Facial implant

Abstract

The invention discloses a face implant which comprises an outer 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 outer nose prosthesis, the adjacent side of the nasal septum prosthesis is connected with the nasal column prosthesis, and the face implant is symmetrically arranged relative to the plane where the nasal septum prosthesis is located; the facial implant is made on the basis of silk fibroin. The facial implant provided by the invention is prepared from silk fibroin, has good mechanical properties and biocompatibility, can be effectively shaped, and promotes tissue repair and regeneration.

Description

Technical Field

[0001] The present invention relates to the technical field of medical devices, and particularly to a facial implant. Background Art

[0002] Currently, the mainstream material of facial implants is still silicone, and the applications of some biodegradable materials and composite materials are also gradually increasing, such as polylactic acid, titanium alloy and the combination of bioceramics, etc.; however, silicone has a low hardness, a risk of displacement, and is prone to inflammation due to non-degradation after long-term implantation; titanium alloy is difficult to process, and requires a second operation for removal, which is inconvenient to operate; while polylactic acid has too fast a degradation rate, and the degradation products are prone to inflammatory reactions. Summary of the Invention

[0003] In view of the problems existing in the above-mentioned prior art, the present invention provides a facial implant, and the technical solution is as follows: The present invention provides a facial implant, including an external nose prosthesis, a nasal column prosthesis and a nasal septum prosthesis. One side of the nasal septum prosthesis is connected to the inner arc side of the external nose prosthesis, and an adjacent side of the nasal septum prosthesis is connected to the nasal column prosthesis. The facial implant is symmetrically arranged with respect to the plane where the nasal septum prosthesis is located; The facial implant is made based on silk fibroin.

[0004] Further, the external nose prosthesis, the nasal septum prosthesis and the nasal column prosthesis are connected to each other through a mortise and tenon structure.

[0005] Further, the nasal septum prosthesis is in a trapezoidal structure. The nasal septum prosthesis includes a first tenon and a second tenon. The first tenon is located on the hypotenuse of the nasal septum prosthesis, and the second tenon is located on the bottom side of the nasal septum prosthesis; A first mortise is opened on the inner arc side of the external nose prosthesis, and the first mortise is connected to the first tenon; A second mortise is opened on the surface of the nasal column prosthesis facing the nasal septum prosthesis, and the second mortise is connected to the second tenon.

[0006] Further, a mortise groove is provided on the nasal columella prosthesis of the nasal column prosthesis, and the second mortise is located in the mortise groove; One end of the external nose prosthesis is provided with a third tenon. At least part of the mortise groove is connected to the third tenon, and at least part of the mortise groove is mortise-and-tenon connected to the bottom side of the nasal septum prosthesis.

[0007] Further, at least one of the first tenon and the second tenon satisfies at least one of the following characteristics: The width of at least one of the first tenon and the second tenon is 1.5 mm to 2.0 mm; The length of at least one of the first tenon and the second tenon is 1.0 mm to 5.0 mm; The distance between two adjacent first tenons in the direction of the hypotenuse of the nasal septum prosthesis is 0.1 mm to 10.0 mm; The distance between two adjacent second tenons in the direction of the bottom edge of the nasal septum prosthesis is 0.1 mm to 10.0 mm; The number of at least one of the first tenon and the second tenon is 1 to 6.

[0008] Further, the fitting tolerance between any two of the external nasal prosthesis, the nasal septum prosthesis and the nasal column prosthesis is -0.1 mm to +0.1 mm.

[0009] Further, the external nasal prosthesis includes a nasal bridge prosthesis and a nasal dorsum prosthesis. The nasal bridge prosthesis is arranged opposite to the inner arc side, and the nasal dorsum prostheses are symmetrically arranged on both sides of the nasal bridge prosthesis; The nasal column prosthesis includes a nasal columella prosthesis and alar prostheses. The nasal columella prosthesis is connected to the nasal septum prosthesis, and the alar prostheses are symmetrically arranged on both sides of the nasal columella prosthesis.

[0010] Further, the cross-sectional area of one end of the external nasal prosthesis close to the nasal column prosthesis is smaller than the cross-sectional area of the end of the external nasal prosthesis far from the nasal column prosthesis.

[0011] Further, 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 elongation at break of the facial implant is 0.65% to 1.38%.

[0012] Further, the facial implant is made by re-dissolving silk fibroin, injection molding, curing and forming, bubble washing and drying, and machining.

[0013] Implementing the present invention has the following beneficial effects: 1. The facial implant of the present invention is made of silk fibroin, so that the facial implant has good mechanical properties. Matching the overall shape of the external nasal prosthesis, the nasal septum prosthesis and the nasal column prosthesis, it can effectively shape, and the degradation rate is slow, avoiding the premature loss of the supporting force of the facial implant, and can effectively maintain the reliability and stability of shaping; at the same time, silk fibroin contains a large number of amino acids similar to those of the human body, which can also promote tissue repair and regeneration; using silk fibroin makes the facial implant have excellent biocompatibility, and it is not easy to cause risks such as inflammation and bacterial infection after long-term use and final degradation, and has good safety.

[0014] 2. In the facial implant of the present invention, the external nasal prosthesis, the nasal septum prosthesis and the nasal column prosthesis are connected to each other by a mortise and tenon structure, which can be quickly assembled, is simple and convenient to operate, and does not require additional introduction of heterogeneous connecting parts. The connection reliability is good, which is beneficial to maintaining the overall mechanical properties and biocompatibility of the facial implant and promoting tissue repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the technical solutions of the present invention, the drawings used in the embodiments will be briefly introduced below, where the same components are denoted by the same reference numerals. Obviously, the drawings in the following description are only some embodiments of the present invention, and those of ordinary skill in the art can obtain other drawings based on these drawings without creative efforts.

[0016] Figure 1 It is an exploded view of the structure of a facial implant provided by an embodiment of the present invention; Figure 2 It is a schematic diagram of the structure of a facial implant after assembly provided by an embodiment of the present invention; Figure 3 It is a physical diagram of a facial implant provided by an embodiment of the present invention; Figure 4 It is a flowchart of the preparation method of the facial implant in a specific embodiment of the present invention; Figure 5 It is a pathological section of the skin tissue of a mouse in the blank control group at 4 weeks; Figure 6 It is a pathological section of the skin tissue of a mouse in the blank control group at 12 weeks; Figure 7 It is a pathological section of the injection site tissue of a mouse in the positive group at 4 weeks; Figure 8 It is a pathological section of the injection site tissue of a mouse in the positive group at 12 weeks; Figure 9 It is a pathological section of the implantation site tissue of a mouse in the raw material group at 4 weeks; Figure 10 It is a pathological section of the implantation site tissue of a mouse in the raw material group at 12 weeks; Figure 11 It is a pathological section of the implantation site tissue of a mouse in the product group at 4 weeks; Figure 12 It is a pathological section of the implantation site tissue of a mouse in the product group at 12 weeks; Figure 13 It is a pathological section of the spleen tissue of a mouse in the blank control group at 4 weeks; Figure 14 It is a pathological section of the spleen tissue of a mouse in the positive control group at 4 weeks; Figure 15Pathological section of the spleen tissue of mice in the raw material group at 4 weeks; Figure 16 Pathological section of the spleen tissue of mice in the product group at 4 weeks; Figure 17 Pathological section of the thymus tissue of mice in the blank control group at 4 weeks; Figure 18 Pathological section of the thymus tissue of mice in the positive control group at 4 weeks; Figure 19 Pathological section of the thymus tissue of mice in the raw material group at 4 weeks; Figure 20 Pathological section of the thymus tissue of mice in the product group at 4 weeks; Figure 21 Pathological section of the spleen tissue of mice in the blank control group at 12 weeks; Figure 22 Pathological section of the spleen tissue of mice in the positive control group at 12 weeks; Figure 23 Pathological section of the spleen tissue of mice in the raw material group at 12 weeks; Figure 24 Pathological section of the spleen tissue of mice in the product group at 12 weeks; Figure 25 Pathological section of the thymus tissue of mice in the blank control group at 12 weeks; Figure 26 Pathological section of the thymus tissue of mice in the positive control group at 12 weeks; Figure 27 Pathological section of the thymus tissue of mice in the raw material group at 12 weeks; Figure 28 Pathological section of the thymus tissue of mice in the product group at 12 weeks.

[0017] Among them, the reference numerals are: 1 - external nasal prosthesis, 11 - nasal bridge prosthesis, 12 - nasal dorsum prosthesis, 13 - inner arc side, 14 - first mortise hole, 15 - third tenon, 2 - nasal column prosthesis, 21 - columella nasi prosthesis, 22 - alar prosthesis, 23 - second mortise hole, 24 - mortise groove, 3 - nasal septum prosthesis, 31 - first tenon, 32 - second tenon. Detailed implementation manner

[0018] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Therefore, it cannot be understood as a limitation to the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts belong to the scope of protection of the present invention.

[0019] It should be noted that in the description of the present invention, for the terms defined below, unless a different definition is given in the claims or elsewhere in this specification, these definitions shall apply. All numerical values, whether explicitly indicated or not, are hereby defined as being modified by the term "about". The term "about" generally refers to a numerical range that a person 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 the numerical values included in the numerical range and all sub-ranges included in the numerical range.

[0020] It should be noted that in the specification, claims and drawings of the present invention, the terms "first", "second", etc. are used to distinguish similar objects and do not necessarily have to be used to describe a specific order or sequence. It should be understood that the objects so used can be interchanged under appropriate circumstances so that the embodiments of the present invention can be implemented in an order other than the order shown or described below. In addition, the terms "comprising" and "having" and any variations thereof are intended to cover non-exclusive inclusion. For example, a process, method, system, or product that includes a series of steps or units does not necessarily have to be limited to those steps or units clearly listed, but may include other steps or units not clearly listed or inherent to these processes, methods, or products.

[0021] In view of the problems that existing facial implants cannot balance hardness, a suitable degradation rate, good biocompatibility, and operational convenience, etc., the embodiments of the present invention provide a facial implant, such as Figure 1 As shown, the facial implant includes an external nasal prosthesis 1, a nasal column prosthesis 2, and a nasal septum prosthesis 3. Among them, the external nasal prosthesis 1 serves as the external nose in the nose structure, the nasal column prosthesis 2 serves as the nasal column in the nose structure, and the nasal septum prosthesis 3 serves as the nasal septum in the nose structure. 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 position of the external nasal prosthesis 1. An adjacent side of the nasal septum prosthesis 3 is connected to the nasal column prosthesis 2. The facial implant is symmetrically arranged with respect to the plane where the nasal septum prosthesis 3 is located, and has good shaping aesthetics; the whole facial implant is made based on silk fibroin, and the main components include silk fibroin, and also include sterilized injection water or physiological saline. Silk fibroin is a natural polymer protein with good mechanical properties, which can provide good mechanical properties for the facial implant, has a good shaping effect, and also enables the facial implant to be directly carved during use, with good flexibility in shaping; moreover, silk fibroin has good biocompatibility, contains a large number of amino acids similar to those of the human body, and has a promoting effect on tissue restoration. Therefore, after implanting this facial implant, it can promote tissue repair and growth; in addition, silk fibroin is biodegradable, and the degradation rate is slow, which can effectively maintain the shaping stability and is not likely to cause risks such as inflammation and bacterial infection, and has good safety.

