3D Printed Hydrogels with Aligned Microchannels to Guide Neural Stem Cell Migration

Cui Li, Mitchell Kuss, Yunfan Kong, Fujiao Nie, Xiaoyan Liu, Bo Liu, Anna Dunaevsky, Pierre Fayad, Bin Duan, Xiaowei Li

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Following traumatic or ischemic brain injury, rapid cell death and extracellular matrix degradation lead to the formation of a cavity at the brain lesion site, which is responsible for prolonged neurological deficits and permanent disability. Transplantation of neural stem/progenitor cells (NSCs) represents a promising strategy for reconstructing the lesion cavity and promoting tissue regeneration. In particular, the promotion of neuronal migration, organization, and integration of transplanted NSCs is critical to the success of stem cell-based therapy. This is particularly important for the cerebral cortex, the most common area involved in brain injuries, because the highly organized structure of the cerebral cortex is essential to its function. Biomaterials-based strategies show some promise for conditioning the lesion site microenvironment to support transplanted stem cells, but the progress in demonstrating organized cell engraftment and integration into the brain is very limited. An effective approach to sufficiently address these challenges has not yet been developed. Here, we have implemented a digital light-processing-based 3D printer and printed hydrogel scaffolds with a designed shape, uniaxially aligned microchannels, and tunable mechanical properties. We demonstrated the capacity to achieve high shape precision to the lesion site with brain tissue-matching mechanical properties. We also established spatial control of bioactive molecule distribution within 3D printed hydrogel scaffolds. These printed hydrogel scaffolds have shown high neuro-compatibility with aligned neuronal outgrowth along with the microchannels. This study will provide a biomaterial-based approach that can serve as a protective and guidance vehicle for transplanted NSC organization and integration for brain tissue regeneration after injuries.

Original languageEnglish
Pages (from-to)690-700
Number of pages11
JournalACS Biomaterials Science and Engineering
Issue number2
StatePublished - Feb 8 2021


  • aligned microchannel
  • brain injury
  • digital light processing
  • growth factor gradient


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