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Engineering three-dimensional bone macro-tissues by guided fusion of cell spheroids
Vinothini Prabhakaran1,2, Ferry P W Melchels3,4, Lyndsay M Murray1,2,5
1Anatomy@Edinburgh, Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Edinburgh, United Kingdom.
Frontiers in Endocrinology
|January 3, 2024
Summary
Researchers developed a novel bioassembly technique to create large, scaffold-free 3D bone tissue. This method successfully mimics natural bone formation and maturation, offering potential for treating bone diseases like osteoporosis.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Regenerative Medicine
Background:
- Scaffold-free tissue engineering aims to create larger tissue equivalents that mimic native tissues.
- Bioassembly techniques are evolving to achieve this goal.
- Developing functional 3D bone models is crucial for studying bone diseases and testing therapies.
Purpose of the Study:
- To upscale a 3D bone in-vitro model using bioassembly of differentiated rat osteoblast (dROb) spheroids.
- To develop and mature these spheroids into a bone macrotissue.
- To assess the morphological and molecular characteristics of the fabricated bone macrotissue.
Main Methods:
- dROb spheroids were cultured and assessed for viability, proliferation, and mineralization.
- A novel bioassembly system using pillar array supports was developed to fuse spheroids.
- Supports were removed to allow scaffold-free growth and maturation.
- Morphological and molecular analyses were performed.
Main Results:
- Spheroids proliferated, followed by mineralization. Necrotic core size increased with spheroid size.
- Bioassembly resulted in fused spheroids forming macrotissues >2.5 mm with mineral formation.
- Molecular analysis confirmed osteogenic maturation, including osteocalcin presence and alkaline phosphatase upregulation.
Conclusions:
- A novel bioassembly approach successfully fabricated 3D bone macrotissues.
- The fabricated tissues mimicked physiological osteogenesis morphologically and molecularly.
- This approach holds potential for bone tissue engineering and research into bone ailments like osteoporosis.
