Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration

Aim: The success of dental implants depends on osseointegration can be compromised by well-known related adverse biological processes, such as infection and diabetes. Previously, nanohydroxyapatite-coated titanium surfaces (nHA_DAE) have been shown to contain properties that promote osteogenesis by...

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Main Authors: Anderson M. Gomes, Danielle F. da Silva, Fábio J. Bezerra, Willian F. Zambuzzi
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Journal of Functional Biomaterials
Subjects:
Online Access:https://www.mdpi.com/2079-4983/14/4/188
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author Anderson M. Gomes
Danielle F. da Silva
Fábio J. Bezerra
Willian F. Zambuzzi
author_facet Anderson M. Gomes
Danielle F. da Silva
Fábio J. Bezerra
Willian F. Zambuzzi
author_sort Anderson M. Gomes
collection DOAJ
description Aim: The success of dental implants depends on osseointegration can be compromised by well-known related adverse biological processes, such as infection and diabetes. Previously, nanohydroxyapatite-coated titanium surfaces (nHA_DAE) have been shown to contain properties that promote osteogenesis by enhancing osteoblast differentiation. In addition, it was hypothesized to drive angiogenesis in high-glucose microenvironments, mimicking diabetes mellitus (DM). On the other hand, the null hypothesis would be confirmed if no effect was observed in endothelial cells (ECs). Materials and methods: Titanium discs presenting the differential surfaces were previously incubated in an FBS-free cell culture medium for up to 24 h, which was, thereafter, supplemented with 30.5 mM of glucose to expose human umbilical vein endothelial cells (HUVECs, ECs) for 72 h. They were then harvested, and the sample was processed to provide molecular activity of specific genes related to EC survival and activity by using qPCR, and the conditioned medium by ECs was used to evaluate the activity of matrix metalloproteinases (MMPs). Results: Our data guaranteed better performance of this nanotechnology-involved titanium surface to this end once the adhesion and survival characteristics were ameliorated by promoting a higher involvement of β1-Integrin (~1.5-fold changes), Focal Adhesion Kinases (FAK; ~1.5-fold changes) and SRC (~2-fold changes) genes. This signaling pathway culminated with the cofilin involvement (~1.5-fold changes), which guaranteed cytoskeleton rearrangement. Furthermore, nHA_DAE triggered signaling that was able to drive the proliferation of endothelial cells once the cyclin-dependent kinase gene was higher in response to it, while the P15 gene was significantly down-regulated with an impact on the statement of angiogenesis. Conclusions: Altogether, our data show that a nanohydroxyapatite-coated titanium surface ameliorates the EC performance in a high-glucose model in vitro, suggesting its potential application in DM patients.
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spelling doaj.art-aa329737cea04f70a11128c3ad8766a42023-11-17T19:52:57ZengMDPI AGJournal of Functional Biomaterials2079-49832023-03-0114418810.3390/jfb14040188Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose ConcentrationAnderson M. Gomes0Danielle F. da Silva1Fábio J. Bezerra2Willian F. Zambuzzi3São Paulo State University (UNESP), Biosciences Institute, Campus Botucatu, Botucatu 18618-970, SP, BrazilSão Paulo State University (UNESP), Biosciences Institute, Campus Botucatu, Botucatu 18618-970, SP, BrazilSão Paulo State University (UNESP), Biosciences Institute, Campus Botucatu, Botucatu 18618-970, SP, BrazilSão Paulo State University (UNESP), Biosciences Institute, Campus Botucatu, Botucatu 18618-970, SP, BrazilAim: The success of dental implants depends on osseointegration can be compromised by well-known related adverse biological processes, such as infection and diabetes. Previously, nanohydroxyapatite-coated titanium surfaces (nHA_DAE) have been shown to contain properties that promote osteogenesis by enhancing osteoblast differentiation. In addition, it was hypothesized to drive angiogenesis in high-glucose microenvironments, mimicking diabetes mellitus (DM). On the other hand, the null hypothesis would be confirmed if no effect was observed in endothelial cells (ECs). Materials and methods: Titanium discs presenting the differential surfaces were previously incubated in an FBS-free cell culture medium for up to 24 h, which was, thereafter, supplemented with 30.5 mM of glucose to expose human umbilical vein endothelial cells (HUVECs, ECs) for 72 h. They were then harvested, and the sample was processed to provide molecular activity of specific genes related to EC survival and activity by using qPCR, and the conditioned medium by ECs was used to evaluate the activity of matrix metalloproteinases (MMPs). Results: Our data guaranteed better performance of this nanotechnology-involved titanium surface to this end once the adhesion and survival characteristics were ameliorated by promoting a higher involvement of β1-Integrin (~1.5-fold changes), Focal Adhesion Kinases (FAK; ~1.5-fold changes) and SRC (~2-fold changes) genes. This signaling pathway culminated with the cofilin involvement (~1.5-fold changes), which guaranteed cytoskeleton rearrangement. Furthermore, nHA_DAE triggered signaling that was able to drive the proliferation of endothelial cells once the cyclin-dependent kinase gene was higher in response to it, while the P15 gene was significantly down-regulated with an impact on the statement of angiogenesis. Conclusions: Altogether, our data show that a nanohydroxyapatite-coated titanium surface ameliorates the EC performance in a high-glucose model in vitro, suggesting its potential application in DM patients.https://www.mdpi.com/2079-4983/14/4/188dental implantsfunctional surfacesnano-hydroxyapatite coatingdiabetesboneangiogenesis
spellingShingle Anderson M. Gomes
Danielle F. da Silva
Fábio J. Bezerra
Willian F. Zambuzzi
Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
Journal of Functional Biomaterials
dental implants
functional surfaces
nano-hydroxyapatite coating
diabetes
bone
angiogenesis
title Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
title_full Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
title_fullStr Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
title_full_unstemmed Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
title_short Nanohydroxyapatite-Coated Titanium Surface Increases Vascular Endothelial Cells Distinct Signaling Responding to High Glucose Concentration
title_sort nanohydroxyapatite coated titanium surface increases vascular endothelial cells distinct signaling responding to high glucose concentration
topic dental implants
functional surfaces
nano-hydroxyapatite coating
diabetes
bone
angiogenesis
url https://www.mdpi.com/2079-4983/14/4/188
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AT fabiojbezerra nanohydroxyapatitecoatedtitaniumsurfaceincreasesvascularendothelialcellsdistinctsignalingrespondingtohighglucoseconcentration
AT willianfzambuzzi nanohydroxyapatitecoatedtitaniumsurfaceincreasesvascularendothelialcellsdistinctsignalingrespondingtohighglucoseconcentration