[0022] Specifically, as Figure 2 shown, the external nose prosthesis 1 includes a nasal bridge prosthesis 11 and a nasal dorsum prosthesis 12. The external nose prosthesis 1 is the main morphological component of the facial implant and is used for shaping. Among them, as Figure 1 shown, the nasal bridge prosthesis 11 is arranged opposite to the inner arc side 13, and the nasal dorsum prostheses 12 are symmetrically arranged on both sides of the nasal bridge prosthesis 11, so that the symmetry of the external nose prosthesis 1 is good, which is beneficial to improving the shaping aesthetics after implantation; in addition, the external nose prosthesis 1 is an integral structure, that is, the nasal bridge prosthesis 11 and the nasal dorsum prosthesis 12 are integrally formed, streamlining the assembly process in the subsequent use process, improving the operation convenience, and also being beneficial to improving the overall integrity and continuity of the external nose prosthesis 1, maintaining the uniformity of the mechanical properties of the whole external nose prosthesis 1, being able to provide good and reliable supporting force after implantation, having good long-term stability, and being beneficial to improving the durability of the external nose prosthesis 1; in addition, in some alternative embodiments, the nasal dorsum prosthesis 12 extends from the side connected to the nasal bridge prosthesis 11 towards the inner arc side 13, or can be carved into an inclined surface extending towards the inner arc side 13 during use, so that the shape of the external nose prosthesis 1 fits the structure of the human external nose better and the shaping aesthetics is better.

[0023] Specifically, as Figure 2 shown, the cross-sectional area of one end of the external nose prosthesis 1 close to the nasal column prosthesis 2 is smaller than the cross-sectional area of the end of the external nose prosthesis 1 far from the nasal column prosthesis 2. After being implanted into the face, the lower end is narrower, which can better fit the shape of the human nasal bridge and has good adaptability; in some preferred embodiments, as Figure 3 shown, the external nose prosthesis 1 gradually widens and / or thickens from the end close to the nasal column prosthesis 2 to the end far from the nasal column prosthesis 2, which is more ergonomic, has good shaping reliability, and is beneficial to maintaining the support stability.

[0024] Specifically, as Figure 1 and Figure 2 shown, the nasal column prosthesis 2 includes a nasal columella prosthesis 21 and alar prostheses 22. Among them, the nasal column prosthesis 2 is used to replace the original nasal column. The nasal columella prosthesis 21 serves as the nasal columella in the nose structure, and the alar prostheses 22 serve as the alar support cartilage in the nose structure. The nasal columella prosthesis 21 is connected to the nasal septum prosthesis 3, and the alar prostheses 22 are symmetrically arranged on both sides of the nasal columella prosthesis 21, so that the nasal column prosthesis 2 is also arranged in a symmetric structure, which not only conforms to ergonomics and has good stability, but also can improve the overall shaping aesthetics after implantation; in some preferred embodiments, the nasal column prosthesis 2 is an integral structure, that is, the nasal columella prosthesis 21 and the alar prostheses 22 are integrally formed, reducing the assembly process in the subsequent use process, improving the operation convenience, and being beneficial to maintaining the overall structural integrity and the uniformity of the mechanical properties of the nasal column prosthesis 2, having good support stability and durability after implantation.

[0025] AsFigure 2 As shown, in some preferred embodiments, the nasal column prosthesis 2 is generally in a trident shape, with the tip facing away from the inner arc side 13 of the external nasal prosthesis 1, that is, facing the direction of the nasal bridge prosthesis 11. It can effectively shape the nose and improve the aesthetics after implantation. Moreover, the alar prosthesis 22 can reserve a channel for the nasal cavity, effectively shaping the alar shape, improving the aesthetics of the alae nasi, and at the same time enhancing the safety and comfort of use.

[0026] In some preferred embodiments, the nasal septum prosthesis 3 is a sheet-like structure with a relatively thin overall thickness. In the plane where this sheet-like structure is located, the nasal septum prosthesis 3 is a trapezoidal structure; further, the nasal septum prosthesis 3 can be a right trapezoidal structure; the inner arc side 13 of the external nasal prosthesis 1 is connected to the hypotenuse of the nasal septum prosthesis 3, and specifically, the middle of the inner arc side 13 is connected to the hypotenuse of the nasal septum prosthesis 3. In the nasal column, the columella prosthesis 21 is connected to the bottom edge of the nasal septum prosthesis 3, specifically to the lower bottom of the nasal septum prosthesis 3, so that the overall facial implant is symmetrically arranged with respect to the plane where the nasal bridge prosthesis 11, the columella prosthesis 21, and the nasal septum prosthesis 3 are located, with good overall symmetry, which is beneficial to improving the shaping aesthetics, support balance, and stability after implantation.

[0027] Specifically, the external nasal prosthesis 1, the nasal septum prosthesis 3, and the nasal column prosthesis 2 are connected to each other through mortise and tenon structures, that is, the external nasal prosthesis 1 and the nasal septum prosthesis 3 are connected through a mortise and tenon structure, the external nasal prosthesis 1 and the nasal column prosthesis 2 are connected through a mortise and tenon structure, and the nasal septum prosthesis 3 and the nasal column prosthesis 2 are connected through a mortise and tenon structure. All the connection methods in this facial implant are mortise and tenon structure connections, without introducing additional heterogeneous connectors, which is beneficial to maintaining the overall mechanical properties, biocompatibility, and degradation properties of the facial implant, and is also beneficial to maintaining the uniformity and stability of the above properties. At the same time, the mortise and tenon structure connection is convenient and fast to assemble. Only need to connect the external nasal prosthesis 1 and the nasal column prosthesis 2 to the nasal septum prosthesis 3 through mortise and tenon respectively, and the remaining connection between the external nasal prosthesis 1 and the nasal column prosthesis 2 will also be completed accordingly, with fast and efficient assembly and good usability.

[0028] It should be noted that the nasal septum prosthesis 3 is used for installation and positioning. During the implantation process, the original nasal septum can be removed and replaced with this nasal septum prosthesis 3 to improve the implantation stability of the external nasal prosthesis 1, the nasal column prosthesis 2, and the overall facial implant, and prevent the external nasal prosthesis 1, the nasal column prosthesis 2, and the facial implant from shifting after implantation. At the same time, the mechanical properties of this facial implant are similar to those of the human nasal bone, and it has good biocompatibility. After implantation, it is almost indistinguishable from the human nasal bone, and it is not easy to have adverse reactions such as rejection reactions and inflammatory reactions, with good safety.

[0029] Specifically, as Figure 1As shown, the nasal septum prosthesis 3 includes a first tenon 31, which is located on the hypotenuse of the nasal septum prosthesis 3 and is used for mortise and tenon connection with the external nose prosthesis 1; a first mortise 14 is formed on the inner arc side 13 of the external nose prosthesis 1, and the first mortise 14 is connected to the first tenon 31 to achieve the mortise and tenon connection between the nasal septum prosthesis 3 and the external nose prosthesis 1, which is convenient for assembly and has good connection stability; further, the first mortise 14, the middle part of the nasal bridge prosthesis 11, and the nasal septum prosthesis 3 are arranged on the same plane to effectively maintain the symmetry of the assembled external nose prosthesis 1 and the overall facial implant.

[0030] Specifically, as Figure 1 shown, the nasal septum prosthesis 3 further includes a second tenon 32, which is located on the bottom edge of the nasal septum prosthesis 3, specifically on the lower bottom edge of the nasal septum prosthesis 3. The lower bottom edge is located at the lower end after the facial implant is implanted. The second tenon 32 is used for mortise and tenon connection with the nasal column prosthesis 2, specifically for mortise and tenon connection with the nasal columella prosthesis 21. The nasal columella prosthesis 21 is located in the middle of the nasal column prosthesis 2 and can serve as the axis of symmetry of the nasal column prosthesis 2. Used for connection with the second tenon 32, it can effectively maintain the symmetry of the entire facial implant; a second mortise 23 is formed on the side of the nasal column prosthesis 2 facing the nasal septum prosthesis 3. Specifically, the second mortise 23 is located on the nasal columella prosthesis 21. The second mortise 23 is connected to the second tenon 32 to achieve the mortise and tenon connection between the nasal septum prosthesis 3 and the nasal columella prosthesis 21, which is convenient for assembly and has good connection firmness.

[0031] Moreover, 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 external nose prosthesis 1 is greater than the thickness of the nasal septum prosthesis 3, and the width of the nasal columella prosthesis 21 is greater than the thickness of the nasal septum prosthesis 3. Compared with the method of forming the mortise on the nasal septum prosthesis 3, this mortise and tenon structure avoids the damage to the mechanical properties of the nasal septum prosthesis 3 caused by opening holes in the relatively thin nasal septum prosthesis 3, and also avoids the risks such as the failure of the mortise and tenon connection caused by the instability of the mortise in the relatively thin nasal septum prosthesis 3 after opening the hole. Setting the first tenon 31 and the second tenon 32 on the nasal septum prosthesis 3 makes the overall mortise and tenon connection reliable and firm, and has high use safety.

[0032] Specifically, as Figure 1As shown, a mortise groove 24 is provided on the columella prosthesis 21 of the nasal column prosthesis 2. The mortise groove 24 is recessed in the columella prosthesis 21, and the second mortise hole 23 is located in the mortise groove 24. One end of the external nose prosthesis 1 is provided with a third tenon 15, which is specifically located at the narrower end of the external nose prosthesis 1 and protrudes outward from the end of the external nose prosthesis 1. Correspondingly, at least part of the groove area in the mortise groove 24 is connected to the third tenon 15 to achieve the mortise and tenon connection between the external nose prosthesis 1 and the nasal column prosthesis 2. At the same time, at least part of the groove area in the mortise groove 24 is also connected to the bottom edge of the nasal septum prosthesis 3 by mortise and tenon, further improving the fastening of the mortise and tenon connection between the nasal column prosthesis 2 and the nasal septum prosthesis 3 on the basis of the matching mortise and tenon connection between the second tenon 32 and the second mortise hole 23.

