Multifunctional biological material with photoprotection and repair functions as well as preparation method and application of multifunctional biological material

Abstract

The invention discloses a multifunctional biological material with photoprotection and repair functions. The multifunctional biological material is prepared from the following components in percentage by mass: 4 to 8 percent of methacrylated gelatin, 0.5 to 2 percent of nano-micelle of ferulic acid, 0.5 to 1 percent of adhesion peptide, 0.5 to 1.5 percent of hyaluronic acid and 0.5 to 1 percent of Ectoine. The invention further discloses a preparation method and application of the multifunctional biological material. The multifunctional biological material disclosed by the invention realizes a three-in-one synergistic effect of'protection-repair-regeneration 'and targeted enrichment of active ingredients to damaged parts, can stimulate revascularization and improve skin microcirculation, has the functions of resisting oxidation, resisting inflammation and promoting healing, and promotes repair of skin with light injury.

Description

Technical Field

[0001] The present invention belongs to the field of skin repair, and specifically relates to a multifunctional biomaterial with light protection and repair functions, a preparation method and an application thereof. Background Art

[0002] Skin photoaging is mainly caused by ultraviolet (UV) radiation, and its pathological mechanism involves dual damage to the epidermis and dermis: UVB (290-320nm) has high energy but weak penetration, and mainly acts on the epidermis, inducing keratinocytes to release soluble mediators (such as proinflammatory cytokines and matrix metalloproteinases (MMPs), indirectly triggering ECM degradation in the dermis; UVA (320-400nm, especially UVA1 / 340-400nm) has strong penetration and can directly damage dermal fibroblasts, leading to mitochondrial DNA mutations and oxidative stress, and driving ECM remodeling imbalance by regulating fibroblast secretion.

[0003] Existing photoaging repair materials are mainly divided into the following two categories: (1) Barrier repair materials (such as hyaluronic acid and ceramide) improve barrier function by physically filling or enhancing epidermal hydration, but cannot inhibit the activity of MMPs in the epidermis or repair collagen fiber rupture; (2) Active repair materials (such as vitamin C and polyphenol antioxidants) reduce oxidative damage by scavenging free radicals or inhibiting inflammatory pathways, but are easily deactivated by photothermal degradation and lack direct regulation of the ECM synthesis ability of fibroblasts.

[0004] However, existing photoaging repair materials have the following disadvantages: (1) Single repair dimension: Most materials only focus on anti-oxidation or moisturizing, and lack synergistic intervention in the "UV signal transduction-MMPs activation-collagen degradation" pathway. For example: Although traditional sunscreens (such as titanium dioxide and zinc oxide) can physically block ultraviolet rays, they lack the ability to repair damaged skin barriers and cannot inhibit UV-induced matrix metalloproteinase (MMPs) activity. (2) Poor targeting: Active molecules (such as polyphenols and vitamins) are easily inactivated by environmental factors, making it difficult to target and regulate the function of dermal fibroblasts to promote extracellular matrix (ECM) regeneration, limiting their clinical application. For example, although antioxidant active ingredients (such as vitamin C derivatives and polyphenols) can neutralize free radicals, they have poor photostability and low transdermal efficiency. (3) Low delivery efficiency: Traditional carriers cannot achieve specific penetration into the dermis, resulting in limited repair efficacy. Existing delivery systems (such as liposome-encapsulated resveratrol) are difficult to simultaneously achieve broad-spectrum light protection (covering the entire UVA1 / UVB band), epidermal-dermal double-layer repair (barrier reconstruction and ECM remodeling), and long-term biological activity maintenance due to their complex ingredients and high costs, resulting in fragmented and unsustainable clinical efficacy.

[0005] Therefore, there is an urgent need to develop a multifunctional biomaterial with strong photostability, high transdermal targeting, UV shielding, anti-inflammatory, anti-oxidative stress and fibroblast regeneration activation, so as to break through the limitations of a single intervention strategy and provide a systematic repair solution for photoaging damage. Summary of the Invention

[0006] In view of the shortcomings of the existing technology, the present invention aims to provide a multifunctional integrated biomaterial to solve the following technical problems: (1) Design a material system with the triple functions of UV shielding (covering the entire UVA1 / UVB band), MMPs activity inhibition and activation of fibroblast regeneration, and achieve full-chain intervention from signal blocking, enzyme activity regulation to ECM remodeling. (2) Construct a targeted transdermal carrier (such as microneedles) and protect active molecules from environmental degradation through nanoencapsulation; at the same time, introduce a ROS response system for targeted transdermal treatment to improve the penetration efficiency of the ingredients into the epidermal barrier and the enrichment of damaged areas. (3) Develop a multifunctional carrier that integrates light protection, anti-inflammatory, antioxidant and promotion of ECM remodeling to achieve the dual-level needs of "barrier protection-dermal repair".

