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The extracellular matrix or ECM holds cells together to form a tissue and allows the cells within the tissue to communicate. ECM comprises proteins such as fibronectin, collagen, laminin, etc. The most abundant protein in this space is collagen. Collagen fibers are interwoven with carbohydrate-containing protein molecules called proteoglycans. ECM allows cell migration and provides a structural scaffold at cell adhesion that anchors the cell when the extracellular matrix proteins interact with...
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3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures

Raphaël F Canadas1, João B Costa2, Zhengwei Mao3

  • 13B's Research Group, I3Bs, Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Zona Industrial da Gandra, AvePark, Barco GMR, 4805-017, Portugal; ICVS/3B's, PT Government Associate Laboratory, Braga, Guimarães, Portugal; Tech4MED™, UPTEC, ASPRELA I, Office-Lab 0.16, Business Campus, n.° 455/461, 4200-135 Porto, Portugal.

Biomaterials
|September 6, 2021
PubMed
Summary

A novel three-directional ice crystal elongation (3DICE) system creates complex, programmable macro-architectures in cryogels. This ice-templating method enables precise control over pore orientation for advanced tissue modeling and regenerative medicine applications.

Keywords:
BiomaterialsCryogelHepatic cirrhosisIce-templatingRegenerative medicineTissue engineering

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Area of Science:

  • Biomaterials Science
  • Tissue Engineering
  • Bioprinting

Background:

  • Natural extracellular matrix (ECM) provides essential biomechanical and biofunctional properties to tissues.
  • Tissues exhibit specialized macro-architectures (e.g., hepatic lobules, vascular sinusoids) crucial for function.
  • Mimicking complex tissue architectures, especially with oriented macro-structures and micro-channels, remains a challenge.

Purpose of the Study:

  • To present a novel three-directional ice crystal elongation (3DICE) system for programming geometries in cryogels.
  • To demonstrate the fabrication of cryogels with tunable mechanical properties and controlled pore orientations (vertical, radial, 3D combinations).
  • To investigate cellular responses to these engineered macro-architectures, focusing on liver tissue models.

Main Methods:

  • Development and application of the three-directional ice crystal elongation (3DICE) system.
  • Fabrication of cryogels with guided ice crystal growth to template pores.
  • Characterization of cryogel architectures (isotropic, anisotropic) and mechanical properties.
  • In vitro assessment of cell morphology, endothelial segment formation, CYP450 activity, and osteopontin expression in response to different architectures.

Main Results:

  • 3DICE system successfully created centimeter-scale cryogels with programmable vertical and radial pore orientations.
  • Tunable mechanical responses were achieved in both isotropic and anisotropic cryogel architectures.
  • Engineered macro-architectures significantly influenced cell morphology and the expression of liver-specific biomarkers (endothelial segments, CYP450, osteopontin).

Conclusions:

  • Ice-templating via 3DICE offers a powerful method to create complex, biomimetic macro-architectures.
  • The study highlights the critical role of macro-architecture in directing cellular behavior and function.
  • This technology holds significant potential for applications in drug testing, tissue engineering, and regenerative medicine.