[0033] As Figure 1 shown, in this embodiment, the mortise groove 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 groove 24 in the direction of the columella prosthesis 21 is equal to the length of the columella prosthesis 21, so as to respectively reserve a matching connection space for the third tenon 15 and the bottom edge of the nasal septum prosthesis 3, facilitating the realization of the mortise and tenon structure connection, and further improving the connection tightness among the external nose prosthesis 1, the nasal column prosthesis 2, and the nasal septum prosthesis 3. Moreover, through the mating connection of the second tenon 32 and the second mortise hole 23, the relative movement of the nasal septum prosthesis 3 in the mortise groove 24 can also be avoided, playing a certain limiting effect, without the need to additionally set up a complex limiting structure, making the overall structure of the facial implant simple, and having good connection tightness and firmness.

[0034] It should be noted that the sizes of each tenon and the corresponding mortise hole are the same to improve the matching and the connection tightness among the components after assembly. The following takes the sizes and positions of each tenon as an example for description, and the corresponding mortise hole can refer to the sizes and positions of the tenon, which will not be elaborated here.

[0035] Specifically, the width of at least one of the first tenon 31 and the second tenon 32 is 1.5 mm to 2.0 mm. Herein, the first tenon 31 and the second tenon 32 can be square or circular. Correspondingly, this width refers to the side length of the square tenon or the diameter of the circular tenon. Understandably, the width of at least one of the first tenon 31 and the second tenon 32 can be any point value within 1.5 mm to 2.0 mm. Exemplarily, the width of at least one of the first tenon 31 and the second tenon 32 can be 1.5 mm, 1.6 mm, 1.7 mm, 1.75 mm, 1.8 mm, 1.9 mm, 2.0 mm, 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 achieve good connection tightness, and the corresponding opening of the first mortise 14 and the second mortise 23 will not cause structural damage to the external nose prosthesis 1 and the nasal column prosthesis 2, which is beneficial to maintaining the mechanical properties of the overall structure. In some exemplary embodiments, the width of the first tenon 31 is 1.5 mm to 2.0 mm. In some other exemplary embodiments, the width of the second tenon 32 is 1.5 mm to 2.0 mm. In some preferred embodiments, the width of the first tenon 31 is 1.5 mm to 2.0 mm, and the width of the second tenon 32 is 1.5 mm to 2.0 mm.

[0036] Specifically, the length of at least one of the first tenon 31 and the second tenon 32 is 1.0 mm to 5.0 mm. Herein, the length of the first tenon 31 refers to the length that the first tenon 31 protrudes from the hypotenuse of the nasal septum prosthesis 3, which is the same as the depth of the first mortise 14. The length of the second tenon 32 refers to the length that the second tenon 32 protrudes from the bottom edge of the nasal septum prosthesis 3, which is the same as the depth of the second mortise 23. Understandably, the length of at least one of the first tenon 31 and the second tenon 32 can be any point value within 1.0 mm to 5.0 mm. Exemplarily, the length of at least one of the first tenon 31 and the second tenon 32 can be 1.0 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 4.0 mm, 5.0 mm, etc. Within this length range, the first tenon 31 and the second tenon 32 are not easily broken, and can effectively improve the accuracy and stability of the mortise and tenon structure connection, and are not easily disengaged to cause connection failure. In some exemplary embodiments, the length of the first tenon 31 is 1.0 mm to 5.0 mm. In some other exemplary embodiments, the length of the second tenon 32 is 1.0 mm to 5.0 mm. In some preferred embodiments, the length of the first tenon 31 is 1.0 mm to 5.0 mm, and the length of the second tenon 32 is 1.0 mm to 5.0 mm.

[0037] Specifically, the distance between two adjacent first tenons 31 in the hypotenuse direction of the nasal septum prosthesis 3 is 0.1 mm to 10.0 mm; it can be understood that the distance between two adjacent first tenons 31 in the hypotenuse direction of the nasal septum prosthesis 3 can be any point value within 0.1 mm to 10.0 mm; exemplarily, the distance between two adjacent first tenons 31 in the hypotenuse direction of the nasal septum prosthesis 3 can be 0.1 mm, 0.5 mm, 1.0 mm, 2.0 mm, 5.0 mm, 7.5 mm, 8.0 mm, 10.0 mm, etc.

[0038] Specifically, the distance between two adjacent second tenons 32 in the bottom side direction of the nasal septum prosthesis 3 is 0.1 mm to 10.0 mm; it can be understood that the distance between two adjacent second tenons 32 in the bottom side direction of the nasal septum prosthesis 3 can be any point value within 0.1 mm to 10.0 mm; exemplarily, the distance between two adjacent second tenons 32 in the bottom side direction of the nasal septum prosthesis 3 can be 0.1 mm, 0.5 mm, 1.0 mm, 2.0 mm, 5.0 mm, 7.5 mm, 8.0 mm, 10.0 mm, etc.

[0039] Within this distance range, the balance of the mortise and tenon joints on each side can be improved, which is beneficial to enhancing the tightness and reliability of the mortise and tenon joints between the external nose prosthesis 1, the nasal column prosthesis 2, and the nasal septum prosthesis 3, and the operation is simple and convenient.

[0040] In addition, when there are multiple first tenons 31 on the hypotenuse of the nasal septum prosthesis 3, the distances between two adjacent first tenons 31 can be the same or different. When there are multiple second tenons 32 on the bottom side of the nasal septum prosthesis 3, the distances between two adjacent second tenons 32 can be the same or different, so as to flexibly adapt to different structural strength requirements and stability requirements.

[0041] Specifically, the number of at least one of the first tenon 31 and the second tenon 32 is 1 to 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 from 1 to 6; exemplarily, the number of at least one of the first tenon 31 and the second tenon 32 can be 1, 2, 3, 4, 5, 6; in this way, not only can good mortise and tenon connection accuracy and reliability be maintained, but also the difficulty of preparing the first tenon 31 and the second tenon 32 is reduced, correspondingly reducing the difficulty of opening the first mortise 14 and the second mortise 23, saving costs, and also reducing the structural damage to the external nose prosthesis 1 and the columella prosthesis 21, which is beneficial to maintaining the overall mechanical properties of the external nose prosthesis 1, the nasal column prosthesis 2 and the nasal septum prosthesis 3, and the overall mechanical properties and biocompatibility of the facial implant are good; in some exemplary embodiments, the number of the first tenons 31 is 1 to 6; in some other exemplary embodiments, the number of the second tenons 32 is 1 to 6; in some preferred embodiments, the number of the first tenons 31 is 1 to 6 and the number of the second tenons 32 is 1 to 6.

[0042] Specifically, the fit tolerance between the external nose prosthesis 1, the nasal septum prosthesis 3 and the nasal column prosthesis 2 in pairs is -0.1 mm to +0.1 mm; it can be understood that the fit tolerance between the external nose prosthesis 1, the nasal septum prosthesis 3 and the nasal column prosthesis 2 in pairs can be any point value from -0.1 mm to +0.1 mm; exemplarily, the fit tolerance between the external nose prosthesis 1, the nasal septum prosthesis 3 and the nasal column prosthesis 2 in pairs can be -0.1 mm, -0.08 mm, -0.05 mm, -0.02 mm, 0 mm, +0.02 mm, +0.05 mm, +0.08 mm, +0.1 mm, etc.; within this fit tolerance range, the mortise and tenon connection between the external nose prosthesis 1, the nasal septum prosthesis 3 and the nasal column prosthesis 2 in pairs is tight and reliable, and can effectively maintain the shaping stability for a long time.

[0043] It should be noted that this fit tolerance refers to the fit tolerance of the facial implant in the hard state, specifically, it can be the fit tolerance after injection molding (or machining). The facial implant needs to be soaked in water during use, and there will be a phenomenon of swelling after soaking, so that the fit tolerance between the external nose prosthesis 1, the nasal septum prosthesis 3 and the nasal column prosthesis 2 in pairs is further reduced, and the overall mortise and tenon structure connection is tighter.

[0044] Specifically, the tensile modulus of the facial implant is 28.85 MPa to 82.45 MPa; it can be understood that the tensile modulus of the facial implant can be any point value within 28.85 MPa to 82.45 MPa; exemplarily, the tensile modulus of the facial implant can be 28.85 MPa, 31.73 MPa, 44.96 MPa, 58.27 MPa, 70.52 MPa, 82.45 MPa, etc.; within this tensile modulus range, the facial implant has good tensile deformation resistance, is not easily deformed during the implantation process, improves the operation convenience, and can also effectively maintain the durability of the shaping effect.

[0045] Specifically, the tensile strength of the facial implant is 6.35 MPa to 9.84 MPa; it can be understood that the tensile strength of the facial implant can be any point value within 6.35 MPa to 9.84 MPa; exemplarily, the tensile strength of the facial implant can be 6.35 MPa, 6.92 MPa, 7.38 MPa, 8.01 MPa, 8.97 MPa, 9.84 MPa, etc.; within this tensile strength range, the facial implant has good fracture resistance, is not easily broken or damaged during use, reduces the operation difficulty, is beneficial to improving the implantation efficiency, and is also beneficial to improving the shaping reliability.

[0046] Specifically, the elongation at break of the facial implant is 0.65% to 1.38%; it can be understood that the elongation at break of the facial implant can be any point value within 0.65% to 1.38%; exemplarily, the elongation at break of the facial implant can be 0.65%, 0.79%, 0.91%, 1.03%, 1.25%, 1.38%, etc.; thus, the facial implant has good structural strength and toughness, good impact resistance, is not easily deformed, and is not easily broken, with excellent mechanical properties.

[0047] During assembly, the narrower end of the external nasal prosthesis 1 is oriented towards the lower base of the nasal septum prosthesis 3. The first mortise holes 14 of the external nasal prosthesis 1 and the first tenons 31 of the nasal septum prosthesis 3 are connected in one-to-one correspondence so that the external nasal prosthesis 1 is assembled on the inclined side of the nasal septum prosthesis 3. The three-pronged tip of the nasal column prosthesis 2 is placed towards the nasal bridge prosthesis 11 of the external nasal prosthesis 1. The side of the columella nasi prosthesis 21 with the mortise groove 24 and the second mortise hole 23 is aligned with the lower base of the nasal septum prosthesis 3, and the second mortise hole 23 and the second tenon 32 on the lower base of the nasal septum prosthesis 3 are connected in one-to-one correspondence so that the nasal column prosthesis 2 is assembled on the lower base of the nasal septum prosthesis 3. Among them, the assembly order of the external nasal prosthesis 1 and the nasal column prosthesis 2 with the nasal septum prosthesis 3 can be partial before or after; and after the second tenon 32 and the second mortise hole 23 are connected, the lower base edge of the nasal septum prosthesis 3 is then snapped into the mortise groove 24 of the columella nasi prosthesis 21, further enhancing 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 15 on the external nasal prosthesis 1 is also connected with the mortise groove 24 by mortise and tenon, realizing the mortise and tenon connection between the external nasal prosthesis 1 and the nasal column prosthesis 2, further enhancing the stability and reliability of the mortise and tenon connection among the external nasal prosthesis 1, the nasal column prosthesis 2, and the nasal septum prosthesis 3, and also being beneficial to enhancing the overall structural stability of the facial implant, improving the shaping effectiveness and shaping stability. As a combined medical device, the facial implant has excellent overall mechanical properties and biocompatibility. The entire assembly process is fast, the operation is simple and convenient, and it can be directly carved during implantation to improve the adaptability. It has good applicability and has a good application prospect.

