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Peer-reviewedCC BY-NC-NDNano convergence

An interstitial fluid-like NICHE-chip for neural stem cell niche modeling and nanoscale neurotrophic delivery.

  • Surim Shim1
  • Yejin Lee1
  • Hyun Lee2
  • Nayoung Lee3
  • Da Eun Kim4
  • Jongsoo Han1
  • Kang Moo Huh5,6
  • Hyun-Do Jung7
  • Kisuk Yang8,9,10
10 affiliations
  1. 1Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea.
  2. 2Research Institute of Intelligent Manufacturing & Materials Technology, Korea Institute of Industrial Technology, Incheon, 21999, Republic of Korea.
  3. 3Division of Materials Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea.
  4. 4Department of Materials Science and Engineering, Chungnam National University, Daejeon, 34134, Republic of Korea.
  5. 5Department of Materials Science and Engineering, Chungnam National University, Daejeon, 34134, Republic of Korea. [email protected].
  6. 6Department of Polymer Science and Engineering, Chungnam National University, Daejeon, 34134, Republic of Korea. [email protected].
  7. 7Division of Materials Science and Engineering, Hanyang University, Seoul, 04763, Republic of Korea. [email protected].
  8. 8Department of Bioengineering and Nano-Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea. [email protected].
  9. 9Division of Bioengineering, Incheon National University, Incheon, 22012, Republic of Korea. [email protected].
  10. 10Research Center for Bio Materials & Process Development, Incheon National University, Incheon, 22012, Republic of Korea. [email protected].
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Abstract

Neural stem cells (NSCs) reside in anatomically confined niches, where three-dimensional (3D) geometry and interstitial fluid (ISF) flow collectively regulate NSC behavior. However, in vitro platforms that simultaneously recapitulate size-controlled 3D architecture, ISF-like dynamics, and nanoscale therapeutic delivery remain limited. Here, we present a 3D printing-based platform with multi-sized microwells, termed the Neural-Inspired Culture for a Hydrodynamic Environment (NICHE)-chip, which incorporates an osmosis-driven flow system to generate ISF-like flow. The NICHE-chip enabled stable formation of uniform human neural stem cell (hNSC) neurospheres across defined microwell sizes. Under ISF-like flow, hNSC neurospheres showed enhanced viability, reduced apoptosis, and increased self-renewal and differentiation marker expression, particularly in 100 μm microwells. ISF-like flow also promoted laminin-rich extracellular matrix (ECM) deposition and cell-cell interactions, suggesting niche-like remodeling of the 3D microenvironment. In the ISF-integrated 100 μm neurosphere model, amyloid-β (Aβ) was introduced to establish an Alzheimer's disease (AD)-like neurotoxicity model, which was then used to evaluate nanoparticle-mediated neurotrophic factor delivery using brain-derived neurotrophic factor (BDNF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. BDNF-loaded PLGA nanoparticles (BDNF-NPs) enabled sustained BDNF delivery, attenuated Aβ-induced neuronal marker loss, and counter-regulated a subset of Aβ-induced transcriptional alterations associated with neuroprotection. Overall, the NICHE-chip provides an ISF-integrated 3D neurosphere culture platform for NSC niche modeling, AD-like neurotoxicity assessment, and nanoscale neurotrophic factor delivery.

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Cite

BibTeXRIS
BibTeX
@article{shim2026interstitial,
  title = {{An interstitial fluid-like NICHE-chip for neural stem cell niche modeling and nanoscale neurotrophic delivery.}},
  author = {Surim Shim and Yejin Lee and Hyun Lee and Nayoung Lee and Da Eun Kim and Jongsoo Han and Kang Moo Huh and Hyun-Do Jung and Kisuk Yang},
  journal = {Nano convergence},
  year = {2026},
  month = oct,
  doi = {10.1186/s40580-026-00584-8},
  url = {https://europepmc.org/article/MED/42900421},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - An interstitial fluid-like NICHE-chip for neural stem cell niche modeling and nanoscale neurotrophic delivery.
AU  - Surim Shim
AU  - Yejin Lee
AU  - Hyun Lee
AU  - Nayoung Lee
AU  - Da Eun Kim
AU  - Jongsoo Han
AU  - Kang Moo Huh
AU  - Hyun-Do Jung
AU  - Kisuk Yang
PY  - 2026
DA  - 2026/10/20
JO  - Nano convergence
DO  - 10.1186/s40580-026-00584-8
UR  - https://europepmc.org/article/MED/42900421
AB  - Neural stem cells (NSCs) reside in anatomically confined niches, where three-dimensional (3D) geometry and interstitial fluid (ISF) flow collectively regulate NSC behavior. However, in vitro platforms that simultaneously recapitulate size-controlled 3D architecture, ISF-like dynamics, and nanoscale therapeutic delivery remain limited. Here, we present a 3D printing-based platform with multi-sized microwells, termed the Neural-Inspired Culture for a Hydrodynamic Environment (NICHE)-chip, which incorporates an osmosis-driven flow system to generate ISF-like flow. The NICHE-chip enabled stable formation of uniform human neural stem cell (hNSC) neurospheres across defined microwell sizes. Under ISF-like flow, hNSC neurospheres showed enhanced viability, reduced apoptosis, and increased self-renewal and differentiation marker expression, particularly in 100 μm microwells. ISF-like flow also promoted laminin-rich extracellular matrix (ECM) deposition and cell-cell interactions, suggesting niche-like remodeling of the 3D microenvironment. In the ISF-integrated 100 μm neurosphere model, amyloid-β (Aβ) was introduced to establish an Alzheimer's disease (AD)-like neurotoxicity model, which was then used to evaluate nanoparticle-mediated neurotrophic factor delivery using brain-derived neurotrophic factor (BDNF)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles. BDNF-loaded PLGA nanoparticles (BDNF-NPs) enabled sustained BDNF delivery, attenuated Aβ-induced neuronal marker loss, and counter-regulated a subset of Aβ-induced transcriptional alterations associated with neuroprotection. Overall, the NICHE-chip provides an ISF-integrated 3D neurosphere culture platform for NSC niche modeling, AD-like neurotoxicity assessment, and nanoscale neurotrophic factor delivery.
SN  - 2196-5404
ER  -