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.
Highlights
Predictive power of existing methods is p oor[14], indicating a need for new, robust, human-relevant systems that strongly correlate with clinical outcomes
We tested Ti and SS implants since these materials produce different outcomes in vivo[17,18], with Ti implants leading to the formation of a stronger bond with the surrounding bone compared to stainless steel implants
We used decellularized cow bone scaffolds because their trabecular architecture provides a good representation of the tissue environment at the site of implantation[19], and because they support osteogenic differentiation of human mesenchymal stem cells well as scaffolds derived from human bone[20]
Summary
Predictive power of existing methods is p oor[14], indicating a need for new, robust, human-relevant systems that strongly correlate with clinical outcomes. By using a biomimetic approach to bone development, we recently engineered functional bone tissue, i.e. displaying architectural and biological features typical of the native tissue, from human induced pluripotent stem cells (iPSC)[15,16], with significant potential to serve as replacement product for clinical applications and as an in vitro system for advanced screening of drugs and biomaterials. We have developed a novel, biomimetic platform to test titanium (Ti) and stainless steel (SS) implants. These implants elicit different biological responses in vivo, which lead to different integration strengths[17,18]. This study demonstrates our testing platform can simulate the tissue-implant interaction process in vitro, offering a powerful system to advance the development of new orthopedic implants and biomaterials with enhanced osseointegration potential
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