[0048] Specifically, the facial implant is made by re-dissolving silk fibroin, injection molding, curing and forming, bubble washing and drying, and machining. The preparation is convenient and fast, and the preparation accuracy of each tenon and mortise hole structure is high, which can improve the connection matching degree among the prepared external nasal prosthesis 1, nasal column prosthesis 2, and nasal septum prosthesis 3. And this silk fibroin is also self-made, and has better mechanical properties and biocompatibility compared with commercially available silk fibroin.

[0049] Correspondingly, as Figure 4 shown, the embodiment of the present invention also provides a preparation method of a facial implant, including: S1, dissolving silk fibroin in a solvent to obtain a silk fibroin re-dissolved solution; S2, placing the silk fibroin re-dissolved solution in an injection mold for injection molding to obtain an injection-molded sheet; S3, curing the injection-molded sheet to obtain a cured and formed sheet; S4, performing bubble washing on the cured and formed sheet, and drying to obtain a dried sheet; S5, machining the dried sheet to obtain a facial implant.

[0050] Among them, in some exemplary embodiments, during the reconstitution process in step S1, the silk fibroin used to obtain the silk fibroin reconstitution solution is silk fibroin freeze-dried powder, which can be formed by degumming, rinsing and air-drying, silk dissolution, dialysis, centrifugation and freeze-drying. Specifically, it can be prepared through the following steps: Immerse the silkworm cocoons in a sodium carbonate solution and heat to obtain degummed silk; Rinse the degummed silk and air-dry it to obtain degummed dry silk; Dissolve the degummed dry silk in a lithium salt aqueous solution to obtain a silk fibroin lithium salt solution; Dialyze the silk fibroin lithium salt solution to remove the lithium salt and obtain a silk fibroin dialysate; Centrifuge the silk fibroin dialysate and take the supernatant to obtain a silk fibroin centrifugate; Freeze-dry the silk fibroin centrifugate to obtain silk fibroin freeze-dried powder.

[0051] First, during the process of immersing the silkworm cocoons in a sodium carbonate solution and heating for degumming, the silkworm cocoons are dry silkworm cocoons after impurity removal, and can be cut into pieces and then added to the sodium carbonate solution for continuous heating to improve the degumming efficiency and reliability.

[0052] Among them, the concentration of the sodium carbonate solution is 0 g / L to 100 g / L and not 0, the ratio of the mass of the silkworm cocoons to the volume of the sodium carbonate solution is 0.1 g / L to 10 g / L, the heating method can include electric heating or steam heating. Electric heating can be carried out using an electric furnace, and steam heating can be carried out using a steam boiler. The heating temperature is 50°C to 121°C, the pressure is 0.1 MPa to 2 MPa, and the time is 1 s to 1000 h. It can be understood that the concentration of the sodium carbonate solution can be any non-zero point value within 0 g / L to 100 g / L, the ratio of the mass of the silkworm cocoons to the volume of the sodium carbonate solution can be any point value within 0.1 g / L to 10 g / L, the heating temperature can be any point value within 50°C to 121°C, the pressure can be any point value within 0.1 MPa to 2 MPa, and the time can be any point value within 1 s to 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 the mass of the silkworm cocoons to the volume of the sodium carbonate solution 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. Thus, it can effectively soften sericin, weaken the adhesion between silk filaments in the silkworm cocoons, and facilitate the separation of silk.

[0053] Next, the degummed silk is rinsed with purified water or ultrapure water. The rinsing is carried out according to the ratio of the mass of the degummed silk to the volume of water used for each rinsing being 0.1 g / L to 10 g / L. The rinsing is carried out at least three times, and the time for each rinsing is 0.1 h to 10 h. Fresh purified water or ultrapure water is replaced each time after rinsing.

[0054] After that, during the drying process, the drying time is 1 h to 100 h, and the drying temperature is 5°C to 100°C. It can be understood that the drying time can be any point value within 1 h to 100 h, and the drying temperature can be any point value within 5°C to 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. Thus, degummed dry silk with a relatively high purity can be obtained.

[0055] Next, weigh the degummed dry silk, dissolve it in a lithium salt solution for silk dissolution, and keep it sealed and insulated during the dissolution process until the degummed dry silk is fully dissolved to obtain a lithium salt solution of silk fibroin; wherein, the lithium salt includes at least one of lithium bromide (LiBr) and lithium thiocyanate (LiSCN), the concentration of the lithium salt in the lithium salt solution is 0.01 g / mL to 2 g / mL, the mass ratio 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, and the preset dissolution time is 1.5 h to 2.5 h; it can be understood that the concentration of the lithium salt in the lithium salt solution can be any point value between 0.01 g / mL and 2 g / mL, the mass ratio of the degummed dry silk to the volume of the lithium salt solution can be any point value between 0.01 g / mL and 1 g / mL, the dissolution temperature can be any point value between 20°C and 100°C, and the preset dissolution time can be any point value between 1.5 h and 2.5 h; for example, the concentration of the 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 mass ratio 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.; 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, that is, the dissolution time is greater than or equal to 2 h; thus, the degummed dry silk is fully softened and evenly dispersed, facilitating subsequent processing.

[0056] Next, during dialysis, load the lithium salt solution of silk fibroin into a semipermeable membrane with a semipermeable membrane specification of 10 Da to 10000000 Da, place the semipermeable membrane containing the lithium salt solution of silk fibroin in ultrapure water, continuously stir and dialyze, and the stirring method includes at least one of air stirring, mechanical stirring, and magnetic stirring, the stirring speed is 1 r / min to 2000 r / min, and change the water every 0.1 h to 100 h. The volume ratio of the ultrapure water replaced for the first time and each time to the volume of the lithium salt solution of silk fibroin is 0.01:1 to 1000:1, and the number of water replacements is greater than or equal to 4 times, so as to effectively remove the lithium salt therein and obtain a silk fibroin dialysis solution with a higher purity. The mass concentration of silk fibroin in the silk fibroin dialysis solution is 1% to 15%.

[0057] Next, during the centrifugation process, the centrifuge speed used is 1 r / min to 40,000 r / min, the centrifugation time is 1 s to 10 h, and the centrifugation temperature is -5°C to 10°C. The supernatant is taken as the silk fibroin centrifugate. It can be understood that the centrifuge speed can be any point value within 1 r / min to 40,000 r / min, the centrifugation time can be any point value within 1 s to 10 h, and the centrifugation temperature can be any point value within -5°C to 10°C, which will not be enumerated here.

[0058] Next, during the freeze-drying process, the silk fibroin centrifugate is first frozen in an environment of -80°C to 0°C, and then placed in a vacuum freeze-dryer for freeze-drying. The freeze-drying time is 1 h to 500 h, the freezing temperature is -80°C to 0°C, and the pressure is 0.1 Pa to 100 Pa, obtaining silk fibroin lyophilized powder.

[0059] Next, in some exemplary embodiments, the solvent used in the reconstitution process of step S1 is a protein solvent, including at least one of hexafluoroisopropanol, trifluoroacetic acid, dimethyl sulfoxide, and lithium bromide solution; in some preferred embodiments, the solvent is hexafluoroisopropanol. The container is sealed during the reconstitution process to prevent the volatilization of hexafluoroisopropanol. Hexafluoroisopropanol has good solubility and stability, and can interact with the hydrophilic groups in the silk fibroin molecules, breaking the hydrogen bonds and electrostatic interactions between proteins, which is beneficial to promoting the dissolution of silk fibroin, accelerating the dissolution efficiency, and also improving the dispersion of silk fibroin in the reconstituted solution.

[0060] During this reconstitution process, the ratio of the mass of silk fibroin to the volume of the solvent is 0.1 g / mL to 1 g / mL, the dissolution temperature is 5°C to 80°C, and the dissolution time is 0.1 h to 100 h. It can be understood that the ratio of the mass of silk fibroin to the volume of the solvent can be any point value within 0.1 g / mL to 1 g / mL, the dissolution temperature can be any point value within 5°C to 80°C, and the dissolution time can be any point value within 0.1 h to 100 h; for example, the ratio of the mass of silk fibroin to the volume of the solvent 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°C, 15°C, 30°C, 45°C, 55°C, 60°C, 80°C, 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 dissolution efficiency of silk fibroin is high, the dispersion uniformity is good, which is beneficial to improving the structural accuracy, structural stability, and performance uniformity of the final facial implant.

[0061] Next, the finally prepared facial implant includes an external nose prosthesis, a nasal column prosthesis, and a nasal septum prosthesis. During the injection molding process in step S2, the injection mold can include an external nose mold, a nasal column mold, and a nasal septum mold. The silk fibroin reconstituted solution is placed in the external nose mold, the nasal column mold, and the nasal septum mold respectively for injection molding, and wait for solidification. The solidification time is 7 days to 60 days. After that, the obtained injection-molded plates include an external nose injection-molded plate, a nasal column injection-molded plate, and a nasal septum injection-molded plate, with fast preparation efficiency and high forming accuracy.

[0062] Next, during the curing process in step S3, the injection-molded plates are soaked in methanol to achieve curing, and the cured and formed plates are obtained after air-drying. Specifically, the external nose injection-molded plate, the nasal column injection-molded plate, and the nasal septum injection-molded plate can all be soaked in methanol for curing, and the cured and formed plates obtained after air-drying also include an external nose cured and formed plate, a nasal column cured and formed plate, and a nasal septum cured and formed plate; during this curing process, methanol can transform the fiber structure of silk fibroin, making the structure of silk fibroin change from α-helix to β-sheet, which is beneficial to improving the tensile modulus, increasing the crystallinity and mechanical properties of the cured and formed plates, enabling the finally prepared facial implant to better fit the structural characteristics of the human nasal cartilage, having good mechanical properties, and also being able to reduce the degradation rate to a certain extent.

