4D spatiotemporal modulation of biomolecules distribution in anisotropic corrugated microwrinkles via electrically manipulated microcapsules within hierarchical hydrogel for spinal cord regeneration

Min Yu Chiang, Hung Wei Cheng, Yu Chun Lo, Wei Chun Wang, Shwu Jen Chang, Chu Hsun Cheng, Yu Chang Lin, Huai En Lu, Ming Wen Sue, Nien Ti Tsou, Yu Chun Lo, Ssu Ju Li, Chao Hung Kuo, You Yin Chen, Wei Chen Huang, San Yuan Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Although traditional 3D scaffolds or biomimetic hydrogels have been used for tissue engineering and regenerative medicine, soft tissue microenvironment usually has a highly anisotropic structure and a dynamically controllable deformation with various biomolecule distribution. In this study, we developed a hierarchical hybrid gelatin methacrylate-microcapsule hydrogel (HGMH) with Neurotrophin-3(NT-3)-loaded PLGA microcapsules to fabricate anisotropic structure with patterned NT-3 distribution (demonstrated as striped and triangular patterns) by dielectrophoresis (DEP). The HGMH provides a dynamic biomimetic sinuate-microwrinkles change with NT-3 spatial gradient and 2-stage time-dependent distribution, which was further simulated using a 3D finite element model. As demonstrated, in comparison with striped-patterned hydrogel, the triangular-patterned HGMH with highly anisotropic array of microcapsules exhibits remarkably spatial NT-3 gradient distributions that can not only guide neural stem cells (NSCs) migration but also facilitate spinal cord injury regeneration. This approach to construct hierarchical 4D hydrogel system via an electromicrofluidic platform demonstrates the potential for building various biomimetic soft scaffolds in vitro tailed to real soft tissues.

Original languageEnglish
Article number120762
JournalBiomaterials
Volume271
DOIs
Publication statusPublished - Apr 2021

Keywords

  • 4D hydrogel
  • Biomimetic corrugation
  • Biomolecules distribution
  • Electromicrofluidic platform
  • Spinal cord injury repair

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Ceramics and Composites
  • Biomaterials
  • Mechanics of Materials

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