Nanoparticle and nanotopography-induced activation of the Wnt pathway in bone regeneration

Jagannathan, Chitra, Waddington, Rachel and Nishio Ayre, Wayne ORCID: https://orcid.org/0000-0003-2405-1876 2023. Nanoparticle and nanotopography-induced activation of the Wnt pathway in bone regeneration. Tissue Engineering Part B: Reviews 10.1089/ten.TEB.2023.0108

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Abstract

Background and Aims: Recent research has focused on developing nanoparticle and nanotopography-based technologies for bone regeneration. The Wnt signalling pathway has been shown to play a vital role in this process, in particular in osteogenic differentiation and proliferation. The exact mechanisms by which nanoparticles and nanotopographies activate the Wnt signalling pathway however are not fully understood. This review aimed to elucidate the mechanisms by which nano-scale technologies activate the Wnt signalling pathway during bone regeneration. Methods: The terms "Wnt", "bone", and "nano*" were searched on PubMed and Ovid with no date limit. Only original research articles related to Wnt signalling and bone regeneration in the context of nanotopographies, nanoparticles or scaffolds with nanotopographies or nanoparticles were reviewed. Results: The primary mechanism by which nanoparticles activated the Wnt pathway was by internalisation via the endocytic pathway or diffusion through the cell membrane, leading to accumulation of non-phosphorylated β-catenin in the cytoplasm and subsequently downstream osteogenic signalling (e.g. upregulation of RUNX2). The specific size of the nanoparticles and the process of endocytosis itself has been shown to modulate the Wnt-β-catenin pathway. Nanotopographies were shown to directly activate frizzled receptors, initiating Wnt/β-catenin pathway signalling. Additional studies showed nanotopographies to activate the Wnt/Ca2+ dependent and Wnt/planar cell polarity pathways via nuclear factor of activated T-cells, and α5β1 integrin stimulation. Finally, scaffolds containing nanotopographies/nanoparticles were found to induce Wnt signalling via a combination of ion release (e.g. lithium, boron, lanthanum and icariin) which inhibited GSK-3β activity, and via similar mechanisms to the nanotopographies. Conclusion: This review concludes that nanoparticles and nanotopographies cause Wnt activation via several different mechanisms, specific to the size, shape and structure of the nanoparticles or nanotopographies. Endocytosis-related mechanisms, integrin signalling and ion release were the major mechanisms identified across nanoparticles, nanotopographies and scaffolds respectively. Knowledge of these mechanisms will help develop more effective targeted nanoscale technologies for bone regeneration.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Dentistry
Publisher:	Mary Ann Liebert, Inc.
ISSN:	1937-3368
Date of First Compliant Deposit:	20 November 2023
Date of Acceptance:	20 September 2023
Last Modified:	23 Nov 2023 16:39
URI:	https://orca.cardiff.ac.uk/id/eprint/164035

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