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Thiolactone-Functional Pullulan for In Situ Forming Biogels.

Stefan Mommer1, David Gehlen1, Takami Akagi2

  • 1DWI - Leibniz Institute for Interactive Materials and Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, Forckenbeckstrasse 50, 52056 Aachen, Germany.

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|September 21, 2021
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Summary
This summary is machine-generated.

Modified pullulan forms biocompatible hydrogels for tissue engineering. These biogels support cell proliferation, demonstrating a versatile and mild strategy for creating advanced biomaterials using biological substrates.

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Tissue Engineering

Background:

  • Developing biocompatible hydrogels with minimal cytotoxicity is crucial for tissue engineering applications.
  • Naturally occurring polysaccharides offer a promising scaffold for biomaterial development.
  • Functionalization of polysaccharides can enhance their cross-linking capabilities and versatility.

Purpose of the Study:

  • To functionalize pullulan with thiolactones for amine-reactive cross-linking.
  • To create versatile biogels using pullulan-based hydrogels cross-linked with biological substrates.
  • To evaluate the cytocompatibility and cell proliferation within the developed hydrogels.

Main Methods:

  • Pullulan functionalization with thiolactones at varying degrees of substitution (2.5 and 5.0 mol %).
  • Hydrogel formation via ring-opening addition of amines with diamines or amine-containing biological substrates (gelatin, GHK, GRGDS).
  • Characterization of hydrogel mesh sizes and rheological properties (G' ≅ 500 Pa).
  • Cell proliferation studies using normal human dermal fibroblasts (NHDFs) and hepatocytes (HepG2) over 14 days.

Main Results:

  • Achieved thiolactone degrees of substitution of 2.5 or 5.0 mol %, resulting in hydrogel mesh sizes from 27.8 to 49.1 nm.
  • Demonstrated successful cross-linking with gelatin, GHK, and GRGDS, creating versatile biogels.
  • NHDFs showed equal proliferation on gelatin and GRGDS-functionalized gels.
  • HepG2 cells exhibited a 10-fold increase in proliferation on GRGDS and GHK-functionalized gels compared to gelatin.
  • Confirmed cell viability and successful encapsulation via *in situ* gelation.

Conclusions:

  • The functionalized pullulan system provides a mild and biocompatible method for creating hydrogels.
  • Utilizing biologically active substrates as cross-linkers enhances the utility of pullulan-based biogels for specific cell types.
  • This strategy offers a versatile platform for developing advanced biomaterials in tissue engineering.