Delivery of miRNAs Using Porous Silicon Nanoparticles Incorporated into 3D Hydrogels Enhances MSC Osteogenesis by Modulation of Fatty Acid Signaling and Silicon Degradation

Surakshya Shrestha; Terence Tieu; Marcin Wojnilowicz; Nicolas H Voelcker; John S Forsythe; Jessica E Frith

doi:10.1002/adhm.202400171

Delivery of miRNAs Using Porous Silicon Nanoparticles Incorporated into 3D Hydrogels Enhances MSC Osteogenesis by Modulation of Fatty Acid Signaling and Silicon Degradation

Adv Healthc Mater. 2024 Apr 24:e2400171. doi: 10.1002/adhm.202400171. Online ahead of print.

Authors

Surakshya Shrestha¹, Terence Tieu^{2

3

4}, Marcin Wojnilowicz^{3

4}, Nicolas H Voelcker^{1

2

3

4

5}, John S Forsythe^{1

5}, Jessica E Frith^{1

5

6}

Affiliations

¹ Department of Materials Science and Engineering, Monash University, Clayton, VIC, 3800, Australia.
² Melbourne Centre for Nanofabrication, Victorian Node of the Australian National Fabrication Facility, Clayton, VIC, 3168, Australia.
³ Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia.
⁴ Commonwealth Scientific and Industrial Research Organisation (CSIRO) Manufacturing, Bayview Avenue, Clayton, VIC, 3168, Australia.
⁵ ARC Training Centre for Cell and Tissue Engineering Technologies, Monash University, Clayton, VIC, 3800, Australia.
⁶ Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia.

PMID: 38657207
DOI: 10.1002/adhm.202400171

Abstract

Strategies incorporating mesenchymal stromal cells (MSC), hydrogels and osteoinductive signals offer promise for bone repair. Osteoinductive signals such as growth factors face challenges in clinical translation due to their high cost, low stability and immunogenicity leading to interest in microRNAs as a simple, inexpensive and powerful alternative. The selection of appropriate miRNA candidates and their efficient delivery must be optimised to make this a reality. This study evaluated pro-osteogenic miRNAs and used porous silicon nanoparticles modified with polyamidoamine dendrimers (PAMAM-pSiNP) to deliver these to MSC encapsulated within gelatin-PEG hydrogels. miR-29b-3p, miR-101-3p and miR-125b-5p are strongly pro-osteogenic and are shown to target FASN and ELOVL4 in the fatty acid biosynthesis pathway to modulate MSC osteogenesis. Hydrogel delivery of miRNA:PAMAM-pSiNP complexes enhanced transfection compared to 2D. The osteogenic potential of hBMSC in hydrogels with miR125b:PAMAM-pSiNP complexes is evaluated. Importantly, a dual-effect on osteogenesis occurred, with miRNAs increasing expression of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (RUNX2) whilst the pSiNPs enhanced mineralisation, likely via degradation into silicic acid. Overall, this work presents insights into the role of miRNAs and fatty acid signalling in osteogenesis, providing future targets to improve bone formation and a promising system to enhance bone tissue engineering.

Keywords: fatty acid biosynthesis; hydrogels; mesenchymal stromal cells; microRNAs; osteogenesis; porous silicon nanoparticles.

Abstract

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