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Using dihydropyridine-release strategies to enhance load effects in engineered human bone constructs.
Mairead A Wood1, Ying Yang, Peter B M Thomas
1Institute of Science and Technology in Medicine, Keele University, Stoke-on-Trent, United Kingdom.
Tissue Engineering
|September 26, 2006
Summary
Novel biodegradable scaffolds deliver the calcium channel agonist Bay K8644 to enhance mechanical signaling for bone tissue engineering. This promotes osteoid production and mineralization, leading to stronger engineered bone tissue.
Area of Science:
- Biomaterials Science
- Tissue Engineering
- Biomedical Engineering
Background:
- Mechanotransduction is crucial for bone formation, often stimulated by mechanical bioreactors in tissue engineering.
- Voltage-operated calcium channels (VOCCs) mediate early mechanotransduction signals.
- Bay K8644 (Bay) prolongs the opening of mechanosensitive L-type VOCCs.
Purpose of the Study:
- To develop novel biodegradable scaffolds encapsulating Bay K8644 for enhanced bone tissue engineering.
- To investigate the effect of Bay-released scaffolds on osteoid production and mineralization under mechanical loading.
- To augment mechanical signaling for improved load-bearing engineered tissue.
Main Methods:
- Fabrication of 3D porous poly(L-lactide) acid scaffolds using solvent-casting and salt-leaching.
- Encapsulation of Bay K8644 within the scaffolds for sustained release.
- In vitro evaluation using human bone cells in a perfusion-compression bioreactor, analyzed by Western blotting and calcium assays.
Main Results:
- Scaffolds demonstrated sustained release of Bay K8644, confirmed by ultraviolet spectroscopy.
- Bay-releasing scaffolds significantly enhanced collagen I production and osteoid calcification compared to controls under physiological loading.
- Increased levels of Osteopontin and the alpha2delta1 VOCC subunit were observed with perfusion-compression conditioning.
Conclusions:
- Bay-encapsulated scaffolds effectively enhance mechanical signals by modulating VOCCs.
- These scaffolds promote key bone formation markers, including collagen and mineralization.
- The developed scaffolds show potential for creating load-bearing engineered bone tissue.
