A biomimetic engineered bone platform for advanced testing of prosthetic implants

Abstract Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advan...

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Main Authors: Martina Sladkova-Faure, Michael Pujari-Palmer, Caroline Öhman-Mägi, Alejandro López, Hanbin Wang, Håkan Engqvist, Giuseppe Maria de Peppo
Format: Article
Language:English
Published: Nature Publishing Group 2020-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-78416-w
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spelling doaj-992c43244ca644bbb1a7810e08b137672020-12-20T12:33:17ZengNature Publishing GroupScientific Reports2045-23222020-12-0110111510.1038/s41598-020-78416-wA biomimetic engineered bone platform for advanced testing of prosthetic implantsMartina Sladkova-Faure0Michael Pujari-Palmer1Caroline Öhman-Mägi2Alejandro López3Hanbin Wang4Håkan Engqvist5Giuseppe Maria de Peppo6The New York Stem Cell Foundation Research InstituteDivision of Applied Materials Sciences, Uppsala UniversityDivision of Applied Materials Sciences, Uppsala UniversityDivision of Applied Materials Sciences, Uppsala UniversityThe New York Stem Cell Foundation Research InstituteDivision of Applied Materials Sciences, Uppsala UniversityThe New York Stem Cell Foundation Research InstituteAbstract Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scientific validity and predictive value of this approach using an assortment of complementary evaluation methods. We anchored titanium (Ti) and stainless steel (SS) implants into biomimetic scaffolds, seeded with human induced mesenchymal stem cells, to recapitulate the osseointegration process in vitro. We show distinct patterns of gene expression, matrix deposition, and mineralization in response to the two materials, with Ti implants ultimately resulting in stronger integration strength, as seen in other preclinical and clinical studies. Interestingly, RNAseq analysis reveals that the TGF-beta and the FGF2 pathways are overexpressed in response to Ti implants, while the Wnt, BMP, and IGF pathways are overexpressed in response to SS implants. High-resolution imaging shows significantly increased tissue mineralization and calcium deposition at the tissue-implant interface in response to Ti implants, contributing to a twofold increase in pullout strength compared to SS implants. Our technology creates unprecedented research opportunities towards the design of implants and biomaterials that can be personalized, and exhibit enhanced osseointegration potential, with reduced need for animal testing.https://doi.org/10.1038/s41598-020-78416-w
collection DOAJ
language English
format Article
sources DOAJ
author Martina Sladkova-Faure
Michael Pujari-Palmer
Caroline Öhman-Mägi
Alejandro López
Hanbin Wang
Håkan Engqvist
Giuseppe Maria de Peppo
spellingShingle Martina Sladkova-Faure
Michael Pujari-Palmer
Caroline Öhman-Mägi
Alejandro López
Hanbin Wang
Håkan Engqvist
Giuseppe Maria de Peppo
A biomimetic engineered bone platform for advanced testing of prosthetic implants
Scientific Reports
author_facet Martina Sladkova-Faure
Michael Pujari-Palmer
Caroline Öhman-Mägi
Alejandro López
Hanbin Wang
Håkan Engqvist
Giuseppe Maria de Peppo
author_sort Martina Sladkova-Faure
title A biomimetic engineered bone platform for advanced testing of prosthetic implants
title_short A biomimetic engineered bone platform for advanced testing of prosthetic implants
title_full A biomimetic engineered bone platform for advanced testing of prosthetic implants
title_fullStr A biomimetic engineered bone platform for advanced testing of prosthetic implants
title_full_unstemmed A biomimetic engineered bone platform for advanced testing of prosthetic implants
title_sort biomimetic engineered bone platform for advanced testing of prosthetic implants
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2020-12-01
description Abstract Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scientific validity and predictive value of this approach using an assortment of complementary evaluation methods. We anchored titanium (Ti) and stainless steel (SS) implants into biomimetic scaffolds, seeded with human induced mesenchymal stem cells, to recapitulate the osseointegration process in vitro. We show distinct patterns of gene expression, matrix deposition, and mineralization in response to the two materials, with Ti implants ultimately resulting in stronger integration strength, as seen in other preclinical and clinical studies. Interestingly, RNAseq analysis reveals that the TGF-beta and the FGF2 pathways are overexpressed in response to Ti implants, while the Wnt, BMP, and IGF pathways are overexpressed in response to SS implants. High-resolution imaging shows significantly increased tissue mineralization and calcium deposition at the tissue-implant interface in response to Ti implants, contributing to a twofold increase in pullout strength compared to SS implants. Our technology creates unprecedented research opportunities towards the design of implants and biomaterials that can be personalized, and exhibit enhanced osseointegration potential, with reduced need for animal testing.
url https://doi.org/10.1038/s41598-020-78416-w
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