[0007] In order to achieve the above invention objectives, the present invention provides a multifunctional biomaterial with light protection and repair functions, which includes a microneedle tip component and a microneedle base component;

[0008] The microneedle tip component comprises, by mass volume percentage, 4-8% methacrylated gelatin, 0.5-2% ferulic acid, and 0.5-1% adhesive peptide hyaluronic acid complex.

[0009] Calculated by mass volume percentage, the microneedle base component includes 0.5% to 1.5% of hyaluronic acid and 0.5% to 1% of ectoine.

[0010] Preferably, the multifunctional biomaterial comprises the following components: the microneedle tip component comprises 8% methacryloyl gelatin, 1% ferulic acid and 1% adhesive peptide hyaluronic acid complex, and the microneedle base component comprises 1.5% hyaluronic acid and 1% ectoine.

[0011] Preferably, the methacrylated gelatin is prepared by the following steps:

[0012] 5.0 g of gelatin was weighed and added to 50 mL of PBS buffer. The solution was dissolved in a 50°C water bath under magnetic stirring until completely transparent. Subsequently, 3 mL of methacrylic anhydride was slowly added dropwise to the gelatin solution and magnetically stirred at 700 rpm for 1 hour. The reaction temperature was maintained at 50°C. After the reaction was completed, the reaction solution was transferred to a cellulose dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed in deionized water at a constant temperature of 40°C for 3 days to remove by-products. The dialyzed reaction solution was collected and centrifuged at 5000 rpm for 10 minutes to remove the precipitate. The supernatant was collected and freeze-dried at -80°C to obtain the final product, methacrylated gelatin GelMA.

[0013] Preferably, the ferulic acid is in the form of nanomicelles, and the ferulic acid nanomicelles are prepared by the following steps:

[0014] Step 1: Preparation of polypropylene sulfide PPS:

[0015] To 30 mL of anhydrous tetrahydrofuran, add 100 μL of 3-mercaptopropionic acid in an ice bath and mix thoroughly with magnetic stirring. Add 524 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene and stir under nitrogen for 30 minutes. Then, add 1.9 mL of propylene sulfide dropwise and stir at 60°C overnight. The reaction is quenched by adding 5 mL of H2O, purified by precipitation in cold methanol, and the solvent evaporated under reduced pressure to yield PPS as a yellow oil.

[0016] Step 2: Preparation of amination polypropylene sulfide PPS-NH2:

[0017] Add 158.6 mg of dried PPS to 20 mL of dichloromethane and dissolve under magnetic stirring. Add 23 mg of N-hydroxysuccinimide and 48 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and stir at room temperature for 30 min until dissolved. Then, add 133 μL of ethylenediamine dropwise to the mixture and continue stirring at room temperature overnight. Then, dilute the reaction solution with 20 mL of dichloromethane, wash with H2O and saturated NaCl, dry over MgSO4, and filter. Concentrate the solution under reduced pressure to obtain PPS-NH2, which is dried for later use.

[0018] Step 3: Preparation of hyaluronic acid-polypropylene sulfide complex PPS-HA:

[0019] Hyaluronic acid was dialyzed against a 0.01M HCl solution overnight and then freeze-dried to obtain acidic hyaluronic acid. 10mL of H2O and 100mg of acidic hyaluronic acid were added to a 50mL beaker and dissolved by magnetic stirring. 7mg of NHS and 14.5mg of EDC were then added and the mixture was stirred at room temperature for 30min until completely dissolved. 40mg of PPS-NH2 was dissolved in 1mL of tetrahydrofuran and added dropwise to the reaction system. The reaction was continued with stirring at room temperature under N2 protection for 24 hours. The solution was dialyzed against water / methanol at a volume ratio of 1:1 three times for one day and then against distilled water three times for one day. The solvent was removed by freeze-drying to obtain PPS-HA.

[0020] Step 4: Preparation of ferulic acid nanomicelles PPS-HA@FA:

[0021] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 10 mg of FA and dissolve it in 1 mL of acetone / ethanol solution; add the organic phase liquid to the aqueous phase, rotary evaporate for 3-5 minutes at 40°C, 45 rpm, ultrasonicate for 10 minutes, and filter through a 0.45 μm microporous membrane to obtain PPS-HA@FA.

