Method for retaining a subperiosteal implant at the base of the alar wings

Abstract

The present application relates to a kind of nasal ala base subperiosteal implant retention method, belong to plastic surgery medical instrument technical field.The present application provides a kind of nasal ala base subperiosteal implant soft tissue suspension retention method and its implant and system.The method includes: implant is placed into maxillary bone subperiosteal interstice, and implant fixed wing is fixed with the soft tissue anchor point such as alar base ligament of alar elevating lip muscle using drug-loaded degradable suture and is suspended and fixed.Implant surface is provided with the microporous structure of guiding tissue ingrowth, and is provided with the drug depot recess of filling load immunomodulator temperature-sensitive hydrogel.Postoperative healing process, suture is released under the action of tension to accelerate proangiogenic factor and promote local vascularization, and temperature-sensitive hydrogel slow-release immunomodulator induces macrophage to repair type polarization, and cooperatively promotes the biological chimeric fixation of implant and soft tissue.The present application can realize the double stable retention of implant, reduces postoperative displacement risk.

Description

Technical Field

[0001] This invention relates to the field of plastic surgery medical device technology, specifically a method for fixing a subperiosteal implant at the base of the nasal alar. Background Technology

[0002] Paranasal concavity is a common maxillofacial deformity, mainly characterized by a flat midface contour, a sunken paranasal region, a smaller nasolabial angle, and a relatively protruding mandible. Current treatments for paranasal concavity primarily include rigid graft nasal alar augmentation, soft tissue injection augmentation, and paranasal alar release suspension. Paranasal alar augmentation involves placing a rigid graft subcutaneously or subperiosteally at the base of the nasal alar to correct the concavity caused by bone loss in the anterior maxilla. Commonly used implant materials include silicone, expanded polytetrafluoroethylene (ePTFE), porous high-density polyethylene (Medpor), hydroxyapatite, and autologous rib cartilage. However, the nasal alar base region is an area of ​​frequent upper lip facial muscle activity. Postoperatively, the implant is prone to displacement under the continuous shear force generated by muscle movement, leading to asymmetry or abnormal contour in mild cases, and requiring secondary surgery in severe cases. Achieving long-term stable implant placement has become a key technical challenge limiting the clinical effectiveness of this procedure.

[0003] Several fixation methods have been proposed in the existing technology to address the problem of implant displacement. Materials such as expanded polytetrafluoroethylene (ePTFE) and porous high-density polyethylene (HDPE), due to their microporous surface structure, allow human tissue to grow into the pores after implantation, forming a certain degree of biological fixation, and their stability is superior to that of smooth-surfaced silicone materials. However, tissue ingrowth requires a certain period, and the implant still faces the risk of displacement during the early postoperative healing stage. In addition, some literature reports the use of titanium screws for bony fixation, but screw fixation carries the risk of accidental implantation into the anterior wall of the maxillary sinus or even perforation into the nasal cavity; other methods use percutaneous fixation with stainless steel pins combined with external fixation with aluminum-plastic plates, but percutaneous fixation increases the probability of bacterial infection, and the external fixation device affects the patient's appearance and daily life. Therefore, the existing technology lacks a non-invasive fixation method that can achieve early stable fixation of the implant using soft tissue anatomy and long-term biological fixation by promoting tissue healing. Summary of the Invention

[0004] In order to solve the problems of the prior art, the present invention provides a method for fixing a subperiosteal implant at the base of the nasal alar.

[0005] To solve the above-mentioned technical problems, the present invention is achieved through the following technical solution: Firstly, a method for fixing a subperiosteal implant at the base of the nasal alar, comprising the following steps: Step 1: Soft tissue anatomy and marking: In the nasal alar base region, the patient's levator labii superioris muscle, nasal alar base ligament and surrounding fascia tissue are anatomically located and marked to determine the location of soft tissue fixation anchor points. Step 2: Subperiosteal cavity preparation: An implant-accommodating cavity is prepared under the periosteum of the maxilla at the base of the nasal alar, the size and shape of which match the pre-implanted implant; Step 3: Implant placement: The implant is placed into the subperiosteal cavity, positioned between the periosteum and the maxillary bone surface. The surface of the implant is provided with fixation wings and a microporous structure. The fixation wings extend outward from the surface of the implant and have through holes for suture material to pass through. The diameter of the through holes is 0.3 mm to 1.5 mm. The diameter of the microporous structure is 50 μm to 500 μm, and the porosity is 20% to 60%. Step 4: Soft tissue suspension and fixation: After passing suture material through the through hole of the fixation wing, the implant is suspended and fixed to the surrounding soft tissue. The surrounding soft tissue is selected from one or more of the following: levator labii superioris muscle of the nasal alar, nasal alar base ligament, periosteum, and subcutaneous fascia. Step 5: Soft tissue coverage and healing: The suspended and fixed soft tissue is repositioned and covered on the surface of the implant. The microporous structure guides the surrounding soft tissue to grow into the surface of the implant, forming an interlocking fixation between the implant and the soft tissue.

[0006] In one specific embodiment of the first aspect, the suture material in step 4 is a drug-loaded biodegradable suture, which has a core-shell composite structure, including a core layer and a shell layer wrapped around the outside of the core layer; the core layer is an absorbable polymer material bundle, and the shell layer is a porous drug-loaded layer loaded with angiogenesis factors; the angiogenesis factors are selected from at least one of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), with a loading concentration of 0.5 μg / mL to 50 μg / mL.

[0007] In one specific embodiment of the first aspect, the angiogenesis factor is embedded in a biodegradable polymer matrix in the shell of the drug-loaded biodegradable suture in the form of microspheres or nanospheres. The biodegradable polymer is selected from polylactic-co-glycolic acid copolymer (PLGA), polycaprolactone (PCL), or a combination thereof. The particle size of the microspheres or nanospheres is 100 nm to 50 μm. The tensile strength of the drug-loaded biodegradable suture is 20 MPa to 80 MPa, and the degradation period is 4 to 24 weeks.

[0008] In one specific embodiment of the first aspect, at least one surface of the implant is provided with a drug reservoir groove, the groove having a depth of 0.2 mm to 1.0 mm and a width of 0.5 mm to 2.0 mm; the groove is filled with a thermosensitive hydrogel loaded with an immunomodulator, the immunomodulator being selected from at least one of IL-4 or IL-10, with a loading concentration of 10 ng / mL to 500 ng / mL; the thermosensitive hydrogel is liquid at temperatures below 25°C and undergoes a sol-gel phase transition to form a gel at temperatures between 25°C and 37°C.

[0009] In one specific embodiment of the first aspect, the soft tissue fixation anchor point in step 1 is selected from one or more of the following locations: the attachment point of the alar base ligament, the origin or insertion point of the levator labii superioris muscle, the junction of the periosteum of the maxilla and the soft tissue, and the soft tissue attachment point at the edge of the piriform aperture.

[0010] In one specific embodiment of the first aspect, the subperiosteal cavity in step 2 is prepared by an intraoral or intranasal approach, and blunt or sharp dissection is performed under the periosteum to form a pouch-shaped cavity consistent with the shape of the implant.

