Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration

Abstract 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 f...

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Main Authors: Ning Liu, Shuo Huang, Fang Guo, Shafei Zhai, Danyang Wang, Fang Li, Changkui Liu
Format: Article
Language:English
Published: BMC 2022-12-01
Series:BioMedical Engineering OnLine
Subjects:
Online Access:https://doi.org/10.1186/s12938-022-01052-0
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author Ning Liu
Shuo Huang
Fang Guo
Shafei Zhai
Danyang Wang
Fang Li
Changkui Liu
author_facet Ning Liu
Shuo Huang
Fang Guo
Shafei Zhai
Danyang Wang
Fang Li
Changkui Liu
author_sort Ning Liu
collection DOAJ
description Abstract 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 × 10–4 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.
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spelling doaj.art-2f65e822d83a483ea8614cdcc74f81172022-12-25T12:23:34ZengBMCBioMedical Engineering OnLine1475-925X2022-12-0121111810.1186/s12938-022-01052-0Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regenerationNing Liu0Shuo Huang1Fang Guo2Shafei Zhai3Danyang Wang4Fang Li5Changkui Liu6Department of Oral and Maxillofacial Surgery, School of Stomatology, Xi’an Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Xi’an Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Xi’an Medical UniversityDepartment of Oral Histopathology, School of Stomatology, Xi’an Medical UniversityDepartment of Prosthodontics, School of Stomatology, Xi’an Medical UniversityState Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi Key Laboratory of Stomatology, Department of Prosthodontics, School of Stomatology, Air Force Military Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Xi’an Medical UniversityAbstract 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 × 10–4 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.https://doi.org/10.1186/s12938-022-01052-0IcariinGelatin microspheresCalcium phosphate cementControlled releaseBone regeneration
spellingShingle Ning Liu
Shuo Huang
Fang Guo
Shafei Zhai
Danyang Wang
Fang Li
Changkui Liu
Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
BioMedical Engineering OnLine
Icariin
Gelatin microspheres
Calcium phosphate cement
Controlled release
Bone regeneration
title Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
title_full Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
title_fullStr Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
title_full_unstemmed Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
title_short Calcium phosphate cement with icariin-loaded gelatin microspheres as a local drug delivery system for bone regeneration
title_sort calcium phosphate cement with icariin loaded gelatin microspheres as a local drug delivery system for bone regeneration
topic Icariin
Gelatin microspheres
Calcium phosphate cement
Controlled release
Bone regeneration
url https://doi.org/10.1186/s12938-022-01052-0
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