[0022] Preferably, the adhesion peptide hyaluronic acid complex is prepared by the following steps:

[0023] 1 g of hyaluronic acid was weighed, added to 100 mL of pure water, and dissolved. 0.8 g of EDC was added to activate the carboxyl groups for 15 minutes, and then 1.2 g of NHS was added. After 15 minutes, the activated hyaluronic acid solution was added dropwise to 10 mL of 0.05 g / mL RGD solution, and then reacted at room temperature for 12 hours. After the reaction was completed, the solution was dialyzed in pure water for 3 days. The solution was frozen at -80°C for 12 hours and then lyophilized to obtain the adhesive peptide hyaluronic acid complex.

[0024] On the other hand, the present invention also provides a method for preparing the multifunctional biomaterial of the present invention, the method comprising the following steps:

[0025] The adhesive peptide hyaluronic acid complex and methacrylated gelatin are dissolved in deionized water to form a GM / HR solution; nano-micelles of ferulic acid are added to the GM / HR solution, and then LAP is added to the prepolymer solution. After mixing evenly, the mixture is dripped into a microneedle mold to fill the mold with the solution. Vacuum degassing is repeated multiple times to expel air from the mold and the solution; finally, the mixture is cured by ultraviolet light, and then a composite solution of hyaluronic acid and ectoine is added, followed by drying and demolding to obtain the multifunctional biomaterial.

[0026] Preferably, the composite solution of hyaluronic acid and ectoine is obtained by mixing the ectoine aqueous solution with the hyaluronic acid aqueous solution and stirring the mixture.

[0027] On the other hand, the present invention also provides the use of the multifunctional biomaterial of the present invention in the preparation of light protection and repair products.

[0028] Compared with the prior art, the present invention has the following advantages:

[0029] (1) Multiple mechanisms work together to achieve full-pathway photoaging intervention and realize the synergistic effect of the trinity of "protection-repair-regeneration".

[0030] (2) Through high stability and targeted delivery design, the utilization rate of ingredients is improved, and a dual loading structure is used to protect and target the release of ferulic acid, thereby achieving targeted enrichment of active ingredients to damaged areas.

[0031] (3) Epidermal-dermal double-layer repair, long-term maintenance of biological activity, using microneedle-shaped carriers to load ROS-responsive nanomicelles, which are released in a targeted manner in areas where ROS increases, while activating fibroblasts, rebuilding the collagen network, and stimulating angiogenesis to improve skin microcirculation.

[0032] (4) Integrate UV shielding, antioxidant, anti-inflammatory and healing functions to promote the repair of photodamaged skin. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 1 is an image of the appearance of the hydrogel microneedle according to an embodiment of the present invention.

[0034] Figure 2 The cumulative release rate of FA from the hydrogels of the examples of the present invention is shown.

[0035] Figure 3 The results of cell compatibility evaluation of the hydrogels according to the examples of the present invention are shown.

[0036] Figure 4 The results of the evaluation of the anti-inflammatory effect of the hydrogels of the examples of the present invention are shown. DETAILED DESCRIPTION

[0037] The present invention will be further described below with reference to specific examples. It should be understood that the following examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0038] Unless otherwise specified, the solvent of the solutions in the embodiments of the present invention is water.

[0039] 1. Preparation of methacrylated gelatin (GelMA):

[0040] First, 5.0 g of gelatin was weighed and added to 50 mL of PBS buffer. The solution was dissolved in a 50°C water bath with magnetic stirring until completely transparent. 3 mL of methacrylic anhydride was then slowly added dropwise to the gelatin solution. The solution was magnetically stirred at 700 rpm for 1 hour, maintaining the reaction temperature at 50°C. The reaction solution contained a large number of oily droplets. After the reaction was complete, the reaction solution was transferred to a cellulose dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed in deionized water at a constant temperature of 40°C for 3 days to remove by-products. The dialyzed reaction solution was collected and centrifuged at 5000 rpm for 10 minutes to remove the precipitate. The supernatant was collected and freeze-dried at -80°C to obtain the final product, GelMA.