[0011] Secondly, a subperiosteal implant for implementing a method of fixing a subperiosteal implant at the alar base, the implant being a nasal alar base filling prosthesis, comprising a left nasal alar base filling portion corresponding to the left nasal alar base of the human body and a right nasal alar base filling portion corresponding to the right nasal alar base of the human body, the left nasal alar base filling portion and the right nasal alar base filling portion being connected by a nasal floor connecting bridge respectively; soft tissue fixation structures are respectively provided on the left nasal alar base filling portion and the right nasal alar base filling portion, the soft tissue fixation structures including: A fixation wing extends outward from the surface of the implant, and the fixation wing is provided with a through hole for suture material to pass through; And a microporous surface layer, disposed on at least one surface of the implant, having a pore size of 50 μm to 500 μm and a porosity of 20% to 60%.

[0012] In one specific embodiment of the second aspect, the number of fixing wings is 2 to 6, symmetrically or asymmetrically distributed on the upper surface and / or side surface of the left nasal wing base filling portion and the right nasal wing base filling portion; each fixing wing extends outward from the implant surface for a length of 1 mm to 5 mm and a thickness of 0.5 mm to 2.0 mm; each fixing wing is provided with 1 to 3 through holes, the diameter of which is 0.3 mm to 1.5 mm.

[0013] In one specific embodiment of the second aspect, the implant is selected from one of the following materials: silicone, expanded polytetrafluoroethylene, porous high-density polyethylene, hydroxyapatite, autologous rib cartilage, or a combination thereof; the Shore A hardness of the implant is 20A to 80A.

[0014] Thirdly, a soft tissue suspension and fixation system for a subperiosteal implant at the base of the nasal alar includes: An implant having a surface provided with fixing wings and a microporous structure, the fixing wings extending outward from the surface of the implant, the fixing wings having through holes for suture material to pass through, and the microporous structure having a pore size of 50μm to 500μm and a porosity of 20% to 60%; Drug-loaded biodegradable sutures are used to suture and fix the fixation wings of the implant to the surrounding soft tissue. The drug-loaded biodegradable sutures have a core-shell composite structure, including a core layer and a shell layer wrapped around the outside of the core layer. The shell layer is loaded with angiogenesis factors, which are selected from at least one of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), with a loading concentration of 0.5 μg / mL to 50 μg / mL. The surface of the implant is also provided with a drug reservoir groove, which is filled with a thermosensitive hydrogel loaded with an immunomodulator. The immunomodulator is selected from at least one of IL-4 or IL-10, and the loading concentration is 10 ng / mL to 500 ng / mL.

[0015] The beneficial effects of this invention are as follows: 1. Mechanical anchoring of the implant is achieved through suturing and suspension of the implant fixation wings to the soft tissue (tension 3N-8N); combined with a microporous structure (pore size 50μm-500μm, porosity 20%-60%) to guide tissue ingrowth and form a biological chimera (animal experiments have shown that the ingrowth depth can reach 265μm-542μm at 12 weeks), achieving a dual fixation mechanism of "mechanical anchoring + biological fusion", which significantly reduces the risk of postoperative implant displacement (displacement <0.5mm at 6 months in clinical examples). 2. Drug-loaded biodegradable sutures release pro-angiogenic factors on demand under tension (3N-50N) (Experiment 1 confirmed that the release rate was 38.5% in 1 day under 50N tension, which was 4 times that of the tension-free group), achieving targeted drug release in the area of ​​maximum tension, improving drug utilization efficiency, and promoting vascularization of the implant-soft tissue interface (Experiment 3 confirmed that the vascular density in the 200μm pore size group was 14.2 vessels / HPF at 12 weeks). 3. Thermosensitive hydrogel (phase transition temperature 25℃~37℃) continuously releases immunomodulators IL-4 / IL-10 at body temperature (experimental example 2 confirmed a cumulative release rate of 89.6% over 14 days), inducing macrophages to polarize towards the M2 type, promoting the secretion of repair-type extracellular matrix (directed arrangement of collagen fibers), and reducing complications such as fibrous capsule contracture. 4. Under continuous tensile stress (3N-8N), the extracellular matrix undergoes directional remodeling, and the resulting tissue contractile force (approximately 20%-40% of the mechanical tension) is in the same direction as the suture tension, working synergistically to the implant fixation wings to achieve dynamic self-reinforcement of implant fixation—the more frequent the facial movements, the tighter the tissue intercalation, and the more stable the implant. Attached Figure Description

[0016] Figure 1 This is a schematic diagram of the surgical method process framework of the present invention. Detailed Implementation

[0017] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0018] like Figure 1 This illustrates a method for securing a subperiosteal implant at the base of the nasal ala.

[0019] I. This invention provides a method for soft tissue suspension and fixation of a subperiosteal implant at the base of the nasal alar, as well as the implant and system thereof. The invention is described in detail below with reference to specific embodiments, but the embodiments of this invention are not limited thereto. Those skilled in the art can make appropriate modifications and combinations to the following embodiments without departing from the essence of this invention.

[0020] II. Structure and Materials of the Implant 2.1 Overall structure of the implant The subperiosteal implant at the alar base of this invention is an alar base filling prosthesis, comprising a left alar base filling portion corresponding to the left alar base and a right alar base filling portion corresponding to the right alar base. The left and right alar base filling portions are connected by a nasal base connecting bridge. Soft tissue fixation structures are respectively provided on the left and right alar base filling portions. The implant is integrally injection molded or CNC machined, with the fixation wing and implant body forming a single integrated structure without a connecting interface, ensuring overall mechanical integrity.

[0021] 2.2 Structure and Parameters of Fixed-Wing Aircraft The fixation wings extend outward from the implant surface and have through-holes for suture material to pass through. There are 2 to 6 fixation wings, symmetrically or asymmetrically distributed on the upper and / or lateral surfaces of the left and right nasal wing base filling portions. Each fixation wing extends outward from the implant surface for 1 mm to 5 mm in length and 0.5 mm to 2.0 mm in thickness, and each fixation wing has 1 to 3 through-holes with a diameter of 0.3 mm to 1.5 mm.

[0022] The aforementioned ranges for the extension length, thickness, and through-hole diameter of the fixation wing were determined through extensive anatomical measurements and biomechanical finite element analysis. When the extension length is less than 1 mm, suture material is difficult to pass through and fix effectively; when it is greater than 5 mm, the fixation wing may cause excessive irritation or compression to the surrounding soft tissue. When the through-hole diameter is less than 0.3 mm, conventional medical suture needles (common specifications are 3 / 8 arc and 1 / 2 arc, needle diameter 0.3 mm to 1.3 mm) are difficult to pass through; when it is greater than 1.5 mm, the suture may slip excessively within the hole, affecting the fixation effect. The edges of the fixation wing are all rounded (radius of curvature R ≥ 0.2 mm) to reduce cutting and friction on soft tissue.

[0023] 2.3 Parameters and Formation Methods of Microporous Structures The implant surface has a microporous structure with pore sizes ranging from 50 μm to 500 μm and porosity ranging from 20% to 60%. This microporous structure guides the ingrowth of surrounding soft tissue into the implant surface, forming an interlocking fixation between the implant and the soft tissue during the soft tissue coverage and healing process.

