Multifunctional biomaterial with photoprotection and repair functions and preparation method and application thereof

Abstract

The application discloses a multifunctional biomaterial with light protection and repair functions, which comprises the following components in percentage by mass: 4-8% of methacrylated gelatin, 0.5-2% of nanomicelles of ferulic acid, 0.5-1% of adhesive peptides, 0.5-1.5% of hyaluronic acid and 0.5-1% of ekdromicin. The application further discloses a preparation method of the multifunctional biomaterial and application thereof. The multifunctional biomaterial realizes a trinity synergistic effect of 'protection-repair-regeneration', target enrichment of active ingredients to damaged parts, and can stimulate vascular regeneration, improve skin microcirculation, has antioxidant, anti-inflammatory and healing functions, and promotes repair of light-damaged skin.

Description

Technical Field

[0001] This invention belongs to the field of skin repair, specifically relating to a multifunctional biomaterial with photoprotection and repair functions, its preparation method, and its application. Background Technology

[0002] Photoaging of the skin is mainly caused by ultraviolet (UV) radiation. Its pathological mechanism involves dual damage to the epidermis and dermis: UVB (290-320 nm) has high energy but weak penetration. It mainly acts on the epidermis and indirectly causes ECM degradation in the dermis by inducing keratinocytes to release soluble mediators (such as pro-inflammatory cytokines and matrix metalloproteinases MMPs); UVA (320-400 nm, especially UVA1 / 340-400 nm) 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 epidermal MMPs or repair collagen fiber breakage; (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 degraded and inactivated by photothermal degradation, and lack direct regulation of fibroblast ECM synthesis capacity.

[0004] However, existing photoaging repair materials have the following drawbacks: (1) Single repair dimension: Most materials only focus on anti-oxidation or moisturizing, lacking synergistic intervention on the "UV signal transduction-MMP activation-collagen degradation" pathway. For example, traditional sunscreens (such as titanium dioxide and zinc oxide) can physically block ultraviolet rays, but lack the ability to repair damaged skin barriers and cannot inhibit UV-induced matrix metalloproteinase (MMP) 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, thus limiting their clinical application. For example, antioxidant active ingredients (such as vitamin C derivatives and polyphenols) can neutralize free radicals, but their photostability is poor and their transdermal efficiency is low. (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 complex in composition and expensive, making it difficult to simultaneously achieve broad-spectrum photoprotection (covering the entire UVA1 / UVB band), epidermal-dermal dual-layer repair (barrier reconstruction and ECM remodeling), and long-term maintenance of bioactivity, resulting in fragmented and unsustainable clinical efficacy.

[0005] Therefore, there is an urgent need to develop a multifunctional biomaterial that is highly photostable, has high transdermal targeting, and combines UV shielding, anti-inflammatory, antioxidant stress, and fibroblast regeneration activation to overcome the limitations of single intervention strategies and provide a systematic repair solution for photoaging damage. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention aims to provide a multifunctional integrated biomaterial to solve the following technical problems: (1) Designing a material system with synergistic functions of UV shielding (covering the entire UVA1 / UVB band), MMP activity inhibition, and fibroblast regeneration activation, achieving full-chain intervention from signal blocking, enzyme activity regulation to ECM remodeling. (2) Constructing targeted transdermal carriers (such as microneedles) and protecting active molecules from environmental degradation through nano-encapsulation; simultaneously introducing ROS-responsive systems for targeted transdermal therapy to improve the penetration efficiency of components to the epidermal barrier and the enrichment of damaged sites. (3) Developing multifunctional carriers that integrate photoprotection, anti-inflammation, anti-oxidation, and ECM remodeling promotion to achieve the dual-level needs of "barrier protection-dermal repair".

[0007] To achieve the above-mentioned objectives, this invention provides a multifunctional biomaterial with photoprotection and repair functions, comprising a microneedle tip component and a microneedle base component;

[0008] The microneedle tip component, by weight-volume percentage, comprises 4-8% methacrylamide gelatin, 0.5-2% ferulic acid, and 0.5-1% an adhesion peptide-hyaluronic acid complex.