[0041] 2. Preparation of ferulic acid nanomicelles (PPS-HA@FA)

[0042] (1) Preparation of polypropylene sulfide PPS

[0043] To 30 mL of anhydrous tetrahydrofuran in an ice bath, 100 μL (1.15 mmol) of 3-mercaptopropionic acid (3-MPA) was added and magnetically stirred to mix thoroughly. 524 μL (3.45 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene was then added, and the reaction mixture was stirred under nitrogen for 30 min. Then, 1.9 mL (21.15 mmol) of propylene sulfide was added dropwise, and the reaction mixture was stirred at 60°C overnight. The reaction was then quenched by adding 5 mL of HO, purified by precipitation in cold methanol, and the solvent evaporated under reduced pressure to yield PPS as a yellow oil.

[0044] (2) Preparation of amino polypropylene sulfide PPS-NH2

[0045] Add 158.6 mg (100 μmol) of dried PPS to 20 mL of dichloromethane and dissolve under magnetic stirring. Add 23 mg (200 μmol) of N-hydroxysuccinimide (NHS) and 48 mg (250 μmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and stir at room temperature for 30 minutes until dissolved. Then, add 133 μL (2 mmol) of ethylenediamine dropwise to the mixture and continue stirring at room temperature overnight. Afterwards, dilute the reaction solution with 20 mL of dichloromethane, wash with H2O and saturated NaCl, dry over MgSO4, and filter. Concentrate the solution under reduced pressure to obtain PPS-NH2, which is then dried for later use.

[0046] (3) Preparation of hyaluronic acid-polypropylene sulfide complex (PPS-HA)

[0047] Hyaluronic acid was dialyzed overnight against a 0.01M HCl solution and then lyophilized to obtain acidic hyaluronic acid. To a 50mL beaker, add 10mL of H2O and 100mg of acidic hyaluronic acid (HA) and dissolve under magnetic stirring. Then, add 7mg (60μmol) of NHS and 14.5mg (75μmol) of EDC, and stir the mixture at room temperature for 30 minutes until completely dissolved. Dissolve 40mg of PPS-NH2 in 1mL of tetrahydrofuran and add dropwise to the reaction system. Stir and react at room temperature under N2 protection for 24 hours. Dialyze the solution three times against water / methanol at a 1:1 volume ratio for one day, then three times against distilled water for one day. Remove the solvent by lyophilization to obtain PPS-HA.

[0048] (4) Preparation of PPS-HA@FA

[0049] PPS-HA was dissolved in PBS; FA was dissolved in acetone / ethanol solution (volume ratio 3:2); the organic phase liquid was added to the aqueous phase (added under stirring, using a rotary evaporator), rotary evaporated for 3-5 minutes (40°C, 45rpm), ultrasonicated for 10 minutes, and filtered through a 0.45um microporous filter membrane to obtain PPS-HA@FA nanomicelles.

[0050] 3. Preparation of Adhesion Peptide Hyaluronic Acid Complex (HA-RGD)

[0051] Weigh 1g of hyaluronic acid and add 100mL of pure water. Once dissolved, add 0.8g of EDC to activate the carboxyl groups for 15 minutes. Then, add 1.2g of NHS. After 15 minutes, slowly add the activated hyaluronic acid solution dropwise to a 10mL, 0.05g / mL RGD solution. The solution is then allowed to react at room temperature for 12 hours. After the reaction is complete, the solution is placed in a dialysis bag (molecular weight cutoff: 2000Da) and dialyzed in pure water for 3 days. The solution is frozen at -80°C for 12 hours and then lyophilized to obtain HA-RGD.

[0052] 4. Preparation of microneedle-based hyaluronic acid and ectoine complex HA@ECT

[0053] Weigh 0.1-0.2g of ectoine and dissolve it in 10mL of distilled water. Stir on a magnetic stirrer to ensure that the ectoine is completely dissolved. Weigh 0.1-0.3g of hyaluronic acid and dissolve it in 10mL of distilled water. Stir on a magnetic stirrer to ensure that the HA is completely dissolved. Mix the prepared ectoine solution and hyaluronic acid solution in a 1:1 volume ratio. Stir the mixture on a magnetic stirrer for 2-4 hours to obtain the HA@ECT solution.

[0054] 5. Preparation of GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles

[0055] HA-RGD and methacrylated gelatin were dissolved in deionized water to form a GM / HR solution. PPS-HA@FA nanomicelles were added to the GM / HR solution, and LAP was then added to the prepolymer solution to a final concentration of 0.2%. After uniform mixing, the mixture was dripped into a polydimethylsiloxane microneedle mold, which was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured by UV light (365 nm). The HA@ECT solution was then added to the mold in multiple steps: after each addition, some water evaporated, and then additional additions, approximately 300 μL each time, were added until the microneedle base was completely filled in a dry environment (solid). The mold was then dried at 37°C for 72 hours and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0056] Example 1:

[0057] 10 mg of HA-RGD and 160 mg of methacryloyl gelatin (GelMA) were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0058] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 10 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 10 mg / mL.

