Scientists pioneer high-resolution mapping of 3D collagen cell cultures

News & Blog

Scientists pioneer high-resolution mapping of 3D collagen cell cultures

11/07/2025 • by Chloe Gronow

Researchers have unveiled a cutting-edge approach for analysing 3D cell culture systems composed of type I collagen – one of the most abundant structural proteins in the human body.

By combining light and electron microscopy with mass spectrometry imaging (MSI), the researchers performed a multiparametric physicochemical analysis of the 3D matrix, revealing insights into cellular organisation, biochemical environments, and extracellular matrix (ECM) dynamics.

Published in Scientific Reports in March 2025, the study introduces a robust methodological framework for examining collagen-based 3D cultures that more closely mimic the complexity of living tissues than traditional 2D models.

The research team used a multimodal imaging strategy that included:

• Light microscopy to visualise the overall distribution and morphology of cells within the collagen gel. Using phase contrast and fluorescence imaging, the researchers could monitor cell viability, matrix remodeling, and structural integrity.

• Transmission and Scanning Electron Microscopy (TEM & SEM) to provide anometer-scale resolution of collagen fibers and cellular interfaces. TEM captured cross-sections of cells and matrix interactions, while SEM detailed the surface topography of the hydrogel and cell protrusions. These observations confirmed how cells adapt to and remodel their 3D surroundings.

• Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to map the distribution of lipids, amino acids, and other biomolecules within the 3D scaffold. This allowed for spatially resolved chemical profiling – shedding light on how different regions of the matrix may influence or respond to cell behaviour.

By integrating structural and chemical imaging, the researchers achieved a comprehensive physicochemical profile of the 3D collagen model.

In regenerative aesthetics, collagen-based scaffolds are commonly used in dermal fillers, wound healing therapies, and anti-ageing applications.

The ability to precisely analyse how cells behave within these matrices at both structural and molecular levels could lead to the development of more biocompatible, longer lasting, and biologically active aesthetic materials.