[0009] The microneedle base component comprises 0.5% to 1.5% hyaluronic acid and 0.5% to 1% ectoine by weight-volume percentage.

[0010] Preferably, the multifunctional biomaterial comprises the following components: the microneedle tip component comprises 8% methacrylamide 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 methacrylamide gelatin is prepared by the following steps:

[0012] Weigh 5.0 g of gelatin and add it to 50 mL of PBS buffer. Dissolve the gelatin in a 50°C water bath with magnetic stirring until completely transparent. Then, slowly add 3 mL of methacrylic anhydride to the gelatin solution and stir magnetically at 700 rpm for 1 hour, maintaining the reaction temperature at 50°C. After the reaction is complete, transfer the reaction solution to a cellulose dialysis bag with a molecular weight cutoff of 3500 Da and dialyze it in deionized water at 40°C for 3 days to remove byproducts. Collect the dialyzed reaction solution, centrifuge at 5000 rpm for 10 minutes to remove the precipitate, collect the supernatant, and freeze-dry it at -80°C to obtain the final product, methacrylamide 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] Under ice bath conditions, 100 μL of 3-mercaptopropionic acid was added to 30 mL of anhydrous tetrahydrofuran and mixed magnetically. Then, 524 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, and the reaction mixture was stirred for 30 min under a nitrogen atmosphere. Next, 1.9 mL of propylene sulfide was added dropwise, and the reaction mixture was stirred overnight at 60 °C. Afterward, the reaction was quenched by adding 5 mL of H₂O, purified by precipitation in cold methanol, and the solvent was evaporated under reduced pressure to obtain a yellow oily PPS.

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

[0017] 158.6 mg of dried PPS was added to 20 mL of dichloromethane and dissolved by magnetic stirring. Then, 23 mg of N-hydroxysuccinimide and 48 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide were added, and the mixture was stirred at room temperature for 30 min until dissolved. Next, 133 μL of ethylenediamine was added dropwise to the mixture, and stirring was continued overnight at room temperature. Afterward, 20 mL of dichloromethane was added to dilute the reaction solution, which was washed successively with H2O and saturated NaCl, dried over MgSO4, and filtered. The solution was concentrated under reduced pressure to obtain PPS-NH2, which was then dried for later use.

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

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

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

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

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

[0023] Weigh 1 g of hyaluronic acid, add 100 mL of pure water, dissolve completely, add 0.8 g of EDC, activate the carboxyl group for 15 min, then add 1.2 g of NHS, and after 15 min, add the activated hyaluronic acid solution dropwise to 10 mL of RGD solution with a concentration of 0.05 g / mL, and then react at room temperature for 12 hours; after the reaction is complete, dialyze the solution in pure water for 3 days; freeze the solution at -80°C for 12 hours and then freeze dry 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 described herein, the method comprising the following steps:

[0025] Adhesive peptide hyaluronic acid complex and methacrylamide gelatin were dissolved in deionized water to form a GM / HR solution. Ferulic acid nanomicelles were added to the GM / HR solution, and then LAP was added to the prepolymer solution. After mixing evenly, the mixture was dropped into a microneedle mold to fill the mold with solution. Vacuum degassing was repeated several times to remove air from the mold and solution. Finally, the mixture was cured with ultraviolet light, followed by the addition of a composite solution of hyaluronic acid and ectoine. After drying and demolding, the multifunctional biomaterial was obtained.

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

[0027] On the other hand, the present invention also provides the application of the multifunctional biomaterials described herein in the preparation of photoprotective and repair products.

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

[0029] (1) Multi-mechanism synergy enables full-pathway photoaging intervention, achieving a synergistic effect of “protection-repair-regeneration”.

[0030] (2) Through high stability and targeted delivery design, the utilization rate of ingredients is improved. The dual load structure protects and targets the release of ferulic acid, so as to achieve targeted enrichment of active ingredients to damaged sites.

[0031] (3) Epidermal-dermal dual-layer repair, long-term maintenance of biological activity. The carrier in the form of microneedles loads ROS-responsive nanomicelles, which are targeted and released in areas where ROS increases. At the same time, it activates fibroblasts, rebuilds collagen network, stimulates angiogenesis, and improves skin microcirculation.