[0059] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0060] Weigh 0.1 g of ectoine (ECT) and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.1 g of hyaluronic acid (HA) and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution and hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0061] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0062] The hydrogel microneedle of the embodiment of the present invention has the following appearance: Figure 1 shown.

[0063] Example 2:

[0064] 20 mg of HA-RGD and 80 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0065] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 20 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 20 mg / mL.

[0066] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0067] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.1 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0068] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0069] Example 3:

[0070] 20 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0071] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 0.04 g of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 40 mg / mL.

[0072] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0073] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.1 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0074] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0075] Example 4:

[0076] 10 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0077] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 10 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 10 mg / mL.

[0078] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0079] Weigh 0.1 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.2 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0080] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0081] Example 5:

[0082] 20 mg of HA-RGD and 80 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0083] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 20 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 20 mg / mL.

[0084] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0085] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.2 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0086] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0087] Example 6:

[0088] 20 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0089] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 20 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 20 mg / mL.

[0090] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0091] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.3 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0092] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0093] Example 7:

[0094] 10 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0095] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 10 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 10 mg / mL.

[0096] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0097] Weigh 0.1 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.3 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0098] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0099] Example 8:

[0100] 20 mg of HA-RGD and 80 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0101] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 20 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 20 mg / mL.

[0102] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0103] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.3 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0104] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0105] Example 9:

[0106] 20 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0107] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 0.04 g of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 40 mg / mL.

[0108] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0109] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.3 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0110] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0111] Comparative Example 1:

[0112] 20 mg of HA-RGD and 160 mg of methacryloyl gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution.

[0113] Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 20 mg of FA and dissolve it in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add under stirring, using a rotary evaporator), rotary evaporate for 3-5 minutes (40°C, 45 rpm), ultrasonicate for 10 minutes, and pass through a 0.45 um microporous filter membrane to obtain PPS-HA@FA nanomicelles with a FA content of 20 mg / mL.

[0114] 1 mL of PPS-HA@FA nanomicelles was added to the GM / HR solution to obtain a prepolymer solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm).

[0115] Weigh 0.2 g of ectoine and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the ectoine. Weigh 0.3 g of hyaluronic acid and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure complete dissolution of the HA. Mix the prepared ectoine solution with the hyaluronic acid solution in a 1:1 ratio and continue stirring on a magnetic stirrer overnight to obtain the HA@ECT solution.

[0116] Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0117] Comparative Example 2:

[0118] 20 mg of HA-RGD and 160 mg of methacryloyl-gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution. 0.2% LAP was then added to the prepolymer solution, mixed thoroughly, and then dripped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. The vacuum level in the chamber was then adjusted to -100 kPa to fill the mold with the solution. Vacuum degassing was repeated several times to expel air from the mold and the solution. Finally, the composite prepolymer solution was cured using UV light (365 nm). 0.15 g of hyaluronic acid was weighed and dissolved in 10 mL of distilled water. Stirring was performed on a magnetic stirrer to ensure complete dissolution of the HA. The prepared ectoine solution and hyaluronic acid solution were then mixed in a 1:1 ratio and stirred overnight on a magnetic stirrer to obtain the HA@ECT solution. Subsequently, HA@ECT solution was added to the mold until the microneedle mold was filled (usually 3 to 4 mL), dried at 37°C for 72 h, and demolded to obtain GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles.

[0119] Performance Testing

[0120] 1. Mechanical properties of microneedles

[0121] Test Method: Place the microneedle specimen on the sample stage with the tip pointing upward. Adjust the sample stage height so that both the upper and lower surfaces are in contact with the fixture. Compress at a constant rate of 0.05 mm / s, recording the compression displacement (L) and load (P) until the desired displacement endpoint is reached. The mechanical strength of a single needle is the ratio of the load to the number of needle tips.

[0122] The test results are shown in Table 1.

