Development of peri-implant and oral mucosa model for preclinical assessment of new biomaterials

Abstract

This doctoral thesis project involves a set of studies aiming to develop and characterise the 3D model of peri-implant mucosa, to compare the biological behaviour of the model in contact with implant surfaces with monolayer cultures, to develop and characterise a model with the presence of a bacterial stimulus, and to evaluate the biological response to surfaces with claimed antibacterial properties with bacterial stimuli. The first phase of this study involved the recruitment of volunteers to collect buccal mucosa and gingiva samples, used for comparison with the models. The peri-implant mucosa models were developed using keratinocytes, fibroblasts and monocytes. To compare the tissue response of the 3D model with the 2D culture, both cultures were placed in contact with Zr and Ti implant surfaces. The models were challenged with P. gingivalis LPS and Pam3CSK4 to evaluate their response and construct a peri-implant mucosa model under inflammation conditions. Finally, implant surfaces of Zirconia and Titanium were coated with MTA and chitosan to contribute to the development of an implant surface with an antibacterial effect and were placed in contact with 2D cultures and 3D models. It was observed that the peri-implant mucosa models developed may be a valid and clinically more relevant alternative to 2D culture. It was also observed that this 3D model responds to the bacterial stimuli used. The results of the study with antibacterial implant surfaces suggest that Chitosan-coated Titanium surfaces appear to be beneficial for peri-implant mucosal cells and MTA/chitosan coating did not show benefits to cellular behaviour in the presence of bacterial stimuli. As a global conclusion, the peri-implant mucosa model can be used for preclinical evaluation of implant surfaces in complement with in vivo analysis. Further in vitro studies with larger sample sizes and complementary study variables should be performed.