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3D Bioprinted Osteogenic Tissue Models for In Vitro Drug Screening
Erick Breathwaite1, Jessica Weaver1, Justin Odanga1
1Institute of Regenerative Medicine, LifeNet Health, 1864 Concert Drive, Virginia Beach, VA 23453, USA.
Molecules (Basel, Switzerland)
|August 6, 2020
Summary
This study developed a 3D bioprinted bone model for drug screening. The 3D model showed increased sensitivity in detecting drug effects on osteogenesis compared to traditional 2D cultures.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Drug Discovery
Background:
- Metabolic bone diseases affect millions globally, necessitating advanced in vitro models for research.
- Targeting signaling pathways like Hedgehog, Wnt/β-catenin, and PI3K-AKT is crucial for developing bone-forming or bone-impairing drugs.
- Existing in vitro models require enhancement for accurate drug screening and therapeutic strategy development.
Purpose of the Study:
- To evaluate a scaffold-free 3D bioprinted bone model using bone marrow-derived mesenchymal stem cells (BM-MSCs) for drug screening.
- To compare the efficacy of the 3D bioprinted model against traditional 2D monolayer cultures in assessing drug-induced osteogenic differentiation.
- To screen four drugs (Icariin, Purmorphamine, PD98059, U0126) for their effects on osteogenesis.
Main Methods:
- Utilized differentiated BM-MSC scaffold-free 3D bioprinted constructs and 2D monolayer cultures.
- Treated cultures with drugs predicted to promote (Icariin, Purmorphamine) or impair (PD98059, U0126) osteogenesis.
- Assessed osteogenic differentiation over four weeks by measuring mineralization, alkaline phosphatase (ALP) activity, and gene expression of bone markers, signaling molecules, and transcription factors.
Main Results:
- Both 3D and 2D models showed increased mineralization, ALP activity, and expression of osteogenesis markers (BGLAP, SSP1, COL1A1) and related genes (MAPK1, WNT1, AKT1, RUNX2, GLI1) with Icariin and Purmorphamine.
- Both models showed decreased mineralization, ALP activity, and gene expression with PD98059 and U0126.
- The 3D bioprinted model exhibited greater differences in ALP activity and gene expression compared to the 2D model, indicating higher sensitivity.
Conclusions:
- The scaffold-free 3D bioprinted bone model is a more sensitive and biologically relevant platform for drug screening than traditional 2D monolayer cultures.
- This advanced model can aid in analyzing bone pathogenesis and developing therapeutic strategies for metabolic bone diseases.
- The findings support the use of 3D bioprinted constructs for more accurate in vitro drug testing in bone research.
