85MPa-82.45MPa;

[0024] The tensile strength of the face implant is 6.35MPa-9.84MPa;

[0025] The elongation at break of the face implant is 0.65%-1.38%.

[0026] Further, the face implant is made by resolubilizing, injection molding, curing forming, bubble washing and drying and machining of silk fibroin.

[0027] The implementation of the present application has the following beneficial effects:

[0028] 1. The facial implant of the present invention is made of silk fibroin, which gives the facial implant good mechanical properties. Combined with the overall shape of the external nasal implant, nasal septum implant, and nasal columella implant, it can be effectively shaped and has a slow degradation rate, preventing the facial implant from losing its support too early and effectively maintaining the reliability and stability of the shaping. At the same time, silk fibroin contains a large number of amino acids similar to those in the human body, which can also promote tissue repair and regeneration. The use of silk fibroin gives the facial implant excellent biocompatibility. Even after long-term use and eventual degradation, it is not likely to cause risks such as inflammation and bacterial infection, and has good safety.

[0029] 2. In the facial implant of the present invention, the external nasal prosthesis, the nasal septum prosthesis and the nasal columella prosthesis are connected in pairs by a mortise and tenon structure, which can be quickly assembled, is simple and convenient to operate, and does not require the introduction of additional heterogeneous connecting parts. The connection has good reliability, which is conducive to maintaining the overall mechanical properties and biocompatibility of the facial implant and promoting tissue repair. Attached Figure Description

[0030] To more clearly illustrate the technical solution of the present invention, the accompanying drawings used in the embodiments will be briefly described below, wherein the same components are represented by the same reference numerals. Obviously, the drawings described below are merely some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0031] Figure 1 An exploded view of the structure of a facial implant provided in an embodiment of the present invention;

[0032] Figure 2 This is a schematic diagram of the structure of a facial implant after assembly, provided by an embodiment of the present invention;

[0033] Figure 3 This is a physical image of a facial implant provided in an embodiment of the present invention;

[0034] Figure 4 This is a flowchart of a method for preparing a facial implant in a specific embodiment of the present invention;

[0035] Figure 5 This is a pathological image of skin tissue from mice in the blank control group at 4 weeks.

[0036] Figure 6 This is a pathological image of skin tissue from mice in the blank control group at 12 weeks.

[0037] Figure 7 Histopathological images of the injection site in positive group mice at 4 weeks;

[0038] Figure 8 Histopathological images of the injection site in positive group mice at 12 weeks;

[0039] Figure 9 Histopathology of implant site tissue of raw material group mice at 4 weeks;

[0040] Figure 10 Histopathology of implant site tissue of raw material group mice at 12 weeks;

[0041] Figure 11 Histopathology of implant site tissue of product group mice at 4 weeks;

[0042] Figure 12 Histopathology of implant site tissue of product group mice at 12 weeks;

[0043] Figure 13 Histopathology of spleen tissue of blank control group mice at 4 weeks;

[0044] Figure 14 Histopathology of spleen tissue of positive control group mice at 4 weeks;

[0045] Figure 15 Histopathology of spleen tissue of raw material group mice at 4 weeks;

[0046] Figure 16 Histopathology of spleen tissue of product group mice at 4 weeks;

[0047] Figure 17 Histopathology of thymus tissue of blank control group mice at 4 weeks;

[0048] Figure 18 Histopathology of thymus tissue of positive control group mice at 4 weeks;

[0049] Figure 19 Histopathology of thymus tissue of raw material group mice at 4 weeks;

[0050] Figure 20 Histopathology of thymus tissue of product group mice at 4 weeks;

[0051] Figure 21 Histopathology of spleen tissue of blank control group mice at 12 weeks;

[0052] Figure 22 Histopathology of spleen tissue of positive control group mice at 12 weeks;

[0053] Figure 23 Histopathology of spleen tissue of raw material group mice at 12 weeks;

[0054] Figure 24 Histopathology of spleen tissue of product group mice at 12 weeks;

[0055] Figure 25 Histopathology of thymus tissue of blank control group mice at 12 weeks;

[0056] Figure 26 Figure 8 is a histopathology of the thymus tissue of the raw material group mice at 12 weeks;

[0057] Figure 27 Figure 9 is a histopathology of the thymus tissue of the product group mice at 12 weeks;

[0058] Figure 28 Figure 10 is a histopathology of the thymus tissue of the positive control group mice at 12 weeks.

[0059] Wherein, the reference signs are:

[0060] 1-outer nose prosthesis, 11-nose bridge prosthesis, 12-nose back prosthesis, 13-inner arc side, 14-first tenon hole, 15-third tenon head, 2-nose column prosthesis, 21-nose columnlet prosthesis, 22-nose wing prosthesis, 23-second tenon hole, 24-tenon slot, 3-nasal septum prosthesis, 31-first tenon head, 32-second tenon head. DETAILED DESCRIPTION

[0061] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all the embodiments, and therefore cannot be understood as limiting the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of the present application.

[0062] It should be noted that in the description of the present application, the following defined terms, unless otherwise indicated in the claims or elsewhere in the specification, should be applied. All numerical values, whether explicitly stated or implicitly understood from the context, are defined as being "about" unless specifically indicated otherwise. The term "about" generally refers to a numerical range that those of ordinary skill in the art would consider equivalent to the stated value to produce substantially the same properties, functions, results, etc. A numerical range indicated by a lower value and a higher value is defined to include all numerical values included in the numerical range and all sub-ranges included in the numerical range.

[0063] It should be noted that the terms "first," "second," etc., in the specification, claims, and drawings of this invention are used to distinguish similar objects and are not necessarily used to describe a specific order or sequence. It should be understood that such objects can be used interchangeably where appropriate so that embodiments of the invention can be implemented in orders other than those illustrated or described below. Furthermore, the terms "comprising" and "having," and any variations thereof, are intended to cover non-exclusive inclusion; for example, a process, method, system, or product comprising a series of steps or units is not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to these processes, methods, or products.

[0064] To address the shortcomings of existing facial implants in simultaneously achieving adequate rigidity, suitable degradation rate, good biocompatibility, and ease of use, this invention provides a facial implant, such as... Figure 1 As shown, the facial implant includes an external nasal prosthesis 1, a columellar prosthesis 2, and a nasal septum prosthesis 3. The external nasal prosthesis 1 serves as the external nose, the columellar prosthesis 2 serves as the columella, and the nasal septum prosthesis 3 serves as the nasal septum. One side of the nasal septum prosthesis 3 is connected to the inner arc side 13 of the external nasal prosthesis 1, and the nasal septum prosthesis 3 is located in the middle of the external nasal prosthesis 1. An adjacent side of the nasal septum prosthesis 3 is connected to the columellar prosthesis 2. The facial implant is symmetrically arranged about the plane containing the nasal septum prosthesis 3, resulting in good aesthetic shaping. The entire facial implant is made of silk fibroin, and its main components include silk fibroin. Including sterile water for injection or physiological saline, silk fibroin is a natural high-molecular-weight protein with good mechanical properties, providing excellent mechanical properties for facial implants and good shaping effects. This allows the facial implants to be directly sculpted during use, offering good flexibility in shaping. Furthermore, silk fibroin has good biocompatibility, containing a large number of amino acids similar to those in the human body, which promotes tissue recovery, thus promoting tissue repair and growth after implantation. In addition, silk fibroin is biodegradable, but the degradation rate is slow, effectively maintaining shaping stability and reducing the risk of inflammation and bacterial infection, resulting in good safety.

[0065] Specifically, such as Figure 2 As shown, the external nasal implant 1 includes a nasal bridge implant 11 and a nasal dorsum implant 12. The external nasal implant 1 is the main morphological component of the facial implant, used for shaping. (The text repeats itself here.) Figure 1As shown, the nose bridge prosthesis 11 is arranged opposite to the inner arch side 13, and the nose back prosthesis 12 is symmetrically arranged on both sides of the nose bridge prosthesis 11, so that the symmetry of the external nose prosthesis 1 is good, and the appearance of the plastic shape is improved after implantation. In addition, the external nose prosthesis 1 is an integral structure, that is, the nose bridge prosthesis 11 and the nose back prosthesis 12 are integrally formed, which simplifies the assembly process in the subsequent use process, improves the operation convenience, and is also beneficial to improve the overall integrity and continuity of the external nose prosthesis 1, maintains the uniformity of the mechanical properties of the external nose prosthesis 1 as a whole, and can provide good and reliable support force after implantation, has good long-term stability, and is beneficial to improve the durability of the external nose prosthesis 1. In addition, in some optional embodiments, the nose back prosthesis 12 extends from the side connected to the nose bridge prosthesis 11 towards the inner arch side 13, or can be sculpted as a slope extending towards the inner arch side 13 in use, so that the shape of the external nose prosthesis 1 is more in line with the structure of the human external nose, and the appearance of the plastic shape is better.

[0066] Specifically, as shown in Figure 2 , the cross-sectional area of the end of the external nose prosthesis 1 close to the nose column prosthesis 2 is smaller than the cross-sectional area of the end of the external nose prosthesis 1 away from the nose column prosthesis 2, so that the end located below is narrower after implantation on the face, which can better fit the shape of the human nose bridge, and has good adaptability. In some preferred embodiments, as shown in Figure 3 , the external nose prosthesis 1 gradually widens and / or thickens from the end close to the nose column prosthesis 2 to the end away from the nose column prosthesis 2, which is more in line with ergonomics, has good plastic shape reliability, and is beneficial to maintain support stability.

[0067] Specifically, as shown in Figure 1 and Figure 2 , the nose column prosthesis 2 includes a nasal columella prosthesis 21 and a nasal ala prosthesis 22, wherein the nose column prosthesis 2 is used to replace the original nose column, the nasal columella prosthesis 21 is used as the nasal columella in the nose structure, and the nasal ala prosthesis 22 is used as the nasal ala support cartilage in the nose structure. The nasal columella prosthesis 21 is connected with the nasal septum prosthesis 3, and the nasal ala prosthesis 22 is symmetrically arranged on both sides of the nasal columella prosthesis 21, so that the nose column prosthesis 2 is also arranged in a symmetrical structure, which is in line with ergonomics, has good stability, and can improve the overall plastic appearance after implantation. In some preferred embodiments, the nose column prosthesis 2 is an integral structure, that is, the nasal columella prosthesis 21 and the nasal ala prosthesis 22 are integrally formed, which reduces the assembly process in the subsequent use process, improves the operation convenience, and is beneficial to maintain the structural integrity and the uniformity of the mechanical properties of the nose column prosthesis 2 as a whole, has good support stability after implantation, and has good durability.