[0032] (4) It integrates UV shielding, anti-oxidation, anti-inflammation and healing functions to promote the repair of photodamaged skin. Attached Figure Description

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

[0034] Figure 2 The cumulative FA release rate of the hydrogel in an embodiment of the present invention is shown.

[0035] Figure 3 The cell compatibility evaluation results of the hydrogels in embodiments of the present invention are shown.

[0036] Figure 4 The anti-inflammatory effect evaluation results of the hydrogel of the present invention are shown. Detailed Implementation

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

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

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

[0040] First, 5.0 g of gelatin was weighed and added to 50 mL of PBS buffer. The solution was dissolved until completely transparent under magnetic stirring in a 50°C water bath. Then, 3 mL of methacrylic anhydride was slowly added dropwise to the gelatin solution, and the mixture 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 40°C for 3 days to remove byproducts. The dialyzed reaction solution was collected, centrifuged at 5000 rpm for 10 minutes to remove the precipitate, and 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] Under ice bath conditions, 100 μL (1.15 mmol) of 3-mercaptopropionic acid (3-MPA) was added to 30 mL of anhydrous tetrahydrofuran and mixed magnetically. Then, 524 μL (3.45 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, and the reaction mixture was stirred for 30 min under a nitrogen atmosphere. Next, 1.9 mL (21.15 mmol) of propylene sulfide was added dropwise, and the reaction mixture was stirred overnight at 60 °C. Subsequently, the reaction was quenched by adding 5 mL of H₂O, purified by precipitation in cold methanol, and the solvent was evaporated under reduced pressure to obtain a yellow oily PPS.

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

[0045] 158.6 mg (100 μmol) of dried PPS was added to 20 mL of dichloromethane and dissolved by magnetic stirring. Then, 23 mg (200 μmol) of N-hydroxysuccinimide (NHS) and 48 mg (250 μmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) were added, and the mixture was stirred at room temperature for 30 min until dissolved. Next, 133 μL (2 mmol) of ethylenediamine was added dropwise to the mixture, and stirring was continued overnight at room temperature. Afterward, 20 mL of dichloromethane was added to dilute the reaction solution, which was washed successively with H₂O and saturated NaCl, dried over MgSO₄, and filtered. The solution was concentrated under reduced pressure to obtain PPS-NH₂, which was then dried for later use.

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

[0047] Hyaluronic acid was dialyzed overnight in 0.01 M HCl solution and then lyophilized to obtain acidic hyaluronic acid. 10 mL of H₂O and 100 mg of acidic hyaluronic acid (HA) were added to a 50 mL beaker and dissolved by magnetic stirring. Then, 7 mg (60 μmol) of NHS and 14.5 mg (75 μol) of EDC were added, and the mixture was stirred at room temperature for 30 min until completely dissolved. 40 mg of PPS-NH₂ was dissolved in 1 mL of tetrahydrofuran and added dropwise to the reaction system. The reaction was continued with stirring for 24 hours at room temperature under N₂ protection. The mixture was dialyzed three times with water / methanol at a 1:1 volume ratio, for one day each time, followed by three times with distilled water, for one day each time. The solvent was removed 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 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous membrane to obtain PPS-HA@FA nanomicelles.

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

[0051] Weigh 1 g of hyaluronic acid and add it to 100 mL of pure water. After dissolving, add 0.8 g of EDC and activate the carboxyl groups for 15 min. Then add 1.2 g of NHS and after 15 min, slowly add the activated hyaluronic acid solution dropwise to the RGD solution (10 mL, 0.05 g / mL). React at room temperature for 12 hours. After the reaction is complete, transfer the solution to a dialysis bag (molecular weight cutoff: 2000 Da) and dialyze it in pure water for 3 days. Freeze the solution at -80°C for 12 hours and then lyophilize it to obtain HA-RGD.

