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载盐酸米诺环素明胶微球的磷酸钙骨水泥用于种植体周围炎的治疗。

Calcium phosphate cement with minocycline hydrochloride-loaded gelatine microspheres for peri-implantitis treatment.

机构信息

Research Center for Tooth and Maxillofacial Tissue Regeneration and Restoration, Department of Oral and Maxillofacial Surgery, School of Stomatology, Xi'an Medical University, Xi'an, Shaanxi 710021, China.

Research Center for Tooth and Maxillofacial Tissue Regeneration and Restoration, Department of Prosthodontics, School of Stomatology, Xi'an Medical University, Xi'an, Shaanxi 710021, China.

出版信息

J Dent. 2023 Sep;136:104624. doi: 10.1016/j.jdent.2023.104624. Epub 2023 Jul 17.

DOI:10.1016/j.jdent.2023.104624
PMID:37459952
Abstract

OBJECTIVES

This study aimed to fabricate an antibacterial calcium phosphate cement (CPC) with minocycline hydrochloride (MINO)-loaded gelatine microspheres (GMs) as a local drug delivery system for the treatment of peri‑implantitis.

METHODS

CPC/GMs(MINO), incorporating MINO-loaded GMs into CPC, was developed and characterised using scanning electron microscopy (SEM), X-ray diffraction (XRD), and drug release profiling. The antibacterial activity against Porphyromonas gingivalis and Fusobacterium nucleatum was evaluated. Bone mesenchymal stem cells (BMSCs) were cultured in the extracts of the developed cements to evaluate osteoinductivity in vitro. Furthermore, a rabbit femoral model was established to evaluate osteogenic ability in vivo.

RESULTS

SEM and XRD confirmed the porous structure and chemical stability of CPC/GMs(MINO). The release profile showed a sustained release of MINO from CPC/GMs(MINO), reaching an equilibrium state on the 14th day with a cumulative release ratio of approximately 84%. For antibacterial assays, the inhibition zone of CPC/GMs(MINO) was 3.67 ± 0.31 cm for P. gingivalis and 7.47 ± 0.50 cm for F. nucleatum. Most bacteria seeded on CPC/GMs(MINO) died after 24 h of culture. In addition, CPC/GMs(MINO) significantly enhanced alkaline phosphatase activity, osteogenic gene expression, and BMSC mineralisation compared with CPC/GMs and the control group (P < 0.05). The in vivo results showed that CPC/GMs(MINO) possessed a higher quality and quantity of bone formation and maturation than CPC/GMs and CPC.

CONCLUSIONS

CPC/GMs(MINO) showed excellent antibacterial activity against pathogens associated with peri‑implantitis and demonstrated good osteoinductivity and osteogenic ability.

CLINICAL SIGNIFICANCE

Peri-implantitis is among the most common and challenging biological complications associated with dental implants. In this study, MINO-loaded GMs were incorporated into CPC, which endowed the composite cement with excellent antibacterial and osteogenic abilities, demonstrating its potential as a bone graft substitute for treating peri‑implantitis.

摘要

目的

本研究旨在制备一种载盐酸米诺环素(MINO)的明胶微球(GMs)的抗菌磷酸钙水泥(CPC),作为治疗种植体周围炎的局部药物递送系统。

方法

开发并通过扫描电子显微镜(SEM)、X 射线衍射(XRD)和药物释放分析对 CPC/GMs(MINO)进行了表征,其中 CPC/GMs(MINO)是将 MINO 载入 GMs 后形成的。评价其对牙龈卟啉单胞菌和核梭杆菌的抗菌活性。将开发的水泥提取物用于培养骨髓间充质干细胞(BMSCs),以体外评价其成骨性。此外,建立兔股骨模型以体内评估其成骨能力。

结果

SEM 和 XRD 证实了 CPC/GMs(MINO)的多孔结构和化学稳定性。药物释放曲线显示 MINO 从 CPC/GMs(MINO)中的释放呈持续释放,在第 14 天达到平衡状态,累积释放率约为 84%。对于抗菌试验,CPC/GMs(MINO)对牙龈卟啉单胞菌和核梭杆菌的抑菌圈直径分别为 3.67±0.31cm 和 7.47±0.50cm。接种在 CPC/GMs(MINO)上的大多数细菌在培养 24 小时后死亡。此外,与 CPC/GMs 和对照组相比,CPC/GMs(MINO)显著提高了碱性磷酸酶活性、成骨基因表达和 BMSC 矿化(P<0.05)。体内结果表明,与 CPC/GMs 和 CPC 相比,CPC/GMs(MINO)具有更高质量和成熟度的骨形成。

结论

CPC/GMs(MINO)对与种植体周围炎相关的病原体具有优异的抗菌活性,表现出良好的成骨诱导性和成骨能力。

临床意义

种植体周围炎是与牙种植体相关的最常见和最具挑战性的生物学并发症之一。在本研究中,将 MINO 载入 GMs 后形成的 GM 载入 CPC,赋予了复合水泥优异的抗菌和成骨能力,表明其具有作为治疗种植体周围炎的骨替代物的潜力。

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