[0063] During this curing process, the methanol is made to cover the cured and formed plates, and the soaking time in methanol is 10 days to 30 days. Among them, fresh methanol is replaced every 1 day to 7 days, and the air-drying time after soaking is 1 day to 60 days, and the air-drying temperature is 20°C to 30°C; it can be understood that the soaking time in methanol can be any time within 10 days to 30 days, among which, fresh methanol can be replaced at any time interval within 1 day to 7 days, the air-drying time after soaking can be any time within 1 day to 60 days, and the air-drying temperature can be any point value within 20°C to 30°C, which will not be enumerated here; in this way, the mechanical properties of the cured and formed plates and the final facial implant can be effectively enhanced, and the degradation rate can be slowed down.

[0064] Next, during the soaking and washing process of the solidified and formed sheet in step S4, the solidified and formed sheet is soaked and washed by immersing it in ultrapure water. Specifically, the outer nose solidified and formed sheet, the nasal column solidified and formed sheet, and the nasal septum solidified and formed sheet can all be soaked and washed with ultrapure water. Among them, the water is changed every 6h to 24h, which can effectively remove the residual hexafluoroisopropanol and methanol on the solidified and formed sheet, reduce the possible harm to the human body after the finally prepared facial implant is implanted, and has good safety. The drying here can be air drying, and the air drying time is 7 days to 30 days, and the air drying temperature is 20°C to 30°C. It can be understood that the air drying time can be any time within 7 days to 30 days, and the air drying temperature can be any point value within 20°C to 30°C, which will not be enumerated here, and the dried sheet can be conveniently obtained. Correspondingly, the dried sheet also includes the outer nose dried sheet, the nasal column dried sheet, and the nasal septum dried sheet.

[0065] Next, during the machining process in step S5, the corresponding dried sheets are machined according to the shapes of the outer nose, nasal column, and nasal septum respectively, so that the outer nose dried sheet has the shape of the outer nose, the nasal column dried sheet has the shape of the nasal column, and the nasal septum dried sheet has the shape of the nasal septum. A plurality of first mortise holes are opened on the inner arc side of the outer nose dried sheet to obtain an outer nose prosthesis. A plurality of second mortise holes are opened at the columella nasi part of the nasal column dried sheet to obtain a nasal column prosthesis. And a plurality of corresponding first tenons and a plurality of second tenons are respectively machined on the bevel edge and the lower bottom of the nasal septum dried sheet. 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 a nasal septum prosthesis. Among them, the diameter of the machining tool bit is 1mm to 4mm, and during the machining process, it is cooled by air cooling to prevent the denaturation of silk fibroin caused by overheating during the machining process.

[0066] In addition, in some exemplary embodiments, before this machining step, the shapes of the respective injection-molded sheets can be the same or different, the shapes of the respective solidified and formed sheets can be the same or different, and the shapes of the respective dried sheets can be the same or different. The final outer nose prosthesis, nasal column prosthesis, and nasal septum prosthesis are formed through the machining step, which is simple to prepare and saves mold and preparation costs. In some other exemplary embodiments, during the injection molding process, the respective injection-molded sheets can also be formed into corresponding initial shapes, and finally, fine adjustment is further performed in the machining step, with high forming accuracy.

[0067] Specifically, in some exemplary embodiments, after the machining step, the method further includes: At 20°C to 30°C, the facial implant is soaked in water for 2 days to 10 days to obtain a water-absorbed facial implant.

[0068] During this soaking process, specifically, the facial implant can be soaked in normal saline or sterile water for injection. The facial implant fully absorbs water, swells, and softens, facilitating carving. Among them, the fit tolerance between the tenons and mortises for the tenon-and-mortise connection between the external nose prosthesis, nasal column prosthesis, and nasal septum prosthesis is further reduced, which is beneficial to the tightness and firmness of the overall facial implant after implantation. Moreover, after absorbing water, the facial implant has swelled, and it is not prone to additional water absorption deformation after implantation. The overall shaping accuracy is good, and the shaping durability is good.

[0069] In addition, after machining, the external nose prosthesis, nasal column prosthesis, and nasal septum prosthesis in a dry and hard state can be stored separately. When in use, they are taken out, soaked respectively, and then the three are assembled; or the external nose prosthesis, nasal column prosthesis, and nasal septum prosthesis in a hard state can be assembled and stored, and directly soaked when in use; or the external nose prosthesis after absorbing water, the nasal column prosthesis after absorbing water, and the nasal septum prosthesis after absorbing water can all be stored in a swollen state after absorbing water, and can be directly assembled when in use, further reducing the usage difficulty, shortening the operation time, and improving the safety.

[0070] The following introduces the embodiments of the present invention in combination with the above technical solutions.

[0071] Embodiment 1 The facial implant of this embodiment is prepared through the following steps: 1. Degumming: Remove impurities and cut the silkworm cocoons into pieces, weigh 10 g, add 8.48 g of sodium carbonate to 4 L of purified water to obtain a 2.12 g / L sodium carbonate solution. Heat the sodium carbonate solution on an electric furnace to 121 °C, immerse the weighed silkworm cocoons in the heated sodium carbonate solution, and continuously heat for 30 min for degumming to obtain degummed silk.

[0072] 2. Rinsing and air-drying: Place the degummed silk in 5 L of ultrapure water for rinsing, replace the same amount of ultrapure water, with a 20-min interval for each water change, and rinse 4 times; then, place it in a 30 °C environment, spread it out flat, and air-dry for 72 h to obtain degummed dry silk.

[0073] 3. Dissolving silk: Take 280 mL of ultrapure water and 273.7 g of lithium bromide to prepare a 0.977 g / mL lithium bromide solution. Dissolve 70 g of degummed dry silk in the lithium bromide solution, place it in a 60 °C environment, and dissolve for 4 h to obtain a silk fibroin lithium salt solution.

[0074] 4. Dialysis: Dispense the silk fibroin lithium salt solution into an 8 kDa semi-permeable membrane, place it in 5 L of ultrapure water, turn on the magnetic stirrer, with a stirring speed of 100 r / min, and change the water at 1 h, 2 h, 4 h, 16 h, 20 h, and 24 h. After multiple dialysis, a silk fibroin dialysis solution is obtained.

[0075] 5. Centrifugation: Collect the dialysate of silk fibroin and place it in a centrifuge. Set the centrifugation speed at 12,000 r / min, the centrifugation temperature at 5°C, and the centrifugation time at 20 min. Centrifuge the dialysate of silk fibroin to obtain the centrifuged solution of silk fibroin.

[0076] 6. Freeze-drying: First, place the centrifuged solution of silk fibroin in a -80°C refrigerator and freeze it for 4 h. Then, set the temperature of the vacuum freeze-dryer at -40°C and conduct freeze-drying for 72 h to obtain the freeze-dried powder of silk fibroin.

[0077] 7. Reconstitution: Add 60 mL of hexafluoroisopropanol to 15.5 g of the freeze-dried powder of silk fibroin to dissolve the freeze-dried powder of silk fibroin in hexafluoroisopropanol. Seal it and dissolve it at room temperature for 72 h to obtain the reconstituted solution of silk fibroin.

[0078] 8. Injection molding: Pour the reconstituted solution of silk fibroin into a syringe and slowly inject it into a rectangular mold. After covering the lid, let it stand horizontally for 45 days to obtain the injection-molded plate.

[0079] 9. Curing and forming: Take out the injection-molded plate and soak it in methanol for curing. The added methanol should cover the plate. Seal it and replace the fresh methanol every 3 days. After 21 days, take it out and air-dry it at room temperature to obtain the cured and formed plate.

[0080] 10. Soaking and washing: Soak the cured and formed plate in ultrapure water for soaking and washing. The liquid level should cover the cured and formed plate. Soak it for 20 days and replace the fresh ultrapure water every day. Air-dry it at room temperature for 7 days. After drying, obtain the dried plate.

[0081] 11. Machining: Machine the dried plate according to the external nose, nasal septum, and nasal column in the nose structure. Use a lathe to drill circular holes on the inner arc side of the external nose prosthesis and the columella prosthesis of the nasal column respectively to form the first mortise hole and the second mortise hole. Turn out cylindrical tenons on the hypotenuse and the lower bottom of the nasal septum prosthesis respectively, which are the first tenon and the second tenon. The number of each type of mortise hole and each type of tenon is 3, the diameter is 2 mm, and the length is 3 mm. The distance between two adjacent first mortise holes is 2 mm, and the distance between two adjacent second mortise holes is 2 mm. Correspondingly, the shape and position of the first tenon on the hypotenuse of the nasal septum prosthesis correspond to those of the first mortise hole one by one, and the shape and position of the second tenon on the lower bottom of the nasal septum prosthesis correspond to those of the second mortise hole one by one.

[0082] 12. Soaking: Soak the external nose prosthesis, nasal septum prosthesis, and columella prosthesis in sterile injection water for 7 days to obtain the facial implants after water absorption.

[0083] Finally, when in use, connect the external nose prosthesis, nasal septum prosthesis, and columella prosthesis through the mortise and tenon structure to complete the assembly.

[0084] Example 2 The difference between this embodiment and Embodiment 1 is that both the first mortise hole and the second mortise hole are square holes with a side length of 2 mm. Correspondingly, the shape and position of the first tenon on the hypotenuse of the nasal septum prosthesis correspond one by one to those of the first mortise hole, and the shape and position of the second tenon on the bottom of the nasal septum prosthesis correspond one by one to those of the second mortise hole; the rest is the same as Embodiment 1.

[0085] Embodiment 3 The difference between this embodiment and Embodiment 1 is that, as Figure 1 shown, in the direction of the bottom on the hypotenuse, the distance between the first tenon and the second tenon is 4 mm, and the distance between the corresponding two first mortise holes is also 4 mm; in the direction of the external nasal prosthesis on the bottom, the distance between the first second tenon and the second second tenon is 4 mm, and the distance between the corresponding two second mortise holes is also 4 mm; the rest is the same as Embodiment 2.

[0086] Embodiment 4 The difference between this embodiment and Embodiment 1 is that both the first mortise hole and the second mortise hole are square holes with a side length of 1.5 mm; the rest is the same as Embodiment 1.

[0087] Embodiment 5 The difference between this embodiment and Embodiment 1 is that fresh methanol is changed every 1 day during the curing and molding process in Step S3, and it is soaked and washed for 18 days; the rest is the same as Embodiment 1.

[0088] Comparative Example 1 This comparative example is some conventional facial implants obtained commercially. The sample was purchased from Guangzhou Vanward Silicone Rubber Facial Plastic Filling Material.

[0089] Test the tensile properties of the facial implants in the above Embodiments 1-5, and the test results are shown in Table 1 below.

[0090] Table 1 Tensile Property Test Results of Facial Implants in Embodiments 1-5

[0091] Test the tensile properties of the facial implants in the above Comparative Example 1, and the test results are shown in Table 2 below.

