Developing tissue-engineered bone with pre-vascularization and innervation using a bottom-up approach involving...

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Bone regeneration requires coordinated blood vessel (angiogenesis) and nerve (neurogenesis) development.
• Current tissue-engineered bone (TEB) strategies often struggle to integrate vascular and neural components effectively.
• A bottom-up approach using modular microtissues offers a novel strategy for TEB construction.

Purpose of the Study:

• To develop a novel vascular-nerve-tissue-engineered bone (TEB) using a bottom-up modular microtissue approach.
• To investigate the feasibility of constructing TEB by encapsulating vascular-neural-bone microtissues within gelatin methacrylate (GelMA) hydrogels.
• To evaluate the concurrent capabilities of angiogenesis, neurogenesis, and osteogenesis in the developed TEB for bone repair.

Main Methods:

• Generated vascular-nerve-bone microtissues via 3D co-culture of bone marrow mesenchymal stem cells (BMSCs), endothelial progenitor cells (EPCs), and Schwann cells (SCs).
• Encapsulated these microtissues as modular units within GelMA hydrogels to create large-scale vascular-neural TEB.
• Assessed the construct's functionality at molecular, cellular, and tissue/organ levels, focusing on regenerative capacities.

Main Results:

• Successfully constructed vascular-neural TEB using a microtissue-based, bottom-up approach.
• Demonstrated the feasibility of the protocol at multiple biological levels.
• The GelMA/MSC/EPC/SC TEB exhibited concurrent angiogenesis, neurogenesis, and osteogenesis capabilities.

Conclusions:

• The microtissue-based modular construction is a feasible strategy for creating multifunctional TEB.
• The developed TEB shows promise for simultaneous blood vessel and nerve regeneration alongside bone formation.
• This approach offers novel insights for designing advanced bone grafts for clinical applications in bone defect treatment.