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Open AccessArticle
Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices
by
Harrison P. Ryan
Harrison P. Ryan ,
Bruce K. Milthorpe
Bruce K. Milthorpe
and
Jerran Santos
Jerran Santos
Dr. Jerran Santos is the Group Leader of the Advanced Tissue Engineering and Stem Cell Biology Group [...]
Dr. Jerran Santos is the Group Leader of the Advanced Tissue Engineering and Stem Cell Biology Group at the University of Technology Sydney and holds an Honorary Professorship at the University of Toulouse. He has been awarded over USD 5 million for research programs and has established several international collaborations. Dr. Santos is an active consultant for the TGA and a member of the Academy of Science.
He possesses a broad spectrum of expertise across various areas, including next-generation genome sequencing, biomaterial design, 3D printing, organoid synthesis, microfluidics, cytokine and immunomodulation, 3D molecular modelling, and protein interaction network building. His primary interests lie in employing a systems biology approach using both bulk and single-cell multi-omics technologies, alongside modern and classical molecular biology, biochemistry, and microscopy techniques, to examine phenotypic shifts.
His research also focuses on utilizing stem cells to develop models for degenerative diseases and identify biomarkers, thereby contributing to the expansion of knowledge through the discovery of key pathways involved in disease development.
*
Advanced Tissue Engineering and Stem Cell Biology Group, School of Life Sciences, University of Technology Sydney, Ultimo, NSW 2007, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(15), 7494; https://doi.org/10.3390/ijms26157494 (registering DOI)
Submission received: 23 June 2025
/
Revised: 27 July 2025
/
Accepted: 31 July 2025
/
Published: 2 August 2025
Abstract
Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis.
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MDPI and ACS Style
Ryan, H.P.; Milthorpe, B.K.; Santos, J.
Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices. Int. J. Mol. Sci. 2025, 26, 7494.
https://doi.org/10.3390/ijms26157494
AMA Style
Ryan HP, Milthorpe BK, Santos J.
Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices. International Journal of Molecular Sciences. 2025; 26(15):7494.
https://doi.org/10.3390/ijms26157494
Chicago/Turabian Style
Ryan, Harrison P., Bruce K. Milthorpe, and Jerran Santos.
2025. "Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices" International Journal of Molecular Sciences 26, no. 15: 7494.
https://doi.org/10.3390/ijms26157494
APA Style
Ryan, H. P., Milthorpe, B. K., & Santos, J.
(2025). Osteogenic Differentiation of Mesenchymal Stem Cells Induced by Geometric Mechanotransductive 3D-Printed Poly-(L)-Lactic Acid Matrices. International Journal of Molecular Sciences, 26(15), 7494.
https://doi.org/10.3390/ijms26157494
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