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CN-122005951-A - Self-pumping support material with double-layer heterogeneous structure and preparation method and application thereof

CN122005951ACN 122005951 ACN122005951 ACN 122005951ACN-122005951-A

Abstract

The invention belongs to the technical field of biomedical materials and tissue engineering, and particularly relates to a self-pumping support material with a double-layer heterogeneous structure, and a preparation method and application thereof. Hydrophobic membranes are prepared by electrostatic spinning technology, and hydrophilic microgel assemblies are prepared by an emulsion method. Adding a dopamine modified polymer, and establishing a dynamic phenylboronic acid ester bond between microgels through a dopamine group to form a hydrophilic microgel assembly; the adhesion connection of the microgel assembly and the hydrophobic membrane is realized through the mussel bionic chemical reaction of the dopamine group, a double-layer heterogeneous structure based on the hydrophilic assembly and the hydrophobic membrane is constructed, the self-pumping effect is generated, and the unidirectional flow of the liquid component from the hydrophobic side of the bracket to the hydrophilic side of the bracket can be realized. The scaffold is implanted into the alveolar bone defect, wherein the hydrophobic membrane contacts the gingiva, the hydrophilic microgel assembly fills the bone defect, and nutrient components in the gingiva are unidirectionally pumped to the alveolar bone defect by the self-pumping effect of the scaffold, so that the regeneration of the alveolar bone is promoted.

Inventors

  • FENG QI
  • HUANG YUE
  • LAN RONG

Assignees

  • 暨南大学

Dates

Publication Date
20260512
Application Date
20260127

Claims (10)

  1. 1. The self-pumping scaffold material with the double-layer heterogeneous structure is characterized by being formed by combining a hydrophilic microgel assembly and a single-layer disordered hydrophobic membrane through dopamine.
  2. 2. The self-pumping scaffold material of claim 1, wherein the preparation of the hydrophilic microgel assembly comprises the steps of: a1 Dissolving the material A and the material B in PBS, and stirring at 40-60 ℃ until the materials A and the material B are completely dissolved; a2 Adding the photoinitiator into the material solution dissolved in the step a 1), and continuously stirring in a dark place at 40-60 ℃ until the initiator is completely dissolved; a3 Step a 2) is added into fluorinated oil containing an emulsifier, and vortex oscillation is continued for a plurality of seconds to form micro-droplets; the duration of the vortex oscillation is 10-20 s; a4 Using 365nm ultraviolet LED lamp or 405nm blue light solidifying lamp to irradiate for several seconds, using photo-crosslinking mode to promote micro-droplet solidification to form micro-gel; The irradiation time is 30-60 s; a5 Transferring the microgel to a fluorinated oil wash without an emulsifier; a6 Taking out the microgel in the step (5), adding fluorinated oil without an emulsifier, waiting for natural volatilization, washing with PBS solution, and filtering and collecting to obtain the microgel; a7 Adding the material C and a sodium hydroxide solution, adjusting the pH to 7.5-8, continuously stirring, promoting the microgel to form chemical crosslinking, and completing the microgel assembly.
  3. 3. The self-pumping stent material according to claim 2, wherein the material A is a double-modified polymer material through esterification and amidation, and the concentration of the material A is 5-20 mg/mL, and the preparation method comprises the steps of dissolving a polymer with a molecular weight of 10W in deionized water, adding excessive methacrylic anhydride, adjusting the pH to 8.0-8.5, centrifuging after the reaction, transferring the solution to a dialysis bag for dialysis, adding morpholinoethanesulfonic acid and 4- (4, 6-dimethoxy-1, 3, 5-triazin-2-yl) -4-methylmorpholine hydrochloride to activate the carboxyl group of the polymer, then adding 3-aminophenylboric acid to react under dark condition, transferring the solution to the dialysis bag for dialysis, and obtaining a product through freeze drying; The material B is a polymer modified through esterification reaction, and the use concentration is 25-100 mg/mL, and the preparation method comprises the steps of dissolving a polymer with the molecular weight of 10W in PBS, adding methacrylic anhydride under intense stirring, diluting 5 times with warm PBS to terminate the reaction, transferring the solution into a dialysis bag for dialysis, and obtaining a product through freeze-drying; The material C is a polymer modified through amidation reaction, and the use concentration is 20-80 mg/mL, and the preparation method comprises the steps of dissolving a polymer with the molecular weight of 10W in morpholine ethanesulfonic acid buffer solution, then adding morpholine ethanesulfonic acid and 4- (4, 6-dimethoxy-1, 3, 5-triazine-2-yl) -4-methylmorpholine hydrochloride to activate carboxyl of the polymer, then adding dopamine hydrochloride to perform amidation reaction under the condition of avoiding light, transferring the solution to a dialysis bag, and freeze-drying to obtain a product; the polymers in the material A, the material B and the material C are degradable biomedical high polymer materials, and one of hyaluronic acid, gelatin, chitosan and sodium alginate is preferably selected.
  4. 4. The self-pumping scaffold material of claim 2, wherein the initiator comprises phenyl (2, 4, 6-trimethylbenzoyl) phosphate lithium salt at a concentration of 0.5-2 mg/mL.
  5. 5. The self-pumping scaffold material of claim 2, wherein the emulsifier comprises fluorinated oil containing 10% fluo Surf surfactant.
  6. 6. The self-pumping scaffold material according to claim 1, wherein the preparation of the single layer disordered hydrophobic film comprises the steps of: b1 Dissolving biodegradable hydrophobic high molecular polymer solid in N, N-dimethylformamide, and stirring to obtain a mixed solution; The hydrophobic high molecular polymer comprises polylactic acid or polycaprolactone; b2 Adding a certain volume percentage of ethyl distearate-based hydroxyethyl methyl ammonium methyl sulfate additive into the solution, and injecting the prepared electrostatic spinning solution into a spinning solution stock solution storage; b3 Setting spinning temperature and output voltage, adjusting the interval between the receiving screen and the spinning nozzle for electrostatic spinning, and forming a uniform and compact white fiber film on the collecting screen as a material D.
  7. 7. A method for preparing a self-pumping scaffold material with a double-layer heterogeneous structure according to any one of claims 1 to 6, comprising the following steps: And uniformly coating the material C on a single-layer disordered hydrophobic membrane, uniformly coating the microgel assembly on the surface of the material C, and combining the microgel assembly on the surface of the hydrophobic membrane through dopamine-mediated covalent bonding in the material C, namely the self-pumping stent material with a double-layer heterogeneous structure.
  8. 8. Use of the microgel assembly of claim 2 in the preparation of a drug loaded and controlled release product.
  9. 9. Use of the monolayer disordered hydrophobic film of claim 6 in the preparation of a biological barrier product.
  10. 10. Use of a self-pumping scaffold material with a double-layer heterogeneous structure according to any one of claims 1-6 in the preparation of a product for promoting tissue regeneration and repair.

