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Reengineering Bone-Implant Interfaces for Improved Mechanotransduction and Clinical Outcomes

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Abstract

The number of patients undergoing joint replacement surgery has progressively increased worldwide due to world population ageing. In the Unites States, for example, the prevalence of hip and knee replacements has increased more than 6 and 10 times, respectively, since 1980. Despite advances in orthopaedic implant research, including the development of novel implantable biomaterials, failures are still observed due to inadequate biomechanical compliance at the bone-implant interface. This comprises static and dynamic mechanical mismatch between the bone and the implant surface. The importance and robustness of biomechanical cues for controlling osteogenic differentiation of mesenchymal stem cells (MSC) have been highlighted in recent studies. However, in the context of bone regenerative medicine, it remains elusive how mechanobiological signals controlling MSC osteogenic differentiation dynamics are modulated in their interaction with the bone and with implants. In this review, we highlight recent technological advances aiming to improve host bone-implant interactions based on the osteogenic and mechanoresponsive potential of MSC, in the context of joint replacement surgery. First, we discuss the extracellular and intracellular mechanical forces underlying proper receptivity and stimulation of physiological MSC differentiation and linked osteogenic activity. Second, we provide a critical overview on how this knowledge can be integrated towards the development of biomaterials for improved bone-implant interfaces. Third, we discuss cross-disciplinarily which contributes to the next generation design of novel pro-active orthopaedic implants and their implantation success.

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Acknowledgements

This work was supported by FCT (Fundação para a Ciência e Tecnologia) through the grant SFRH/BD/141056/2018 and the projects FCT/PTDC/EMSTEC/5422/20 and POCI-01-0145-FEDER-030498. Additionally, this work was supported by FEDER fund through the project reference NORTE-01-0247-FEDER-034074, by European Cooperation in Science and Technology through the project reference COST Action MP1301 and also Marie Sklodowska-Curie COFUND Programme ‘NanoTRAINforGrowth’, from the European Union’s Seventh Framework Programme for research, technological development and demonstration.

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Francisca Melo-Fonseca: Literature search; Data analysis; Writing – Original Draft. Georgina Miranda: Conceptualization; Writing - Review & Editing; Supervision. Helena S. Domingues: Writing - Review & Editing. Inês Mendes Pinto: Writing - Review & Editing. Michael Gasik: Writing - Review & Editing; Supervision. Filipe Samuel Silva: Conceptualization; Writing - Review & Editing; Supervision.

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Correspondence to F. Melo-Fonseca.

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Highlights

- Aseptic orthopaedic implants failures are still being observed, often due to improper static and dynamic biomechanical compliance at the bone-implant interface;- Osteointegration involves proper activity of MSC, which mechanosensitivity exploiting with the extracellular and intracellular biomechanical cues, responsible for modulating MSC osteogenic differentiation, remains poorly specified and implemented;- Biomaterials surface design improvements should be targeted on optimization to induce proper osteogenic lineage commitment of MSC;- This cross-disciplinary review aims to highlight impacts of the design for the next generation of pro-active orthopaedic implants.

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Michael Gasik and F. S. Silva share co-last authorship

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Melo-Fonseca, F., Miranda, G., Domingues, H.S. et al. Reengineering Bone-Implant Interfaces for Improved Mechanotransduction and Clinical Outcomes. Stem Cell Rev and Rep 16, 1121–1138 (2020). https://doi.org/10.1007/s12015-020-10022-9

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