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粒细胞集落刺激因子/锂皂石/胶原蛋白复合材料诱导根尖乳头干细胞归巢以实现牙髓再生

G-CSF/laponite/collagen composite inducing stem cells of apical papilla homing for dental pulp regeneration.

作者信息

Zhao Yi, He Jiawei, Liang Cheng, Hong Mengru, Liao Li, Su Xiaoxia

机构信息

State Key Laboratory of Oral Diseases and National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

State Key Laboratory of Oral Diseases and National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

出版信息

Dent Mater. 2025 Aug;41(8):974-985. doi: 10.1016/j.dental.2025.06.001. Epub 2025 Jun 12.

Abstract

OBJECTIVE

Irreversible pulpitis in immature teeth is a serious dental disease which may lead to unclosed apical foramen and even tooth loss. Our study proposed a system of G-CSF/laponite/collagen composite and investigated its effects for stem cells of apical papilla (SCAPs) homing, targeting a potential treatment for immature dental pulp regeneration.

METHODS

In vitro, the effect of G-CSF on SCAPs proliferation, migration and differentiation was investigated. The microporous scaffold structure, sustained-release capability and cytotoxic effects of G-CSF/laponite/collagen composite was evaluated. In vivo, dentin cannulas model filled with G-CSF/laponite/collagen composite implanted in the back of nude mice was utilized to verify the effects of SCAPs homing for pulp regeneration.

RESULTS

In our study, the promoting effects of G-CSF on SCAPs proliferation and migration were verified, and the optimal concentration was chosen at 10 and 50 ng/ml. Interestingly, G-CSF had a slight effect on osteogenesis but significantly increased the gene expression of odontogenesis (DSPP, DMP-1). Laponite was observed to adsorb and slowly release G-CSF in a sustained manner, and the "laponite + collagen" contained micropore scaffold structure without biotoxicity for SCAPs. In vivo, 50 ng/ml G-CSF/laponite/collagen composite appeared to be the best combination for pulp regeneration, among the aspects of neo-tissue area, regenerative cells, odontoblast-like ratio, and number of blood vessels.

CONCLUSION

Our study proposed that 50 ng/ml G-CSF/laponite/collagen composite has a great potential to induce SCAPs homing for immature dental pulp regeneration, providing a new strategy to treat irreversible pulpitis in immature teeth.

摘要

目的

年轻恒牙的不可逆性牙髓炎是一种严重的牙科疾病,可能导致根尖孔未闭合甚至牙齿脱落。我们的研究提出了一种G-CSF/锂皂石/胶原蛋白复合材料体系,并研究了其对根尖乳头干细胞(SCAPs)归巢的影响,旨在为年轻恒牙牙髓再生提供一种潜在的治疗方法。

方法

在体外,研究了G-CSF对SCAPs增殖、迁移和分化的影响。评估了G-CSF/锂皂石/胶原蛋白复合材料的微孔支架结构、缓释能力和细胞毒性作用。在体内,利用在裸鼠背部植入填充有G-CSF/锂皂石/胶原蛋白复合材料的牙本质套管模型,验证SCAPs归巢对牙髓再生的作用。

结果

在我们的研究中,证实了G-CSF对SCAPs增殖和迁移有促进作用,最佳浓度选择为10和50 ng/ml。有趣的是,G-CSF对成骨作用影响较小,但显著增加了牙本质形成相关基因(DSPP、DMP-1)的表达。观察到锂皂石能吸附并持续缓慢释放G-CSF,且“锂皂石+胶原蛋白”组成的微孔支架结构对SCAPs无生物毒性。在体内,就新组织面积、再生细胞、成牙本质细胞样比例和血管数量而言,50 ng/ml G-CSF/锂皂石/胶原蛋白复合材料似乎是牙髓再生的最佳组合。

结论

我们的研究表明,50 ng/ml G-CSF/锂皂石/胶原蛋白复合材料在诱导SCAPs归巢以实现年轻恒牙牙髓再生方面具有巨大潜力,为治疗年轻恒牙不可逆性牙髓炎提供了一种新策略。

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