[0024] The selection of micropore size is based on the following criteria: When the pore size is less than 50 μm, fibroblasts (approximately 10 μm to 20 μm in diameter) and vascular endothelial cells have difficulty effectively migrating in; when the pore size is greater than 500 μm, although it is conducive to tissue ingrowth, it will significantly reduce the mechanical strength of the implant and may lead to excessive tissue ingrowth, affecting the removability of the implant. When the porosity is less than 20%, the amount of tissue ingrowth is insufficient, and effective biological fixation cannot be formed; when the porosity is greater than 60%, the overall mechanical properties of the implant decrease, and there is a risk of rupture during implantation and long-term use.

[0025] The methods for forming microporous structures vary depending on the implant material: For silicone materials: The salting-out pore-forming method is used. Sodium chloride particles (particle size 50μm~500μm) are mixed evenly with silicone prepolymer. After molding, the implant is placed in deionized water for ultrasonic extraction for 48~72 hours to dissolve sodium chloride particles and form a microporous structure. For expanded polytetrafluoroethylene (ePTFE) material: a microporous structure is formed by biaxial stretching and expansion process, and the pore size and porosity are adjusted by controlling the stretching ratio (longitudinal stretching ratio 1.5:1 to 4:1, transverse stretching ratio 2:1 to 6:1) and sintering temperature (320℃ to 380℃). For porous high-density polyethylene (Medpor) material: the injection molding sintering method is adopted, the high-density polyethylene powder is mixed with the pore-forming agent and then injection molded, and the powder is sintered at high temperature (180℃~220℃) to fuse the powder. Then the pore-forming agent is removed by solvent extraction to form a connected microporous structure. For hydroxyapatite materials: a porous structure is formed by foaming or adding pore-forming agents and then sintering at high temperature (1100℃~1300℃).

[0026] 2.4 Parameters of the Drug Storage Tank At least one surface of the implant has a drug reservoir groove with a depth of 0.2 mm to 1.0 mm and a width of 0.5 mm to 2.0 mm. The groove is filled with a thermosensitive hydrogel loaded with an immunomodulator.

[0027] When the groove depth is less than 0.2 mm, the hydrogel loading is insufficient, and the effective drug release concentration cannot be achieved; when the depth is greater than 1.0 mm, it may affect the structural integrity of the implant. When the width is less than 0.5 mm, hydrogel filling is difficult; when the width is greater than 2.0 mm, it occupies too much surface area of ​​the implant, which may affect the fit between the implant and the bone surface.

[0028] The cross-sectional shape of the groove is selected from U-shape, V-shape, or semi-circular, with U-shape being preferred to facilitate the filling and retention of hydrogel. The bottom and sides of the groove are transitioned by a rounded arc (radius of curvature R ≥ 0.1 mm) to avoid stress concentration.

[0029] 2.5 Implant Materials The implant is selected from one of the following materials: silicone, expanded polytetrafluoroethylene (ePTFE), porous high-density polyethylene (Medpor), hydroxyapatite, autologous rib cartilage, or a combination thereof. The Shore A hardness of the implant is 20A to 80A.

[0030] When the Shore hardness is below 20A, the implant is too soft and cannot provide sufficient support for the nasal alar base; when it is above 80A, the implant is too hard and does not match the mechanical properties of the surrounding tissues, which may lead to complications such as tissue compression and wear.

[0031] 2.6 Sterilization of the implant Implants are sterilized using one of the following methods after packaging: Ethylene oxide sterilization: temperature 37℃~55℃, relative humidity 40%~80%, ethylene oxide concentration 400mg / L~800mg / L, sterilization time 2~4 hours, desorption time 7~14 days, residual ethylene oxide content ≤10μg / g; Cobalt-60 irradiation sterilization: irradiation dose 15kGy~25kGy.

[0032] III. Preparation of Drug-Loaded Biodegradable Sutures 3.1 Overall structure of the suture Drug-loaded biodegradable sutures have a core-shell composite structure, comprising a core layer and a shell layer surrounding the core layer. The core layer is a bundle of absorbable polymer filaments that provides the suture with mechanical strength; the shell layer is a porous drug-loaded layer loaded with pro-angiogenic factors.

[0033] 3.2 Core Material and Parameters The core material is selected from polyglycolic acid (PGA), polylactic acid-glycolic acid copolymer (PLGA), polycaprolactone (PCL), or a combination thereof. The diameter of the core filament bundle is 0.1 mm to 0.5 mm, and it is made of 5 to 20 monofilaments twisted together, with a twist of 10 to 30 twists / 10 cm.

[0034] 3.3 Shell Material and Drug Delivery Method Within the shell, pro-angiogenic factors are embedded in a biodegradable polymer matrix in the form of microspheres or nanospheres. The biodegradable polymer is selected from PLGA, PCL, or combinations thereof. The particle size of the microspheres or nanospheres ranges from 100 nm to 50 μm. The tensile strength of the drug-loaded biodegradable suture is 20 MPa to 80 MPa, and the degradation period is 4 to 24 weeks.

[0035] When the tensile strength is below 20 MPa, the suture may break during suspension and fixation; when it is above 80 MPa, the suture is too rigid, which is not conducive to knotting and operation. When the degradation period is less than 4 weeks, the suture has degraded before the soft tissue has formed a sufficiently strong fibrous wrapping, thus losing its suspension function; when it is longer than 24 weeks, the long-term retention of the suture may cause a chronic inflammatory response.

[0036] In PLGA, the molar ratio of lactic acid to glycolic acid monomers is 50:50 to 90:10. Adjusting this ratio can control the degradation cycle (degradation is faster at 50:50, about 4 to 8 weeks; degradation is slower at 90:10, about 16 to 24 weeks). PCL has a molecular weight of 50,000 to 150,000 Da and a degradation cycle of about 12 to 24 weeks.

[0037] 3.4 Selection and Concentration of Pro-angiogenic Factors The pro-angiogenic factor is selected from at least one of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), with a loading concentration of 0.5 μg / mL to 50 μg / mL. VEGF and bFGF are known potent pro-angiogenic factors that can promote the proliferation, migration, and lumen formation of vascular endothelial cells. When the loading concentration is below 0.5 μg / mL, the pro-angiogenic effect is not significant; when it is above 50 μg / mL, it may induce adverse reactions such as excessive angiogenesis.

[0038] 3.5 Preparation method of drug-loaded suture The preparation method of drug-loaded biodegradable sutures is as follows: (1) Core layer preparation: PGA, PLGA or PCL polymers are melt-spun or wet-spun into monofilaments. The spinning temperature varies depending on the material: PGA 220℃~240℃, PLGA 180℃~220℃, PCL 70℃~100℃. 5 to 20 monofilaments are twisted into a bundle to form the core layer filament bundle.

[0039] (2) Preparation of drug-loaded microspheres / nanospheres: VEGF or bFGF was dissolved in phosphate buffer (PBS, pH 7.2-7.4, 4℃) and the concentration was adjusted to 0.5 μg / mL-50 μg / mL; PLGA or PCL was dissolved in dichloromethane and the concentration was adjusted to 5%-20% (w / v); the two-phase solutions were combined to form drug-loaded microspheres / nanospheres by a double emulsion method (water / oil / water) or a double emulsion method. The specific steps were as follows: high-speed shearing (8000-15000 rpm, 2-5 minutes) or ultrasonic emulsification (power 100-300W). Under conditions of 1-3 minutes, a primary emulsion is formed, and then an external aqueous phase (containing 1%-5% polyvinyl alcohol as an emulsifier) ​​is added to form a secondary emulsion. The organic solvent is evaporated by magnetic stirring (300-600 rpm, 2-4 hours), and the emulsion is collected by centrifugation (10000-20000 g, 10-20 minutes). The emulsion is then freeze-dried for 24-48 hours to obtain drug-loaded microspheres / nanospheres. The particle size is controlled between 100 nm and 50 μm by adjusting the shear rate and emulsifier concentration.

