PMID- 31247598 OWN - NLM STAT- MEDLINE DCOM- 20200129 LR - 20200802 IS - 1758-5090 (Electronic) IS - 1758-5082 (Print) IS - 1758-5082 (Linking) VI - 11 IP - 4 DP - 2019 Aug 1 TI - Neural layer self-assembly in geometrically confined rat and human 3D cultures. PG - 045011 LID - 10.1088/1758-5090/ab2d3f [doi] AB - Neurological disorders affect millions of Americans and this number is expected to rise with the aging population. Development of drugs to treat these disorders may be facilitated by improved in vitro models that faithfully reproduce salient features of the relevant brain regions. Current 3D culture methods face challenges with reliably reproducing microarchitectural features of brain morphology such as cortical or hippocampal layers. In this work, polydimethylsiloxane (PDMS) mini-wells were used to create low aspect ratio, adherent 3D constructs where neurons self-assemble into layers. Layer self-assembly was determined to depend on the size of the PDMS mini-well. Layer formation occurred in cultures composed of primary rat cortical neurons or human induced pluripotent stem cell-derived neurons and astrocytes and was robust and reproducible. Layered 3D constructs were found to have spontaneous neural activity characterized by long bursts similar to activity in the developing cortex. The responses of layered 3D cultures to drugs were more similar to in vivo data than those of 2D cultures. 3D constructs created with this method may be thus suitable as in vitro models for drug discovery for neurological disorders. FAU - Hasan, Md Fayad AU - Hasan MF AD - Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, PA 18015, United States of America. FAU - Ghiasvand, Shabnam AU - Ghiasvand S FAU - Wang, Huaixing AU - Wang H FAU - Miwa, Julie M AU - Miwa JM FAU - Berdichevsky, Yevgeny AU - Berdichevsky Y LA - eng GR - R21 NS088358/NS/NINDS NIH HHS/United States GR - R33 NS088358/NS/NINDS NIH HHS/United States GR - R44 DA032464/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190801 PL - England TA - Biofabrication JT - Biofabrication JID - 101521964 RN - 4368-28-9 (Tetrodotoxin) RN - H030S2S85J (Kynurenic Acid) SB - IM MH - Animals MH - Cell Culture Techniques/*methods MH - Excitatory Postsynaptic Potentials/drug effects MH - Humans MH - Induced Pluripotent Stem Cells/cytology/drug effects MH - Kynurenic Acid/pharmacology MH - Neurons/*cytology/drug effects MH - Rats, Sprague-Dawley MH - Spheroids, Cellular/cytology/drug effects MH - Tetrodotoxin/pharmacology PMC - PMC6908307 MID - NIHMS1061109 COIS- Conflicts of Interest The authors declare no conflict of interest. EDAT- 2019/06/28 06:00 MHDA- 2020/01/30 06:00 PMCR- 2020/08/01 CRDT- 2019/06/28 06:00 PHST- 2019/06/28 06:00 [pubmed] PHST- 2020/01/30 06:00 [medline] PHST- 2019/06/28 06:00 [entrez] PHST- 2020/08/01 00:00 [pmc-release] AID - 10.1088/1758-5090/ab2d3f [doi] PST - epublish SO - Biofabrication. 2019 Aug 1;11(4):045011. doi: 10.1088/1758-5090/ab2d3f.