[0123] Table 1: Single needle mechanical strength values

[0124] Grouping Mechanical strength Example 1 0.35±0.15N Example 2 0.13±0.14N Example 3 0.40±0.09N Example 4 0.35±0.13N Example 5 0.12±0.08N Example 6 0.40±0.14N Example 7 0.35±0.24N Example 8 0.14±0.11N Example 9 0.38±0.16N Comparative Example 1 0.37±0.19N Comparative Example 2 0.37±0.07N

[0125] As shown in Table 1, a too low concentration of methacrylated gelatin compromises the stability of the three-dimensional network structure within the needle tip and hinders molding. Literature research indicates that a single needle mechanical strength greater than 0.2N ensures epidermal penetration. Examples 2, 5, and 8 all failed to meet this requirement.

[0126] 2. UVA / UVB transmittance

[0127] The hydrogel was prepared into a uniform circular sheet with a diameter of 4 mm and a thickness of approximately 1 mm and was equilibrated in PBS for 24 h. Excess surface water was gently removed with absorbent paper before testing.

[0128] Each hydrogel sample was sandwiched between two quartz glass slides and placed vertically in the spectrophotometer's colorimetric cell. The scanning wavelength range was set to 200 to 800 nm with a 1 nm step size. A quartz glass slide without hydrogel served as a blank control, with transmittance set to 100%. The transmittance (T%) at specific wavelengths, including 280 nm, 320 nm, 365 nm, and 400 nm, was recorded and compared between different groups of samples. All tests were performed at room temperature.

[0129] Table 2: UV transmittance analysis

[0130]

[0131] As can be seen from Table 2, ECT and PPS-HA@FA have obvious UV shielding effects, and the two have a synergistic effect.

[0132] 3. Release of FA

[0133] Test method: The hydrogel was placed in 1 mL of sterile PBS solution and incubated in a constant temperature shaking incubator at 37°C and 100 rpm. Samples were taken at different time points (1, 3, 6, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours). 1 mL of the culture medium was removed and replaced with an equal amount of fresh PBS. The sample was centrifuged at 4000 rpm for 5 minutes. The absorbance of ferulic acid in PBS solution was measured using UV spectrophotometry at an excitation wavelength of 325 nm.

[0134] The cumulative release rate is calculated as follows:

[0135] Cumulative release rate (%) = (cumulative drug release amount / dose) × 100%

[0136] Figure 2 The cumulative release rate of FA from the hydrogel of Example 6 is shown. Figure 2 As shown, when FA is loaded into PPS-HA@FA and dispersed in GelMA hydrogel, drug release proceeds in two distinct phases: rapid release within the first 24 hours, with approximately 45.19% of the drug released. Thereafter, the drug release rate gradually slows, reaching a cumulative release of 74.33% at 72 hours and 93.54% at 216 hours. The initial rapid release is likely due to the drug molecules being loosely adsorbed on or near the surface of the nanomicelles, allowing them to easily diffuse into the external environment. Furthermore, the hydrogel material rapidly swells upon contact with liquid, accelerating initial drug release. Over time, the drug is slowly released from deep within the nanomicelles, and the release rate gradually slows. The hydrogel's network structure delays drug release. The rapid early release provides sufficient drug concentration for rapid therapeutic effects, while the slower later release maintains the drug's long-lasting effects. This demonstrates that the PPS-HA@FA and GelMA hydrogel composite material of the present invention exhibits excellent sustained-release properties.

[0137] The relevant experimental results show that compared with comparative examples 1-2, the hydrogels of examples 1-5 and 7-9 also have good sustained-release properties.

[0138] 4. Antioxidant capacity test

[0139] Test Method: The antioxidant properties of various examples and comparative examples were evaluated using a 1,1-diphenyl-2-pyridylhydrazine (DPPH) free radical scavenging method. A mixture of the various examples and comparative examples with a DPPH reagent was incubated in the dark with stirring for 30 minutes. The residual DPPH was analyzed using UV-visible spectroscopy.

[0140] The formula for determining the clearance rate of DPPH is:

[0141] D (%) = [[A blank - (A measurement - A control)] / A blank] × 100%

[0142] Table 3: Antioxidant capacity analysis

[0143]

[0144] like Figure 3 As shown, the efficiency of free radical scavenging increases with the increase of FA, indicating that FA can be effectively released from PPS-HA, effectively scavenging free radicals and having a better antioxidant effect. In addition, it can be seen that the free radical scavenging efficiency at a FA content of 0.5% is comparable to that at 1%, indicating that a FA content of 0.5% already has strong free radical scavenging ability.