[0040] (3) Shell coating: The drug-loaded microspheres / nanospheres are dispersed in an organic solution of PLGA or PCL (concentration 2% to 10%, w / v) and coated onto the surface of the core fiber bundle by dip coating (dip time 10 to 60 seconds, lifting speed 1 to 10 mm / s), spray coating (spraying pressure 0.2 to 0.6 MPa, spraying distance 10 to 30 cm) or electrospinning to form a shell. The shell thickness is controlled between 10 μm and 100 μm.

[0041] (4) Drying and sterilization: The prepared drug-loaded sutures are dried under vacuum conditions (vacuum degree ≤ -0.08MPa, temperature 25℃~40℃) for 24~48 hours to remove organic solvent residue (residual amount ≤0.5%), and then sterilized by ethylene oxide or cobalt-60 irradiation (15kGy~25kGy).

[0042] IV. Preparation of Thermosensitive Hydrogels 4.1 Material Selection for Thermosensitive Hydrogels The thermosensitive hydrogel is made from poloxamer (Pluronic F127, Pluronic P407), poly(N-isopropylacrylamide) (PNIPAAm), or combinations thereof. Poloxamer is a thermosensitive synthetic polymer that can undergo a sol-gel transition with temperature changes, exhibiting good biocompatibility and injectability.

[0043] 4.2 Phase transition properties of thermosensitive hydrogels Thermosensitive hydrogels are liquid below 25°C and undergo a sol-gel phase transition between 25°C and 37°C to form a gel. This phase transition characteristic allows the hydrogel to be injected into the groove in liquid form at room temperature, and then rapidly gels under body temperature after implantation, preventing premature drug loss.

[0044] Methods for controlling phase transition temperature: For the poloxamer system: the total concentration of Pluronic F127 and Pluronic P407 is 15%–30% (w / v). By adjusting the F127:P407 ratio (e.g., 20:5–25:8, w / w), the phase transition temperature can be precisely controlled within the range of 25℃–33℃. Increasing the F127 ratio decreases the phase transition temperature; increasing the P407 ratio increases the phase transition temperature.

[0045] For the PNIPAMAm system: its phase transition temperature can be adjusted from 32℃ to the range of 25℃ to 37℃ by copolymerization modification (such as introducing the hydrophilic monomer acrylamide, in a molar ratio of 5% to 15%). The higher the proportion of hydrophilic monomer, the higher the phase transition temperature.

[0046] 4.3 Selection and Concentration of Immunomodulators The immunomodulator is selected from at least one of IL-4 or IL-10, with a loading concentration ranging from 10 ng / mL to 500 ng / mL. IL-4 and IL-10 are known M2 macrophage polarization inducing factors that can inhibit pro-inflammatory responses and promote tissue repair and extracellular matrix secretion. Immunomodulatory effects are not significant at loading concentrations below 10 ng / mL; concentrations above 500 ng / mL may excessively suppress the immune response, increasing the risk of infection.

[0047] 4.4 Preparation method of thermosensitive hydrogel The preparation method of thermosensitive hydrogel is as follows: (1) Dissolve poloxamer (Pluronic F127 and / or Pluronic P407) in pre-cooled PBS (pH 7.2-7.4) at 4°C, adjust the total concentration to 15%-30% (w / v), and stir magnetically at 4°C (200-400 rpm, 2-4 hours) until completely dissolved to form a homogeneous and transparent solution.

[0048] (2) Dissolve IL-4 or IL-10 in PBS pre-cooled at 4°C and adjust the concentration to 10 ng / mL to 500 ng / mL.

[0049] (3) Gently mix the immunomodulator solution and poloxamer solution at 4°C (stirring speed 100-200 rpm, 10-20 minutes) to form a thermosensitive hydrogel precursor solution loaded with immunomodulator.

[0050] (4) Before use, store the hydrogel precursor solution at 4°C (the storage period shall not exceed 7 days). When using, use a sterile syringe to draw an appropriate amount (determined according to the volume of the groove, usually 5μL~50μL) and inject it into the drug reservoir groove of the implant.

[0051] V. Specific Implementation Methods of the Surgical Procedure 5.1 Preoperative preparation A comprehensive preoperative assessment of the patient is conducted, including a 3D facial CT scan (slice thickness ≤1mm) and measurement of the degree of nasal alar base depression (using Gilles classification or a custom classification standard) to determine the implant size and placement. Prophylactic antibiotics (cefazoline 1.0g or clindamycin 0.6g intravenously) are administered 30 minutes preoperatively.

[0052] 5.2 Step (1): Soft tissue anatomy and marking In the nasal alar base region, the levator labii superioris muscle, nasal alar base ligament, and surrounding fascia are anatomically located and marked to determine the positions of soft tissue fixation anchor points. Soft tissue fixation anchor points are selected from one or more of the following locations: the attachment point of the nasal alar base ligament, the origin or insertion point of the levator labii superioris muscle, the junction of the maxillary periosteum and soft tissue, and the soft tissue attachment point at the edge of the piriform foramen.

[0053] Specific procedures: Use methylene blue or gentian violet to mark the corresponding locations on the skin surface. Before marking, confirm the bony landmarks below the base of the nasal alar (the edge of the piriform aperture and the frontal process of the maxilla) by palpation, and determine the precise location of the soft tissue anchor points by combining the preoperative CT images.

[0054] Input: Patient's facial anatomical landmarks, preoperative CT images.

[0055] Output: Locations of soft tissue anchor points marked on the body surface.

[0056] 5.3 Step (2): Preparation of subperiosteal space An implant-accommodating cavity is prepared subperiosteally in the maxilla at the base of the nasal alar. The size and shape of the cavity match the pre-implanted implant. The subperiosteal cavity is prepared via an intraoral approach (oral vestibule incision) or an intranasal approach (nasal vestibule incision). Blunt or sharp dissection is performed subperiosteally to form a pouch-like cavity that conforms to the shape of the implant.

[0057] Specific procedures (taking the intraoral approach as an example): (1) Make a mucosal incision of about 1.0cm to 1.5cm in length at the oral vestibule, cut open the mucosa and submucosa, and stop bleeding with an electrocautery or ultrasonic scalpel.

[0058] (2) Use a periosteal elevator (3mm to 8mm wide) to perform blunt dissection along the maxillary bone surface to expose the maxillary bone surface in the nasal alar base area.

[0059] (3) A cavity is formed by dissecting along the maxillary bone surface under the periosteum. The cavity should be slightly larger than the projected area of ​​the implant (about 2mm to 3mm larger), and the depth should be just enough to accommodate the implant. During the dissection, care should be taken to protect the vascular nerve bundles in the nasal alar base area (mainly the nasal alar branch of the infraorbital nerve).