[0068] As shown in Figure 2As shown, in some preferred embodiments, the nose column prosthesis 2 is trident-shaped as a whole, with the tip pointing towards the direction away from the inner arc side 13 of the outer nose prosthesis 1, i.e. towards the direction of the nose bridge prosthesis 11, which can effectively shape and improve the appearance after implantation, and the nose wing prosthesis 22 can reserve a passage for the nasal cavity, effectively shaping the nose wing shape, improving the appearance of the nose wing, while improving the safety and comfort of use.

[0069] In some preferred embodiments, the nasal septum prosthesis 3 is a sheet structure with a relatively thin overall thickness, and in the plane where the sheet structure is located, the nasal septum prosthesis 3 is a trapezoidal structure; further, the nasal septum prosthesis 3 can be a right-angled trapezoidal structure; the inner arc side 13 of the outer nose prosthesis 1 is connected to the hypotenuse of the nasal septum prosthesis 3, and the middle of the inner arc side 13 is connected to the hypotenuse of the nasal septum prosthesis 3, while in the nose column, the nasal columella prosthesis 21 is connected to the bottom of the nasal septum prosthesis 3, specifically to the lower bottom of the nasal septum prosthesis 3, so that the face implant is symmetrically arranged about the plane where the nose bridge prosthesis 11, the nasal columella prosthesis 21 and the nasal septum prosthesis 3 are located, with good overall symmetry, which is conducive to improving the shaping appearance, support balance and stability after implantation.

[0070] Specifically, the outer nose prosthesis 1, the nasal septum prosthesis 3 and the nose column prosthesis 2 are connected to each other by a mortise and tenon structure, i.e. the outer nose prosthesis 1 and the nasal septum prosthesis 3 are connected by a mortise and tenon structure, the outer nose prosthesis 1 and the nose column prosthesis 2 are connected by a mortise and tenon structure, and the nasal septum prosthesis 3 and the nose column prosthesis 2 are connected by a mortise and tenon structure, all the connection modes in the face implant are mortise and tenon structure connection, without introducing additional heterogeneous connectors, which is conducive to maintaining the mechanical properties, biocompatibility and degradation performance of the face implant as a whole, and also conducive to maintaining the uniformity and stability of the above properties, while the mortise and tenon structure connection is convenient and fast to assemble, only the outer nose prosthesis 1 and the nose column prosthesis 2 need to be connected with the nasal septum prosthesis 3 by mortise and tenon connection, and the remaining outer nose prosthesis 1 and nose column prosthesis 2 will also be connected by mortise and tenon connection, which is fast and efficient in assembly, with good convenience.

[0071] It should be noted that the nasal septum prosthesis 3 is used for installation and positioning, which can remove the original nasal septum during implantation, replace it with the nasal septum prosthesis 3, improve the implant stability of the outer nose prosthesis 1 and the nose column prosthesis 2 and the face implant as a whole, and prevent the outer nose prosthesis 1 and the nose column prosthesis 2 and the face implant from shifting after implantation, at the same time, the face implant has similar mechanical properties to the human nasal bone, and has good biocompatibility, which is almost the same as the human nasal bone after implantation, and is not easy to cause adverse reactions such as rejection reaction and inflammatory reaction, with good safety.

[0072] Specifically, as shown in FIG. 1, the face implant is a nose prosthesis, which is composed of an outer nose prosthesis 1, a nose bridge prosthesis 11, a nose columella prosthesis 21, a nose column prosthesis 2 and a nasal septum prosthesis 3. Figure 1As shown, the nasal septum prosthesis 3 comprises a first tenon 31 located on the hypotenuse of the nasal septum prosthesis 3 for tenon-mortise connection with the outer nose prosthesis 1; the inner arc side 13 of the outer nose prosthesis 1 is provided with a first mortise hole 14 connected with the first tenon 31 to realize tenon-mortise connection between the nasal septum prosthesis 3 and the outer nose prosthesis 1, which is convenient for assembly and has good connection stability; further, the first mortise hole 14 is arranged on the same plane as the middle part of the nasal ridge prosthesis 11 and the nasal septum prosthesis 3 to effectively maintain the symmetry of the whole outer nose prosthesis 1 and facial implant after assembly.

[0073] Specifically, as shown in the drawings, Figure 1 the nasal septum prosthesis 3 further comprises a second tenon 32 located on the bottom edge of the nasal septum prosthesis 3, specifically on the lower bottom edge of the nasal septum prosthesis 3, which is located at the lower end after the facial implant is implanted, and the second tenon 32 is used for tenon-mortise connection with the nasal column prosthesis 2, specifically with the columella nasi prosthesis 21, which is located in the middle part of the nasal column prosthesis 2 and can be used as the symmetry axis of the nasal column prosthesis 2 to connect with the second tenon 32, thereby effectively maintaining the symmetry of the whole facial implant; the nasal column prosthesis 2 is provided with a second mortise hole 23 on the side facing the nasal septum prosthesis 3, specifically on the columella nasi prosthesis 21, and the second mortise hole 23 is connected with the second tenon 32 to realize tenon-mortise connection between the nasal septum prosthesis 3 and the columella nasi prosthesis 21, which is convenient for assembly and has good connection stability.

[0074] Further, it should be noted that in the direction perpendicular to the sheet structure of the nasal septum prosthesis 3, the width of the inner arc side 13 of the outer nose prosthesis 1 is greater than the thickness of the nasal septum prosthesis 3, and the width of the columella nasi prosthesis 21 is greater than the thickness of the nasal septum prosthesis 3, so compared with the mode that the mortise hole is provided on the nasal septum prosthesis 3, the tenon-mortise structure avoids damage to the mechanical properties of the relatively thin nasal septum prosthesis 3 caused by the hole on the nasal septum prosthesis 3, and also avoids the risk of tenon-mortise connection failure caused by the instability of the mortise hole on the relatively thin nasal septum prosthesis 3, and the arrangement of the first tenon 31 and the second tenon 32 on the nasal septum prosthesis 3 makes the whole tenon-mortise connection reliable and firm, and has high safety in use.

[0075] Specifically, as shown in the drawings, Figure 1As shown, the columella prosthesis 21 of the nasal column prosthesis 2 is provided with a mortise 24 recessed in the columella prosthesis 21, and the second tenon hole 23 is located in the mortise 24; one end of the outer nose prosthesis 1 is provided with a third tenon 15, which is specifically located at the narrower end of the outer nose prosthesis 1 and protrudes outward from the end of the outer nose prosthesis 1, and correspondingly, at least part of the recessed area in the mortise 24 is connected with the third tenon 15, realizing the mortise-and-tenon connection between the outer nose prosthesis 1 and the nasal column prosthesis 2; at the same time, at least part of the recessed area in the mortise 24 is also connected with the bottom edge of the nasal septum prosthesis 3 in a mortise-and-tenon connection, and on the basis of the matching mortise-and-tenon connection between the second tenon 32 and the second tenon hole 23, the fastening of the mortise-and-tenon connection between the nasal column prosthesis 2 and the nasal septum prosthesis 3 is further improved.

[0076] As shown in the drawings, Figure 1 In this embodiment, the mortise 24 extends along the extension direction of the columella prosthesis 21 and can penetrate the columella prosthesis 21 in this direction, that is, the extension length of the mortise 24 in the direction of the columella prosthesis 21 is equal to the length of the columella prosthesis 21, thereby reserving matching connection spaces for the third tenon 15 and the bottom edge of the nasal septum prosthesis 3, respectively, facilitating the realization of the mortise-and-tenon structure connection and further improving the connection tightness between the outer nose prosthesis 1, the nasal column prosthesis 2 and the nasal septum prosthesis 3; and through the matching connection of the second tenon 32 and the second tenon hole 23, the relative movement of the nasal septum prosthesis 3 in the mortise 24 can also be avoided, thereby playing a certain limiting effect, and there is no need to additionally set a complex limiting structure, so that the overall structure of the facial implant is simple, and the connection tightness and firmness are good.

[0077] It should be noted that the sizes of the tenons and the corresponding tenon holes are consistent to improve the matching and the connection tightness between the components after assembly, and the sizes and positions of the tenons are taken as examples for description, and the sizes and positions of the corresponding tenon holes can be referred to the sizes and positions of the tenons, which will not be described here.

[0078] Specifically, the width of at least one of the first tenon 31 and the second tenon 32 is 1.5mm-2.0mm, wherein the first tenon 31 and the second tenon 32 can be square or circular, and the width refers to the side length of the square tenon or the diameter of the circular tenon; it can be understood that the width of at least one of the first tenon 31 and the second tenon 32 can be any point value in 1.5mm-2.0mm; for example, the width of at least one of the first tenon 31 and the second tenon 32 can be 1.5mm, 1.6mm, 1.7mm, 1.75mm, 1.8mm, 1.9mm, 2.0mm, etc.; within the range of the first tenon 31 and the second tenon 32, the contact surface of the mortise and tenon structure connection is moderate, which can realize good connection tightness, and the opening of the corresponding first tenon hole 14 and the second tenon hole 23 will not cause structural damage to the external nasal prosthesis 1 and the nasal column prosthesis 2, which is beneficial to maintain the mechanical properties of the overall structure; in some exemplary embodiments, the width of the first tenon 31 is 1.5mm-2.0mm; in other exemplary embodiments, the width of the second tenon 32 is 1.5mm-2.0mm; in some preferred embodiments, the width of the first tenon 31 is 1.5mm-2.0mm, and the width of the second tenon 32 is 1.5mm-2.0mm.