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

[0053] Weigh 0.1-0.2 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 0.1-0.3 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 and hyaluronic acid solution at a 1:1 volume ratio and 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 methacrylamide gelatin were dissolved in deionized water to form a GM / HR solution. PPS-HA@FA nanomicelles were added to the GM / HR solution, and then LAP was added to the prepolymer solution to a final concentration of 0.2%. After thorough mixing, the solution was dropped into a polydimethylsiloxane microneedle mold and transferred to an acrylic vacuum degassing chamber. The vacuum level in the degassing chamber was then adjusted to -100 kPa to fill the mold with the solution, and vacuum degassing was repeated several times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet light (365 nm), and then HA@ECT solution was added to the mold (added in multiple batches: after each addition, some water evaporated, and then more was added, approximately 300 μL each time (in liquid form, filling the microneedle mold), until the microneedle substrate was completely filled in a dry environment (in solid form, filling the microneedle mold)). The solution was dried at 37°C for 72 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0056] Example 1:

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

[0058] Dissolve 5 mg of PPS-HA in 4 mL of PBS; dissolve 10 mg of FA in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add while stirring, using a rotary evaporator), rotary evaporate for 3-5 min (40℃, 45 rpm), sonicate for 10 min, and filter through a 0.45 μm microporous membrane to obtain PPS-HA@FA nanomicelles with an FA content of 10 mg / mL.

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

[0060] Weigh 0.1g of ectoine (ECT) and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure the ectoine is completely dissolved. Weigh 0.1g of hyaluronic acid (HA) and dissolve it in 10 mL of distilled water. Stir on a magnetic stirrer to ensure the HA is completely dissolved. Mix the prepared ectoine solution and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0062] The appearance of the hydrogel microneedles in this embodiment of the invention is as follows: Figure 1 As shown.

[0063] Example 2:

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

[0065] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 20 mg of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0069] Example 3:

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

[0071] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 0.04 g of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0075] Example 4:

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

[0077] Dissolve 5 mg of PPS-HA in 4 mL of PBS; dissolve 10 mg of FA in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add while stirring, using a rotary evaporator), rotary evaporate for 3-5 min (40℃, 45 rpm), sonicate for 10 min, and filter through a 0.45 μm microporous membrane to obtain PPS-HA@FA nanomicelles with an FA content of 10 mg / mL.

[0078] 1 mL of PPS-HA@FA nanomicelles was added to a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0081] Example 5:

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

[0083] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 20 mg of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0087] Example 6:

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

[0089] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 20 mg of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0093] Example 7:

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

[0095] Dissolve 5 mg of PPS-HA in 4 mL of PBS; dissolve 10 mg of FA in 1 mL of acetone / ethanol solution (3:2); add the organic phase liquid to the aqueous phase (add while stirring, using a rotary evaporator), rotary evaporate for 3-5 min (40℃, 45 rpm), sonicate for 10 min, and filter through a 0.45 μm microporous membrane to obtain PPS-HA@FA nanomicelles with an FA content of 10 mg / mL.

[0096] 1 mL of PPS-HA@FA nanomicelles was added to a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0099] Example 8:

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

[0101] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 20 mg of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0105] Example 9:

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

[0107] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 0.04 g of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0111] Comparative Example 1:

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

[0113] 5 mg of PPS-HA was dissolved in 4 mL of PBS; 20 mg of FA was dissolved in 1 mL of acetone / ethanol solution (3:2); the organic phase liquid was added to the aqueous phase (with stirring, using a rotary evaporator), rotary evaporated for 3-5 min (40℃, 45 rpm), sonicated for 10 min, and filtered through a 0.45 μm microporous 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 a GM / HR solution to obtain a prepolymer solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum level in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated multiple times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet 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 and hyaluronic acid solution in a 1:1 ratio and stir continuously 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0117] Comparative Example 2:

[0118] 20 mg of HA-RGD and 160 mg of methacrylamide gelatin were dissolved in 1 mL of deionized water to form a GM / HR solution. Then, 0.2% LAP was added to the prepolymer solution, mixed thoroughly, and dropped into a polydimethylsiloxane microneedle mold. The mold was then transferred to an acrylic vacuum degassing chamber. Subsequently, the vacuum degree in the degassing chamber was adjusted to -100 kPa to fill the mold with solution, and vacuum degassing was repeated several times to remove air from the mold and solution. Finally, the composite prepolymer solution was cured under ultraviolet light (365 nm). 0.15 g of hyaluronic acid was weighed and dissolved in 10 mL of distilled water. The solution was stirred on a magnetic stirrer to ensure complete dissolution of HA. The prepared ectoine solution and hyaluronic acid solution were mixed in a 1:1 ratio and stirred continuously on a magnetic stirrer overnight 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 hours, and after demolding, GM / PPS-HA@FA / HA-RGD / HA@ECT microneedles were obtained.

