载淫羊藿素明胶微球的磷酸钙骨水泥作为骨再生的局部药物递送系统。
Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration.
机构信息
Department of Oral and Maxillofacial Surgery, School of Stomatology, Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
Department of Oral Histopathology, School of Stomatology, Xi'an Medical University, Xi'an, 710021, Shaanxi, China.
出版信息
Biomed Eng Online. 2022 Dec 22;21(1):89. doi: 10.1186/s12938-022-01052-0.
BACKGROUND
Icariin (ICA), a main active ingredient of Herba Epimedium, could promote bone formation, inhibit bone resorption and alleviate inflammatory responses. The aim of this study was to investigate the effect of ICA on the inhibition of bacteria associated with peri-implantitis, and fabricate a calcium phosphate cement (CPC) with ICA-loaded gelatin microspheres (GMs) as a local drug delivery system efficiently promoting bone formation and alleviating inflammation.
RESULTS
In this study, ICA exhibited antibacterial activity against P. gingivalis with a MIC value of 1 × 10 mol/L. When the concentration of ICA was 0.5 mM, the encapsulation efficiency of GMs reached the maximum value of 76.26 ± 3.97%. GMs with ICA revealed a controlled release profile, 0.5 mM ICA exhibited a higher ICA release profile than the other groups during a 21 d monitoring span. The results of SEM and XRD demonstrated successful fabrication of a calcium phosphate cement with ICA-loaded GMs. ICA released from CPC/GMs (ICA) was slower than ICA released from GMs within 10 days. CPC/GMs (ICA) exhibited antibacterial activity against P. gingivalis, but the antibacterial rate of CPC/GMs (ICA) was only 17.15 ± 6.06%. In addition, CPC/GMs (ICA) promoted the proliferation of BMSCs and significantly stimulated the differentiation and maturation of BMSCs. In vivo, H&E and Masson staining experiments demonstrated that CPC/GMs (ICA) exhibited better capacity for bone regeneration than CPC/GMs and CPC, and the expression of TNF-α and IL-1β in the tissue around CPC/GMs (ICA) was significantly lower than CPC/GMs and CPC in IHC staining (P < 0.05).
CONCLUSION
In this study, ICA exhibited limited antibacterial activity against bacteria associated with peri-implantitis. A composite material of calcium phosphate cement with ICA-loaded gelatin microspheres was developed, which not only promoting osteoinductivity and bone formation, but also alleviating inflammation, demonstrating its potential as a promising bone substitute material for treatment of peri-implantitis.
背景
淫羊藿苷（ICA）是淫羊藿的主要活性成分之一，能促进骨形成、抑制骨吸收和减轻炎症反应。本研究旨在探讨 ICA 抑制与种植体周围炎相关细菌的作用，并制备载 ICA 明胶微球（GMs）的磷酸钙水泥（CPC）作为一种高效促进骨形成和减轻炎症的局部药物递送系统。
结果
本研究表明 ICA 对牙龈卟啉单胞菌具有抗菌活性，MIC 值为 1×10-3 mol/L。当 ICA 浓度为 0.5 mM 时，GMs 的包封效率达到最大值 76.26±3.97%。GMs 载 ICA 呈现出控释特性，在 21 天的监测期内，0.5 mM ICA 组显示出比其他组更高的 ICA 释放率。SEM 和 XRD 的结果表明成功制备了载 ICA 的 GMs 磷酸钙水泥。CPC/GMs（ICA）中释放的 ICA 比 10 天内从 GMs 中释放的 ICA 释放速度更慢。CPC/GMs（ICA）对牙龈卟啉单胞菌具有抗菌活性，但 CPC/GMs（ICA）的抗菌率仅为 17.15±6.06%。此外，CPC/GMs（ICA）促进了 BMSCs 的增殖，并显著刺激了 BMSCs 的分化和成熟。体内实验 H&E 和 Masson 染色实验表明，CPC/GMs（ICA）在促进骨再生方面优于 CPC/GMs 和 CPC，且在 IHC 染色中，CPC/GMs（ICA）组织中 TNF-α 和 IL-1β 的表达明显低于 CPC/GMs 和 CPC（P<0.05）。
结论
本研究表明，ICA 对与种植体周围炎相关的细菌的抗菌活性有限。开发了载 ICA 明胶微球的磷酸钙水泥复合材料，不仅能促进成骨和骨形成，还能减轻炎症，有望成为治疗种植体周围炎的一种有前途的骨替代材料。
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