[0092] Table 2 Tensile Property Test Results of the Nasal Prosthesis in Comparative Example 1

[0093] Referring to the tensile property test results in Table 1, the tensile modulus of the facial implant is between 28.85 MPa and 82.45 MPa, the tensile strength is between 6.35 MPa and 9.84 MPa, and the elongation at break is between 0.65 and 1.38, which is close to the mechanical properties of the human nasal bone. It has good mechanical properties when used as a facial implant. As shown in Table 2, for the comparative example, the tensile modulus is between 0.07 MPa and 0.16 MPa, the tensile strength is between 0.55 MPa and 1.08 MPa, and the elongation at break is between 6.35 and 8.07. The hardness of the implant in the comparative example is much smaller than that in the examples. Although the toughness is much stronger than that in the examples, there are still risks such as large displacement and insufficient shaping strength after implantation. It can be seen that by using silk fibroin as the main material and cooperating with the mortise and tenon structure connection in the embodiments of the present invention, the facial implant has good and uniform mechanical properties, close to the mechanical properties of the human nasal bone, is quickly and conveniently assembled during use, and has a good shaping effect.

[0094] The following uses the subcutaneous implantation method in BALB / c mice to test the biocompatibility of the facial implant.

[0095] The experimental animals are BALB / c mice provided by the Institute of Laboratory Animal Resources, National Institutes for Food and Drug Control. The animals are acclimated for at least 5 days, and animal management is carried out according to the standard operating procedures formulated by the specifications for the protection and use of experimental animals. SPF mouse growth feed is supplied every day, and purified water is drunk through a water bottle. Every 3 same-sex mice are housed in an individually ventilated cage lined with corncobs. The room temperature is controlled at 20°C to 25°C, and the relative humidity is controlled at 40% to 70%. The lighting is controlled by an automatic timing method with 12 hours of light and 12 hours of darkness.

[0096] Next, prepare the samples and reagent consumables. Among them, the sample is the facial implant provided in the embodiment of the present invention, batch number: G202007001; the reagents and consumables include bovine serum albumin (Solarbio, A8010), complete Freund's adjuvant (sigma, F5881-10mL), mouse IgG ELISA kit (Sinobestbio, EMC116), mouse IgM detection kit (Sinobestbio, EMC129), 1640 culture medium (Gibco, 8118134), fetal bovine serum (Gibco, 10091-148), CCK8 (Beijing Solarbio Science & 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 lysate (Beijing Keyueda Biotechnology Co., Ltd., KS801-100), 70μm cell sieve (SPL Life Scineces, SPL-93070).

[0097] Next, set up a blank control group (CON), a BSA positive control group (POS), a raw material (silkworm cocoon) group (RAW), and a product group (PRO) respectively; there are 12 BALB / c mice in each group at each time point, with 6 males and 6 females; the implantation period is 4 weeks and 12 weeks for subsequent implantation and detection.

[0098] The implantation method of the facial implant is as follows: After the mice are anesthetized, their backs are depilated, and the operation is performed for implantation under sterile technique; among them, one 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 undergoes a "sham" operation without implanting the sample; the raw material group implants a piece of silkworm cocoon raw material with the same area as the sample in the product group; the positive control group of mice is subcutaneously injected with 0.12 mL of an equal volume mixture of bovine serum albumin (3mg BSA dissolved in 9mL PBS) and complete Freund's adjuvant, and immunized once a week for a total of 4 times.

[0099] The detection and evaluation methods are as follows: After 4 weeks and 12 weeks of implantation, specimens such as blood, spleen, thymus, facial implant and its surrounding tissues are obtained for detection, including: 1. Detection of total IgG and IgM in mouse serum; 1) Total serum IgG: Operate according to the instructions of the mouse IgG detection kit. Select the appropriate serum dilution according to the results of the preliminary experiment, and dilute the mouse serum 1 million times. 2) Total serum IgM: Operate according to the instructions of the mouse IgM detection kit. Select the appropriate serum dilution according to the results of the preliminary experiment, and dilute the mouse serum 100,000 times.

[0100] 2. Detection of cytokines in mouse serum; The cytokine bead array (CBA) technology was used to detect cytokines IFN-γ, IL-4, IL-6, IL-10, and IL-12p70 in mouse serum. According to the reagent instructions, serum and cytokine standards were incubated with beads at room temperature, and then fluorescently labeled antibodies were added and incubated at room temperature. After washing, the fluorescence intensity of the bead samples was detected using a flow cytometer, and then the FCS data file was exported and analyzed using BD FCAP software.

[0101] 3. Detection of lymphocyte subtypes in mouse spleen; After the mice were anesthetized and bled, they were sacrificed by cervical dislocation, soaked in 75% ethanol solution for disinfection, and the spleen was aseptically removed in a laminar flow hood. The spleen was minced and transferred to a 70 µm filter, ground with the end of a syringe piston, rinsed with culture medium, filtered, collected, and centrifuged. After centrifugation, the supernatant was discarded, and erythrocyte lysate was added to lyse for 5 min.

[0102] Centrifuge again and discard the supernatant. After washing with culture medium, the cells were resuspended, and after centrifugation, a single-cell suspension was prepared with PBS containing 1% FBS. After counting, the cell concentration was adjusted to 1×10 7 cells / mL -1 .

[0103] Add 10 µL 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, and CD45, CD3, CD49b, CD69 antibodies for natural killer (NK) and natural killer T cell (NKT) typing. Take 100 µL of the spleen cell suspension with a concentration of 1×10 7 cells / mL -1 and add it to the flow tubes of each sample, mix well, and react at room temperature in the dark for 20 min. Centrifuge and wash twice with PBS containing 1% FBS. After adding 0.5 mL of PBS containing 1% FBS to each tube to resuspend the cells, place them in the dark and wait for flow cytometer detection, and analyze the detection results using FACS DIVA SOFTWARE.

[0104] 4. Mouse spleen lymphocyte proliferation assay; Take the isolated mouse spleen lymphocytes and adjust the cell suspension concentration to 3×10 6 cells / mL -1 using RPMI 1640 medium containing 10% serum. In a 96-well plate, inoculate duplicate wells with the spleen lymphocytes of each mouse, with 200 μL of the cell suspension added to each well. At the same time, use duplicate wells containing only 200 μL of cell culture medium as the absorbance value blank wells. Place the 96-well plate in a cell culture incubator and culture at 37°C and 5% CO2 for 3 days. Four hours before the end of lymphocyte culture, add 20 μL of CCK8 reagent to each well of the 96-well plate, continue culturing for 4 hours, and then end the culture. Use an enzyme-linked immunosorbent assay (ELISA) reader to detect the absorbance value at 450 nm.

[0105] 5. Histopathological analysis of mouse spleen, thymus, samples and the local tissues where they are implanted; For each mouse, take the thymus and spleen and weigh them. At the same time, obtain local tissue specimens that wrap the implant. After fixation with 10% formaldehyde, perform routine paraffin embedding for histological sectioning. After HE staining of the sections, conduct histological pathological evaluation under a microscope. The histological sections of the implant are subjected to semi-quantitative histological evaluation according to the requirements of Appendix E of GB / T 16886.6-2015. For infiltrating cells such as polymorphonuclear leukocytes, lymphocytes, plasma cells, macrophages, and giant cells, score 0-4.0 according to the number of local microscopic fields of view. For local reactions such as necrosis, neovascularization, fibrosis, and fat infiltration, score 0-4.0 according to the severity under the microscope. The total score of the histological evaluation of the implant for each mouse is the sum of the scores of infiltrating cells and local reactions. The score of the histological evaluation of the implant for each experimental group is the average of the scores of all mice in the group. When the average score is 0.0-2.9, it indicates that the local reaction of the implant is non-irritating; when it is 3.0-8.9, it is mildly irritating; when it is 9.0-15.0, it is moderately irritating; when it is >15, it is severely irritating.

[0106] Perform histological pathological observation of the spleen and thymus sections under a microscope, and evaluate the different tissue compartments of the spleen and thymus and the number of cells within them, including the periarteriolar lymphatic sheath, lymphoid follicles, marginal zone, red pulp, thymic cortex, medulla, and cortex-medulla ratio. The grading criteria for cell density (increase or decrease in cell number) or tissue structure: normal is grade 1; compared with normal, a difference <25% is grade 2; compared with normal, a difference of 25-50% is grade 3; compared with normal, a difference >50% is grade 4.

[0107] Next, according to the statistical processing method, measurement data are expressed as (mean ± SD). First, normal distribution and homogeneity of variance tests are performed on the data of each group. If the data of each group conform to normal distribution and have homogeneous variance, one-way ANOVA is carried out; if the data of the experimental group do not conform to normal distribution or have inhomogeneous variance, non-parametric tests are performed, and P < 0.05 is considered to indicate significant differences.

[0108] The experimental results are as follows.

[0109] (I) Detection results of total antibodies in mouse serum The detection results of the contents of total IgG and IgM in mouse serum are shown in Table 3. At 4 weeks and 12 weeks, the contents of total IgG and IgM in the serum of the positive control group (POS) were significantly increased compared with those of the blank control group (CON), and there were highly significant differences statistically (P < 0.01).

[0110] At 4 weeks and 12 weeks, there were no obvious changes in the contents of total IgG and IgM in the serum of the raw material group (RAW) compared with those of the blank control group (CON), and there were no significant differences statistically (P > 0.05). At 4 weeks and 12 weeks, there were no obvious changes in the contents of total IgG and IgM in the serum of the product group (PRO) compared with those of the blank control group (CON), and there were no significant differences statistically (P > 0.05).

[0111] Table 3 Detection results of serum IgG and IgM (unit: mg·mL -1 )

[0112] Note: ** indicates comparison with the blank control group in the same period, P < 0.01.

[0113] (II) Detection results of cytokines in mouse serum As shown in Table 4, at 4 weeks after implantation, the contents of IFN-γ and IL-6 in the serum of mice in the positive control group (POS) were increased compared with those of the blank control group (CON), and there were significant differences statistically (P < 0.05 or P < 0.01). There were no significant differences statistically in the contents of IL-4, IL-10, and IL-12p70 in the serum of mice in the positive control group compared with those of the blank control group (P > 0.05). There were no significant differences statistically in the cytokines in the serum of mice in the raw material group (RAW) compared with those of the blank control group (P > 0.05). The content of IFN-γ in the serum of mice in the product group (PRO) was decreased compared with that of the blank control group (CON), and there was a significant difference statistically (P < 0.05). There were no significant differences statistically in the other cytokines in the serum of mice in the product group (PRO) compared with those of the blank control group (P > 0.05).

[0114] At 12 weeks after implantation, the content of IFN-γ in the serum of mice in the positive control group (POS) was increased compared with that in the blank control group (CON), and there was a very significant statistical difference (P < 0.01). There was no significant statistical difference in the contents of IL-4, IL-6, IL-10, and IL-12p70 in the serum of mice in the positive control group compared with those in the blank control group (P > 0.05). There was no significant statistical difference in the serum cytokines of mice in the raw material group (RAW) and the product group (PRO) compared with those in the blank control group (P > 0.05).

