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SUMMARY OF RESEARCH
Molecular basis of bone mineralization
With an ageing population, degenerative skeletal diseases represent one of the major social and health challenges, causing the highest number of premature deaths and disabilities in the EU and worldwide. Despite their social and economic impact, the mechanisms of bone formation and regeneration remain largely unknown.
Trying to contribute to close this knowledge gap, my line of research is defined in three pillars: 1) a deeper understanding of the role of mineralization regulators (non-collagenous proteins and proteoglycans) that triggers mineralization in the vertebrate skeleton, 2) an evaluation of the structural and biochemical changes at the mineral-collagen interface associated with abnormal expression of these regulators, and 3) a biomimetic approach directed to the development of osteocompatible materials for biomedical applications.
I use a variety of advanced analytical techniques that allow in-depth analysis of tissues beyond the structural changes visible in classical histology. I specialize in Advanced Electron Microscopy, combining high-resolution two-dimensional imaging techniques (HRTEM) with 3D FIB-SEM tomography, diffraction and various spectroscopic techniques (EDS and EELS). This approach, combined with classical biochemical techniques, allow the evaluation of cellular, structural and compositional parameters of tissues at an unprecedented level of detail.
Figure 1. 3D reconstruction of the initial stages of tendon mineralization. Collagen fibers (in different colors) are distributed in parallel. Mineralization starts in the interfibrillar spaces and spreads to the interior of the fibers, forming spherulites that converge until complete mineralization of the structure (adapted from Macías-Sánchez et al. 2022)
These lines of research have been supported by the following funding sources:
- Talent Attraction Program CSIC 2023 (20252AT007). Funding: 100.000 €.
- Ramón y Cajal tenure track contract 2023 (RYC2023-045512-I). Research funding: 50.000 €.
- Knowledge Generation Project 2022: "Unravelling nanoscale interactions between glycosaminoglycans and mineral precursors in bone formation" GLYCOMIN (PID2022-141993NA-I00). 2023-2026. Funding: 118.750 €.
- Precompetitive Projects for Young Researchers (UGR Research Plan 2023): "Deciphering the role of proteoglycans in driving bone mineralization". Funding: 1.500 €.
- Juan de la Cierva Incorporación fellowship 2020 (IJC2020-043639-I). Research funding: 6.000 €.
- Marie Curie Individual Fellowship (H2020-MSCA IF-2020). Research funding: 40.000 €.
In the context of these lines of research, 1 doctoral thesis and 3 master's theses have been developed. Among others, the following papers have been published:
1. Rutten, Macías-Sánchez*, Sommerdijk*. On the Role of Glycosylation of Type I Collagen in Bone. Journal of Structural Biology 206, 108145 (2024) DOI 10.1016/j.jsb.2024.108145
2. Rutten, Joosten, Schaart, de Beer, Roverts, Gräber, Jahnen-Dechent, Akiva, Macías-Sánchez*, Sommerdijk*. A Cryo-to-Liquid Phase Correlative Light Electron Microscopy Workflow for the Visualization of Biological Processes in Graphene Liquid Cells. Advanced Functional Materials 2416938 (2024). DOI 10.1002/adfm.202416938
3. de Beer, Marit; Daviran, Deniz; Roverts, Rona; Rutten, Luco; Macias-Sanchez, Elena; Metz, Juriaan R.; Sommerdijk, Nico; Akiva, Anat. Precise targeting for 3D cryo-correlative light and electron microscopy volume imaging of tissues using a FinderTOP. Communications Biology 6 - 510 (2023). DOI: 10.1038/s42003-023-04887-y
4. Hassani Besheli, Negar; Martens, Martijn; Macias-Sanchez, Elena; Olijve, Jos; Yang, Fang; Sommerdijk, Nico; Leeuwenburgh, Sander C. G. Unraveling the Formation of Gelatin Nanospheres by Means of Desolvation. Nano Letters 23, 11091 - 11098 (2023). DOI: 10.1021/acs.nanolett.3c03459
5. Van der Meijden, Daviran, Rutten, Walboomers, Macías-Sánchez, Sommerdijk*, Akiva*. A 3D cell-free bone model shows collagen mineralization is a physicochemical process driven and controlled by the matrix. Advanced Functional Materials 33, 2212339 (2023). DOI 10.1002/adfm.202212339
6. Macías-Sánchez*, Tarakina, Ivanov, Blouin, Berlanovich, Fratzl*. Spherulitic Crystal Growth Drives Mineral Deposition Patterns in Collagen-based Materials. Advanced Functional Materials 32, 2200504 (2022). DOI 10.1002/adfm.202200504
7. Zou, Xie, Macías-Sánchez, Zhengyi. Nonclassical Crystallization of Amorphous Calcium Carbonate in the Presence of Phosphate Ions. Crystal Growth and Design 21, 414 - 423 (2021) DOI: 10.1021/acs.cgd.0c01245
8. Zou, Tang, Macías-Sánchez, Sviben, Bertinetti, Landis, Fratzl*. Three-dimensional structural interrelations between cells, extracellular matrix and mineral in vertebrate mineralization. Proceedings of the National Academy of Sciences USA 117, 14102-14109 (2020). DOI 10.1073/pnas.1917932117
9. Jehle, Macías-Sánchez, Sviben, Fratzl, Bertinetti*, Harrington*. Hierarchically-structured metalloprotein composite coatings biofabricated from co-existing condensed liquid phases. Nature Communications 11, 862 (2020). DOI 10.1038/s41467-020-14709-y
FUNDING AGENCIES LAST 5 YEARS
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