[0060] (4) After hemostasis, rinse the cavity with normal saline (37°C), check the integrity of the cavity, and confirm that there is no periosteal perforation.

[0061] Input: Anesthetized patient, marked anatomical locations.

[0062] Output: Subperiosteal cavity.

[0063] 5.4 Step (3): Implantation The implant is placed in the subperiosteal space, positioning it between the periosteum and the maxillary bone surface. The implant surface is equipped with fixation wings and microporous structures.

[0064] Specific operations: (1) Select an appropriate size implant (determined based on preoperative measurements and intraoperative assessment).

[0065] (2) If a drug reservoir groove is provided on the surface of the implant, before implantation, inject the thermosensitive hydrogel precursor solution (liquid at 4°C) loaded with immunomodulator into the groove with a sterile syringe. The injection volume should be about 5μL to 50μL, enough to fill the groove and slightly overflow (not exceeding 0.5mm in height).

[0066] (3) Place the implant into the subperiosteal cavity in an appropriate direction, ensuring that the fixation wing faces the soft tissue side (i.e. the periosteal side) and that the concave surface of the implant fits against the maxillary bone surface.

[0067] (4) Gently press the surface of the implant (approximately 1N to 3N) to expel excess air and blood from the cavity and confirm that the implant is in the correct position and is not rotated or tilted.

[0068] Input: subperiosteal space, pre-selected implant, thermosensitive hydrogel precursor solution.

[0069] Output: Correctly placed implant.

[0070] 5.5 Step (4): Soft tissue suspension and fixation The implant is suspended and fixed to the surrounding soft tissue after the suture material is passed through the through-hole of the fixation wing. The surrounding soft tissue is selected from one or more of the following: levator labii superioris muscle, alar base ligament, periosteum, and subcutaneous fascia.

[0071] The suture material is a drug-loaded biodegradable suture (its preparation method is described in Section 3). Specific procedures: (1) Take an appropriate length of drug-loaded biodegradable suture (usually 15cm to 30cm) and soak it in sterile saline.

[0072] (2) Pass the suture needle (3 / 8 arc or 1 / 2 arc, needle diameter 0.3mm to 1.3mm) through the through hole on the fixed wing.

[0073] (3) Continue passing the suture needle through the pre-marked soft tissue fixation anchor point (such as the alar base ligament or the levator labii superioris muscle of the alar), and use mattress suture or interrupted suture to fix the implant to the soft tissue. The specific method of mattress suture is as follows: The suture needle enters from one side of the soft tissue anchor point, passes through the full or partial layer of the soft tissue (approximately 3mm to 8mm deep), and then exits from the other side. The suture needle is then passed through the fixation wing through-hole and finally returned to the soft tissue anchor point to be knotted and fixed. Mattress suture provides a larger soft tissue contact area (approximately 5mm to 10mm wide), disperses tension, and reduces the risk of cutting.

[0074] (4) Adjust the tension of the sutures according to the thickness and tension of the soft tissue. The tension applied to the sutures is measured using a tension meter (spring balance type tension meter, accuracy 0.1N) and controlled within the range of 3N to 8N. When the tension is below 3N, the implant is not securely fixed and there is a risk of postoperative displacement; when the tension is above 8N, it may cause soft tissue cutting, ischemic necrosis, or nerve damage. The specific value of the tension is determined according to the thickness of the patient's soft tissue: when the soft tissue thickness is <5mm, the tension is controlled between 3N and 5N; when the soft tissue thickness is ≥5mm, the tension is controlled between 5N and 8N.

[0075] (5) Secure with a knot (surgical knot recommended, 4 to 6 square knots), and cut off excess suture (leaving the suture tail about 2 to 3 mm long).

[0076] Input: Correctly placed implant, drug-eluting biodegradable suture, marked soft tissue anchors.

[0077] Output: Suspension and fixation connection between the implant and soft tissue (tension 3N~8N).

[0078] 5.6 Step (5): Soft tissue coverage and healing The suspended and fixed soft tissue is then repositioned and placed over the implant surface. The microporous structure guides the surrounding soft tissue to grow into the implant surface, forming a mating and fixation between the implant and the soft tissue.

[0079] Specific operations: (1) Check the position and fixation effect of the implant. Gently touch the surface of the implant with tweezers to confirm that there is no abnormal displacement (displacement < 0.5 mm is considered qualified).

[0080] (2) Reposition the dissected soft tissue (including periosteum, muscle and mucosa) and cover the surface of the implant. Use your fingers to press lightly (approximately 1N to 2N) to make the soft tissue fit tightly against the implant.

[0081] (3) Layered suturing with absorbable sutures (such as PGA or PLGA sutures, specifications 4-0 to 6-0, non-drug loaded): First, suture the periosteal layer with interrupted suturing (3 to 5 stitches), then suture the submucosal layer continuously, and finally close the mucosal layer incision with interrupted or continuous suturing.

[0082] (4) Apply pressure bandage for 24 to 48 hours postoperatively, with the pressure controlled at 15 mmHg to 25 mmHg (applied with an elastic bandage or pressure mask, and the pressure monitored by a pressure sensor or airbag pressure gauge). If the pressure is below 15 mmHg, the hemostatic effect will be poor and hematoma may form; if the pressure is above 25 mmHg, it may compress local tissues and cause ischemia.

[0083] During the postoperative healing process: Postoperative weeks 0–4 (acute inflammatory phase): Under the traction tension (3N–8N) generated by suspension fixation, the microscopic molecular chains of the PLGA / PCL polymer matrix in the drug-eluting suture shell align oriented along the tension direction, increasing the porosity of the polymer matrix and enlarging the release channels of the embedded VEGF or bFGF microspheres / nanospheres. In vitro release experiments (see Experimental Example 1 in Section 7) showed that under a 50N traction tension, the cumulative release rate reached 38.5% ± 4.2% over 24 hours, compared to only 9.6% ± 1.8% under tension-free conditions. The released angiogenic factors promoted the proliferation of surrounding capillary endothelial cells, which migrated directionally into the microporous structure of the implant, forming a neovascular network at the implant-soft tissue interface.

[0084] During weeks 2–8 post-surgery (repair period): Thermosensitive hydrogels undergo a sol-gel phase transition at body temperature (37°C) to form a gel state, immobilizing IL-4 or IL-10 within the grooves and releasing it slowly. In vitro release assays (see Experimental Example 2 in Section VII) showed that the cumulative release rate of IL-4 at 37°C was 32.5% ± 3.8% after 24 hours, 71.2% ± 5.1% after 7 days, and 89.6% ± 4.3% after 14 days. The released IL-4 / IL-10 induced local macrophage polarization from M1 (pro-inflammatory) to M2 (repair) types. M2 macrophages secreted TGF-β, IL-10, and collagen, promoting fibroblast migration and proliferation.

