8.3 Cell-biomaterial interactions in tissue engineering

Cell-biomaterial interactions are key to tissue engineering success. They influence cell attachment, growth, and differentiation on scaffolds. Understanding these interactions helps design better biomaterials that guide cellular responses and promote tissue regeneration.

Surface properties, topography, and biochemical factors all play a role in how cells behave on scaffolds. By tweaking these elements, we can control cell adhesion, spreading, and function. This is crucial for creating engineered tissues that mimic natural ones.

Cell-Biomaterial Interactions in Tissue Engineering

Fundamentals of Cell-Biomaterial Interactions

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• Cell-biomaterial interactions directly influence cell behavior, tissue formation, and overall construct performance
• These interactions determine initial cell attachment, subsequent proliferation, and eventual differentiation of cells on biomaterial scaffolds
• Nature of cell-biomaterial interactions affects long-term viability and functionality of engineered tissues, impacting integration with host tissues upon implantation
• Understanding and controlling these interactions allows design of biomaterials that guide desired cellular responses and promote tissue regeneration
• Cell-biomaterial interactions play a crucial role in maintaining phenotype and function of cells within engineered construct, essential for replicating native tissue structure and function

Impact on Tissue Engineering Success

• Cell-biomaterial interactions fundamental to success of tissue engineering strategies
• Proper interactions crucial for initial cell adhesion (fibroblasts attaching to collagen scaffold)
• Interactions influence cell proliferation rates (smooth muscle cells dividing on biodegradable polymer)
• Cell differentiation guided by biomaterial properties (mesenchymal stem cells differentiating into osteoblasts on hydroxyapatite scaffold)
• Successful interactions promote formation of functional tissue structures (hepatocytes forming liver-like tissue on 3D porous scaffold)
• Long-term stability of engineered tissues depends on sustained positive cell-biomaterial interactions (chondrocytes maintaining cartilage phenotype in hydrogel matrix)

Factors Influencing Cell Behavior on Scaffolds

Surface Properties and Topography

• Surface chemistry of biomaterials, including presence of specific functional groups, significantly affects cell adhesion through interactions with cell surface receptors
  • Carboxyl groups promote protein adsorption and cell attachment
  • Amine groups enhance cell adhesion and spreading
• Topographical features of scaffold influence cell attachment, spreading, and subsequent behavior
  • Roughness affects cell morphology and adhesion strength
  • Porosity impacts cell infiltration and nutrient diffusion
  • Micro/nanostructures guide cell alignment and migration
• Mechanical properties of biomaterial play critical role in cell fate determination and differentiation through mechanotransduction pathways
  • Substrate stiffness influences stem cell lineage commitment (soft substrates promote neurogenesis, stiff substrates promote osteogenesis)
  • Elasticity affects cell spreading and cytoskeletal organization

Biochemical and Structural Factors

• Presence and distribution of cell adhesion molecules mediate initial attachment and subsequent signaling events that regulate cell behavior
  • Integrins bind to specific ligands on biomaterial surface
  • Cadherins facilitate cell-cell interactions within the scaffold
• Soluble factors modulate cell proliferation and differentiation through various signaling pathways
  • Growth factors incorporated into scaffold (VEGF for angiogenesis)
  • Cytokines produced by cells in response to biomaterial interactions
• Degradation rate and products of biodegradable scaffolds influence cell behavior by altering local microenvironment and releasing bioactive molecules
  • Gradual degradation of poly(lactic-co-glycolic acid) (PLGA) releases acidic byproducts
  • Calcium phosphate dissolution from bioactive glass stimulates osteoblast activity
• Three-dimensional architecture of scaffold affects cell migration, nutrient diffusion, and formation of cell-cell contacts
  • Pore size influences cell infiltration and tissue ingrowth
  • Interconnectivity of pores impacts mass transport and vascularization

Surface Properties for Modulating Cell Interactions

Chemical and Physical Surface Modifications

• Surface charge and hydrophobicity/hydrophilicity of biomaterials impact protein adsorption and subsequent cell adhesion
  • Negatively charged surfaces attract positively charged proteins
  • Hydrophilic surfaces generally promote cell adhesion
• Chemical modifications enhance cell attachment and guide cellular responses
  • Incorporation of specific functional groups (carboxyl, hydroxyl, amine)
  • Addition of biomolecules (growth factors, enzymes)
• Physical surface modifications alter surface topography and chemistry to promote desired cell-biomaterial interactions
  • Plasma treatment increases surface energy and introduces functional groups
  • Laser patterning creates defined micro/nanotopographies
• Immobilization of extracellular matrix (ECM) proteins or peptide sequences on biomaterial surfaces mimics natural cell environment and improves cell adhesion and function
  • Collagen coating enhances cell attachment
  • RGD peptide sequence promotes integrin-mediated adhesion

Advanced Surface Modification Techniques

• Surface modifications create gradients of properties or bioactive molecules, allowing spatial control of cell behavior within scaffold
  • Concentration gradients of growth factors guide cell migration
  • Stiffness gradients influence stem cell differentiation
• Stability and longevity of surface modifications in physiological conditions crucial for maintaining effectiveness over time
  • Covalent bonding of bioactive molecules increases stability
  • Controlled release systems prolong activity of immobilized factors
• Novel surface modification techniques offer precise control over presentation of bioactive cues to cells
  • Layer-by-layer assembly creates multilayered coatings with defined compositions
  • Click chemistry allows specific and efficient attachment of biomolecules

Biomaterial Degradation and Tissue Regeneration

Temporal Effects of Degradation

• Rate of biomaterial degradation affects temporal changes in scaffold properties, dynamically influencing cell behavior throughout tissue regeneration process
  • Fast-degrading materials (collagen) provide initial support but rapid remodeling
  • Slow-degrading materials (polycaprolactone) offer prolonged structural integrity
• Degradation products of biomaterials modulate local pH and ionic environment, potentially affecting cell viability, proliferation, and differentiation
  • Lactic acid from PLA degradation temporarily lowers local pH
  • Calcium ions released from bioactive glass stimulate osteoblast activity
• Release of bioactive molecules or growth factors during controlled degradation provides temporal cues for tissue formation and maturation
  • Gradual release of BMP-2 from degrading PLGA microspheres promotes bone formation
  • Controlled release of VEGF supports angiogenesis in degrading hydrogels

Structural and Biological Implications

• Changes in scaffold mechanical properties due to degradation alter mechanical signals received by cells, influencing their phenotype and function over time
  • Decreasing stiffness of hydrogels affects stem cell differentiation trajectory
  • Gradual loss of compressive strength in bone scaffolds impacts osteoblast activity
• Creation of space through scaffold degradation crucial for allowing cell migration, matrix deposition, and formation of new tissue structures
  • Pore enlargement in degrading scaffolds facilitates cell infiltration
  • Void spaces created by degradation allow for new ECM deposition
• Balance between scaffold degradation and new tissue formation critical for maintaining structural integrity and mechanical support during regeneration process
  • Matching degradation rate with tissue growth rate ensures continuous support
  • Gradual transfer of load-bearing function from scaffold to newly formed tissue
• Potential immune responses to degradation products must be considered, as they can impact overall success of tissue regeneration and integration with host tissues
  • Inflammatory response to degradation byproducts can affect tissue formation
  • Adaptive immune recognition of scaffold materials may lead to rejection