[0119] Performance testing

[0120] 1. Mechanical properties of microneedles

[0121] Test method: Place the microneedle sample on the sample stage with the tip pointing upwards, and adjust the height of the sample stage so that both the upper and lower surfaces are in contact with the fixture. Compress at a constant rate of 0.05 mm / s, and record the compression displacement (L) and load (P) until the set displacement endpoint is reached. The mechanical strength of a single needle is the ratio of 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]

[0125] Table 1 shows that a low concentration of methacrylamide gelatin is detrimental to the stability of the three-dimensional network structure inside the needle tip, hindering molding. Literature research indicates that a single needle mechanical strength greater than 0.2 N is required to ensure 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 about 1 mm, and equilibrated in PBS for 24 hours. Before the test, excess moisture on the surface was gently removed with absorbent paper.

[0128] Each hydrogel sample was sandwiched between two quartz glass slides and placed vertically in the spectrophotometer cuvette. The scanning wavelength range was set to 200 to 800 nm with a step size of 1 nm. The quartz glass slide without hydrogel served as a blank control, with transmittance set to 100%. Transmittance (T%) was recorded at specific wavelengths of 280 nm, 320 nm, 365 nm, and 400 nm, and different groups of samples were compared and analyzed. All tests were performed at room temperature.

[0129] Table 2: UV Transmittance Analysis

[0130]

[0131] As shown in Table 2, ECT and PPS-HA@FA have significant UV shielding effects and a synergistic effect.

[0132] 3. FA release amount

[0133] Test method: The hydrogel was placed in 1 mL of sterile PBS solution and incubated in a constant temperature shaking incubator at 37℃ 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), with 1 mL of culture medium taken and replaced with an equal volume of fresh PBS. The samples were centrifuged at 4000 rpm for 5 min. The absorbance of ferulic acid in PBS solution was measured using UV spectrophotometry at an excitation wavelength of 325 nm.

[0134] The formula for calculating the cumulative release rate is as follows:

[0135] Cumulative release rate (%) = (Cumulative drug release / Drug dosage) × 100%

[0136] Figure 2 The cumulative FA release rate of the hydrogel in Example 6 is shown. From... Figure 2 It is known that when FA is loaded in PPS-HA@FA and dispersed in GelMA hydrogel, drug release exhibits two distinct phases: In the initial 24 hours, the release rate is rapid, with approximately 45.19% of the drug released; subsequently, the release rate gradually slows down, reaching a cumulative release of 74.33% at 72 hours and 93.54% at 216 hours. The initial rapid release may be due to the drug molecules being loosely adsorbed on or near the surface of the nanomicelles, facilitating diffusion into the external environment. Furthermore, the rapid swelling of the hydrogel upon contact with liquid also accelerates the initial drug release. Over time, the drug is slowly released from deep within the nanomicelles, and the release rate gradually decreases. The network structure of the hydrogel plays a role in delaying drug release. The early rapid release provides sufficient drug concentration to quickly exert a therapeutic effect, while the later slow release maintains the long-term effect of the drug. This indicates that the PPS-HA@FA / GelMA hydrogel composite material of this invention possesses 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 different examples and comparative examples were evaluated by scavenging 1,1-diphenyl-2-pyridylhydrazide (DPPH) free radicals. The mixtures of the different examples and comparative examples with DPPH reagent were incubated in the dark for 30 minutes with stirring, and the remaining DPPH was analyzed by UV-Vis spectroscopy.

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

[0141] D (%) = [[A blank - (A assay - 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 increasing FA content, indicating that FA can be effectively released from PPS-HA and can effectively scavenge free radicals, thus exhibiting better antioxidant effects. Furthermore, it can be seen that the free radical scavenging efficiency at 0.5% FA content is comparable to that at 1%, indicating that 0.5% FA already possesses a strong free radical scavenging ability.

