含BGN温敏粘接剂的制备及其对屏障膜的固定性能研究OA
A study on the preparation of a BGN-loaded thermosensitive adhesive and its performance in barrier mem-brane fixation
目的 探讨含生物活性玻璃纳米颗粒的温敏型粘接剂对屏障膜的固定性能及增强引导骨再生(guided bone regeneration,GBR)的能力,为GBR术中屏障膜固定提供新方案.方法 通过自由基聚合构建以丙烯酸甲氧基乙酯、N-异丙基丙烯酰胺和原儿茶酸为基础粘接剂,掺入生物活性玻璃纳米颗粒(bioactive glass nanoparticle,BGN)制备温敏型粘接剂 M2NP@BGN(methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle).利用衰减全反射傅里叶变换红外光谱、核磁共振波谱对基础粘接剂M2NP进行合成表征,利用扫描电镜、流变仪对BGN掺入后的温敏粘接剂M2NP@BGN(BGN浓度为1 mg/mL)进行合成表征.随后调控BGN的浓度(0.1 mg/mL、0.5 mg/mL、1 mg/mL、2 mg/mL),利用万能试验机评估各组材料的粘接强度和机械强度,并采用CCK-8细胞增殖与毒性实验和溶血实验评估各组材料生物相容性,以优选出性能最佳的粘接剂配比.将优选的材料浸提液与小鼠骨髓间充质干细胞共孵育,通过RT-qPCR、碱性磷酸酶染色和茜素红染色检测其体外促成骨能力.最后,建立大鼠下颌骨缺损模型,并充填骨粉,随后采用不同方式固定屏障膜,分为M2NP@BGN(BGN浓度为1 mg/mL)固定组(M2NP@BGN组)、钛钉固定组(Nail组)及未固定组(Negative组),于术后8周通过微计算机断层扫描技术和组织学染色分析其体内引导骨再生效果.结果 成功构建了M2NP@BGN(BGN浓度为1 mg/mL)粘接剂,在湿热环境下能快速成胶.其中 BGN浓度为 1 mg/mL的粘接剂在 37℃湿条件下粘接强度最高(P<0.001),机械强度明显增强(P<0.001),且各组材料细胞活性>80%,溶血率<5%,生物相容性良好.M2NP@BGN(BGN浓度为1 mg/mL)还能上调成骨基因Runt相关转录因子2(runt-related transcription factor 2,Runx2)和Ⅰ型胶原(collagen type Ⅰ,Col Ⅰ)的表达(P<0.001),并增强成骨分化标志物的活性(P<0.05).动物实验表明,与Negative组和Nail组相比,M2NP@BGN(BGN浓度为1 mg/mL)组能显著增加新生骨的体积分数(P<0.05)和成熟度.结论 M2NP@BGN(BGN浓度为1 mg/mL)兼具优异的湿粘接性和促成骨活性,能够增强屏障膜的骨增量效果,为GBR术提供了一种具有临床转化潜力的新固定方案.
Objective To investigate the barrier membrane fixation performance and enhanced guided bone regen-eration(GBR)capability of a thermosensitive adhesive containing bioactive glass nanoparticles in order to provide a novel solution for membrane fixation during GBR procedures.Methods M2NP@BGN(methoxyethyl acrylate-co-N-isopropylacrylamide-co-protocatechuic acid@Bioactive glass nanoparticle),a thermosensitive adhesive,was synthesized via free radical polymerization by compositing methoxyethyl acrylate,N-isopropylacrylamide,and protocatechuic acid into a basic adhesive that was modified with bioactive glass nanoparticle(BGN).The successful fabrication of basic ad-hesive M2NP was characterized by attenuated total reflection-Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy.The thermosensitive adhesive M2NP@BGN(BGN concentration of 1 mg/mL)was characterized by scanning electron microscopy and a rheometer.By adjusting the BGN concentration(0.1 mg/mL,0.5 mg/mL,1 mg/mL,and 2 mg/mL),the adhesive and mechanical strengths were investigated with a universal testing machine.Biocompatibility was evaluated with a cell counting kit-8 assay and hemolysis test to identify the optimal for-mulation.The optimal material's extract was co-cultured with mouse bone marrow mesenchymal stem cells,and its os-teogenic activity was examined in vitro by quantitative real-time PCR,alkaline phosphatase,and alizarin red S staining.The rat mandibular defect model was established,filled with bone graft,and divided into 3 groups based on membrane fixation method:M2NP@BGN(BGN concentration of 1 mg/mL)fixation group(M2NP@BGN),titanium nail fixation group(Nail),and unfixed control group(Negative).Bone regeneration was analyzed after 8 weeks by micro computed to-mography and histological staining.Results M2NP@BGN(BGN concentration of 1 mg/mL)was successfully synthe-sized and demonstrated rapid gelation under warm,humid conditions.The adhesive with a BGN concentration of 1 mg/mL exhibited the highest adhesive strength(P<0.001)and significantly enhanced mechanical strength(P<0.001)under 37℃ wet conditions.All formulations showed excellent biocompatibility,with cell viability>80%and hemolysis ratio<5%.M2NP@BGN(BGN concentration of 1 mg/mL)significantly upregulated the expression of Runx2 and Col I(P<0.001)and enhanced the activity of osteogenic differentiation markers(P<0.05).In the animal model,the M2NP@BGN group(BGN concentration of 1 mg/mL)achieved significantly higher bone volume fraction and better bone maturity compared to the negative and nail groups(P<0.05).Conclusion M2NP@BGN(BGN concentration of 1 mg/mL)combines excellent wet adhesion with potent osteogenic activity,enhances the bone augmentation efficacy of mem-branes,and presents a novel fixation strategy with significant clinical translation potential for GBR therapy.
王雨竹;顾俊婷;李之婷;白鹊;党高鹏;汪亦菲;孙小棠;牛丽娜;方明
口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)口颌系统重建与再生全国重点实验室,国家口腔疾病临床医学研究中心,陕西省口腔医学重点实验室,空军军医大学口腔医院修复科,陕西 西安(710032)
医药卫生
引导骨再生屏障膜固定粘合剂生物活性玻璃纳米颗粒湿粘接温敏材料骨缺损骨修复成骨分化
guided bone regenerationbarrier membranefixationadhesivebioactive glass nanoparticlewet adhesionthermosensitive materialsbone defectbone repairosteogenic differentiation
《口腔疾病防治》 2026 (1)
41-53,13
国家自然科学基金项目(8232501282301043) This study was supported by the grants from the National Natural Science Foundation of China(No.82325012,No.82301043).
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