Biomimetic open porous structured core-shell microtissue with enhanced mechanical properties for bottom-up bone...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Hydrogel-based microtissues mimic native tissue microarchitecture for cell expansion and differentiation.
• Natural polymer microtissues often have suboptimal mechanical properties and osteogenic activity for bone reconstruction.
• Core-shell structures combine materials to enhance microtissue mechanical properties.

Purpose of the Study:

• To develop and evaluate a core-shell microtissue scaffold for enhanced bone regeneration.
• To improve the mechanical properties and osteogenic potential of microtissues for bone repair applications.

Main Methods:

• Fabrication of core-shell micro-scaffolds using a micro-stencil array chip (gelatin shell, demineralized bone matrix with BMP-2 core).
• Culture of rat bone marrow mesenchymal stem cells (BMSCs) on scaffolds in bioreactors to form microtissues.
• In vitro evaluation of physical characteristics, biocompatibility, osteogenesis, and drug release.
• In vivo testing via ectopic and orthotopic bone implantation in rat models.

Main Results:

• Core-shell scaffolds exhibited nearly triple the Young's modulus of gelatin scaffolds, indicating superior mechanical properties.
• BMSCs showed rapid proliferation and high viability on core-shell microtissues with enhanced osteogenic potential (increased calcification and gene expression).
• In vivo studies demonstrated significant new bone formation in both ectopic and orthotopic implantation sites at 3 months.

Conclusions:

• The developed core-shell microtissue construction strategy offers improved mechanical strength and osteogenic capacity.
• This novel approach presents a promising cell delivery platform for effective bone regeneration.
• The core-shell design effectively integrates desirable properties for enhanced bone tissue engineering.