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CN-121971701-A - BPDAH/VMA hydrogel slow release microsphere for promoting periodontal bone regeneration and preparation method and application thereof

CN121971701ACN 121971701 ACN121971701 ACN 121971701ACN-121971701-A

Abstract

The invention discloses BPDAH/VMA hydrogel slow-release microspheres for promoting periodontal bone regeneration, a preparation method and application thereof, and provides a new material selection for the clinical treatment of periodontal bone regeneration, so that the microspheres can continuously and efficiently promote periodontal bone tissue regeneration, regulate and control osteogenic microenvironment, reduce postoperative complications such as infection and the like, are expected to become a preferred scheme widely used as clinical treatment materials, have good clinical application potential, and are expected to provide a new direction for the design of other periodontal tissue regeneration and bone regeneration repair materials. The invention creatively grafts VMA on the surface of GelMA hydrogel microsphere and adsorbs loaded B@PH NPs, thereby having the curative effects of adjusting the osteogenic microenvironment and inducing periodontal osteoblast differentiation. In the invention, the hydrogel microsphere is directly injected into periodontal pockets near periodontal bone tissue defects, and the slow release effect of the hydrogel microsphere on the supported osteogenic and anti-inflammatory components can regulate and control the osteogenic microenvironment and induce osteoblast differentiation so as to promote periodontal bone regeneration.

Inventors

  • GUO JINCAI
  • CHEN LINGLI
  • YAO JUN
  • HU LIANG
  • SUN JUNLI
  • LIU JING
  • FENG YANKUN
  • LIU YUANRONG
  • SHEN MI
  • LIU BINWEI
  • LIN ZHENZHEN
  • LU CANCAN

Assignees

  • 中南大学
  • 湖南中医药大学
  • 长沙市口腔医院

Dates

Publication Date
20260505
Application Date
20260205

Claims (10)

  1. 1. A preparation method of BPDAH/VMA hydrogel slow release microspheres for promoting periodontal bone regeneration is characterized by comprising the following specific steps: (1) Firstly, preparing polydopamine-heparin nano particles PDAHNPs by taking dopamine hydrochloride DH and heparin sodium Hep as raw materials; (2) Then PDAH NPs is loaded with bone growth factor BMP-2 to obtain B@PH NPs; (3) Then dissolving methacrylic acylated gelatin GelMA in a photoinitiator LAP solution to obtain a prepolymer solution, and then fully dispersing B@PH NPs and vanillin methacrylate VMA in the prepolymer solution to obtain BPDAH/VMA microsphere precursor solution; (4) Finally, using BPDAH/VMA microsphere precursor solution as a disperse phase, using oil as a continuous phase, adopting a capillary glass microfluidic chip, and polymerizing and curing under ultraviolet and UV irradiation to obtain the BPDAH/VMA hydrogel slow-release microsphere.
  2. 2. The preparation method of the polydopamine-heparin nanoparticle PDAH NPs is characterized in that the specific method of the step (1) comprises the steps of firstly uniformly mixing ammonia water, absolute ethyl alcohol and a first part of deionized water to obtain a premixed solution, then dissolving dopamine hydrochloride DH and heparin sodium Hep in a second part of deionized water, then adding the premixed solution, fully mixing, stirring and crosslinking under a light-shielding condition, and performing aftertreatment.
  3. 3. The preparation method of the kit according to claim 1, wherein the specific method of the step (2) is that PDAHNPs and the bone growth factor BMP-2 are dissolved in PBS, and the mixture is stirred and loaded with the BMP-2 at room temperature under the condition of light shielding.
  4. 4. The preparation method according to claim 1, wherein in the step (3), the amount ratio of the methacryloylated gelatin GelMA, the photoinitiator LAP solution, the B@PH NPs, and the vanillin VMA methacrylate is 100g:1mL:1mg:1mg, wherein the mass concentration of the photoinitiator LAP solution is 0.05%, and the photoinitiator LAP solution is obtained by dissolving LAP in PBS.
  5. 5. The method according to claim 1, wherein in the step (3), the prepolymer solution is prepared by heating at 60℃for 30 minutes in the absence of light.
  6. 6. The method of claim 1, wherein in step (4), the continuous phase is 2% drop-Surf droplet-forming oil.
  7. 7. The method according to claim 1, wherein in the step (4), the flow rate of the dispersed phase is 96. Mu.L/min, the flow rate of the continuous phase is 120. Mu.L/min, and the microfluidic outlet tube 30s is irradiated with UV light of 405nm to effect polymerization curing.
  8. 8. The preparation method of the emulsion breaker according to claim 1, wherein in the step (4), after polymerization and solidification are completed, fresh microspheres are collected and purified, and the preparation method comprises the steps of uniformly mixing the fresh microspheres with the emulsion breaker according to a volume ratio of 1:1, standing, centrifuging, immersing in deionized water, centrifuging, immersing in 75% ethanol solution with a volume concentration, centrifuging, immersing in PBS, centrifuging, freezing at-80 ℃ for 8-12 h, vacuum drying for 8-12 h, and storing at 4 ℃ in a dark place at a low temperature.
  9. 9. BPDAH/VMA hydrogel slow release microsphere for promoting periodontal bone regeneration is characterized in that the microsphere is obtained by the preparation method of any one of claims 1-8.
  10. 10. Use of the BPDAH/VMA hydrogel sustained-release microsphere of claim 9 in the preparation of a repair material for promoting periodontal bone regeneration.