[0079] Specifically, the length of at least one of the first tenon 31 and the second tenon 32 is 1.0mm-5.0mm, wherein the length of the first tenon 31 refers to the length of the first tenon 31 protruding from the hypotenuse of the nasal septum prosthesis 3, which is the same as the depth of the first tenon hole 14; the length of the second tenon 32 refers to the length of the second tenon 32 protruding from the bottom edge of the nasal septum prosthesis 3, which is the same as the depth of the second tenon hole 23; it can be understood that the length of at least one of the first tenon 31 and the second tenon 32 can be any point value in 1.0mm-5.0mm; for example, the length of at least one of the first tenon 31 and the second tenon 32 can be 1.0mm, 1.5mm, 2.0mm, 2.5mm, 3.0mm, 4.0mm, 5.0mm, etc.; within the length range, the first tenon 31 and the second tenon 32 are not easy to break, and can effectively improve the accuracy and stability of the mortise and tenon structure connection, and are not easy to be pulled out to cause connection failure; in some exemplary embodiments, the length of the first tenon 31 is 1.0mm-5.0mm; in other exemplary embodiments, the length of the second tenon 32 is 1.0mm-5.0mm; in some preferred embodiments, the length of the first tenon 31 is 1.0mm-5.0mm, and the length of the second tenon 32 is 1.0mm-5.0mm.

[0080] Specifically, the distance between the two adjacent first tenons 31 in the direction of the hypotenuse of the nasal septum prosthesis 3 is 0.1mm-10.0mm; it can be understood that the distance between the two adjacent first tenons 31 in the direction of the hypotenuse of the nasal septum prosthesis 3 can be any point value in 0.1mm-10.0mm; for example, the distance between the two adjacent first tenons 31 in the direction of the hypotenuse of the nasal septum prosthesis 3 can be 0.1mm, 0.5mm, 1.0mm, 2.0mm, 5.0mm, 7.5mm, 8.0mm, 10.0mm, etc.

[0081] Specifically, the distance between the two adjacent second tenons 32 in the direction of the bottom edge of the nasal septum prosthesis 3 is 0.1mm-10.0mm; it can be understood that the distance between the two adjacent second tenons 32 in the direction of the bottom edge of the nasal septum prosthesis 3 can be any point value in 0.1mm-10.0mm; for example, the distance between the two adjacent second tenons 32 in the direction of the bottom edge of the nasal septum prosthesis 3 can be 0.1mm, 0.5mm, 1.0mm, 2.0mm, 5.0mm, 7.5mm, 8.0mm, 10.0mm, etc.

[0082] Within this range of distances, the balance of the mortise and tenon connection on each edge can be improved, which is beneficial to improve the tightness and reliability of the mortise and tenon connection between the external nasal prosthesis 1, the nasal column prosthesis 2 and the nasal septum prosthesis 3, and the operation is simple and convenient.

[0083] In addition, in the case of multiple first tenons 31 provided on the hypotenuse of the nasal septum prosthesis 3, the distance between the two adjacent first tenons 31 can be the same or different, and in the case of multiple second tenons 32 provided on the bottom edge of the nasal septum prosthesis 3, the distance between the two adjacent second tenons 32 can be the same or different, to flexibly adapt to different structural strength requirements and stability requirements.

[0084] Specifically, the number of at least one of the first tenon 31 and the second tenon 32 is 1-6; it can be understood that the number of at least one of the first tenon 31 and the second tenon 32 can be any integer in 1-6; for example, the number of at least one of the first tenon 31 and the second tenon 32 can be 1, 2, 3, 4, 5, or 6; in this way, both the good mortise and tenon connection accuracy and reliability can be maintained, and the difficulty of preparing the first tenon 31 and the second tenon 32 is reduced, and the difficulty of opening the first tenon hole 14 and the second tenon hole 23 is reduced accordingly, the cost is saved, the structural damage to the external nasal prosthesis 1 and the columella nasi prosthesis 21 is reduced, and the mechanical properties of the external nasal prosthesis 1, the columella nasi prosthesis 2, and the nasal septum prosthesis 3 are maintained, the mechanical properties and biocompatibility of the facial implant are good; in some exemplary embodiments, the number of the first tenon 31 is 1-6; in other exemplary embodiments, the number of the second tenon 32 is 1-6; in some preferred embodiments, the number of the first tenon 31 is 1-6, and the number of the second tenon 32 is 1-6.

[0085] Specifically, the cooperation tolerance between the external nasal prosthesis 1, the nasal septum prosthesis 3, and the columella nasi prosthesis 2 is -0.1mm to +0.1mm; it can be understood that the cooperation tolerance between the external nasal prosthesis 1, the nasal septum prosthesis 3, and the columella nasi prosthesis 2 can be any point value in -0.1mm to +0.1mm; for example, the cooperation tolerance between the external nasal prosthesis 1, the nasal septum prosthesis 3, and the columella nasi prosthesis 2 can be -0.1mm, -0.08mm, -0.05mm, -0.02mm, 0mm, +0.02mm, +0.05mm, +0.08mm, +0.1mm, etc.; within this cooperation tolerance range, the mortise and tenon connection between the external nasal prosthesis 1, the nasal septum prosthesis 3, and the columella nasi prosthesis 2 is tight and reliable, and can effectively maintain the shaping stability for a long time.

[0086] It should be noted that the cooperation tolerance refers to the cooperation tolerance of the facial implant in a hard state, specifically, the cooperation tolerance after injection molding (or machining), the facial implant needs to be soaked in water during use, and the phenomenon of water swelling will occur, so that the cooperation tolerance between the external nasal prosthesis 1, the nasal septum prosthesis 3, and the columella nasi prosthesis 2 is further reduced, and the mortise and tenon structure connection is more tight.

[0087] Specifically, the tensile modulus of the facial implant is 28.85MPa-82.45MPa; it can be understood that the tensile modulus of the facial implant can be any point value in 28.85MPa-82.45MPa; for example, the tensile modulus of the facial implant can be 28.85MPa, 31.73MPa, 44.96MPa, 58.27MPa, 70.52MPa, 82.45MPa, etc.; within this tensile modulus range, the facial implant has good tensile deformation resistance, is not easy to deform during implantation, improves operation convenience, and can effectively maintain the durability of the shaping effect.

[0088] Specifically, the tensile strength of the facial implant is 6.35MPa-9.84MPa; it can be understood that the tensile strength of the facial implant can be any point value in 6.35MPa-9.84MPa; for example, the tensile strength of the facial implant can be 6.35MPa, 6.92MPa, 7.38MPa, 8.01MPa, 8.97MPa, 9.84MPa, etc.; within this tensile strength range, the facial implant has good fracture resistance and is not easy to break and damage during use, reducing the operation difficulty, improving the implant efficiency, and improving the shaping reliability.

[0089] Specifically, the elongation at break of the facial implant is 0.65%-1.38%; it can be understood that the elongation at break of the facial implant can be any point value in 0.65%-1.38%; for example, the elongation at break of the facial implant can be 0.65%, 0.79%, 0.91%, 1.03%, 1.25%, 1.38%, etc.; in this way, the facial implant has good structural strength and toughness, good impact resistance, is not easy to deform, and is not easy to break, and has excellent mechanical properties.

[0090] When assembled, the narrower end of the outer nose prosthesis 1 is directed towards the lower bottom of the nasal septum prosthesis 3, the first tenon hole 14 of the outer nose prosthesis 1 and the first tenon head 31 of the nasal septum prosthesis 3 are connected one by one to enable the outer nose prosthesis 1 to be assembled on the hypotenuse of the nasal septum prosthesis 3; the three-pronged tip of the nasal column prosthesis 2 is placed towards the nasal ridge prosthesis 11 of the outer nose prosthesis 1, one side of the tenon slot 24 and the second tenon hole 23 of the nasal columella prosthesis 21 is aligned with the lower bottom of the nasal septum prosthesis 3, and the second tenon hole 23 and the second tenon head 32 on the lower bottom of the nasal septum prosthesis 3 are connected one by one to enable the nasal column prosthesis 2 to be assembled on the lower bottom of the nasal septum prosthesis 3; wherein the assembly sequence of the outer nose prosthesis 1 and the nasal column prosthesis 2 with the nasal septum prosthesis 3 can be partially sequential; and after the connection of the second tenon head 32 and the second tenon hole 23, the lower edge of the nasal septum prosthesis 3 is clamped into the tenon slot 24 of the nasal columella prosthesis 21, further improving the stability of the mortise and tenon connection between the nasal septum prosthesis 3 and the nasal column prosthesis 2, at the same time, the third tenon head 15 on the outer nose prosthesis 1 is also connected with the tenon slot 24, realizing the mortise and tenon connection between the outer nose prosthesis 1 and the nasal column prosthesis 2, further improving the stability and reliability of the mortise and tenon connection among the outer nose prosthesis 1, the nasal column prosthesis 2 and the nasal septum prosthesis 3, which is also conducive to improving the overall structural stability of the facial implant, improving the shaping effectiveness and stability; as a combined medical device, the facial implant has excellent mechanical properties and biocompatibility, the entire assembly process is fast, simple and convenient to operate, and the implant can be directly carved during implantation to improve the adaptability, has good applicability, and has good application prospects.

[0091] Specifically, the facial implant is made by resolubilizing, injection molding, solidifying and forming, bubble washing and drying, and machining of silk fibroin, which is convenient and fast to prepare, has high preparation precision of each tenon head and tenon hole structure, can improve the connection matching degree among the outer nose prosthesis 1, the nasal column prosthesis 2 and the nasal septum prosthesis 3, and the silk fibroin is self-made, which has better mechanical properties and biocompatibility than commercially available silk fibroin.

[0092] Correspondingly, as shown in Figure 4 the embodiment of the present application also provides a preparation method of a facial implant, comprising:

[0093] S1, dissolving silk fibroin in a solvent to obtain a silk fibroin resolubilization solution;

[0094] S2, placing the silk fibroin resolubilization solution in an injection mold for injection molding to obtain an injection molded plate;

[0095] S3, solidifying the injection molded plate to obtain a solidified and formed plate;

[0096] S4, bubble washing the solidified and formed plate, and drying to obtain a dried plate;

[0097] S5, machining the dried plate to obtain a facial implant.

