Matrix Vesicle Nanostructures Guide Spatially Organized Bone-Like Mineralization in Biomimetic Collagen Scaffolds
Abstract
Bone formation is tightly regulated by osteoblasts, which secrete extracellular matrix (ECM) components and heterogeneous populations of extracellular vesicles (EVs). Among EVs, matrix vesicles (MVs) are uniquely associated with mineralization and act as bioactive extracellular nanostructures that initiate and spatially direct mineral growth within the ECM. However, how MVs interact with the ECM and how their functions differ from the functions of medium-derived EVs (mEVs) remain unclear. To address this question, we developed a bioinspired collagen-based scaffold designed to mimic the bone ECM organic phase and to recreate MV-mediated mineralization in vitro. Type I collagen scaffolds were slowly concentrated and exposed to NH3(g) to induce fibrillogenesis and stabilize supramolecular organization, while 5 wt % κ-carrageenan, a sulfated polysaccharide that functionally emulates glycosaminoglycans, was incorporated to support mineral nucleation. MC3T3-E1 pre-osteoblasts were cultured under osteogenic conditions to induce differentiation and vesicle secretion. Biochemical, microscopic, and spectroscopic analyses revealed that MVs and mEVs exhibit distinct nano-biointerface behaviors, particularly regarding ECM anchoring and the ability to initiate mineral deposition. Furthermore, Raman chemical imaging and X-ray nanotomography demonstrated that MVs not only trigger mineral formation but also direct the spatial organization of phosphate deposition within the ECM at the micro/nanoscale. By distinguishing MV- from mEV-mediated mineralization in a biomimetic ECM system, this study provides new insights into vesicle-guided biomineralization and spatial matrix organization, with implications for skeletal development, pathological calcification, and vesicle-based regenerative strategies.
Related
- Designing Well-Organized Touch-Spun 3D Scaffolds: The Role of Interfiber Spacing in Cell Proliferation
- Acute nicotine exposure produces a spatially organized transcriptional response in mouse olfactory cortex
- Multichannel, biomimetic scaffolds improve functional connectivity following traumatic long-gap peripheral nerve injury.
- Biomimetic scaffolds mimic human subretinal debris for preclinical testing of prosthetic vision
- Assessment of Microbial Consortia for Biogenic Mineralization Potential of Lead (Pb) using Microbiologically Induced Calcite Precipitation and Nitrate Reduction
BibTeX
@article{nogueira2026matrix,
title = {{Matrix Vesicle Nanostructures Guide Spatially Organized Bone-Like Mineralization in Biomimetic Collagen Scaffolds}},
author = {Lucas Fabricio Bahia Nogueira and Yuri Ferreira Da Silva and Maryanne Trafani de Melo and Juçara Gastaldi Cominal and Keteryne Rodrigues da Silva and Sandra Yasuyo Fukada and Fausto Almeida and Patrick Perré and Pedro E D Augusto and Pietro Ciancaglini and Ana Paula Ramos},
journal = {ACS Biomaterials Science and Engineering},
year = {2026},
month = sep,
doi = {10.1021/acsbiomaterials.6c00914},
url = {https://hal.science/hal-05740751v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Matrix Vesicle Nanostructures Guide Spatially Organized Bone-Like Mineralization in Biomimetic Collagen Scaffolds
AU - Lucas Fabricio Bahia Nogueira
AU - Yuri Ferreira Da Silva
AU - Maryanne Trafani de Melo
AU - Juçara Gastaldi Cominal
AU - Keteryne Rodrigues da Silva
AU - Sandra Yasuyo Fukada
AU - Fausto Almeida
AU - Patrick Perré
AU - Pedro E D Augusto
AU - Pietro Ciancaglini
AU - Ana Paula Ramos
PY - 2026
DA - 2026/09/05
JO - ACS Biomaterials Science and Engineering
DO - 10.1021/acsbiomaterials.6c00914
UR - https://hal.science/hal-05740751v1
AB - Bone formation is tightly regulated by osteoblasts, which secrete extracellular matrix (ECM) components and heterogeneous populations of extracellular vesicles (EVs). Among EVs, matrix vesicles (MVs) are uniquely associated with mineralization and act as bioactive extracellular nanostructures that initiate and spatially direct mineral growth within the ECM. However, how MVs interact with the ECM and how their functions differ from the functions of medium-derived EVs (mEVs) remain unclear. To address this question, we developed a bioinspired collagen-based scaffold designed to mimic the bone ECM organic phase and to recreate MV-mediated mineralization in vitro. Type I collagen scaffolds were slowly concentrated and exposed to NH3(g) to induce fibrillogenesis and stabilize supramolecular organization, while 5 wt % κ-carrageenan, a sulfated polysaccharide that functionally emulates glycosaminoglycans, was incorporated to support mineral nucleation. MC3T3-E1 pre-osteoblasts were cultured under osteogenic conditions to induce differentiation and vesicle secretion. Biochemical, microscopic, and spectroscopic analyses revealed that MVs and mEVs exhibit distinct nano-biointerface behaviors, particularly regarding ECM anchoring and the ability to initiate mineral deposition. Furthermore, Raman chemical imaging and X-ray nanotomography demonstrated that MVs not only trigger mineral formation but also direct the spatial organization of phosphate deposition within the ECM at the micro/nanoscale. By distinguishing MV- from mEV-mediated mineralization in a biomimetic ECM system, this study provides new insights into vesicle-guided biomineralization and spatial matrix organization, with implications for skeletal development, pathological calcification, and vesicle-based regenerative strategies.
SN - 2373-9878
ER -