3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres
Autor: | Ruchi Sharma, Imke P. M. Smits, Laura De La Vega, Christopher Lee, Stephanie M. Willerth |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Histology lcsh:Biotechnology Biomedical Engineering regenerative medicine Bioengineering 02 engineering and technology guggulsterone Regenerative medicine Fibrin law.invention 03 medical and health sciences chemistry.chemical_compound Tissue engineering law lcsh:TP248.13-248.65 stems cells Induced pluripotent stem cell Original Research 3D bioprinting Glial fibrillary acidic protein biology Bioengineering and Biotechnology 021001 nanoscience & nanotechnology Neural stem cell 3. Good health Cell biology small molecules 030104 developmental biology chemistry tissue engineering drug delivery biology.protein Guggulsterone 0210 nano-technology Biotechnology |
Zdroj: | Frontiers in Bioengineering and Biotechnology Frontiers in Bioengineering and Biotechnology, Vol 8 (2020) |
ISSN: | 2296-4185 |
Popis: | 3D bioprinting combines cells with a supportive bioink to fabricate multiscale, multi-cellular structures that imitate native tissues. Here, we demonstrate how our novel fibrin-based bioink formulation combined with drug releasing microspheres can serve as a tool for bioprinting tissues using human induced pluripotent stem cell (hiPSC)-derived neural progenitor cells (NPCs). Microspheres, small spherical particles that generate controlled drug release, promote hiPSC differentiation into dopaminergic neurons when used to deliver small molecules like guggulsterone. We used the microfluidics based RX1 bioprinter to generate domes with a 1 cm diameter consisting of our novel fibrin-based bioink containing guggulsterone microspheres and hiPSC-derived NPCs. The resulting tissues exhibited over 90% cellular viability 1 day post printing that then increased to 95% 7 days post printing. The bioprinted tissues expressed the early neuronal marker, TUJ1 and the early midbrain marker, Forkhead Box A2 (FOXA2) after 15 days of culture. These bioprinted neural tissues expressed TUJ1 (15 ± 1.3%), the dopamine marker, tyrosine hydroxylase (TH) (8 ± 1%) and other glial markers such as glial fibrillary acidic protein (GFAP) (15 ± 4%) and oligodendrocyte progenitor marker (O4) (4 ± 1%) after 30 days. Also, quantitative polymerase chain reaction (qPCR) analysis showed these bioprinted tissues expressed TUJ1, NURR1 (gene expressed in midbrain dopaminergic neurons), LMX1B, TH, and PAX6 after 30 days. In conclusion, we have demonstrated that using a microsphere-laden bioink to bioprint hiPSC-derived NPCs can promote the differentiation of neural tissue. |
Databáze: | OpenAIRE |
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