[0085] During weeks 8–24 post-surgery (remodeling phase): Neovascularization provides ample blood supply and nutrition to the implant-soft tissue interface. Extracellular matrix (mainly type I and type III collagen) secreted by M2 macrophages is deposited and remodeled in an orderly manner along the direction of tension. The directional alignment of collagen fibers is consistent with the direction of tension, and the resulting tissue contractile force (approximately 20%–40% of the mechanical tension of the suture) is in the same direction as the mechanical tension of the suture (3N–8N). Both act together on the implant fixation wings, firmly fixing the implant to the soft tissue anchor point. As the implantation time increases (after 12 weeks post-surgery), the suture gradually degrades and is absorbed (degradation period 4–24 weeks), but the vascularized tissue and directional collagen fibers at the implant-soft tissue interface have formed a stable structure, continuously providing fixation force and achieving long-term biological stability of the implant.

[0086] Input: The implant and surrounding tissues after suspension and fixation.

[0087] Output: Fully healed implant-soft tissue complex.

[0088] 5.7 Postoperative follow-up and evaluation Follow-up was conducted at 1 month, 3 months, 6 months, and 12 months post-surgery, and evaluation was performed using 3D facial scanning (accuracy ≤0.5mm), CT imaging (slice thickness ≤1mm), and clinical examination. Positional stability of the implant (three-dimensional coordinate displacement <1mm is considered stable); The effect of nasal alar base depression correction (the depression depth improvement rate ≥50% is considered effective); Complications (infection, displacement, exposure, hematoma, nerve damage, etc.)

[0089] VI. Examples Example 1 Implant Specifications: Bilateral nasal alar base prosthesis, made of medical-grade silicone with a Shore A hardness of 45A. The fixation wings are integrally injection molded with the implant body. There are four fixation wings (two on each side), symmetrically distributed on the upper surface of the left and right nasal alar base filling areas. Each fixation wing has an extension length of 3mm, a thickness of 1.0mm, and a rounded edge radius R=0.3mm. Each fixation wing has two through holes with a diameter of 0.8mm. The microporous structure is formed by salting-out pore creation, with a pore size of 200μm±50μm and a porosity of 40%±5%. The drug reservoir groove has a U-shaped cross-section, a depth of 0.5mm, a width of 1.0mm, and a rounded transition radius R=0.2mm between the bottom and side surfaces.

[0090] Drug-loaded biodegradable suture: Core-sheath composite structure. The core layer consists of PGA filament bundles (0.3 mm in diameter, 12 twisted monofilaments, 20 twists / 10 cm); the shell layer consists of PLGA (lactic acid:glycolic acid = 75:25, molecular weight 100 kDa) encapsulated with VEGF microspheres (particle size 5 μm ± 2 μm, VEGF loading concentration 10 μg / mL). The suture has a tensile strength of 45 MPa ± 5 MPa and a degradation period of 12 weeks ± 2 weeks. Sterilized with ethylene oxide (concentration 600 mg / L, temperature 50℃, humidity 60%, sterilization time 3 hours, degradation time 10 days).

[0091] Thermosensitive hydrogel: Pluronic F127:P407 = 22:7, w / w, total concentration 20% (w / v), phase transition temperature 28℃ ± 1℃. Loaded with IL-4, concentration 100 ng / mL ± 20 ng / mL. Store at 4℃, inject 15 μL into the groove using a sterile syringe before use.

[0092] Surgical procedure: The patient was a 32-year-old female with moderate bilateral alar base depression (Gillies grade II). Preoperative 3D CT scan measured the depth of the alar base depression as 3.2 mm on the left and 2.8 mm on the right.

[0093] The surgical procedure was performed as described above: a subperiosteal cavity was created via an intraoral approach. After the implant was placed, mattress sutures were performed using drug-eluting biodegradable sutures (3 / 8 arc, 0.8 mm needle diameter). The implant fixation wings were sutured and fixed to the bilateral alar base ligaments. Two fixation points were established on each side. The suture tension was measured with a tension meter: 4.5 N on the left and 4.2 N on the right. After closing the incision, a pressure dressing was applied (20 mmHg, for 24 hours).

[0094] Postoperative results: One-month follow-up: The depression at the base of the nasal alar base was significantly improved, with the depth of the depression on the left side decreasing to 0.5 mm and on the right side decreasing to 0.3 mm. There was no displacement of the implant (three-dimensional coordinate displacement < 0.3 mm), the incision healed well, and there was no infection or hematoma.

[0095] Three-month follow-up: 3D CT showed that the implant was in a stable position, without rotation or displacement. Enhanced CT scan showed significant neovascularization at the implant-soft tissue interface. The patient's self-rated satisfaction score (VAS, 0-10) was 9.

[0096] Six-month follow-up: The implant was firmly fixed, and there was no abnormal movement during facial expressions. No complications such as implant exposure or skin thinning were observed. The improvement rate of depression depth was 84.4% on the left side and 89.3% on the right side.

[0097] Example 2 Implant Specifications: Bilateral nasal alar base prosthesis, made of expanded polytetrafluoroethylene (ePTFE), Shore A hardness 55A, with one-piece molded fixation wings. There are 6 fixation wings (3 on each side), asymmetrically distributed on the upper and side surfaces of the left and right nasal alar base filling areas. Each fixation wing has an extension length of 2mm, a thickness of 0.8mm, and a rounded corner radius R=0.2mm. Each fixation wing has one through-hole with a diameter of 0.5mm. The microporous structure is formed through a biaxial stretching expansion process, with a pore size of 100μm±30μm and a porosity of 50%±5%. The drug reservoir groove has a depth of 0.3mm and a width of 0.8mm.

[0098] Drug-loaded biodegradable suture: Core-sheath composite structure. The core layer consists of PLGA (lactic acid:glycolic acid = 85:15) filaments (0.4 mm diameter, 10 twisted monofilaments); the shell layer consists of PCL (molecular weight 80 kDa) embedded bFGF nanospheres (particle size 200 nm ± 50 nm, bFGF loading concentration 25 μg / mL). The suture has a tensile strength of 60 MPa ± 5 MPa and a degradation period of 16 weeks ± 2 weeks. Sterilized by cobalt-60 irradiation (dose 20 kGy). Thermosensitive hydrogel: PNIPAAAm-acrylamide copolymer system (acrylamide molar ratio 10%), concentration 15% (w / v), phase transition temperature 32℃±1℃. Loading IL-10, concentration 250ng / mL±50ng / mL. Injection volume 12μL.

[0099] Surgical procedure: The patient was a 45-year-old male with severe bilateral nasal alar base depression (Gillies grade III) accompanied by a flat midface contour. Preoperative 3D CT measurements showed the depth of the nasal alar base depression to be 4.5 mm on the left and 4.1 mm on the right.

[0100] The surgical procedure was performed as described above: a subperiosteal cavity was created via an intranasal approach. After the implant was placed, interrupted sutures were made using drug-eluting biodegradable sutures (1 / 2 arc, 0.6 mm diameter). The implant fixation wings were sutured and fixed to the origins of the levator labii superioris muscles and the alar base ligaments on both sides (3 fixation points on each side). The suture tension was 6.5 N on the left and 6.0 N on the right. After closing the incision, a pressure dressing was applied (22 mmHg, for 48 hours).

[0101] Postoperative results: One-month follow-up: The depression at the base of the nasal alar base has significantly improved, with the depth of the depression on the left side decreasing to 0.8 mm and on the right side decreasing to 0.6 mm. There was no displacement of the implant, and the incision healed well.

[0102] Three-month follow-up: CT scan showed stable implant position and good soft tissue-implant interface fusion. The patient's facial contours improved significantly, with a VAS score of 9.

