9.2 Vascular Tissue Engineering Approaches

Tissue engineering aims to create functional blood vessels for transplantation. Two main approaches exist: scaffold-based, using pre-formed structures, and scaffold-free, relying on cell self-assembly. Each has pros and cons in mimicking natural tissue architecture and providing mechanical support.

Creating blood vessels involves careful cell selection, seeding, and culturing. Bioreactors play a crucial role in vessel maturation by providing nutrients and mechanical stimuli. However, challenges persist in replicating complex vascular networks and ensuring long-term functionality after implantation.

Scaffold-Based and Scaffold-Free Approaches

Scaffold-based vs scaffold-free approaches

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Top images from around the web for Scaffold-based vs scaffold-free approaches

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• Scaffold-based approaches utilize pre-formed structures made from synthetic polymers (polylactic acid), natural biomaterials (collagen), or hybrid composites
  • Provide mechanical support and control over structure and porosity enhancing tissue stability
  • May trigger foreign body response or produce degradation products affecting cell behavior
• Scaffold-free approaches rely on cell self-assembly techniques like cell sheets, spheroids, or bioprinting
  • Create more physiologically relevant structures mimicking native tissue architecture
  • Lack initial mechanical strength and face challenges in creating complex geometries
• Comparison points highlight differences in cell seeding ease, tissue architecture mimicry, and scalability potential
  • Scaffold-based offers easier initial cell distribution but may not replicate natural tissue structure
  • Scaffold-free provides better tissue mimicry but struggles with larger construct creation

Cell seeding and culturing process

• Cell sources include endothelial cells, smooth muscle cells, fibroblasts, and stem cells (mesenchymal stem cells)
• Cell isolation involves tissue biopsy or stem cell harvesting followed by in vitro culture and proliferation
• Seeding techniques encompass static (gravity-driven) and dynamic (rotation or perfusion) methods
  • Efficiency affected by cell concentration, seeding time, and scaffold surface properties
• Culture conditions require specific growth factors, oxygen tension, and mechanical stimulation (shear stress, cyclic strain)
• Monitoring uses cell viability assays and functional markers (endothelial cell alignment, smooth muscle cell contractility)

Bioreactors and Vascular Network Formation

Bioreactors for blood vessel maturation

• Types include perfusion, pulsatile flow, and rotating wall vessel bioreactors
• Functions involve nutrient and oxygen delivery, waste removal, and mechanical stimuli application
• Mechanical stimulation promotes cell alignment, enhances extracellular matrix production, and improves tissue strength
• Biochemical environment control regulates pH and maintains appropriate gas concentrations
• Maturation indicators include increased mature cell marker expression, enhanced mechanical properties, and improved barrier function

Challenges in vascular network creation

• Scale and complexity issues arise when replicating hierarchical blood vessel structure and creating microvasculature
• Cell sourcing difficulties include obtaining sufficient quantities and maintaining phenotype during culture
• Anastomosis with host vasculature requires proper integration and thrombosis prevention at the interface
• Achieving appropriate mechanical properties involves matching compliance with native vessels and withstanding physiological pressures
• Maintaining long-term patency requires preventing intimal hyperplasia and resisting thrombosis
• Functional assessment needs methods to evaluate tissue perfusion and oxygen delivery in thick tissues
• Regulatory challenges include meeting safety standards and scaling up production for clinical use