Description

BPDAH/VMA hydrogel slow release microsphere for promoting periodontal bone regeneration and preparation method and application thereof Technical Field The invention relates to BPDAH/VMA hydrogel slow-release microspheres for promoting periodontal bone regeneration, a preparation method and application thereof. Belongs to the technical field of periodontal tissue regeneration materials. Background Periodontitis is a chronic infectious progressive periodontal tissue disease characterized by loss of periodontal attachment, periodontal pocket formation and alveolar bone resorption, and is the leading cause of tooth loss in adults. The incidence of severe periodontitis worldwide is reported to be 8.5%, with a cumulative population of 7.43 million, and its prevalence and severity increasing with age. Periodontal disease bacteria is a starting factor of periodontitis, dental plaque planted in a gingival and dental junction at an early stage can cause immune inflammatory reaction of a host, if the periodontal disease is not treated in time, gingivitis can develop to tissues of the tooth Zhou Shen, so that periodontal supporting tissues such as alveolar bone, cementum and periodontal ligament are damaged progressively, and symptoms such as gingival recession, mastication difficulty and loosening and displacement of teeth can occur along with progressive development of lesions to the root, and finally tooth loss can be caused. Loss of adhesion and formation of a true periodontal pocket are characteristic pathological manifestations of periodontitis, and clinical manifestations such as alveolar bone resorption, plaque, gingival bleeding, and tooth Zhou Yinong, which are seen in conjunction with imaging, can be used as diagnostic basis for periodontitis. Controlling periodontal disease progression and repairing periodontal tissue defects is the ultimate goal of clinical treatment of periodontal disease. However, traditional periodontitis treatments focus on plaque and inflammatory control, preventing or slowing the progression of the disease, and it is difficult to achieve satisfactory periodontal tissue regeneration. Therefore, it is of great clinical importance to seek effective and stable periodontal tissue regeneration techniques. The treatment difficulty of periodontal bone regeneration is that primary and long combined epithelial healing is a periodontal main healing mode, and regenerative healing is difficult to realize, and the healing mode of periodontal tissues depends on the growth speed of cells from different sources of periodontal, the particle size and the absorption rate of bone grafting materials and other performances. Periodontal ligament precursor cells and alveolar bone marrow stem cells grow at a slower rate than cells derived from gingival epithelium and connective tissue. The newly-born periodontal attachment in the periodontal pocket is often blocked by the root surface growth junction epithelium, and regenerative healing of periodontal tissue is difficult to achieve. 2. The bone forming micro environment is easy to be influenced by inflammatory cells and related factors, wherein the destruction and regeneration of periodontal bone tissue is mainly regulated and controlled by osteoblasts and osteoclasts, while the periodontal barrier epithelial cells and immune cells such as neutrophils, mononuclear/macrophages and the like in gingival crevicular fluid are used as important components of host defense systems, and proinflammatory factors such as interleukin, prostaglandin, protease and the like are released in periodontitis environment, and meanwhile, the osteoclasts are activated to destroy the bone forming micro environment, so that the periodontal tissue regeneration effect and speed are influenced. 3. The periodontal operation has high difficulty, large wound and difficult postoperative complications, the bone grafting operation and the traditional artificial bone material filling operation have long time and obvious wound, and the postoperative complications such as bleeding, infection, rejection reaction and the like are easy to occur. In addition, periodontal regeneration operation has high technical requirements, is complex to operate and is difficult to clinically popularize. Hydrogel microspheres, also called microgels, are an emerging dominant drug-carrying material, can adapt to complex environments of the oral cavity, are widely applied to the treatment of various oral diseases, but are less applied in periodontal bone regeneration, and lack relevant experimental data and clinical transformation application. At present, related researches exist, for example, patent CN117819530B discloses a carbon point and self-triggering slow-release system based on calcium ion doping, a preparation method and application thereof, aspirin, metformin and calcium chloride aqueous solution are mixed and heated to form carbon points in a vacuum environment, and calcium ion positive charge and sodium al