[0098] In some exemplary embodiments, the silk fibroin used in the reconstitution process of S1 is a silk fibroin lyophilized powder, which can be formed by degumming, rinsing, drying, dissolving, dialysis, centrifugation and freeze-drying, and can be prepared by the following steps:

[0099] The cocoon is immersed in a sodium carbonate solution and heated to obtain degummed silk;

[0100] The degummed silk is rinsed and dried to obtain degummed dry silk;

[0101] The degummed dry silk is dissolved in a lithium salt aqueous solution to obtain a silk fibroin lithium salt solution;

[0102] The silk fibroin lithium salt solution is dialyzed to remove lithium salt to obtain a silk fibroin dialysis solution;

[0103] The silk fibroin dialysis solution is centrifuged, and the supernatant is taken to obtain a silk fibroin centrifugate;

[0104] The silk fibroin centrifugate is freeze-dried to obtain a silk fibroin lyophilized powder.

[0105] First, during the process of heating the cocoon in a sodium carbonate solution for degumming, the cocoon is a dry cocoon after impurity removal, and can be cut into pieces before being added to the sodium carbonate solution for continuous heating to improve the degumming efficiency and reliability.

[0106] The concentration of the sodium carbonate solution is 0 g / L-100 g / L and is not 0, the ratio of cocoon mass to sodium carbonate solution volume is 0.1 g / L-10 g / L, the heating method can include electric heating or steam heating, the electric heating can use an electric furnace for heating, the steam heating can use a steam pot for heating, the heating temperature is 50°C-121°C, the pressure is 0.1 MPa-2 MPa, and the time is 1 s-1000 h. Understandably, the concentration of the sodium carbonate solution can be any point value in 0 g / L-100 g / L and not 0, the ratio of cocoon mass to sodium carbonate solution volume can be any point value in 0.1 g / L-10 g / L, the heating temperature can be any point value in 50°C-121°C, the pressure can be any point value in 0.1 MPa-2 MPa, and the time can be any point value in 1 s-1000 h. Exemplarily, the concentration of the sodium carbonate solution can be 0.1 g / L, 0.5 g / L, 1 g / L, 10 g / L, 25 g / L, 50 g / L, 100 g / L, etc. The ratio of cocoon mass to sodium carbonate solution volume can be 0.1 g / L, 0.5 g / L, 1 g / L, 2 g / L, 2.5 g / L, 5 g / L, 7.5 g / L, 10 g / L, etc. The heating temperature can be 50°C, 60°C, 70°C, 80°C, 100°C, 115°C, 121°C, etc. The pressure can be 0.1 MPa, 0.2 MPa, 0.5 MPa, 1 MPa, 1.5 MPa, 1.75 MPa, 2 MPa, etc. The time can be 1 s, 10 s, 30 s, 1 min, 30 min, 1 h, 5 h, 10 h, 50 h, 100 h, 500 h, 1000 h, etc. In this way, the sericin can be effectively softened, the cohesion between cocoon filaments can be weakened, and the silk can be easily separated.

[0107] Then, the degummed silk is rinsed with purified water or ultrapure water, the ratio of degummed silk mass to water volume for each rinsing is 0.1 g / L-10 g / L, the rinsing is performed at least three times, each rinsing time is 0.1 h-10 h, and new purified water or ultrapure water is used for each rinsing.

[0108] After that, the drying time is 1 h-100 h, and the drying temperature is 5°C-100°C. Understandably, the drying time can be any point value in 1 h-100 h, and the drying temperature can be any point value in 5°C-100°C. Exemplarily, the drying time can be 1 h, 5 h, 10 h, 20 h, 50 h, 75 h, 100 h, etc. The drying temperature can be 5°C, 15°C, 25°C, 30°C, 50°C, 75°C, 100°C, etc. In this way, the degummed dry silk with high purity can be obtained.

[0109] Then, the degummed dry silk is weighed, dissolved in a lithium salt solution to dissolve the silk, and the dissolution process is sealed and kept warm until the degummed dry silk is fully dissolved to obtain a silk fibroin lithium salt solution; wherein the lithium salt includes at least one of lithium bromide (LiBr) and lithium thiocyanate (LiSCN), the concentration of lithium salt in the lithium salt solution is 0.01 g / mL to 2 g / mL, the ratio of the mass of the degummed dry silk to the volume of the lithium salt solution is 0.01 g / mL to 1 g / mL, the dissolution temperature is 20°C to 100°C, and the dissolution time is greater than or equal to a preset dissolution time of 1.5 h to 2.5 h. Understandably, the concentration of lithium salt in the lithium salt solution can be any point value in 0.01 g / mL to 2 g / mL, the ratio of the mass of the degummed dry silk to the volume of the lithium salt solution can be any point value in 0.01 g / mL to 1 g / mL, the dissolution temperature can be any point value in 20°C to 100°C, and the preset dissolution time can be any point value in 1.5 h to 2.5 h. Exemplarily, the concentration of lithium salt in the lithium salt solution can be 0.01 g / mL, 0.1 g / mL, 0.5 g / mL, 1 g / mL, 1.5 g / mL, 2 g / mL, etc.; the ratio of the mass of the degummed dry silk to the volume of the lithium salt solution can be 0.01 g / mL, 0.05 g / mL, 0.1 g / mL, 0.5 g / mL, 0.75 g / mL, 0.8 g / mL, 1 g / mL, etc.; the dissolution temperature can be 20°C, 30°C, 40°C, 50°C, 70°C, 90°C, 100°C, etc.; and the preset dissolution time can be 1.5 h, 1.8 h, 2.0 h, 2.2 h, 2.5 h, etc., for example, in a specific embodiment, the preset dissolution time is 2 h, i.e., the dissolution time is greater than or equal to 2 h; in this way, the degummed dry silk is fully softened and uniformly dispersed, facilitating subsequent processing and handling.

[0110] Then, during the dialysis process, the silk fibroin lithium salt solution is loaded into a semi-permeable membrane with a specification of 10 Da to 10,000,000 Da, the semi-permeable membrane loaded with the silk fibroin lithium salt solution is placed in ultrapure water, and dialysis is continuously stirred, the stirring mode includes at least one of air stirring, mechanical stirring and magnetic stirring, the stirring speed is 1 r / min to 2000 r / min, and the water is changed every 0.1 h to 100 h, the volume ratio of the initial and each time changed ultrapure water to the silk fibroin lithium salt solution is 0.01:1 to 1000:1, and the number of water changes is greater than or equal to 4 times, thereby effectively removing the lithium salt therein to obtain a silk fibroin dialysate with high purity, and the mass concentration of silk fibroin in the silk fibroin dialysate is 1% to 15%.

[0111] Then, in the centrifugation process, the centrifuge speed is 1 r / min-40000 r / min, the centrifugation time is 1 s-10 h, and the centrifugation temperature is-5℃-10℃, and the supernatant is taken as the silk fibroin centrifugate; Understandably, the centrifuge speed can be any point value in 1 r / min-40000 r / min, the centrifugation time can be any point value in 1 s-10 h, and the centrifugation temperature can be any point value in-5℃-10℃, which will not be enumerated here.

[0112] Then, in the freeze-drying process, the silk fibroin centrifugate is first frozen at-80℃-0℃, and then placed in a vacuum freeze dryer for freeze-drying, the freeze-drying time is 1 h-500 h, the freezing temperature is-80℃-0℃, and the pressure is 0.1 Pa-100 Pa, to obtain silk fibroin freeze-dried powder.

[0113] Then, in some exemplary embodiments, the solvent used in the S1 step of the reconstitution process is a protein dissolving agent, including at least one of hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide and lithium bromide solution; In some preferred embodiments, the solvent is hexafluoroisopropanol, and the container is sealed during the reconstitution process to prevent hexafluoroisopropanol from evaporating. Hexafluoroisopropanol has good solubility and stability, and can interact with the hydrophilic groups in the silk fibroin molecule, break the hydrogen bonds and electrostatic interaction between proteins, and promote silk fibroin dissolution, speed up the dissolution efficiency, and also improve the dispersion of silk fibroin in the silk fibroin reconstitution solution.

[0114] In the reconstitution process, the ratio of silk fibroin mass to solvent volume is 0.1 g / mL-1 g / mL, the dissolution temperature is 5℃-80℃, and the dissolution time is 0.1 h-100 h; Understandably, the ratio of silk fibroin mass to solvent volume can be any point value in 0.1 g / mL-1 g / mL, the dissolution temperature can be any point value in 5℃-80℃, and the dissolution time can be any point value in 0.1 h-100 h; Exemplarily, the ratio of silk fibroin mass to solvent volume can be 0.1 g / mL, 0.2 g / mL, 0.5 g / mL, 0.75 g / mL, 0.8 g / mL, 1 g / mL, etc.; The dissolution temperature can be 5℃, 15℃, 30℃, 45℃, 55℃, 60℃, 80℃, etc.; The dissolution time can be 0.1 h, 0.5 h, 1 h, 2 h, 5 h, 10 h, 50 h, 100 h, etc.; In this way, the silk fibroin has high dissolution efficiency and good dispersion uniformity, which is beneficial to improve the structure precision, structure stability and performance uniformity of the final facial implant.

[0115] Then, the final facial implant including the outer nose prosthesis, the nose column prosthesis and the nasal septum prosthesis, in the injection molding process of S2 step, the injection mold can include the outer nose mold, the nose column mold and the nasal septum mold, and the silk fibroin resolvent solution is respectively placed in the outer nose mold, the nose column mold and the nasal septum mold for injection molding, and then waiting for solidification, the solidification time is 7 days to 60 days, and then the obtained injection plate material including the outer nose injection plate material, the nose column injection plate material and the nasal septum injection plate material is taken out, the preparation efficiency is fast, and the forming precision is high.

[0116] Then, in the solidification process of S3 step, the injection plate material is soaked in methanol for solidification, and the solidified and formed plate material is obtained after drying, specifically, the outer nose injection plate material, the nose column injection plate material and the nasal septum injection plate material are soaked in methanol for solidification, and the solidified and formed plate material obtained after drying also includes the outer nose solidified and formed plate material, the nose column solidified and formed plate material and the nasal septum solidified and formed plate material; in the solidification process, methanol can change the fiber structure of silk fibroin, so that the structure of silk fibroin changes from α-helix to β-sheet, which is beneficial to improve the tensile modulus, improve the crystallinity and mechanical properties of the solidified and formed plate material, so that the final facial implant can more conform to the structure characteristics of human nasal cartilage, has good mechanical properties, and can also reduce the degradation rate to a certain extent.