[0115] Table 4 Detection results of serum IgG and IgM (unit: pg·mL -1 )

[0116] Note: * or ** indicates comparison with the blank control group in the same period, P < 0.05 or P < 0.01.

[0117] (III) Detection results of lymphocyte subtypes in mouse spleen As shown in Table 5, at 4 weeks after implantation, the percentages of T cells, CD4 T cells, and NK cells in the positive control group (POS) were decreased compared with those in the blank control group (CON), and the percentage of B cells in the positive control group was increased compared with that in the blank control group. All the above changes had very significant statistical differences (P < 0.01); there was no significant statistical difference in the percentages of other lymphocyte subtypes in the positive control group compared with those in the blank control group (P > 0.05). At 4 weeks, there was no significant statistical difference in the percentages of lymphocyte subtypes in the raw material group (RAW) compared with those in the blank control group (P > 0.05). At 4 weeks, the percentage of CD8 T cells in the product group (PRO) was increased compared with that in the blank control group, and there was a significant statistical difference (P < 0.05). There was no significant statistical difference in the percentages of other lymphocyte subtypes in the product group compared with those in the blank control group (P > 0.05).

[0118] At 12 weeks after implantation, the percentages of activated B cells in the spleens of the positive control group (POS) and the raw material group (RAW) were decreased compared with those in the blank control group, and both had significant statistical differences (P < 0.05 or P < 0.01); there was no significant statistical difference in the percentages of other lymphocyte subtypes in the positive control group (POS) and the raw material group (RAW) compared with those in the blank control group (P > 0.05). There was no significant statistical difference in the percentages of lymphocyte subtypes in the spleen of the product group (PRO) compared with those in the blank control group (P > 0.05).

[0119] Table 5 Percentages of splenic lymphocyte subtypes detected by flow cytometry

[0120] (IV) Results of lymphocyte proliferation assay in mouse spleen As shown in Table 6, at 4 weeks and 12 weeks after implantation, lymphocytes were isolated from the spleens of mice for in vitro lymphocyte proliferation assays. The results of culturing for 3 days showed that there were highly significant statistical differences (P < 0.01) in the light absorbance values between the positive control group (POS) and the blank control group (CON), while there were no significant statistical differences (P > 0.05) in the light absorbance values between the raw material group (RAW) and the product group (PRO) and the blank control group.

[0121] Table 6 Results of mouse spleen lymphocyte proliferation assay

[0122] (V) Weights and organ coefficients of mouse spleen and thymus The weights of the spleens and thymuses of mice at 4 weeks and 12 weeks and their organ coefficients are shown in Table 7.

[0123] At 4 weeks, the spleen weights and spleen coefficients of male and female mice in the positive control group (POS) were increased compared with those of the blank control group, showing highly significant statistical differences (P < 0.01); there were no significant statistical differences (P > 0.05) in the thymus weights and their organ coefficients of male and female mice in the positive control group (POS) compared with the blank control group. At 4 weeks, the spleen coefficients of male mice and the thymus coefficients of female mice in the raw material group (RAW) were increased compared with those of the blank control group, showing significant statistical differences (P < 0.05 or P < 0.01); there were no significant statistical differences (P > 0.05) in the weights of other organs and their organ coefficients of mice in the raw material group (RAW) compared with the blank control group. At 4 weeks, there were no significant statistical differences (P > 0.05) in the spleen and thymus weights and their organ coefficients of male and female mice in the product group (PRO) compared with the blank control group.

[0124] At 12 weeks, the spleen weight and spleen coefficient of female mice in the positive control group (POS) were increased compared with those of the blank control group, showing significant statistical differences (P < 0.05 or P < 0.01); there were no significant statistical differences (P > 0.05) in the weights of other organs and their organ coefficients of mice in the positive control group (POS) compared with the blank control group. At 12 weeks, there were no significant statistical differences (P > 0.05) in the spleen and thymus weights and their organ coefficients of male and female mice in the raw material group (RAW) and the product group (PRO) compared with the blank control group.

[0125] Table 7 Weights of mouse spleen and thymus and their organ coefficients

[0126] (VI) Histopathological evaluation of mouse spleen, thymus and implants 1. Histopathological evaluation of facial implants The tissue section images of the blank control group mice at 4 weeks and 12 weeks are shown respectively in Figure 5 , Figure 6 . On the tissue sections, the structures of the epidermis, dermis and subcutaneous connective tissue are clear. The subcutaneous adipose tissue and the underlying striated muscle tissue are closely arranged; there are no abnormalities in the skin appendages such as subcutaneous hair follicles, hair roots and sebaceous glands; a small amount of scattered inflammatory cells can be seen subcutaneously.

[0127] The tissue section images of the positive control group mice implanted at 4 weeks and 12 weeks are shown respectively in Figure 7 , Figure 8 . On the tissue sections, there are no abnormalities in the epidermis and dermis of the skin; multiple round inclusions can be seen in the striated muscle layer of the subcutaneous tissue, and most of them have one larger inclusion; the outer wall of the inclusion is uneven in thickness, the wall of the small inclusion is thinner, and they are all composed of fibroblasts, fibrocytes and collagen fibers; there are significantly more inflammatory cells in the thick-walled part; a small part of the inclusion is inflammatory necrotic residue, and most of it is empty, that is, the cavity after removing the necrotic residue during section preparation.

[0128] The tissue section images of the raw material group mice implanted at 4 weeks and 12 weeks are shown respectively in Figure 9 , Figure 10 . On the tissue sections, there are no abnormalities in the epidermis and dermis of the skin; large rectangular inclusions can be seen in the subcutaneous tissue; the outer wall of the inclusion is thicker than that of the product group, and it is composed of fibroblasts, fibrocytes and collagen fibers, and there are significantly more inflammatory cells, especially neutrophils, between them than in the product group; at 4 weeks, the inclusion is a small piece of homogeneous, structureless, lightly stained substance, and there is no obvious degradation and absorption; at 12 weeks, the inclusion is a small piece of homogeneous, structureless, lightly stained substance, and part of the inclusion near the wall of the inclusion has been degraded and absorbed, and more foam cells are formed around.

[0129] The tissue section image of the product group implanted at 4 weeks is shown in A in Figure 11 , B in Figure 11 . On the tissue sections, there are no abnormalities in the epidermis and dermis of the skin; large rectangular inclusions can be seen in the subcutaneous tissue, that is, the outer wall of the inclusion and the inclusion in the middle; the wall of the inclusion is not thick, and it is composed of fibroblasts, fibrocytes and collagen fibers, and there are some inflammatory cells between them; the inclusion is a whole piece of homogeneous, structureless, lightly stained substance, and there is no obvious degradation and absorption.

[0130] The tissue section image of the product group implanted at 12 weeks is shown in A in Figure 12 , B in Figure 12 . On the tissue sections, there are no abnormalities in the epidermis and dermis of the skin; large rectangular inclusions can be seen in the subcutaneous tissue, that is, the outer wall of the inclusion and the inclusion in the middle; the wall of the inclusion is complete and the thickness is relatively uniform, and it is composed of fibroblasts, fibrocytes and collagen fibers, and there are some inflammatory cells between them; the inclusion is a whole piece of homogeneous, structureless substance, and there is no obvious degradation and absorption.

[0131] At 4 weeks, the local reaction after implantation in the positive control group was severe irritation compared with the blank control group (the difference in histological score was 21.4), the local reaction after implantation in the raw material group was severe irritation compared with the blank control group (the difference in histological score was 17.0), and the local reaction after implantation in the product group was moderate irritation compared with the blank control group (the difference in histological score was 11.4).

[0132] At 12 weeks, the local reaction after implantation in the positive control group was severe irritation compared with the blank control group (the difference in histological score was 16.1), the local reaction after implantation in the raw material group was moderate irritation compared with the blank control group (the difference in histological score was 10.7), and the local reaction after implantation in the product group was mild irritation compared with the blank control group (the difference in histological score was 8.5).

[0133] 2. Histopathological evaluation of the spleen and thymus tissues of mice 4 weeks after implantation As Figure 13 shown, microscopic observation of the spleen sections of mice in the blank control group at 4 weeks showed that the outer fibrous capsule was intact, lymphocytes in the white pulp were dense, and the central artery in the center was not thickened; lymphocytes in the periarteriolar lymphatic sheath were dense, lymphoid follicles were not obvious, and the central germinal centers were mostly not obvious; the outer marginal zone of the white pulp and the splenic sinusoids in the red pulp were filled with red blood cells; a small amount of hemosiderin deposition was visible in the red pulp of the spleen of individual animals; myeloid metaplasia was enhanced in the spleen of 3 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most numerous.

[0134] As Figure 14 shown, microscopic observation of the spleen sections of mice in the positive control group at 4 weeks was basically the same as that of the blank control group. Myeloid metaplasia was enhanced in the spleen of 3 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most numerous.

[0135] As Figure 15 shown, microscopic observation of the spleen sections of mice in the raw material group at 4 weeks was basically the same as that of the blank control group. Myeloid metaplasia was enhanced in the spleen of 4 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most numerous.

[0136] As Figure 16 shown, microscopic observation of the spleen sections of mice in the product group at 4 weeks was the same as that of the blank control group. Myeloid metaplasia was enhanced in the spleen of 4 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most numerous, and the granulocytic and megakaryocytic series were also obvious.

[0137] It can be seen that at 4 weeks after implantation, compared with the blank control group, there were no obvious changes in the spleens of the animals in the product group.

[0138] As Figure 17As shown, microscopic observation of the thymus sections of the mice in the blank control group at 4 weeks showed that the thymic capsule was intact, the thymic lobule structure was clear, and no atrophy or hyperplasia was observed; the boundary between the cortex and the medulla was clear, and the area ratio of the cortex to the medulla was approximately 2:1, with 2 of them being 3:1; a large number of lymphocytes in the cortex were arranged closely, and many visible nucleoli could be seen; the epithelioid cells and a small number of macrophages did not show obvious increase; there were more epithelioid cells and some lymphocytes in the medulla, the lymphocytes were of different sizes and were relatively loose; macrophages that phagocytosed apoptotic lymphocytes were occasionally seen.

[0139] As Figure 18 shown, microscopic observation of the thymus sections of the mice in the positive control group at 4 weeks was the same as that of the animals in the blank control group, and no abnormal changes were observed; the area ratio of the cortex to the medulla was approximately 2:1, with 3 of them being 3:1.

[0140] As Figure 19 shown, microscopic observation of the thymus sections of the mice in the raw material group at 4 weeks was the same as that of the animals in the blank control group, and no abnormal changes were observed. The area ratio of the cortex to the medulla of 7 mice was approximately 2:1, and 5 were 3:1.