[0145] 5. Cytocompatibility evaluation

[0146] Test method: The cultured BMSCs cells were digested with 0.25% trypsin and resuspended at a density of 1×10 5 The cell suspension of 100 μL / mL was quickly mixed with the sterilized hydrogel, printed in a 3D printer, placed in a 24-well plate, and continued to be cultured with α-MEM complete medium. Each group has at least 3 wells. CCK8 was used to quantitatively analyze the cell survival rate. After 24 hours of culture, the well plate was removed, 300 μL of CCK8 working solution was added to each well, and the 3D printed scaffold was broken up as much as possible by blowing with a pipette tip. After incubation in a 37°C constant temperature carbon dioxide incubator (containing 5% CO2) for 1 to 2 hours, the absorbance (OD) was measured at a wavelength of 450 nm using a microplate reader, and the cell survival rate was calculated according to the formula:

[0147]

[0148] Figure 3 The results of the cytocompatibility evaluation are shown. As shown, the hydrogels showed no cytotoxicity, with cell viability exceeding 90% and even exceeding 100%. This indicates that the prepared hydrogel scaffolds have no significant cytotoxicity and can promote cell proliferation to a certain extent.

[0149] 6. Anti-inflammatory evaluation:

[0150] Test method: 8-week-old female C57BL / 6J mice were randomly divided into experimental and control groups. The hair on the back of the mice was first removed with a shaver. Ultraviolet irradiation was started 24 hours after shaving. A UVB light source (wavelength 280–320 nm) was used, with an initial dose of 60 mJ / cm 2 , gradually increasing to 180mJ / cm 2, irradiated continuously for 8 weeks, 5 times a week. After each irradiation, the skin surface was covered with moist gauze to maintain moisture and reduce acute light damage. The criteria for judging the success of the modeling include visible light aging characteristics such as skin thickening, wrinkle formation and pigmentation. After the model was established, according to the experimental design, the corresponding treatment material (such as PBS, drug solution or hydrogel) was applied to the photoaged area daily, and the intervention lasted for 7–14 days. After the treatment, the mice were killed and the skin tissue of the dorsal light-exposed area was obtained. The content of inflammatory factors in skin tissue homogenate or serum was detected using a commercial enzyme-linked immunosorbent assay (ELISA) kit, and the operation was carried out according to the manufacturer's instructions.

[0151] Figure 4 The results of the anti-inflammatory effect evaluation are shown. Figure 4 It can be seen that compared with the normal saline group and the comparative example 1 group, the hydrogel of Example 6 can effectively reduce the expression levels of inflammatory factors TNF-α, IL-6, and IL-1β, and provide a stable microenvironment for the repair tissue of photoaged tissue.

[0152] The relevant experimental results show that compared with comparative examples 1-2, the hydrogels of Examples 1-5 and 7-9 also effectively reduce the expression levels of inflammatory factors TNF-α, IL-6, and IL-1β, and have good anti-inflammatory effects.

Claims

1. A multifunctional biomaterial with light protection and repair functions, characterized in that: It includes a microneedle tip component and a microneedle base component; The microneedle tip component comprises, by mass volume percentage, 4-8% methacrylated gelatin, 0.5-2% ferulic acid, and 0.5-1% adhesive peptide hyaluronic acid complex. Calculated by mass volume percentage, the microneedle base component includes 0.5% to 1.5% of hyaluronic acid and 0.5% to 1% of ectoine.

2. The multifunctional biomaterial according to claim 1, characterized in that The microneedle tip component includes 8% methacryloyl gelatin, 1% ferulic acid and 1% adhesive peptide hyaluronic acid complex, and the microneedle base component includes 1.5% hyaluronic acid and 1% ectoine.

3. The multifunctional biomaterial according to claim 1 or 2, characterized in that: The methacrylated gelatin is prepared by the following steps: 5.0 g of gelatin was weighed and added to 50 mL of PBS buffer. The solution was dissolved in a 50°C water bath under magnetic stirring until completely transparent. Subsequently, 3 mL of methacrylic anhydride was slowly added dropwise to the gelatin solution and magnetically stirred at 700 rpm for 1 hour. The reaction temperature was maintained at 50°C. After the reaction was completed, the reaction solution was transferred to a cellulose dialysis bag with a molecular weight cutoff of 3500 Da and dialyzed in deionized water at a constant temperature of 40°C for 3 days to remove by-products. The dialyzed reaction solution was collected and centrifuged at 5000 rpm for 10 minutes to remove the precipitate. The supernatant was collected and freeze-dried at -80°C to obtain the final product, methacrylated gelatin GelMA.