[0145] 5. Cell compatibility evaluation

[0146] Test method: Cultured BMSCs cells were digested and resuspended with 0.25% trypsin, and then cultured at a density of 1×10⁻⁶ cells / cells. 5 Cell suspension at 1 / mL was rapidly mixed with sterilized hydrogel, printed in a 3D printer, and placed in 24-well plates for further culture in α-MEM complete medium. Each group had at least 3 wells. Cell viability was quantitatively analyzed using CCK8. After 24 hours of culture, the plates were removed, and 300 μL of CCK8 working solution was added to each well. The 3D-printed scaffold was thoroughly broken up using a pipette tip. The plates were incubated at 37°C in a CO2 incubator (containing 5% CO2) for 1–2 hours. The absorbance (OD) was measured at 450 nm using a microplate reader, and cell viability was calculated using the formula:

[0147]

[0148] Figure 3 The results of the cell compatibility evaluation are shown. As shown in the figure, none of the hydrogels exhibited toxicity to cells, and cell viability was above 90%, even exceeding 100%. This indicates that the prepared hydrogel scaffolds have no significant toxicity to cells and can promote cell proliferation to a certain extent.

[0149] 6. Anti-inflammatory evaluation:

[0150] Test Methods: Eight-week-old female C57BL / 6J mice were randomly divided into experimental and control groups. First, the fur on the backs of the mice was removed with a shaver. Twenty-four hours after shaving, ultraviolet (UV) irradiation began. A UVB light source (wavelength 280–320 nm) was used, with an initial dose of 60 mJ / cm², gradually increased to 180 mJ / cm², for 8 consecutive weeks, 5 times per week. After each irradiation, the skin surface was covered with a moist gauze to retain moisture and reduce acute photodamage. Successful modeling was defined by visible photoaging characteristics such as skin thickening, wrinkle formation, and pigmentation. After model establishment, appropriate treatment materials (such as PBS, drug solutions, or hydrogels) were applied topically to the photoaging areas daily for 7–14 days, according to the experimental design. After treatment, the mice were euthanized, and skin tissue from the irradiated areas on the back was collected. The levels of inflammatory factors in the skin tissue homogenate or serum were detected using a commercially available enzyme-linked immunosorbent assay (ELISA) kit, performed according to the manufacturer's instructions.

[0151] Figure 4 The results of the anti-inflammatory effect evaluation are shown. From... Figure 4 It can be seen that, compared with the 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 of photo-aged tissues.