[0117] In the solidification process, methanol is poured over the solidified and formed plate material, the soaking time in methanol is 10 days to 30 days, wherein fresh methanol is replaced every 1 day to 7 days, and the drying time after soaking is completed is 1 day to 60 days, and the drying temperature is 20℃ to 30℃; Understandably, the soaking time in methanol can be any time within 10 days to 30 days, wherein fresh methanol can be replaced at any time interval within 1 day to 7 days, the drying time after soaking can be any time within 1 day to 60 days, and the drying temperature can be any point value within 20℃ to 30℃, which will not be enumerated here; In this way, the mechanical properties of the solidified and formed plate material and the final facial implant can be effectively enhanced, and the degradation rate can be slowed down.

[0118] Then, in the process of bubble washing the cured and formed plate in S4, the cured and formed plate is immersed in ultrapure water for bubble washing. Specifically, the cured and formed plate of the outer nose, the cured and formed plate of the nasal column, and the cured and formed plate of the nasal septum are all subjected to bubble washing with ultrapure water. The water is changed every 6-24 hours, which can effectively remove the residual hexafluoroisopropanol and methanol on the cured and formed plate, thereby reducing the harm of the finally prepared facial implant to the human body after implantation and improving the safety. The drying can be performed by air drying. The air drying time is 7-30 days, and the air drying temperature is 20-30°C. Understandably, the air drying time can be any time within 7-30 days, and the air drying temperature can be any value within 20-30°C. The dried plate includes the dried plate of the outer nose, the dried plate of the nasal column, and the dried plate of the nasal septum.

[0119] Then, in the machining process of S5, the corresponding dried plate is machined according to the shape of the outer nose, the nasal column, and the nasal septum, so that the dried plate of the outer nose has the shape of the outer nose, the dried plate of the nasal column has the shape of the nasal column, and the dried plate of the nasal septum has the shape of the nasal septum. A plurality of first mortise holes are formed on the inner arc side of the dried plate of the outer nose to obtain the outer nose prosthesis. A plurality of second mortise holes are formed on the nasal column part of the dried plate of the nasal column to obtain the nasal column prosthesis. A plurality of first tenons and a plurality of second tenons are respectively machined on the bevel and the lower base of the dried plate of the nasal septum. The first tenons and the first mortise holes correspond to each other one by one, and the second tenons and the second mortise holes correspond to each other one by one to obtain the nasal septum prosthesis. The diameter of the machining tool bit is 1-4 mm, and the tool bit is cooled by air cooling during the machining process to prevent overheating and denaturation of the silk fibroin.

[0120] In addition, in some example embodiments, the shapes of the injection molded plates can be the same or different, the shapes of the cured and formed plates can be the same or different, and the shapes of the dried plates can be the same or different. The final outer nose prosthesis, nasal column prosthesis, and nasal septum prosthesis are formed by the machining step, which is simple to prepare and saves mold and preparation costs. In other example embodiments, the injection molded plates can be formed into corresponding initial shapes during the injection molding process, and further fine adjustment is performed in the machining step to improve the forming precision.

[0121] Specifically, in some example embodiments, after the machining step, the method further comprises:

[0122] The facial implant is soaked in water at 20-30°C for 2-10 days to obtain a facial implant after water absorption.

[0123] During the soaking process, the facial implant can be soaked in physiological saline or sterile water for injection, and the facial implant is fully soaked and swells and softens, facilitating engraving, wherein the matching tolerance between the tenons and mortises of the external nose prosthesis, the nose column prosthesis and the nasal septum prosthesis is further reduced, which is beneficial to the connection tightness and firmness of the facial implant as a whole after implantation, and the facial implant has been soaked and swelled, and is not easy to produce additional water absorption deformation after implantation, and the overall shaping precision and shaping durability are good.

[0124] In addition, the facial implant can be stored in a dry and hard state after machining, and the external nose prosthesis, the nose column prosthesis and the nasal septum prosthesis are respectively taken out for soaking before assembly; or the external nose prosthesis, the nose column prosthesis and the nasal septum prosthesis in a hard state can be assembled and stored, and soaked directly when used; or the external nose prosthesis after water absorption, the nose column prosthesis after water absorption and the nasal septum prosthesis after water absorption are all stored in a swollen state after water absorption, and can be directly assembled when used, which further reduces the difficulty of use, shortens the operation time and improves the safety.

[0125] The embodiments of the present application are described below in combination with the above technical solutions.

[0126] Embodiment 1

[0127] The facial implant of the present embodiment is prepared by the following steps:

[0128] 1. Degumming: 10g of cocoon after impurity removal and cutting is weighed, 8.48g of sodium carbonate is added to 4L of purified water to obtain a 2.12g / L sodium carbonate solution, the sodium carbonate solution is heated to 121℃ in an electric furnace, and the weighed cocoon is immersed in the heated sodium carbonate solution, and the heating is continued for 30min to degum, obtaining degummed silk.

[0129] 2. Rinsing and drying: the degummed silk is placed in 5L of ultrapure water for rinsing, and the same amount of ultrapure water is replaced every 20min, and the rinsing is repeated 4 times; then, it is laid flat and dried at 30℃ for 72h to obtain degummed dry silk.

[0130] 3. Dissolving silk: 280mL of ultrapure water and 273.7g of lithium bromide are mixed to form a 0.977g / mL lithium bromide solution, and 70g of degummed dry silk is dissolved in the lithium bromide solution, which is placed in a 60℃ environment for 4h to obtain a silk fibroin lithium salt solution.

[0131] 4. Dialysis: the silk fibroin lithium salt solution is divided into 8kDa semi-permeable membranes, placed in 5L of ultrapure water, and stirred at a speed of 100r / min, and the water is changed at 1h, 2h, 4h, 16h, 20h and 24h, and the silk fibroin dialysate is obtained after multiple dialyses.

[0132] 5. Centrifugation: Collect the silk fibroin dialysate and place it in a centrifuge, set the centrifugal speed to 12000 r / min, the centrifugal temperature to 5℃, and the centrifugal time to 20 min, centrifuge the silk fibroin dialysate, and take the silk fibroin centrifugal liquid.

[0133] 6. Freeze-drying: first freeze the silk fibroin centrifugal liquid in a-80℃ refrigerator for 4 h, then set the temperature of the vacuum freeze-drying machine to-40℃, and freeze-dry for 72 h to obtain silk fibroin freeze-dried powder.

[0134] 7. Resolubilization: add 60 mL of hexafluoroisopropanol to 15.5 g of silk fibroin freeze-dried powder to dissolve the silk fibroin freeze-dried powder in hexafluoroisopropanol, seal, and dissolve at room temperature for 72 h to obtain a silk fibroin resolubilization solution.

[0135] 8. Injection molding: pour the silk fibroin resolubilization solution into a syringe, slowly inject it into a rectangular mold, cover the mold, and then horizontally stand it for 45 days to obtain an injection-molded plate.

[0136] 9. Solidification molding: take out the injection-molded plate and soak it in methanol for solidification, add methanol to cover the plate, seal, replace the freshly prepared methanol every 3 days, take it out after 21 days, and air dry at room temperature to obtain a solidification-molded plate.

[0137] 10. Soaking: soak the solidification-molded plate in ultrapure water, cover the solidification-molded plate with liquid, soak for 20 days, replace the freshly prepared ultrapure water every day, and air dry for 7 days at room temperature to obtain a dried plate.

[0138] 11. Machining: machine the dried plate according to the outer nose, nasal septum, and nasal column in the nose structure, and use a lathe to punch circular holes on the inner arc side of the outer nose prosthesis and the nasal column prosthesis to form a first mortise hole and a second mortise hole, respectively, and punch cylindrical tenons on the bevel and lower bottom of the nasal septum prosthesis to form a first tenon and a second tenon, respectively. Each type of mortise hole and each type of tenon has 3 pieces, with a diameter of 2 mm and a length of 3 mm. The distance between adjacent two first mortise holes is 2 mm, and the distance between adjacent two second mortise holes is 2 mm. Correspondingly, the shape and position of the first tenon on the bevel of the nasal septum prosthesis correspond to the shape and position of the first mortise hole, and the shape and position of the second tenon on the lower bottom of the nasal septum prosthesis correspond to the shape and position of the second mortise hole.

[0139] 12. Soaking: soak the outer nose prosthesis, nasal septum prosthesis, and nasal column prosthesis in sterilized water for injection for 7 days to obtain a water-absorbed facial implant.

[0140] Finally, the outer nose prosthesis, nasal septum prosthesis, and nasal column prosthesis can be assembled by connecting them through the mortise and tenon structure.

[0141] Example 2

[0142] The difference between this embodiment and embodiment 1 is that the first mortise hole and the second mortise hole are both square holes, the side length of the square hole is 2mm, correspondingly, the shape position of the first tenon on the bevel of the nasal septum prosthesis and the shape position of the first mortise hole are one-to-one corresponding, the shape position of the second tenon on the lower base of the nasal septum prosthesis and the shape position of the second mortise hole are one-to-one corresponding; the rest is the same as embodiment 1.

[0143] Embodiment 3

[0144] The difference between this embodiment and embodiment 1 is that, as shown in Figure 1 , the distance between the first first tenon and the second first tenon in the direction of the bevel towards the lower base is 4mm, and the distance between the two first mortise holes is also 4mm; the distance between the first second tenon and the second second tenon in the direction of the lower base towards the external nasal prosthesis is 4mm, and the distance between the two second mortise holes is also 4mm; the rest is the same as embodiment 2.

[0145] Embodiment 4

[0146] The difference between this embodiment and embodiment 1 is that the first mortise hole and the second mortise hole are both square holes, the side length of the square hole is 1.5mm; the rest is the same as embodiment 1.

[0147] Embodiment 5

[0148] The difference between this embodiment and embodiment 1 is that fresh methanol is replaced every 1 day during the curing forming process of S3 step, and the soaking and washing is 18 days; the rest is the same as embodiment 1.

[0149] Comparative Example 1

[0150] This comparative example is some conventional facial implants commercially available, the sample is purchased from Guangzhou Wanhe Silicone Facial Plastic Filling Material.

[0151] The tensile properties of the facial implants in the above embodiments 1-5 are tested, and the test results are shown in Table 1.

[0152] Table 1 Tensile property test results of facial implants in embodiments 1-5

[0153]

[0154] The tensile properties of the facial implants in the above comparative example 1 are tested, and the test results are shown in Table 2.

