Surface modification of titanium substrate via combining photothermal therapy and quorum-sensing-inhibition strategy for improving osseointegration and treating biofilm-associated bacterial infection

Jingwei Hu; Yao Ding; Bailong Tao; Zhang Yuan; Yulu Yang; Kun Xu; Xuan Li; Peng Liu; Kaiyong Cai

doi:10.1016/j.bioactmat.2022.03.011

Surface modification of titanium substrate via combining photothermal therapy and quorum-sensing-inhibition strategy for improving osseointegration and treating biofilm-associated bacterial infection

Bioact Mater. 2022 Mar 16:18:228-241. doi: 10.1016/j.bioactmat.2022.03.011. eCollection 2022 Dec.

Authors

Jingwei Hu¹, Yao Ding¹, Bailong Tao², Zhang Yuan³, Yulu Yang¹, Kun Xu¹, Xuan Li¹, Peng Liu¹, Kaiyong Cai¹

Affiliations

¹ Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China.
² Laboratory Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
³ Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, China.

Abstract

Insufficient osseointegration and biofilm-associated bacterial infection are important challenges for clinical application of titanium (Ti)-based implants. Here, we constructed mesoporous polydopamine (MPDA) nanoparticles (NPs) loaded with luteolin (LUT, a quorum sensing inhibitor), which were further coated with the shell of calcium phosphate (CaP) to construct MPDA-LUT@CaP nanosystem. Then, MPDA-LUT@CaP NPs were immobilized on the surface of Ti implants. Under acidic environment of bacterial biofilm-infection, the CaP shell of MPDA-LUT@CaP NPs was rapidly degraded and released LUT, Ca²⁺ and PO₄ ^3- from the surface of Ti implant. LUT could effectively inhibit and disperse biofilm. Furthermore, under near-infrared irradiation (NIR), the thermotherapy induced by the photothermal conversion effect of MPDA destroyed the integrity of the bacterial membrane, and synergistically led to protein leakage and a decrease in ATP levels. Combined with photothermal therapy (PTT) and quorum-sensing-inhibition strategy, the surface-functionalized Ti substrate had an antibacterial rate of over 95.59% against Staphylococcus aureus and the elimination rate of the formed biofilm was as high as 90.3%, so as to achieve low temperature and efficient treatment of bacterial biofilm infection. More importantly, the modified Ti implant accelerated the growth of cell and the healing process of bone tissue due to the released Ca²⁺ and PO₄ ^3-. In summary, this work combined PTT with quorum-sensing-inhibition strategy provides a new idea for surface functionalization of implant for achieving effective antibacterial and osseointegration capabilities.

Keywords: Biofilm infection; Osseointegration; Photothermal therapy; Quorum sensing; Titanium implant.