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Influence of biomaterial (Ti) experimental biological aging in the outcome of host response to biomaterial grafting in vivo and stem cells (SCAPs) differentiation in vitro

Grant number: 15/18162-2
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 15, 2016
Effective date (End): February 14, 2017
Field of knowledge:Health Sciences - Dentistry
Principal Investigator:Gustavo Pompermaier Garlet
Grantee:Claudia Cristina Biguetti
Supervisor abroad: Renato Menezes Silva
Home Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
Local de pesquisa : University of Texas Health Science Center at Houston (UTHealth), United States  
Associated to the scholarship:14/09590-8 - Role of DAMPs in the modulation of macrophage response after classical biomaterial (Ti) implantation and its impact in the subsequent repair and osseointegration processes, BP.DR

Abstract

The integration and maintenance of permanent biomaterials, such as titanium(Ti)-based devices, depends on its ability to not elicit a damaging immune response and its capacity to trigger and support an appropriate healing process. However, the molecular and cellular basis of immediate and long-term host/biomaterial interaction is poorly understood, even in classical biomaterials such as Ti. Our research group is currently investigating how biomaterial implantation triggers host response, which special focus on the release and action of DAMPs (damage-associated molecular patterns)(FAPESP 2014/09590-8). Our current findings confirm the DAMPs release upon different biomaterials grafting, DAMPs adsorption on the biomaterial surface, and a significant role for such molecules in mediating a 'constructive' inflammatory process that positively influence repair outcome, which include an activation of the chemoattraction and the supposed activation of mesenchymal stem cells (MSCs) at the biomaterial grafting area. However, even primarily successful biomaterials implantation may turn into clinically unsuccessful outcomes with time. Recent studies focused on the aging of permanent biomaterials suggests that aging could alter biomaterial-related factors (composition, surface energy, roughness and topography; as well release of some components or fragmentation) and consequently could change the interaction with host cells/tissues resulting in a long-term failure. In this context, it is assumable that such alterations could result in a differential release and/or differential adsorption of DAMPS on biomaterials surface, which in turn modulate the response of cells/tissues in an unfavorable way. The present project aims to study the influence of biomaterials (Ti) experimental biological aging in the outcome of host response to biomaterial grafting in vivo and in the pattern of stem cells from the apical papilla (SCAPS) differentiation in vitro. This project will be conducted at the University of Texas Health Science Center at Houston's School of Dentistry (UTHeath), taking advantage of the Houston Center for Biomaterials and Biomimetics (HCBB), with the proper facilities for biomaterials aging; and the expertise of supervisors at UTHealth, Dr Silva and Dr Kasper, in the SCAPs culture and the biomaterials fields. In summary, Ti disks submitted to experimental biological aging will be implanted in the subcutaneous tissue of C57Bl/6 mice, and evaluated for: (1) dynamic of DAMPs' adsorption on aged biomaterial (Ti disk) surfaces compared to control biomaterial surface, by ELISA; and (2) outcome of host inflammatory and healing response after biomaterial grafting, to be evaluated by histomorphometric and molecular methods (PCR Array). Regarding in vitro experiments, SCAPs will be grown in standard or osteogenic medium, for 2d, 7d, 14d and 28d in different conditions: over the surface of a Ti disk (aged and control biomaterial surface) or in a plastic culture dish (negative control); and over the same previous surfaces, in the presence/absence of DAMPs (HMGB1 and HSP), and then evaluated by multiparametric cytotoxicity assays, ELISA (ALP and OCN secretion), Alizarin red assay, and by RealTimePCR to address stem cells (Mesenchymal Stem Cell PCR Array, PAHS-082A-QIAGEN) and osteoblastic (Alpl, OCN, and OPN) markers expression. Additionally, during the period proposed, Ti-screws (used by our group in a recently developed oral implant osseointegration mice model) and additional Ti-disks will be prepared (experimental aging) at the HCBB facilities for further in vivo (osseointegration) and in vitro (culture with macrophages) analysis at FOB/USP. We believe that the results obtained from proponent process 2014/09590-8 in progress (role DAMPs in the modulation of macrophage response to classical biomaterial) integrated with the outcomes of the present proposal, will be complementary and will provide a foundation for future research.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BIGUETTI, CLAUDIA CRISTINA; CAVALLA, FRANCO; SILVEIRA, ELCIA VARIZE; TABANEZ, ANDRE PETENUCI; FRANCISCONI, CAROLINA FAVARO; TAGA, RUMIO; CAMPANELLII, ANA PAULA; TROMBONE, ANA PAULA FAVARO; RODRIGUES, DANIELI C.; GARLET, GUSTAVO POMPERMAIER. HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice. FRONTIERS IN IMMUNOLOGY, v. 10, APR 5 2019. Web of Science Citations: 0.
CLAUDIA CRISTINA BIGUETTI; FRANCO CAVALLA; ELCIA M. SILVEIRA; ANGÉLICA CRISTINA FONSECA; ANDREIA ESPINDOLA VIEIRA; ANDRE PETENUCI TABANEZ; DANIELI C. RODRIGUES; ANA PAULA FAVARO TROMBONE; GUSTAVO POMPERMAIER GARLET. Oral implant osseointegration model in C57Bl/6 mice: microtomographic, histological, histomorphometric and molecular characterization. Journal of Applied Oral Science, v. 26, p. -, 2018.

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