[0155] Table 2 Tensile property test results of nasal prosthesis in comparative example 1

[0156]

[0157] It can be seen from the tensile property test results in Table 1 that the tensile modulus of the facial implant is 28.85 MPa to 82.45 MPa, the tensile strength is 6.35 MPa to 9.84 MPa, and the elongation at break is 0.65 to 1.38, which is close to the mechanical properties of human nasal bone, and the facial implant has good mechanical properties; as shown in Table 2, the tensile modulus of the comparative example is 0.07 MPa to 0.16 MPa, the tensile strength is 0.55 MPa to 1.08 MPa, and the elongation at break is 6.35 to 8.07. The hardness of the implant in the comparative example is much smaller than that in the example, although the toughness is much stronger than that in the example, but there is still a great risk of displacement after implantation, insufficient plasticizing strength, etc. It can be seen that, by using silk fibroin as the main material and cooperating with the mortise and tenon structure connection, the facial implant has good and uniform mechanical properties, which is close to the mechanical properties of human nasal bone, and the assembly is fast and convenient during use, and the plasticizing effect is good.

[0158] The following tests the biocompatibility of the facial implant by subcutaneous implantation of BALB / c mice.

[0159] BALB / c mice are used as test animals, which are provided by the Experimental Animal Resources Institute of China Institute for Food and Drug Control; the animal adaptation time is at least 5 days, and the animal management is carried out according to the standard operation specification formulated in accordance with the experimental animal protection and use specification; the SPF mouse growth feed is provided every day, and the purified water is drunk through the water bottle; every 3 mice of the same sex are raised in an independent ventilated cage, and the cage is paved with corn cobs; the room temperature is controlled at 20℃ to 25℃, and the relative humidity is controlled at 40% to 70%; the light is controlled by automatic timing for 12 hours of light and 12 hours of darkness.

[0160] Then, the sample and reagent consumables are prepared, wherein the sample is a facial implant provided by the embodiment of the present application, batch number: G202007001; the reagents and consumables include bovine serum albumin (Solarbio, A8010), complete Freund's adjuvant (sigma, F5881-10mL), mouse IgG ELISA kit (Xinboseng, EMC116), mouse IgM detection kit (Xinboseng, EMC129), 1640 culture solution (Gibco, 8118134), fetal bovine serum (Gibco, 10091-148), CCK8 (Beijing Solabio Technology Co., Ltd., CA1210), cytokine test kit (BD Biosciences, 502246, 562233, 562263, 562264, 562272, 562236), cell surface antibody test kit (BioLegend, 100305, 100707, 104507, 103132, 100412, 115512, 108910), phosphate buffer solution (PBS, Hyclone, SH30256.01B), 96-well plate (Thermo, 167425), red blood cell lysis solution (Beijing Keyeida Biological Technology Co., Ltd., KS801-100), 70μm cell screen (SPL Life Scineces, SPL-93070).

[0161] Then, a blank control group (CON), a BSA positive control group (POS), a raw material (cocoon) group (RAW), and a product group (PRO) are respectively set; 12 BALB / c mice are included in each group at each time point, and half of them are male and half of them are female; the implantation period is 4 weeks and 12 weeks, so as to facilitate subsequent implantation and detection.

[0162] The implantation method of the facial implant is as follows: after the mice are anesthetized, the skin is prepared, and the operation implantation is performed under sterile technique; wherein one piece of round sample (diameter 5.5mm, thickness 0.28mm) is implanted subcutaneously on the back of each mouse in the product group; the blank control group is subjected to “false” operation without implanting the sample; the raw material group is implanted with one piece of cocoon raw material with the same area as the sample in the product group; the positive control group of mice is subcutaneously injected with a mixture of bovine serum albumin (3mg BSA dissolved in 9mL PBS) and complete Freund's adjuvant with the same volume, 0.12mL, once a week, a total of 4 times.

[0163] The detection and evaluation method is as follows: after 4 weeks and 12 weeks of implantation, blood, spleen, thymus, facial implant and its surrounding tissue and other specimens are obtained for detection, including:

[0164] 1. Detection of total IgG and IgM in mouse serum;

[0165] 1) Serum total IgG: according to the mouse IgG detection kit instructions, select the appropriate serum dilution according to the pre-experiment results, dilute the mouse serum 100 times;

[0166] 2) Serum total IgM: according to the mouse IgM detection kit instructions, select the appropriate serum dilution according to the pre-experiment results, dilute the mouse serum 10 times.

[0167] 2, Mouse serum cytokine detection;

[0168] Cytometric Bead Array (CBA) was used to detect mouse serum cytokines IFN-γ, IL-4, IL-6, IL-10 and IL-12p70. According to the reagent instructions, serum and cytokine standards were incubated with microspheres at room temperature, then fluorescently labeled antibodies were added and incubated at room temperature. After washing, the fluorescence intensity of the microsphere sample was detected by flow cytometry, and then the FCS data file was exported, and the data was analyzed by BD FCAP software.

[0169] 3, Mouse spleen lymphocyte subtype detection;

[0170] After the mouse was anesthetized and blood was taken, the mouse was decapitated and immersed in 75% ethanol solution for disinfection. The spleen was taken aseptically in a clean bench, cut into small pieces and transferred to a 70µm filter screen. The spleen tissue was ground with the end of a syringe piston, washed with culture medium, filtered and centrifuged. After centrifugation, the supernatant was discarded, and red blood cell lysing solution was added to lyse for 5 minutes.

[0171] Centrifuge again and discard the supernatant, resuspend the cells after washing with culture medium, centrifuge and prepare a single cell suspension with 1% FBS in PBS. After counting, adjust the cell concentration to 1×10 7 mL -1 .

[0172] Add 10µL of the corresponding mixed labeled antibodies to each flow tube, including CD45, CD3, CD4, CD8 antibodies for T lymphocyte typing, CD45, CD3, CD19, CD69 antibodies for B lymphocyte typing, CD45, CD3, CD49b, CD69 antibodies for natural killer (NK) and natural killer T cell (NKT) typing. Take 100µL of the concentration of 1×10 7 mL -1Spleen cell suspension was added to each sample flow cytometry tube, mixed thoroughly, and incubated at room temperature in the dark for 20 min. The cells were washed twice by centrifugation with PBS containing 1% FBS. After resuspending the cells in 0.5 mL of PBS containing 1% FBS in each tube, the tubes were stored in the dark for flow cytometry analysis. The results were analyzed using FACS DIVA SOFTWARE software.

[0173] 4. Mouse spleen lymphocyte proliferation test;

[0174] Mouse spleen lymphocytes obtained from isolation were collected, and the cell suspension concentration was adjusted to 3 × 10⁻⁶ cells / mL using 1640 culture medium containing 10% serum. 6 pcs·mL -1 In 96-well plates, each mouse spleen lymphocyte was seeded in duplicate, with 200 μL of cell suspension in each well. A control well containing only 200 μL of cell culture medium was used for absorbance measurement. The 96-well plates were placed in a cell culture incubator and incubated at 37°C and 5% CO2 for 3 days. Four hours before the end of lymphocyte culture, 20 μL of CCK8 reagent was added to each well of the 96-well plate, and culture was continued for another 4 hours. The absorbance was then measured at 450 nm using a microplate reader.

[0175] 5. Pathological analysis of mouse spleen, thymus, samples, and implanted local tissues;

[0176] Thymus and spleen were harvested and weighed from each mouse. Simultaneously, local tissue specimens encasing the implant were obtained, fixed in 10% formaldehyde, and then routinely sectioned in paraffin. After HE staining, the sections were evaluated for histopathological examination under a microscope. The histological evaluation of the implant was performed semi-quantitatively according to Appendix E of GB / T 16886.6-2015. Infiltrating cells such as polymorphonuclear leukocytes, lymphocytes, plasma cells, macrophages, and giant cells were scored from 0 to 4.0 based on the number of cells in the local microscopic field. Local reactions such as necrosis, angiogenesis, fibrosis, and fatty infiltration were scored from 0 to 4.0 based on their microscopic severity. The total histological evaluation score for each mouse was the sum of the scores for infiltrating cells and local reactions. The histological evaluation score for each experimental group was the average score of all mice in that group. A score of 0.0–2.9 indicates no local irritation of the implant; 3.0–8.9 indicates mild irritation; 9.0–15.0 indicates moderate irritation; and >15 indicates severe irritation.

[0177] The spleen and thymus sections were observed under microscope for histopathology, and the different tissue compartments and cell numbers in the spleen and thymus were evaluated, including the splenic periarteriolar lymphoid sheaths, lymphoid follicles, marginal zone, red pulp, thymus cortex, medulla, and cortex-medulla ratio. The rating criteria for cell density (cell number increase or decrease) or tissue structure are as follows: normal, grade 1; difference < 25% compared with normal, grade 2; difference 25-50% compared with normal, grade 3; and difference > 50% compared with normal, grade 4.

[0178] Then, according to the statistical processing method, the measurement data were expressed as (mean SD), and the data of each group were subjected to normal distribution and variance homogeneity test. If the data of each group were in accordance with the normal distribution and variance homogeneity, single-factor variance analysis was performed. If the data of an experimental group were not in accordance with the normal distribution or variance homogeneity, non-parametric test was performed. P < 0.05 was considered to be significantly different.

[0179] The test results are shown below.

[0180] (I) The detection results of total antibodies in mouse serum

[0181] The detection results of total IgG and IgM contents in mouse serum are shown in Table 3. The total IgG and IgM contents in the positive control group (POS) at 4 weeks and 12 weeks were significantly increased compared with the blank control group (CON), and the statistical differences were very significant (P < 0.01).

[0182] The total IgG and IgM contents in the raw material group (RAW) at 4 weeks and 12 weeks were not significantly changed compared with the blank control group (CON), and the statistical differences were not significant (P > 0.05).

[0183] The total IgG and IgM contents in the product group (PRO) at 4 weeks and 12 weeks were not significantly changed compared with the blank control group (CON), and the statistical differences were not significant (P > 0.05).

[0184] Table 3. Detection results of IgG and IgM in serum (unit: mg·mL -1 )

[0185]

[0186] Note: ** indicates comparison with the blank control group of the same period, P < 0.01.

