3D Bioprinting Pluripotent Stem Cell Derived Neural Tissues Using a Novel Fibrin Bioink Containing Drug Releasing Microspheres
Why this work is in the frame
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Bibliographic record
Abstract
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, can provide a controlled release rate for drugs like guggulsterone, shown to promote hiPSC differentiation into dopaminergic neurons, making them a valuable tool for tissue engineering. We printed dome shaped structures with a 1 cm diameter using the Aspect Biosystems RX1 bioprinter with our novel bioink consisting of fibrin, alginate and genipin containing guggulsterone microspheres crosslinked by a mixture of calcium chloride, chitosan and thrombin. Cell viability one day post printing was over 90% for the cells printed using our bioink containing guggulsterone microspheres that increased to 95%, 7 days after printing. The bioprinted tissues expressed the early neuronal marker, TUJ1 and the early midbrain marker, forkhead/winged helix transcription factor (FOXA2) (Forkhead Box A2) after 15 days of culture. These bioprinted neural tissues expressed TUJ1, (15 ± 1.3%), the dopamine marker, tyrosine hydroxylase (TH) (8 ± 0.6%) and other glial markers such as glial fibrillary acidic protein (GFAP) (15 ± 3.5%) and oligodendrocyte progenitor marker (O4) (4 ± 0.9%) as showed by flow cytometry after 30 days. Also, relative gene expression by quantitative polymerase chain reaction (qPCR) showed expression of TUBB3 (TUJ1) and specific midbrain dopaminergic neurons Nuclear receptor related 1 protein (NURR1), LIM Homeobox Transcription Factor 1 Beta (LMX1B), TH, and Paired Box 6 (PAX6) in these tissues after 30 days. In conclusion, we have demonstrated that 3D bioprinting pluripotent stem cell derived neural tissues using a microsphere-laden bioink can promote the differentiation of neural tissue when used to bioprint hiPSC-derived NPCs.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it