[0141] As Figure 20 shown, microscopic observation of the thymus sections of the mice in the product group at 4 weeks was basically the same as that of the blank control group. The area ratio of the cortex to the medulla of 7 mice was approximately 2:1, and 5 were 3:1.

[0142] It can be seen that at 4 weeks after implantation, compared with the blank control group, there were no obvious changes in the thymus of the animals in the product group.

[0143] 3. Histopathological evaluation of the spleen and thymus tissues of mice 12 weeks after implantation As Figure 21 shown, microscopic observation of the spleen sections of the mice in the blank control group at 12 weeks showed that the outer fibrous capsule was intact; the lymphocytes in the white pulp were dense, and the central arteriole in the center was not thickened; the lymphocytes in the periarteriolar lymphatic sheath were dense, the lymph follicles were not obvious, and most of the central germinal centers were not obvious; the outer marginal zone of the white pulp and the splenic sinusoids in the red pulp were filled with red blood cells; a small amount of hemosiderin deposition could be seen in the spleen red pulp of individual animals; there was extramedullary hematopoiesis in the spleen, and it was enhanced in 7 cases, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most.

[0144] As Figure 22 shown, microscopic observation of the spleen sections of the mice in the positive group at 12 weeks was basically the same as that of the blank control group. There was extramedullary hematopoiesis in the spleen, and it was enhanced in 5 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most.

[0145] As Figure 23 shown, microscopic observation of the spleen sections of the mice in the raw material group at 12 weeks was basically the same as that of the blank control group. There was extramedullary hematopoiesis in the spleen, and it was enhanced in 6 animals, and cells of the erythroid, granulocytic, and megakaryocytic series were all visible, with the erythroid series being the most.

[0146] As Figure 24 shown, at 12 weeks, microscopic examination of spleen sections of mice in the product group was the same as that of the blank control group. Extramedullary hematopoiesis was observed in the spleen, with 6 cases showing enhancement. Erythroid, granulocytic, and megakaryocytic cells were all visible, with the erythroid series being the most numerous, and the granulocytic and megakaryocytic series being also obvious.

[0147] It can be seen that at 12 weeks after implantation, compared with the blank control group, there were no obvious changes in the spleens of animals in the product group.

[0148] As Figure 25 shown, at 12 weeks, microscopic examination of thymus sections of mice in the blank control group showed that the thymic capsule was intact, the thymic lobule structure was clear, and no atrophy or hyperplasia was observed; the boundary between the cortex and the medulla was clear, and the area ratio of the cortex to the medulla was approximately 2:1, with 1 case being 3:1; a large number of lymphocytes in the cortex were arranged closely, and many had visible nucleoli; the number of epitheloid cells and a small number of macrophages did not increase significantly; there were more epitheloid cells and some lymphocytes in the medulla, with the lymphocytes varying in size and being relatively loose; macrophages phagocytosing apoptotic lymphocytes were occasionally seen.

[0149] As Figure 26 shown, at 12 weeks, microscopic examination of thymus sections of mice in the positive group was the same as that of animals in the blank control group, and no abnormal changes were observed.

[0150] As Figure 27 shown, at 12 weeks, microscopic examination of thymus sections of mice in the raw material group was the same as that of animals in the blank control group, and no abnormal changes were observed.

[0151] As Figure 28 shown, at 12 weeks, microscopic examination of thymus sections of mice in the product group was basically the same as that of the blank control group, and the area ratio of the cortex to the medulla in 12 animals was approximately 2:1.

[0152] It can be seen that at 12 weeks after implantation, compared with the blank control group, there were no obvious changes in the thymus of the product group.

[0153] In summary, compared with the blank control group, the indicators with statistical differences in the positive control group were: (1) At 4 weeks and 12 weeks, the serum total IgG and IgM contents in the positive control group were significantly increased (P < 0.01); (2) At 4 weeks, the serum IFN-γ and IL-6 contents in the positive control group of mice were increased (P < 0.05 or P < 0.01); at 12 weeks, the serum IFN-γ content in the positive control group of mice was increased (P < 0.01); (3) At 4 weeks, the percentage of B cells in the spleen of the positive control group was increased, while 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); (4)At 4 weeks and 12 weeks, the optical density values of the in vitro lymphocyte proliferation assay in the positive control group increased significantly (P < 0.01); (5)At 4 weeks, the spleen weight and spleen coefficient of male and female mice in the positive control group increased (P < 0.01); at 12 weeks, the spleen weight and spleen coefficient of female mice in the positive control group increased (P < 0.05 or P < 0.01).

[0154] The indicators with statistical differences between the raw material group and the blank control group were: (1)At 12 weeks, the percentage of activated B cells in the spleen of the raw material group decreased (P < 0.05); (2)At 4 weeks, the spleen coefficient of male mice and the thymus coefficient of female mice in the raw material group increased (P < 0.05 or P < 0.01).

[0155] The indicators with statistical differences between the product group and the blank control group were: (1)At 4 weeks, the content of IFN-γ in the serum of mice in the product group decreased (P < 0.05); (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 of the relevant indicators of the blank control group ( ±2SD).

[0156] And the histopathological evaluation showed that: (1)At 4 weeks, the local reaction after implantation in the positive control group was severe irritation compared with the blank control group (the difference in histological score was 21.4), the local reaction after implantation in the raw material group was severe irritation compared with the blank control group (the difference in histological score was 17.0), and the local reaction after implantation in the product group was moderate irritation compared with the blank control group (the difference in histological score was 11.4); at 12 weeks, the local reaction after implantation in the positive control group was severe irritation compared with the blank control group (the difference in histological score was 16.1), the local reaction after implantation in the raw material group was moderate irritation compared with the blank control group (the difference in histological score was 10.7), and the local reaction after implantation in the product group was mild irritation compared with the blank control group (the difference in histological score was 8.5).

[0157] (2)At 4 weeks and 12 weeks after implantation, the microscopic observation of the spleen sections of mice in the positive control group and the raw material group was basically the same as that of the blank control group; at 4 weeks and 12 weeks after implantation, the microscopic observation of the thymus sections of mice in the positive control group and the raw material group was the same as that of the animals in the blank control group, and no abnormal changes were found.

[0158] (3)Compared with the blank control group, at 4 weeks and 12 weeks after implantation, there were no obvious changes in the spleens of mice in the product group; compared with the blank control group, at 4 weeks and 12 weeks after implantation, there were no obvious changes in the thymuses of mice in the product group.

[0159] It can be seen that the facial implant provided by the embodiment of the present invention also has excellent biocompatibility, which is beneficial to promoting tissue repair and regeneration, has a slow degradation rate, is not likely to cause risks such as inflammation and bacterial infection, and has high safety in use.

[0160] It should be noted that the various embodiments in this specification are described in a progressive manner. Each embodiment focuses on the differences from other embodiments. For the same or similar parts among the various embodiments, reference can be made to each other.

[0161] The above description only relates to some embodiments of the present invention and is not intended to limit the present invention. Those skilled in the art should understand that the present invention will have various changes and improvements, and any modifications, equivalent replacements, and improvements made in accordance with the present invention fall within the scope of protection required by the present invention.

Claims

1. A facial implant, characterized in that, It includes an external nose prosthesis (1), a nasal column prosthesis (2) and a nasal septum prosthesis (3). One side of the nasal septum prosthesis (3) is connected to the inner arc side (13) of the external nose prosthesis (1), and an adjacent side of the nasal septum prosthesis (3) is connected to the nasal column prosthesis (2). The facial implant is symmetrically arranged with respect to the plane where the nasal septum prosthesis (3) is located; The facial implant is made of silk fibroin.

2. The facial implant according to claim 1, characterized in that, The external nose prosthesis (1), the nasal septum prosthesis (3) and the nasal column prosthesis (2) are connected to each other by a mortise and tenon structure.

3. The facial implant according to claim 2, wherein The nasal septum prosthesis (3) is of a trapezoidal structure. The nasal septum prosthesis (3) includes a first tenon (31) and a second tenon (32). The first tenon (31) is located on the hypotenuse of the nasal septum prosthesis (3), and the second tenon (32) is located on the bottom side of the nasal septum prosthesis (3); A first mortise (14) is provided on the inner arc side (13) of the external nose prosthesis (1), and the first mortise (14) is connected to the first tenon (31); A second mortise (23) is provided on the side of the nasal column prosthesis (2) facing the nasal septum prosthesis (3), and the second mortise (23) is connected to the second tenon (32).

4. The facial implant according to claim 3, wherein A mortise groove (24) is provided on the columella prosthesis (21) of the nasal column prosthesis (2), and the second mortise (23) is located in the mortise groove (24); A third tenon (15) is provided at one end of the external nose prosthesis (1), and at least part of the mortise groove (24) is connected to the third tenon (15), and at least part of the mortise groove (24) is mortise and tenon connected to the bottom side of the nasal septum prosthesis (3).

5. The facial implant according to claim 3, characterized in that, The first tenon (31) and the second tenon (32) satisfy at least one of the following characteristics: The width of at least one of the first tenon (31) and the second tenon (32) is 1.5 mm to 2.0 mm; The length of at least one of the first tenon (31) and the second tenon (32) is 1.0 mm to 5.0 mm; The distance between adjacent first tenons (31) in the hypotenuse direction of the nasal septum prosthesis (3) is 0.1 mm to 10.0 mm; The distance between adjacent second tenons (32) in the bottom side direction of the nasal septum prosthesis (3) is 0.1 mm to 10.0 mm; The number of at least one of the first tenon (31) and the second tenon (32) is 1 to 6.

6. The facial implant according to any one of claims 1-5, characterized in that, The fit tolerance between the external nose prosthesis (1), the nasal septum prosthesis (3) and the nasal column prosthesis (2) is -0.1 mm to +0.1 mm.

7. The facial implant according to any one of claims 1-5, characterized in that, The external nose 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 column prosthesis (2) includes a columella prosthesis (21) and alar prostheses (22). The columella prosthesis (21) is connected to the nasal septum prosthesis (3), and the alar prostheses (22) are symmetrically arranged on both sides of the columella prosthesis (21).

8. The facial implant according to any one of claims 1-5, characterized in that, The cross-sectional area of one end of the external nose prosthesis (1) close to the nasal column prosthesis (2) is smaller than the cross-sectional area of the end of the external nose prosthesis (1) far from the nasal column prosthesis (2).

9. The facial implant according to any one of claims 1-5, 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 elongation at break of the facial implant is 0.65% to 1.38%.

10. The facial implant according to any one of claims 1-5, characterized in that, The facial implant is made by re-dissolving silk fibroin, injection molding, curing and forming, bubble washing and drying, and machining.

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