[0187] (II) The detection results of cytokines in mouse serum

[0188] As shown in Table 4, at 4 weeks after implantation, the serum IFN-γ and IL-6 contents of the positive control group (POS) mice were higher than those of the blank control group (CON), with statistically significant differences (P<0.05 or P<0.01), and the serum IL-4, IL-10 and IL-12p70 contents of the positive control group mice had no statistically significant differences (P>0.05) compared with the blank control group. The serum cytokines of the raw material group (RAW) mice had no statistically significant differences (P>0.05) compared with the blank control group. The serum IFN-γ content of the product group (PRO) mice was lower than that of the blank control group (CON), with a statistically significant difference (P<0.05), and the serum other cytokines of the product group (PRO) mice had no statistically significant differences (P>0.05) compared with the blank control group.

[0189] At 12 weeks after implantation, the serum IFN-γ content of the positive control group (POS) mice was higher than that of the blank control group (CON), with a statistically very significant difference (P<0.01), and the serum IL-4, IL-6, IL-10 and IL-12p70 contents of the positive control group mice had no statistically significant differences (P>0.05) compared with the blank control group. The serum cytokines of the raw material group (RAW) and the product group (PRO) mice had no statistically significant differences (P>0.05) compared with the blank control group.

[0190] Table 4 Serum IgG and IgM detection results (unit: pg·mL -1 )

[0191]

[0192] Note: * or ** indicates comparison with the blank control group in the same period, P<0.05 or P<0.01.

[0193] (Three) Detection results of mouse spleen lymphocyte subtypes

[0194] As shown in Table 5, at 4 weeks after implantation, the percentages of T cells, CD4 T cells and NK cells of the positive control group (POS) were lower than those of the blank control group (CON), the percentage of B cells of the positive control group was higher than that of the blank control group, and the above changes had very statistically significant differences (P<0.01); the percentages of other lymphocyte subtypes of the positive control group had no statistically significant differences (P>0.05) compared with the blank control group. At 4 weeks, the percentages of lymphocyte subtypes of the raw material group (RAW) had no statistically significant differences (P>0.05) compared with the blank control group. At 4 weeks, the percentage of CD8 T cells of the product group (PRO) was higher than that of the blank control group, and the difference was statistically significant (P<0.05); the percentages of other lymphocyte subtypes of the product group had no statistically significant differences (P>0.05) compared with the blank control group.

[0195] At 12 weeks after implantation, the percentages of activated B cells of the positive control group (POS) and the raw material group (RAW) were lower than that of the blank control group, and the differences were statistically significant (P<0.05 or P<0.01); the percentages of other lymphocyte subtypes of the positive control group (POS) and the raw material group (RAW) had no statistically significant differences (P>0.05) compared with the blank control group. The percentages of lymphocyte subtypes of the product group (PRO) had no statistically significant differences (P>0.05) compared with the blank control group.

[0196] Table 5 Percentages of lymphocyte subtypes in spleen detected by flow cytometry

[0197]

[0198] (Four) Results of mouse spleen lymphocyte proliferation test

[0199] As shown in Table 6, at 4 weeks and 12 weeks after implantation, the lymphocytes in the mouse spleen were separated for in vitro lymphocyte proliferation test, and the results after 3 days of culture showed that the optical absorbance values of the positive control group (POS) had very statistically significant differences (P<0.01) compared with the blank control group (CON), and the optical absorbance values of the raw material group (RAW) and the product group (PRO) had no statistically significant differences (P>0.05) compared with the blank control group.

[0200] Table 6 Results of mouse spleen lymphocyte proliferation test

[0201]

[0202] (Five) Weights of mouse spleen and thymus and organ coefficients

[0203] The weights of the mouse spleen and thymus and the organ coefficients thereof at 4 weeks and 12 weeks are shown in Table 7.

[0204] 4 weeks, the spleen weight and the spleen coefficient of the positive control group (POS) male and female mice were increased compared with the blank control group mice, and there was a very significant difference (P<0.01); the thymus weight and the organ coefficient of the positive control group (POS) male and female mice had no significant difference compared with the blank control group (P>0.05). At 4 weeks, the spleen coefficient of the male mice and the thymus coefficient of the female mice of the raw material group (RAW) were increased compared with the blank control group mice, and there was a significant difference (P<0.05 or P<0.01); the weight of other organs and the organ coefficient of the raw material group (RAW) mice had no significant difference compared with the blank control group (P>0.05). At 4 weeks, the spleen, thymus weight and organ coefficient of the product group (PRO) male and female mice had no significant difference compared with the blank control group (P>0.05).

[0205] At 12 weeks, the spleen weight and the spleen coefficient of the positive control group (POS) female mice were increased compared with the blank control group mice, and there was a significant difference (P<0.05 or P<0.01); the weight of other organs and the organ coefficient of the positive control group (POS) mice had no significant difference compared with the blank control group (P>0.05). At 12 weeks, the spleen, thymus weight and organ coefficient of the raw material group (RAW) and the product group (PRO) male and female mice had no significant difference compared with the blank control group (P>0.05).

[0206] Table 7 Spleen, thymus weight and organ coefficient of mice

[0207]

[0208] Six) Histopathological evaluation of mouse spleen, thymus and implant tissue

[0209] 1. Histopathological evaluation of facial implant

[0210] The tissue section images of the blank control group mice at 4 weeks and 12 weeks are respectively shown in Figure 5 , Figure 6 The epidermis, dermis and subcutaneous connective tissue structure on the tissue section were clear, and the subcutaneous adipose tissue and the underlying striated muscle tissue were arranged closely; the subcutaneous hair follicles, hair roots and sebaceous glands and other skin appendages were not abnormal; a small amount of inflammatory cells were scattered in the subcutaneous tissue.

[0211] The tissue section images of the positive control group mice implanted for 4 weeks and 12 weeks are respectively shown in Figure 7 , Figure 8, the epidermis and dermis of the skin on the tissue section were normal; the subcutaneous tissue had multiple round-shaped inclusions, most of which were large; the peripheral inclusion wall was uneven in thickness, the small inclusion wall was thin, and was composed of fibroblasts, fibrocytes and collagen fibers; the thick wall had more inflammatory cells; a small part of the inclusion was inflammatory necrotic residue, and most of the inclusion was empty, i.e. the cavity after removing the necrotic residue during sectioning.

[0212] The images of the tissue sections of the raw material group implanted for 4 weeks and 12 weeks are shown in Figure 9 , Figure 10 , the epidermis and dermis of the skin on the tissue section were normal; the subcutaneous tissue had multiple round-shaped inclusions, most of which were large; the peripheral inclusion wall was uneven in thickness, the small inclusion wall was thin, and was composed of fibroblasts, fibrocytes and collagen fibers; the thick wall had more inflammatory cells; a small part of the inclusion was inflammatory necrotic residue, and most of the inclusion was empty, i.e. the cavity after removing the necrotic residue during sectioning.

[0213] The images of the tissue sections of the product group implanted for 4 weeks are shown in Figure 11 A, Figure 11 B, the epidermis and dermis of the skin on the tissue section were normal; the subcutaneous tissue had a large rectangular inclusion, i.e. the peripheral inclusion wall and the middle inclusion; the inclusion wall was not thick, and was composed of fibroblasts, fibrocytes and collagen fibers, with some inflammatory cells therebetween; the inclusion was a whole piece of homogeneous structureless light-staining material, and no obvious degradation and absorption were observed.

[0214] The images of the tissue sections of the product group implanted for 12 weeks are shown in Figure 12 A, Figure 12 B. The epidermis and dermis of the skin on the tissue section were normal; the subcutaneous tissue had a large rectangular inclusion, i.e. the peripheral inclusion wall and the middle inclusion; the inclusion wall was complete and had a uniform thickness, and was composed of fibroblasts, fibrocytes and collagen fibers, with some inflammatory cells therebetween; the inclusion was a whole piece of homogeneous structureless material, and no obvious degradation and absorption were observed.

[0215] At 4 weeks, the local reaction after implantation of the positive control group was severe stimulation (histological score difference was 21.4) compared with the blank control group, the local reaction after implantation of the raw material group was severe stimulation (histological score difference was 17.0) compared with the blank control group, and the local reaction after implantation of the product group was moderate stimulation (histological score difference was 11.4) compared with the blank control group.

[0216] At 12 weeks, the local reaction after implantation in the positive control group was severe irritation compared to the blank control group (histological score difference of 16.1), the local reaction after implantation in the raw material group was moderate irritation compared to the blank control group (histological score difference of 10.7), and the local reaction after implantation in the product group was mild irritation compared to the blank control group (histological score difference of 8.5).

[0217] 2. Pathological evaluation of spleen and thymus tissues in mice 4 weeks after implantation

[0218] like Figure 13 As shown, microscopic observation of spleen sections from mice in the blank control group at 4 weeks showed that the outer fibrous capsule was intact, the white pulp lymphocytes were dense, and the central artery in the center was not thickened; the lymphocytes in the periarterial lymphatic sheath were dense, the lymphoid follicles were not obvious, and the central germinal centers were mostly not obvious; the outer edge of the white pulp and the red pulp sinus were filled with red blood cells; a small amount of hemosiderin deposition was seen in the red pulp of the spleen in some animals; extramedullary hematopoiesis was enhanced in the spleen in 3 cases, and erythroid, granulocytic and megakaryocytic cells were all visible, with the erythroid being the most abundant.

[0219] like Figure 14 As shown, at 4 weeks, the spleen sections of mice in the positive control group were basically the same as those in the blank control group. Extramedullary hematopoiesis was enhanced in the spleens of the three animals, and erythroid, granulocytic and megakaryocytic cells were all visible, with the erythroid lineage being the most abundant.

[0220] like Figure 15 As shown, at 4 weeks, the spleen sections of mice in the raw material group were observed under a microscope in a manner similar to those in the blank control group. Extramedullary hematopoiesis was enhanced in the spleens of all four animals, and erythroid, granulocytic, and megakaryocytic cells were all visible, with the erythroid lineage being the most abundant.

[0221] like Figure 16 As shown, at 4 weeks, the spleen sections of mice in the product group were observed under a microscope in the same way as the blank control group. Extramedullary hematopoiesis was enhanced in the spleen of all four animals. Erythroid, granulocytic and megakaryocytic cells were all visible, with the erythroid lineage being the most abundant, and the granulocytic and megakaryocytic lineages were also very obvious.