4. The multifunctional biomaterial according to claim 1 or 2, characterized in that: The ferulic acid is in the form of nanomicelles, and the ferulic acid nanomicelles are prepared by the following steps: Step 1: Preparation of polypropylene sulfide PPS: To 30 mL of anhydrous tetrahydrofuran, add 100 μL of 3-mercaptopropionic acid in an ice bath and mix thoroughly with magnetic stirring. Add 524 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene and stir under nitrogen for 30 minutes. Then, add 1.9 mL of propylene sulfide dropwise and stir at 60°C overnight. The reaction is quenched by adding 5 mL of H2O, purified by precipitation in cold methanol, and the solvent evaporated under reduced pressure to yield PPS as a yellow oil. Step 2: Preparation of amination polypropylene sulfide PPS-NH2: Add 158.6 mg of dried PPS to 20 mL of dichloromethane and dissolve under magnetic stirring. Add 23 mg of N-hydroxysuccinimide and 48 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and stir at room temperature for 30 min until dissolved. Then, add 133 μL of ethylenediamine dropwise to the mixture and continue stirring at room temperature overnight. Then, dilute the reaction solution with 20 mL of dichloromethane, wash with H2O and saturated NaCl, dry over MgSO4, and filter. Concentrate the solution under reduced pressure to obtain PPS-NH2, which is dried for later use. Step 3: Preparation of hyaluronic acid-polypropylene sulfide complex PPS-HA: Hyaluronic acid was dialyzed against a 0.01M HCl solution overnight and then freeze-dried to obtain acidic hyaluronic acid. 10mL of H2O and 100mg of acidic hyaluronic acid were added to a 50mL beaker and dissolved by magnetic stirring. 7mg of NHS and 14.5mg of EDC were then added and the mixture was stirred at room temperature for 30min until completely dissolved. 40mg of PPS-NH2 was dissolved in 1mL of tetrahydrofuran and added dropwise to the reaction system. The reaction was continued with stirring at room temperature under N2 protection for 24 hours. The solution was dialyzed against water / methanol at a volume ratio of 1:1 three times for one day and then against distilled water three times for one day. The solvent was removed by freeze-drying to obtain PPS-HA. Step 4: Preparation of ferulic acid nanomicelles PPS-HA@FA: Take 5 mg of PPS-HA and dissolve it in 4 mL of PBS; take 10 mg of FA and dissolve it in 1 mL of acetone / ethanol solution; add the organic phase liquid to the aqueous phase, rotary evaporate for 3-5 minutes at 40°C, 45 rpm, ultrasonicate for 10 minutes, and filter through a 0.45 μm microporous membrane to obtain PPS-HA@FA.

5. The multifunctional biomaterial according to claim 1 or 2, characterized in that: The adhesive peptide hyaluronic acid complex is prepared by the following steps: 1 g of hyaluronic acid was weighed, added to 100 mL of pure water, and dissolved. 0.8 g of EDC was added to activate the carboxyl groups for 15 minutes, and then 1.2 g of NHS was added. After 15 minutes, the activated hyaluronic acid solution was added dropwise to 10 mL of 0.05 g / mL RGD solution, and then reacted at room temperature for 12 hours. After the reaction was completed, the solution was dialyzed in pure water for 3 days. The solution was frozen at -80°C for 12 hours and then lyophilized to obtain the adhesive peptide hyaluronic acid complex.

6. The method for preparing the multifunctional biomaterial according to any one of claims 1 to 5, characterized in that: The method comprises the following steps: The adhesive peptide hyaluronic acid complex and methacrylated gelatin are dissolved in deionized water to form a GM / HR solution; nano-micelles of ferulic acid are added to the GM / HR solution, and then LAP is added to the prepolymer solution. After mixing evenly, the mixture is dripped into a microneedle mold to fill the mold with the solution. Vacuum degassing is repeated multiple times to expel air from the mold and the solution; finally, the mixture is cured by ultraviolet light, and then a composite solution of hyaluronic acid and ectoine is added, followed by drying and demolding to obtain the multifunctional biomaterial.

7. The method according to claim 6, characterized in that The composite solution of hyaluronic acid and ectoine is obtained by mixing the ectoine aqueous solution and the hyaluronic acid aqueous solution and stirring the mixture.

8. Use of the multifunctional biomaterial according to any one of claims 1 to 5 in the preparation of light protection and repair products.

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