Description

Self-pumping support material with double-layer heterogeneous structure and preparation method and application thereof Technical Field The invention belongs to the technical field of biomedical materials and tissue engineering, and particularly relates to a self-pumping support material with a double-layer heterogeneous structure, and a preparation method and application thereof. Background Guided tissue regeneration/guided bone tissue regeneration (GTR/GBR) is a widely used procedure in periodontal, alveolar and maxillofacial surgery, and is one of the most effective and reliable periodontal regeneration strategies at present. In GTR/GBR procedures, the physical barrier formed by the GTR/GBR membrane is typically used to selectively block the expansion of fibroblasts in the gingival tissue into the bone defect, thereby facilitating the growth of osteoblasts or stem cells and guiding bone tissue regeneration. In addition to fibroblasts, gingival tissue contains a number of active factors that promote bone regeneration, such as FGF, TGF- β, etc. The conventional GTR/GBR barrier membrane is only used as a physical barrier for isolating cells, so that the active factors are difficult to introduce into bone defects, and the bone regeneration cannot be promoted. If a material can be developed, which has the functions of fibroblast isolation and growth factor pumping, a better osteogenic microenvironment can be created, and bone regeneration can be promoted. Disclosure of Invention In view of the above problems, the present invention aims to provide a self-pumping scaffold material with a double-layer heterogeneous structure, and a preparation method and application thereof. The technical content of the invention is as follows: The invention provides a self-pumping scaffold material with a double-layer heterogeneous structure, which is formed by combining a hydrophilic microgel assembly and a single-layer disordered hydrophobic membrane through a mussel bionic chemical reaction of an amidation reaction modified polymer. The preparation of the hydrophilic microgel assembly comprises the following steps: a1 Dissolving the material A and the material B in PBS, and stirring at 40-60 ℃ until the materials A and the material B are completely dissolved; a2 Adding a photoinitiator phenyl (2, 4, 6-trimethylbenzoyl) lithium phosphate into the material solution dissolved in the step a 1), and continuously stirring in a dark place at 40-60 ℃ until the initiator is completely dissolved; a3 Step a 2) is added into fluorinated oil containing an emulsifier, and vortex oscillation is continued for a plurality of seconds to form micro-droplets; the duration of the vortex oscillation is 10-20 s; a4 Using 365nm ultraviolet LED lamp or 405nm blue light solidifying lamp to irradiate for several seconds, using photo-crosslinking mode to promote micro-droplet solidification to form micro-gel; The irradiation time is 30-60 s; a5 Transferring the microgel to a fluorinated oil wash free of surfactant; a6 Taking out the microgel in the step (5), adding fluorinated oil without surfactant, waiting for natural volatilization, washing with PBS solution, and filtering and collecting to obtain the microgel; a7 Adding the material C and a sodium hydroxide solution, adjusting the pH to 7.5-8, continuously stirring, promoting the microgel to form chemical crosslinking, and completing the microgel assembly. The material A is a double-modified polymer material through esterification reaction and amidation reaction, the use concentration is 5-20 mg/mL, the preparation method comprises the steps of dissolving a polymer with the molecular weight of 10W in deionized water, adding excessive methacrylic anhydride, adjusting the pH to be between 8.0 and 8.5, centrifuging after the reaction, transferring the solution to a dialysis bag for dialysis, then adding morpholine ethanesulfonic acid and 4- (4, 6-dimethoxy-1, 3, 5-triazin-2-yl) -4-methylmorpholine hydrochloride, activating the carboxyl of the polymer, then adding 3-aminophenylboric acid for reaction under dark condition, transferring the solution to the dialysis bag for dialysis, and freeze-drying to obtain a product. The material B is a polymer modified through esterification reaction, the use concentration of the material B is 25-100 mg/mL, the preparation method comprises the steps of dissolving a polymer with the molecular weight of 10W in PBS, adding methacrylic anhydride under vigorous stirring, diluting 5 times with warm PBS to terminate the reaction, transferring the solution into a dialysis bag for dialysis, and obtaining a product through freeze drying. The material C is a polymer modified through amidation reaction, the use concentration of the material C is 20-80 mg/mL, and the preparation method comprises the steps of dissolving a polymer with the molecular weight of 10W in morpholine ethanesulfonic acid buffer solution, then adding morpholine ethanesulfonic acid and 4- (4, 6-dimethoxy-1,