[0222] It was observed that, 4 weeks after implantation, no significant changes were observed in the spleen of the animals in the product group compared with the blank control group.

[0223] like Figure 17 As shown, microscopic observation of thymic sections from mice in the blank control group at 4 weeks showed that the thymic capsule was intact, the thymic lobules were clearly structured, and no atrophy or hyperplasia was observed; the boundary between the cortex and medulla was clear, with a cortex-to-medulla area ratio of approximately 2:1, and 2 mice showed a ratio of 3:1; a large number of lymphocytes were densely packed in the cortex, and many nucleoli were visible; no significant increase was observed in epithelioid cells and a small number of macrophages; the medulla contained a large number of epithelioid cells and some lymphocytes, which varied in size and were relatively loose; macrophages that phagocytosed apoptotic lymphocytes were occasionally observed.

[0224] likeFigure 18 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0225] As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals. Figure 19 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0226] Figure 20 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0227] As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0228] 3. Histopathological evaluation of mouse spleen and thymus tissue after 12 weeks of implantation

[0229] As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals. Figure 21 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0230] Figure 22 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0231] As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals. Figure 23 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0232] Figure 24 As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0233] As shown in the figure, the thymus section of the mice in the positive control group was observed under a microscope at 4 weeks. No abnormal changes were observed, as seen in the blank control animals. The ratio of the cortical and medullary areas was about 2:1, and 3:1 in 3 animals.

[0234] ​​​As shown in Figure 25 thymus capsule was complete, the structure of thymus lobule was clear, and no atrophy and hyperplasia was observed; the boundary between cortex and medulla was clear, and the area ratio of cortex to medulla was about 2:1, in which one was 3:1; a large number of lymphocytes were arranged closely in the cortex, and many nucleoli were observed; no obvious increase of epithelioid cells and macrophages was observed; there were more epithelioid cells and some lymphocytes in the medulla, and the lymphocytes were loose; phagocytosis of apoptotic lymphocytes by macrophages was occasionally observed.

[0235] As shown in Figure 26 , the thymus section of the positive group mice observed under the microscope at 12 weeks was the same as that observed in the blank control group, and no abnormal change was observed.

[0236] As shown in Figure 27 , the thymus section of the raw material group mice observed under the microscope at 12 weeks was the same as that observed in the blank control group, and no abnormal change was observed.

[0237] As shown in Figure 28 , the thymus section of the product group mice observed under the microscope at 12 weeks was basically the same as that of the blank control group, and the area ratio of cortex to medulla of 12 animals was about 2:1.

[0238] It can be seen that at 12 weeks of implantation, compared with the blank control group, the thymus of the product group showed no obvious change.

[0239] In summary, compared with the blank control group, the statistically significant indicators of the positive control group were:

[0240] (1) At 4 weeks and 12 weeks, the serum total IgG and IgM content of the positive control group was significantly increased (P<0.01);

[0241] (2) At 4 weeks, the serum IFN-γ and IL-6 content of the positive control group mice was increased (P<0.05 or P<0.01); at 12 weeks, the serum IFN-γ content of the positive control group mice was increased (P<0.01);

[0242] (3) At 4 weeks, the percentage of B cells in the spleen of the positive control group was increased, and the percentages of T cells, CD4 T cells and NK cells were decreased (P<0.01); at 12 weeks, the percentage of activated B cells in the spleen of the positive control group was decreased (P<0.01);

[0243] (4) At 4 weeks and 12 weeks, the optical absorbance value of the lymphocyte proliferation test in vitro of the positive control group was significantly increased (P<0.01);

[0244] (5) At 4 weeks, the spleen weight and the spleen coefficient of the positive control group increased (P<0.01); at 12 weeks, the spleen weight and the spleen coefficient of the female mice in the positive control group increased (P<0.05 or P<0.01).

[0245] Compared with the blank control group, the raw material group had statistically significant indicators:

[0246] (1) At 12 weeks, the percentage of activated B cells in the spleen of the raw material group decreased (P<0.05);

[0247] (2) At 4 weeks, the spleen coefficient of the male mice and the thymus coefficient of the female mice in the raw material group increased (P<0.05 or P<0.01).

[0248] Compared with the blank control group, the product group had statistically significant indicators:

[0249] (1) At 4 weeks, the serum IFN-γ content of the product group decreased (P<0.05);

[0250] (2) At 4 weeks, the percentage of CD8 T cells in the product group increased (P<0.05), but the above differences were still within the reference value range (±2SD) of the related indicators of the blank control group.

[0251] And histopathological evaluation showed:

[0252] (1) At 4 weeks, the local reaction after implantation of the positive control group was severe compared with the blank control group (histological score difference was 21.4), the local reaction after implantation of the raw material group was severe compared with the blank control group (histological score difference was 17.0), and the local reaction after implantation of the product group was moderate compared with the blank control group (histological score difference was 11.4); at 12 weeks, the local reaction after implantation of the positive control group was severe compared with the blank control group (histological score difference was 16.1), the local reaction after implantation of the raw material group was moderate compared with the blank control group (histological score difference was 10.7), and the local reaction after implantation of the product group was mild compared with the blank control group (histological score difference was 8.5).

[0253] (2) At 4 weeks and 12 weeks after implantation, the spleen sections of the mice in the positive control group and the raw material group were observed under a microscope, which was basically the same as the blank control group; at 4 weeks and 12 weeks after implantation, the thymus sections of the mice in the positive control group and the raw material group were observed under a microscope, which was the same as the blank control group animals, and no abnormal changes were found.

[0254] (3) Compared with the blank control group, at 4 weeks and 12 weeks after implantation, the spleen of the mice in the product group showed no obvious changes; compared with the blank control group, at 4 weeks and 12 weeks after implantation, the thymus of the mice in the product group showed no obvious changes.​

[0255] It can be seen that the face implant provided by the embodiment of the present application has excellent biocompatibility, is beneficial to promote tissue repair and regeneration, has a slow degradation rate, is not prone to cause risks such as inflammation and bacterial infection, and has high use safety.

[0256] It should be noted that each of the embodiments in the specification is described in a progressive manner, and each embodiment focuses on the difference from other embodiments. The same and similar parts between the embodiments can be referred to each other.

[0257] The above only describes some embodiments of the present application and is not used to limit the present application. It should be understood by those skilled in the art that the present application can have various changes and improvements. Any modification, equivalent replacement and improvement made according to the present application all fall within the scope of protection required by the present application.

Claims

1. A facial implant, characterized in that, The implant includes an external nasal implant (1), a columellar implant (2), and a nasal septum implant (3). One side of the nasal septum implant (3) is connected to the inner arc side (13) of the external nasal implant (1), and the adjacent side of the nasal septum implant (3) is connected to the columellar implant (2). The facial implant is symmetrically arranged about the plane of the nasal septum implant (3). The nasal septum implant (3) serves as the nasal septum in the nasal structure and is used to install and position the external nasal implant (1) and the columellar implant (2). During the implantation process, the nasal septum can be removed and replaced by the nasal septum implant (3). The facial implant is made from silk fibroin; The external nasal implant (1), the nasal septum implant (3), and the columellar implant (2) are connected in pairs by mortise and tenon joints. The nasal septum implant (3) is a trapezoidal structure, and includes a first tenon (31) and a second tenon (32). The first tenon (31) is located on the hypotenuse of the nasal septum implant (3), and the second tenon (32) is located on the bottom edge of the nasal septum implant (3). The inner arc side (13) of the external nasal implant (1) is provided with a first mortise hole (14), which is connected to the first tenon (31). The side of the columellar implant (2) facing the nasal septum implant (3) is provided with a second mortise hole (23), which is connected to the second tenon (32). The nasal columellar prosthesis (2) has a mortise (24) on its columellar prosthesis (2), and the second mortise (23) is located in the mortise (24); one end of the external nasal prosthesis (1) has a third tenon (15), the mortise (24) is at least partially connected to the third tenon (15), and the mortise (24) is at least partially connected to the bottom edge of the nasal septum prosthesis (3) with a tenon joint; The width of at least one of the first tenon (31) and the second tenon (32) is 1.5mm to 2.0mm, and the length of at least one of the first tenon (31) and the second tenon (32) is 1.0mm to 5.0mm; The distance between two adjacent first tenons (31) in the direction of the hypotenuse of the nasal septum prosthesis (3) is 0.1mm to 10.0mm, and the distance between two adjacent second tenons (32) in the direction of the bottom edge of the nasal septum prosthesis (3) is 0.1mm to 10.0mm; The number of at least one of the first tenon (31) and the second tenon (32) is 2 to 6; The fit tolerance between each pair of the external nasal implant (1), the nasal septum implant (3), and the nasal columella implant (2) is -0.1mm to +0.1mm. The fit tolerance is the fit tolerance of the facial implant in a rigid state.

2. The facial implant according to claim 1, characterized in that, The external nasal prosthesis (1) includes a nasal bridge prosthesis (11) and a nasal dorsum prosthesis (12). The nasal bridge prosthesis (11) is arranged opposite to the inner arc side (13), and the nasal dorsum prosthesis (12) is symmetrically arranged on both sides of the nasal bridge prosthesis (11). The nasal columellar prosthesis (2) includes a columellar prosthesis (21) and an alar prosthesis (22). The columellar prosthesis (21) is connected to the nasal septum prosthesis (3), and the alar prosthesis (22) is symmetrically arranged on both sides of the columellar prosthesis (21).

3. The facial implant according to claim 1, characterized in that, The cross-sectional area of ​​the end of the external nasal prosthesis (1) near the nasal columellar prosthesis (2) is smaller than the cross-sectional area of ​​the end of the external nasal prosthesis (1) away from the nasal columellar prosthesis (2).

4. The facial implant according to claim 1, characterized in that, The facial implant satisfies at least one of the following characteristics: The tensile modulus of the facial implant is 28.85 MPa to 82.45 MPa; The tensile strength of the facial implant is 6.35 MPa to 9.84 MPa; The fracture elongation of the facial implant is 0.65% to 1.38%.

5. The facial implant according to claim 1, characterized in that, The facial implant is made by rehydrating, injection molding, curing, soaking, drying and machining silk fibroin.

Images