Development, characterization and in vivo assessment of a chitosan-simvastatin film for titanium coating: evaluation of the osseointegration potential under influence of nicotine

Author(s)

Henrique Rinaldi Matheus

• Document type: Doctoral Thesis
• Press: Araçatuba. 2023-08-30.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
• Defense date: 2023-08-14
• Advisor: Juliano Milanezi de Almeida

Abstract

The osseointegration under systemic modification by nicotine (NIC) remains a great challenge to implantology since the bone reparative potential of resident cells is negatively influenced in the presence of this factor. In this research project, the objective is to develop a chitosan (CH)-simvastatin (SV) film on the surface of titanium in order to modulate and optimize the peri-implant repair process in models of systemic compromise by NIC. Distinct technique for immobilization of CH (directly os by means of an aminosilane [APTMS]) and incorporation of SV at the concentrations of 1, 2.5, and 5 μM were used to obtain greater stability and modulatory capacity. For surface characterization, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and contact angle measurement were applied. The success in CH and SV adsorption were confirmed by the elemental changes observed through XPS. All films exhibited nanofibrillar super hydrophilic characteristics. Porcine bone marrow stem cells (pBMSCs) were used for initial screening. The films obtained by adsorption of CH through APTM and incorporation of SV at 1 and e 2,5 μM (specially) showed the best capacity to induce mineralized matrix deposition by pBMSCs. APTMS-CH_SV 2.5 μM was tested in vitro in SAOS-2 cultures in medium supplemented with NIC. The tested film exerted a bio-stimulatory potential in the presence of NIC (as compared in no-functionalized controls). Therefore, the model was tested in an in vivo model of systemic delivery of NIC. The hazardous effects of NIC on peri-implant bone healing around sandblasted acid etched implants (conventional, NF) were reaffirmed. The CH_SV film proved to be effective in reverting the impact of NIC on peri-implant bone healing. The greater bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) in CH_SV, when compared with control (NF) in the presence of NIC was underlined by the mechanisms of upregulation of bone morphogenetic protein (BMP)-2 and BMP-7, coupled angiogenesis (upregulation of vascular endothelial growth factor [VEGF]), accelerated turnover (osteocalcin), modulation of inflammation (reduced expression of tumor necrosis factor [TNFα] and interleukin [IL] 1β), and reduced osteoclast-mediated bone resorption (tartrateresistant acid phosphatase [TRAP] expression). Additionally, the increased bone formation in initial stages (15 days) did not differ from post-osseointegration phases (45 days), thus indicating that the osseointegration process was accelerated by CH_SV in the presence or absence of NIC. CH_SV film is an effective choice for widening success rate of osseointegration-mediated rehabilitations under systemic influence of NIC and enlarges the application scope of bioactive coatings on the surface of Ti. (AU)

• FAPESP's process: 20/09274-0 - Development, characterization and in vivo assessment of a chitosan-simvastatin film for titanium coating: evaluation of the osseointegration potential under influence of nicotine
• Grantee: Henrique Rinaldi Matheus
• Support Opportunities: Scholarships in Brazil - Doctorate