[0152] Related experimental results show that, compared with comparative examples 1-2, the hydrogels of examples 1-5 and 7-9 also effectively reduced 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 photoprotection and repair functions, characterized in that, Includes microneedle tip components and microneedle base components; The microneedle tip component, by weight-volume percentage, comprises 4-8% methacrylamide gelatin, 0.5-2% ferulic acid, and 0.5-1% an adhesion peptide-hyaluronic acid complex. The microneedle base component comprises 0.5% to 1.5% hyaluronic acid and 0.5% to 1% ectoine by weight-volume percentage. The multifunctional biomaterial was prepared by the following steps: Adhesive peptide-hyaluronic acid complex and methacrylamide gelatin were dissolved in deionized water to form a GM / HR solution; ferulic acid nanomicelles were added to the GM / HR solution, and then LAP was added to the prepolymer solution. After mixing evenly, the mixture was dropped into a microneedle mold to fill the mold with solution. Vacuum degassing was repeated multiple times to remove air from the mold and solution; finally, the mixture was cured under ultraviolet light, followed by the addition of a composite solution of hyaluronic acid and ectoine, drying, and demolding to obtain the multifunctional biomaterial. The ferulic acid nanomicelles were prepared by the following steps: Step 1: Preparation of polypropylene sulfide (PPS): Under ice bath conditions, 100 μL of 3-mercaptopropionic acid was added to 30 mL of anhydrous tetrahydrofuran and mixed with magnetic stirring; 524 μL of 1,8-diazabicyclo[5.4.0]undec-7-ene was added, and the reaction mixture was stirred for 30 min under a nitrogen atmosphere; then, 1.9 mL of propylene sulfide was added dropwise, and the reaction mixture was stirred overnight at 60 °C; afterwards, the reaction was quenched by adding 5 mL of H2O, purified by precipitation in cold methanol, and the solvent was evaporated under reduced pressure to obtain yellow oily PPS; Step 2: Preparation of aminated polypropylene sulfide PPS-NH2: 158.6 mg of dried PPS was added to 20 mL of dichloromethane and dissolved by magnetic stirring. 23 mg of N-hydroxysuccinimide and 48 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide were then added, and the mixture was stirred at room temperature for 30 min until dissolved. Next, 133 μL of ethylenediamine was added dropwise to the mixture, and stirring was continued overnight at room temperature. Afterward, 20 mL of dichloromethane was added to dilute the reaction solution, which was washed successively with H2O and saturated NaCl, dried over MgSO4, and filtered. The solution was concentrated under reduced pressure to obtain PPS-NH2, which was then dried for later use. Step 3: Preparation of hyaluronic acid-polypropylene sulfide composite PPS-HA: Hyaluronic acid was dialyzed overnight in 0.01 M HCl solution and then lyophilized to obtain acidic hyaluronic acid. 10 mL of H₂O and 100 mg of acidic hyaluronic acid were added to a 50 mL beaker and dissolved by magnetic stirring. Then, 7 mg of NHS and 14.5 mg of EDC were added, and the mixture was stirred at room temperature for 30 min until completely dissolved. 40 mg of PPS-NH₂ was dissolved in 1 mL of tetrahydrofuran and added dropwise to the reaction system. The reaction was continued with stirring for 24 hours at room temperature under N₂ protection. The mixture was dialyzed three times with water / methanol at a 1:1 volume ratio for one day, then dialyzed three times with distilled water for one day. The solvent was removed by lyophilization to obtain PPS-HA. Step 4: Preparation of ferulic acid nanomicelles PPS-HA@FA: 5 mg of PPS-HA was dissolved in 4 mL of PBS; 10 mg of FA was dissolved in 1 mL of acetone / ethanol solution; the organic phase was added to the aqueous phase, rotary evaporated for 3-5 min, sonicated at 40℃ and 45 rpm for 10 min, and filtered through a 0.45 μm microporous membrane to obtain PPS-HA@FA; The adhesive peptide hyaluronic acid complex was prepared by the following steps: 1 g of hyaluronic acid was weighed, added to 100 mL of pure water, and dissolved completely. Then, 0.8 g of EDC was added to activate the carboxyl groups for 15 min. After that, 1.2 g of NHS was added, and after 15 min, the activated hyaluronic acid solution was added dropwise to 10 mL of RGD solution with a concentration of 0.05 g / mL. The reaction was then carried out at room temperature for 12 hours. After the reaction was completed, the solution was dialyzed in pure water for 3 days. The solution was then frozen at -80℃ for 12 hours and lyophilized to obtain the adhesive peptide hyaluronic acid complex. A composite solution of hyaluronic acid and ectoine is obtained by mixing an aqueous solution of ectoine with an aqueous solution of hyaluronic acid and stirring.

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

3. The multifunctional biomaterial according to claim 1 or 2, characterized in that, The methacrylamide gelatin is prepared by the following steps: Weigh 5.0 g of gelatin and add it to 50 mL of PBS buffer. Dissolve the gelatin in a 50°C water bath with magnetic stirring until completely transparent. Then, slowly add 3 mL of methacrylic anhydride to the gelatin solution and stir magnetically at 700 rpm for 1 hour, maintaining the reaction temperature at 50°C. After the reaction is complete, transfer the reaction solution to a cellulose dialysis bag with a molecular weight cutoff of 3500 Da and dialyze it in deionized water at 40°C for 3 days to remove byproducts. Collect the dialyzed reaction solution, centrifuge at 5000 rpm for 10 minutes to remove the precipitate, collect the supernatant, and freeze-dry it at -80°C to obtain the final product, methacrylamide gelatin (GelMA).

4. The use of the multifunctional biomaterial as described in any one of claims 1 to 3 in the preparation of photoprotective and repair products.

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