[0103] 12-month follow-up: Long-term effects were stable, with no implant displacement or exposure. The improvement rate in depression depth was 82.2% on the left and 85.4% on the right. Patient satisfaction was high.

[0104] Example 3 Implant Specifications: Bilateral nasal alar base implant, made of porous high-density polyethylene (Medpor), Shore A hardness 65A, with one-piece molded fixation wings. There are two fixation wings (one on each side), located at the center of the upper surface of the left and right nasal alar base filling areas. Each fixation wing has an extension length of 5mm, a thickness of 2.0mm, and a rounded corner radius R=0.4mm. Each fixation wing has three through-holes with a diameter of 1.2mm. The microporous structure is formed by injection molding and sintering, with a pore size of 400μm±80μm and a porosity of 55%±5%. The drug reservoir groove has a depth of 0.6mm and a width of 1.5mm.

[0105] Drug-loaded biodegradable suture: Core-sheath composite structure. The core layer consists of PCL (molecular weight 120kDa) filaments (0.5mm in diameter, 8 monofilaments twisted together); the shell layer is a PLGA / PCL composite (PLGA:PCL=70:30) encapsulating VEGF and bFGF microspheres (particle size 20μm±5μm, VEGF concentration 5μg / mL, bFGF concentration 5μg / mL). The suture has a tensile strength of 35MPa±5MPa and a degradation period of 20 weeks±3 weeks. Sterilized with ethylene oxide.

[0106] Thermosensitive hydrogel: Pluronic F127:P407 = 20:8, w / w, total concentration 25% (w / v), phase transition temperature 26℃ ± 1℃. Loaded with IL-4 and IL-10 (125 ng / mL ± 25 ng / mL each). Injection volume 8 μL.

[0107] Surgical Procedure: The patient was a 28-year-old female with mild bilateral nasal alar base depression (Gillies grade I). She requested surgical correction due to high aesthetic requirements. Preoperative 3D CT measurements showed the depth of the nasal alar base depression to be 1.8 mm on the left and 1.5 mm on the right.

[0108] The surgical procedure was performed as described above: a subperiosteal cavity was created via an intraoral approach. After the implant was placed, mattress sutures were performed using drug-eluting biodegradable sutures (3 / 8 arc, 1.0 mm needle diameter). The implant fixation wings were sutured and fixed to the bilateral alar base ligaments and maxillary periosteum (2 fixation points on each side). The suture tension was 3.5 N on the left and 3.2 N on the right. After closing the incision, a pressure dressing was applied (18 mmHg, for 24 hours).

[0109] Postoperative results: One-month follow-up: Nasal alar base depression was basically corrected, with the depression depth on the left side decreasing to 0.2mm and on the right side decreasing to 0.1mm. The implant was in good position with no displacement.

[0110] Six-month follow-up: The results were stable, and the facial contours appeared natural. The implant integrated well with the soft tissue, and no adverse reactions were observed. The improvement rate in depression depth was 88.9% on the left side and 93.3% on the right side. The VAS score was 10.

[0111] VII. Experimental Examples Experimental Example 1: Tension-Response Drug Release Test of Drug-Loaded Suture Experimental objective: To verify the changes in the release rate of VEGF / bFGF in drug-degradable sutures under different tension conditions.

[0112] Experimental materials: Drug-loaded biodegradable sutures prepared according to the method in Section 3 (VEGF loading concentration 10 μg / mL, PLGA shell, degradation period 12 weeks), and suture segments with a length of 5 cm were cut.

[0113] Experimental methods: The suture segments were placed under the following tension conditions: Tension-free group (0N): The sutures were naturally immersed in PBS release medium (pH 7.4, 37°C); Low tension group (10N): 10N tension was applied to both ends of the suture, fixed on a tension clamp, and immersed in PBS; Medium tension group (30N): Apply 30N tension to both ends of the suture; High tension group (50N): Apply 50N tension to both ends of the suture.

[0114] Three parallel samples were set up in each group. 200 μL of release medium was collected at 1 day, 3 days, 7 days, 14 days and 28 days respectively. VEGF concentration was determined by ELISA and the cumulative release rate (cumulative release amount / total drug load × 100%) was calculated. Results are expressed as mean ± standard deviation.

[0115] Experimental results: ; Experimental conclusions: The VEGF release rate of the drug-loaded biodegradable suture was significantly positively correlated with the tension (Pearson r = 0.94, p < 0.01). The cumulative release rate of the high-tension group (50 N) over 1 day (38.5% ± 4.2%) was approximately four times that of the tension-free group (9.6% ± 1.8%). This indicates that the drug-loaded suture described in this invention has significant tension-responsive drug release characteristics, enabling targeted and accelerated drug release in the area of ​​maximum tension after suspension fixation.

[0116] Experimental Example 2: In vitro drug release test of thermosensitive hydrogel Experimental objective: To verify the sustained-release properties of IL-4-loaded thermosensitive hydrogel under body temperature conditions.

[0117] Experimental materials: Pluronic F127:P407 = 22:7, total concentration 20%, phase transition temperature 28℃, prepared according to the method in Section 4, loaded with IL-4 at a concentration of 100 ng / mL.

[0118] Experimental methods: 200 μL of temperature-sensitive hydrogel precursor solution (liquid at 4°C) was injected into a dialysis bag (molecular weight cutoff 100 kDa), and the bag was placed in a 37°C constant temperature water bath shaker (oscillation frequency 60 rpm) for gelation. Then the dialysis bag was immersed in 10 mL of PBS release medium (pH 7.4, 37°C).

[0119] 1 mL of release medium was collected at 6 hours, 12 hours, 24 hours, 3 days, 7 days, and 14 days, and replenished with an equal volume of fresh PBS. IL-4 concentration was determined using ELISA, and the cumulative release rate was calculated. Three replicates were performed for each group, and results are expressed as mean ± standard deviation.

[0120] Experimental results: ; Experimental conclusion: The temperature-sensitive hydrogel loaded with IL-4 achieved sustained release at a body temperature of 37℃, with a cumulative release rate of 89.6%±4.3% over 14 days. There was no obvious burst release (the 24-hour release rate was 32.5%±3.8%, and the burst release rate was <40%). The release curve was stable and suitable for the long-term regulation of the postoperative immune microenvironment.

[0121] Experiment Example 3: Animal Experiments on the Effect of Different Micropore Sizes on Tissue Infiltration Experimental objective: To verify the effects of different micropore sizes on soft tissue ingrowth depth and vascularization, and to determine the optimal pore size range.

[0122] Experimental materials: Silicone implant specimens (10mm×10mm×3mm) prepared according to the method in Section 2, with micropore diameters of 30μm, 50μm, 200μm, 500μm and 800μm, and porosity controlled at 40%±5%.

[0123] Experimental methods: Five groups of test pieces with different pore sizes (six samples per group) were implanted subcutaneously into the backs of male SD rats (8 weeks old, weighing 250g±20g), with two test pieces implanted in each rat. Animals were sacrificed at 4 and 12 weeks post-surgery, and the test pieces and surrounding tissues were removed. The tissues were fixed in 4% paraformaldehyde, embedded in paraffin, sectioned (5μm thick), stained with hematoxylin and eosin (HE), and stained with Masson's trichrome. Tissue ingrowth depth and neovascularization density (number of vessels per high-power field) were observed under an optical microscope (×200). The animal experiments were approved by the institution's animal ethics committee (approval number IACUC-2023-015).

