Scaffolds are crucial in tissue engineering, providing a framework for cells to grow and form new tissues. They need the right structure, properties, and ability to interact with cells to be effective. This topic dives into what makes a good scaffold.

From porosity to degradation, cell seeding to vascularization, and 3D printing to electrospinning, we'll explore the key aspects of scaffold design and fabrication. Understanding these concepts is essential for creating functional engineered tissues.

Scaffold Structure and Properties

Porosity and Pore Characteristics

• Porosity defines the percentage of void space within a scaffold
• Optimal porosity ranges from 60% to 90% depending on the target tissue type
• High porosity promotes cell migration, nutrient diffusion, and waste removal
• Pore size affects cell behavior and tissue formation
• Optimal pore sizes vary by tissue type (bone: 100-350 μm, skin: 20-125 μm)
• Interconnectivity refers to the network of connected pores throughout the scaffold
• High interconnectivity enhances cell migration and nutrient transport
• Interconnected pores facilitate uniform cell distribution and tissue growth

Mechanical and Degradation Properties

• Mechanical strength must match the target tissue to support tissue formation
• Scaffolds should withstand physiological loads and maintain structural integrity
• Elastic modulus of scaffolds should mimic native tissue (bone: 10-1500 MPa, cartilage: 0.5-1 MPa)
• Biodegradation rate determines how long the scaffold remains in the body
• Controlled degradation allows for gradual replacement of scaffold with new tissue
• Degradation rate can be tuned by altering material composition or crosslinking density
• Ideal scaffolds degrade at a rate that matches new tissue formation

Cell-Scaffold Interactions

Cell Seeding and Attachment

• Cell seeding involves introducing cells onto or into the scaffold
• Seeding methods include static seeding, dynamic seeding, and perfusion seeding
• Static seeding relies on gravity to deposit cells onto the scaffold surface
• Dynamic seeding uses agitation or centrifugation to improve cell distribution
• Perfusion seeding employs fluid flow to enhance cell penetration into the scaffold
• Cell attachment depends on scaffold surface chemistry and topography
• Surface modifications (plasma treatment, protein coating) can enhance cell adhesion
• Cell-adhesive peptides (RGD sequence) improve cell attachment and spreading

Vascularization and Growth Factor Delivery

• Vascularization crucial for supplying oxygen and nutrients to cells within the scaffold
• Strategies to promote vascularization include incorporating angiogenic factors (VEGF, bFGF)
• Co-culturing endothelial cells with tissue-specific cells enhances blood vessel formation
• Microchannels or sacrificial templates create pre-defined vascular networks
• Growth factor incorporation supports cell proliferation and differentiation
• Controlled release of growth factors achieved through encapsulation or covalent binding
• Scaffold-based delivery systems provide spatial and temporal control of growth factor release
• Examples of growth factors: BMP-2 for bone, TGF-β for cartilage, NGF for nerve tissue

Scaffold Fabrication Techniques

Additive Manufacturing Methods

• 3D printing enables precise control over scaffold architecture and composition
• Stereolithography (SLA) uses photopolymerization to create complex structures
• Fused deposition modeling (FDM) extrudes thermoplastic materials layer by layer
• Selective laser sintering (SLS) fuses powder particles to form scaffolds
• Bioprinting combines cells and biomaterials to create tissue-like structures
• 3D printed scaffolds allow for patient-specific designs based on medical imaging data

Fiber-based and Biological Scaffold Fabrication

• Electrospinning produces nano to microscale fibers for tissue engineering applications
• Electrospun scaffolds mimic the fibrous structure of extracellular matrix
• Fiber diameter and alignment can be controlled by adjusting processing parameters
• Electrospun scaffolds used for various tissues (skin, blood vessels, neural tissue)
• Decellularized matrices derived from native tissues or organs
• Decellularization process removes cells while preserving extracellular matrix components
• Decellularized scaffolds maintain natural tissue architecture and composition
• Applications include whole organ engineering (heart, lung, liver)