Engineering of a complex bone tissue model with endothelialised channels and capillary-like networks

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Scaling up engineered tissues to clinically relevant sizes is hindered by poor nutrient and oxygen diffusion.
• Vascularization is crucial for the survival and function of cells in large engineered tissues.
• Engineering vascularized bone tissue presents challenges in material stiffness and cell-type compatibility.

Purpose of the Study:

• To develop a multiscale vascularization strategy for bone tissue engineering.
• To overcome the dilemma of requiring both stiff materials for osteogenesis and soft matrices for capillarization.
• To create a culture medium supporting simultaneous endothelialization, capillarization, and osteogenesis.

Main Methods:

• Tailoring gelatin-methacryloyl hydrogels by adjusting functionalization for cell spreading and surface endothelialization.
• Investigating a new medium composition to support multiple cell types and functions.
• Utilizing multipotent mesenchymal stromal cells and endothelial colony-forming cells (ECFCs).

Main Results:

• Engineered an 8x8x3 mm construct with a 600 µm central channel.
• Achieved endothelialization of the channel by ECFCs.
• Demonstrated osteogenic cells within the hydrogel adjacent to self-assembled capillary-like networks.

Conclusions:

• The study presents a promising strategy for engineering complex vascularized bone tissue constructs.
• The approach utilizes human primary cells and tailored biomaterials.
• This work paves the way for scaling up engineered tissues and overcoming vascularization challenges.