[0124] Experimental results: ; Experimental conclusions: The 30μm pore size group showed the shallowest tissue ingrowth depth (only 82μm after 12 weeks) and the lowest degree of vascularization. The 50μm–500μm pore size groups all exhibited good tissue ingrowth effects, with the 200μm group showing the highest vessel density (14.2±3.8 vessels / HPF) and a moderate tissue ingrowth depth (485μm after 12 weeks), resulting in the best overall performance. While the 800μm pore size group achieved the greatest ingrowth depth, the vessel density decreased, and the mechanical strength of the specimen was significantly reduced (compressive strength decreased by approximately 35%). Therefore, this invention limits the micropore size to 50μm–500μm, with the optimal range being 150μm–300μm.

[0125] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for fixing a subperiosteal implant at the base of the nasal alar, characterized in that, Includes the following steps: Step 1: Soft tissue anatomy and marking: In the nasal alar base region, the patient's levator labii superioris muscle, nasal alar base ligament and surrounding fascia tissue are anatomically located and marked to determine the location of soft tissue fixation anchor points. Step 2: Subperiosteal cavity preparation: An implant-accommodating cavity is prepared under the periosteum of the maxilla at the base of the nasal alar, the size and shape of which match the pre-implanted implant; Step 3: Implant placement: The implant is placed into the subperiosteal cavity, positioned between the periosteum and the maxillary bone surface. The surface of the implant is provided with fixation wings and a microporous structure. The fixation wings extend outward from the surface of the implant and have through holes for suture material to pass through. The diameter of the through holes is 0.3 mm to 1.5 mm. The diameter of the microporous structure is 50 μm to 500 μm, and the porosity is 20% to 60%. Step 4: Soft tissue suspension and fixation: After passing suture material through the through hole of the fixation wing, the implant is suspended and fixed to the surrounding soft tissue. The surrounding soft tissue is selected from one or more of the following: levator labii superioris muscle of the nasal alar, nasal alar base ligament, periosteum, and subcutaneous fascia. Step 5: Soft tissue coverage and healing: The suspended and fixed soft tissue is repositioned and covered on the surface of the implant. The microporous structure guides the surrounding soft tissue to grow into the surface of the implant, forming an interlocking fixation between the implant and the soft tissue.

2. The method according to claim 1, characterized in that, The suture material mentioned in step 4 is a drug-loaded biodegradable suture. The drug-loaded biodegradable suture has a core-shell composite structure, including a core layer and a shell layer wrapped around the outside of the core layer. The core layer is an absorbable polymer material bundle, and the shell layer is a porous drug-loaded layer loaded with angiogenesis factors. The angiogenesis factors are selected from at least one of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), with a loading concentration of 0.5 μg / mL to 50 μg / mL.

3. The method according to claim 2, characterized in that, In the shell of the drug-loaded biodegradable suture, the pro-angiogenic factor is embedded in a biodegradable polymer matrix in the form of microspheres or nanospheres. The biodegradable polymer is selected from polylactic-co-glycolic acid copolymer (PLGA), polycaprolactone (PCL), or a combination thereof. The particle size of the microspheres or nanospheres is 100 nm to 50 μm. The tensile strength of the drug-loaded biodegradable suture is 20 MPa to 80 MPa, and the degradation period is 4 to 24 weeks.

4. The method according to claim 1, characterized in that, At least one surface of the implant is provided with a drug reservoir groove, the groove having a depth of 0.2 mm to 1.0 mm and a width of 0.5 mm to 2.0 mm; the groove is filled with a thermosensitive hydrogel loaded with an immunomodulator, the immunomodulator being selected from at least one of IL-4 or IL-10, with a loading concentration of 10 ng / mL to 500 ng / mL; the thermosensitive hydrogel is liquid below 25°C and undergoes a sol-gel phase transition to form a gel state at 25°C to 37°C.

5. The method according to claim 1, characterized in that, The soft tissue fixation anchor points mentioned in step 1 are selected from one or more of the following locations: the attachment point of the alar base ligament, the origin or insertion point of the levator labii superioris muscle, the junction of the periosteum of the maxilla and soft tissue, and the soft tissue attachment point at the edge of the piriform aperture.

6. The method according to claim 1, characterized in that, The subperiosteal cavity described in step 2 is prepared by an intraoral or intranasal approach, using blunt or sharp dissection under the periosteum to form a pouch-shaped cavity consistent with the shape of the implant.

7. A subperiosteal implant for implementing the method according to any one of claims 1-6, characterized in that, The implant is a nasal alar base filling prosthesis, including a left nasal alar base filling part corresponding to the left nasal alar base of the human body and a right nasal alar base filling part corresponding to the right nasal alar base of the human body. The left nasal alar base filling part and the right nasal alar base filling part are respectively connected by a nasal base connecting bridge. Soft tissue fixation structures are respectively provided on the left nasal wing base filling portion and the right nasal wing base filling portion, the soft tissue fixation structures including: A fixation wing extends outward from the surface of the implant, and the fixation wing is provided with a through hole for suture material to pass through; And a microporous surface layer, disposed on at least one surface of the implant, having a pore size of 50 μm to 500 μm and a porosity of 20% to 60%.

8. The subperiosteal implant at the nasal alar base according to claim 7, characterized in that, The number of fixing wings is 2 to 6, which are symmetrically or asymmetrically distributed on the upper surface and / or side surface of the left nasal wing base filling part and the right nasal wing base filling part; each fixing wing extends outward from the implant surface for a length of 1 mm to 5 mm and a thickness of 0.5 mm to 2.0 mm; each fixing wing is provided with 1 to 3 through holes, and the diameter of the through holes is 0.3 mm to 1.5 mm.

9. The subperiosteal implant at the nasal alar base according to claim 7, characterized in that, The implant is selected from one of the following materials: silicone, expanded polytetrafluoroethylene, porous high-density polyethylene, hydroxyapatite, autologous rib cartilage or a combination thereof; the Shore A hardness of the implant is 20A to 80A.

10. A soft tissue suspension and fixation system for a subperiosteal implant at the base of the nasal alar, characterized in that, include: An implant having a surface provided with fixing wings and a microporous structure, the fixing wings extending outward from the surface of the implant, the fixing wings having through holes for suture material to pass through, and the microporous structure having a pore size of 50μm to 500μm and a porosity of 20% to 60%; Drug-loaded biodegradable sutures are used to suture and fix the fixation wings of the implant to the surrounding soft tissue. The drug-loaded biodegradable sutures have a core-shell composite structure, including a core layer and a shell layer wrapped around the outside of the core layer. The shell layer is loaded with angiogenesis factors, which are selected from at least one of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF), with a loading concentration of 0.5 μg / mL to 50 μg / mL. The surface of the implant is also provided with a drug reservoir groove, which is filled with a thermosensitive hydrogel loaded with an immunomodulator. The immunomodulator is selected from at least one of IL-4 or IL-10, and the loading concentration is 10 ng / mL to 500 ng / mL.

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