# Biotechnical Multiscale Engineering of Scaffolds for Stem Cell and Organoid Research

**Authors:** Merle‐Johanna Küstner, Christian Marx, Peter beim Graben, Serafim Rodrigues, Jörg Hampl, Frank Weise, Michael Gebinoga, Leon Kaysan, Maren Klett, Dana Brauer, Gregor Schlingloff, Doris Heinrich, Insa Sigrid Schroeder, Andreas Schober

PMC · DOI: 10.1002/smll.202504070 · Small (Weinheim an Der Bergstrasse, Germany) · 2025-10-30

## TL;DR

This paper explores how scaffold design impacts stem cell growth and organoid development, comparing it to genetic and biochemical factors.

## Contribution

The paper introduces biotechnical multiscale engineering as a novel approach to influence stem cell and organoid development through geometric and structural parameters.

## Key findings

- Geometric and structural parameters influence stem cell development and organogenesis as much as molecular and biochemical factors.
- Biotechnical multiscale engineering can mimic the hematopoietic stem cell niche, improving amplification in vitro.
- Geometrically suitable structures enhance differentiation protocols for human brain organoids.

## Abstract

The publication describes complex support structures and scaffolds for stem cells and organoids. Consideration of geometric and structural parameters has an influence on stem cell development and organogenesis comparable to that of molecular genetics and biochemical parameters. Two essential representatives are discussed here in more detail: hematopoietic stem cells (HSCs) and brain organoids. Due to their ability to fully regenerate the blood system, HSCs are used for stem cell transplantations. Therefore, efficient approaches to create an artificial but close‐to‐nature stem cell niche in vitro for amplification of HSCs are highly desirable. Apart from biochemical and biological factors, geometrical and biomechanical parameters are important. Biotechnological multiscale engineering is able to mimic the HSC niche, improving their amplification. Another highly dynamic process underlying hierarchic orders is organogenesis. Entire organs develop from individual cells that are spatially arranged in precise patterns and exposed to chemical, mechanical, and structural stimuli. The significance of the different scales during their development is explained using human brain organoids. Here, geometrically suitable structures improve biochemical differentiation protocols. Such technical hybrid systems can foster research of a rather inaccessible organ and possibly serve as a platform for more energy‐efficient computing devices, such as organoid automata, hence, orgamats.

Biotechnical multiscale engineering consideration of geometric and structural parameters, which is called biotechnical multiscale engineering, has an influence on stem cell development and organogenesis comparable to that of molecular genetics and biochemical parameters. Two essential representatives are discussed here in more detail: hematopoietic stem cells (HSC) and brain organoids.

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

109 references — full list in the complete paper: https://tomesphere.com/paper/PMC12934388/full.md

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Source: https://tomesphere.com/paper/PMC12934388