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Journal of Peking University (Health Sciences) ›› 2021, Vol. 53 ›› Issue (4): 758-763. doi: 10.19723/j.issn.1671-167X.2021.04.023

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In vivo study of liposome-modified polyetheretherketone implant on bacteriostasis and osseointegration

WANG Li-xin1,XU Xiao2,Δ(),NI Yao-feng1,SUN Hai-tao1,YU Ri-yue1,WEI Shi-cheng2,Δ()   

  1. 1. Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
    2. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing 100081, China
  • Received:2019-07-20 Online:2021-08-18 Published:2021-08-25
  • Contact: Xiao XU,Shi-cheng WEI E-mail:15266257389@163.com;sc-wei@pku.edu.cn
  • Supported by:
    National Natural Science Foundation of China(81571814)

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Abstract:

Objective: To develop dexamethasone plus minocycline-loaded liposomes (Dex/Mino liposomes) and apply them to improve bioinert polyetheretherketone (PEEK) surface, which could prevent post-operative bacterial contamination, enhance ossification for physiologic osseointegration, and finally reduce implant failure rates. Methods: Dex/Mino liposomes were covalently grafted onto the PEEK surface using polydopamine (pDA) coating as a medium. Confocal laser scanning microscopy was used to confirm the binding of fluorescently labeled liposomes onto the PEEK substrate, and a microplate reader was used to semiquantitatively measure the average fluorescence intensity of fluorescently labeled liposome-decorated PEEK surfaces. Moreover, the mouse subcutaneous infection model and the beagle femur implantation model were respectively conducted to verify the bioactivity of Dex/Mino liposome-modified PEEK in vivo, by means of micro computed tomography (micro-CT) and hematoxylin and eosin (HE) staining analysis. Results: The qualitative and quantitative results of fluorescently labeled liposomes showed that, the red fluorescence intensity of the PEEK-pDA-lipo group was stronger than that of the PEEK-NF-lipo group (P<0.05); the liposomes were successfully and uniformly decorated on the PEEK surfaces due to the pDA coating. After mouse subcutaneous implantation of PEEKs for 24 hours, HE staining results showed that the number of inflammatory cells in the PEEK-Dex/Mino lipo group were lower than that in the inert PEEK group (P<0.05), indicating a lower degree of infection in the test group. These results suggested that the Mino released from the liposome-functionalized surface provided an effective bacteriostasis in vivo. After beagle femoral implantation of PEEK for 8 weeks, micro-CT results showed that the PEEK-Dex/Mino lipo group newly formed more continuous bone when compared with the inert PEEK group; HE staining results showed that more new bones were formed in the PEEK-Dex/Mino lipo group than in the inert PEEK group, which were firmly bonded to the functionalized PEEK surface and extended along the PEEK interface. These results suggested that the Dex released from the liposome-functionalized surface induced effective bone regeneration in vivo. Conclusion: Dex/Mino liposome modification enhanced the bioactivity of inert PEEK, the functionalized PEEK with enhanced antibacterial and osseointegrative capacity has great potential as an orthopedic/dental implant material for clinical application.

Key words: Liposomes, Polyetheretherketone, Osseointegration, Bacteriostasis, Dexamethasone, Minocycline

CLC Number: 

  • R783.1

Figure 1

Schematic illustration of the preparation of Dex/Mino liposome-decorated PEEK through pDA coating, as well as its bacteriostasis and osseointegration in vivo for load-bearing bone repairing PEEK, polyetheretherketone; pDA, polydopamine; Dex, dexamethasone; Mino, minocycline; S. mutans, Streptococcus mutans."

Figure 2

Qualitative and quantitative fluorescence analysis of PEEK-NF-lipo group and PEEK-pDA-lipo group (n=11) NF, non-functionalized; lipo, liposome. Other abbreviations as in Figure 1. *P<0.05."

Figure 3

HE staining and inflammatory cell quantification of mouse after subcutaneous implantation for 24 h (n=5) A, HE staining of mouse after subcutaneous implantation for 24 h; B, quantification of inflammatory cells in Figure A (×20). Abbreviations as in Figure 1 and 2. *P<0.05."

Figure 4

Micro-CT analysis of functionalized PEEK after 8 weeks of Beagle’s femur implantation A, a PEEK implant; B, macroscopic image of a beagle’s femur containing implants; C, micro-CT 3D reconstruction images of PEEK; D, micro-CT 3D reconstruction images of PEEK-Dex/Mino lipo."

Figure 5

Schematic illustration of the transverse perspective and HE staining analysis of functionalized PEEK after 8 weeks of Beagle’s femur implantation Abbreviations as in Figure 1 and 2."

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