7.2 Surface chemistry and topography
6 min read•july 30, 2024
Surface chemistry and topography are crucial in cell-material interactions. They influence how cells attach, spread, and function on biomaterials. Understanding these factors helps engineers design better implants and tissue scaffolds.
Surface modifications can enhance cell responses. Techniques like , , and allow precise control over surface properties. This enables the creation of tailored environments for specific cell types and tissue engineering applications.
Surface Chemistry in Cell Interactions
Role of Surface Chemistry and Topography
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- Surface chemistry and topography play a critical role in determining how cells interact with biomaterials and the extracellular matrix (ECM)
- Cell-material interactions are influenced by surface properties such as , charge, , and the presence of specific functional groups or biomolecules
- Surface chemistry affects , which mediates and signaling through integrin receptors and
- Surface topography, including micro- and nano-scale features, can modulate cell shape, cytoskeletal organization, and pathways
- The interplay between surface chemistry and topography determines cell fate decisions, such as adhesion, proliferation, migration, and differentiation, ultimately impacting tissue formation and regeneration
Effects of Surface Modification Techniques
- Physical surface modification techniques, such as plasma treatment or UV irradiation, can alter surface wettability, roughness, and introduce functional groups to enhance cell adhesion and proliferation
- Chemical surface modification methods, including (SAMs), , and , allow precise control over surface chemistry and the presentation of
- SAMs, formed by the spontaneous assembly of alkanethiols on gold or silanes on oxide surfaces, can present specific functional groups or peptides to promote cell adhesion and proliferation
- Polymer grafting techniques, such as surface-initiated polymerization or layer-by-layer assembly, enable the immobilization of biomolecules and creation of responsive or switchable surfaces
- Biochemical surface modification, through the immobilization of ECM proteins, peptides, or growth factors, can selectively enhance cell adhesion and proliferation by engaging specific cell surface receptors
- Micro- and nano-patterning techniques, such as photolithography, , or , can create controlled topographical features to guide cell alignment, adhesion, and proliferation
- The stability and durability of surface modifications should be considered, as degradation or delamination of the modified layer can affect long-term cell behavior and device performance
Surface Properties for Cell Behavior
Wettability and Charge
- Surface wettability, or /, affects protein adsorption and cell adhesion. Moderately hydrophilic surfaces often promote cell attachment and spreading
- Example: Hydrophilic surfaces modified with polyethylene glycol (PEG) can resist protein adsorption and cell adhesion, while moderately hydrophilic surfaces like tissue culture polystyrene (TCPS) support cell attachment
- Surface charge, either positive or negative, influences the electrostatic interactions between cells and materials. Positively charged surfaces tend to enhance cell adhesion due to the negative charge of cell membranes
- Example: Positively charged polymers like poly-L-lysine (PLL) or polyethylenimine (PEI) can enhance cell adhesion and transfection efficiency
Roughness and Functional Groups
- Surface roughness, at both micro- and nano-scales, can modulate cell morphology, adhesion strength, and differentiation. Optimal roughness varies depending on cell type and desired cellular response
- Example: Nano-scale roughness on titanium surfaces can enhance osteoblast adhesion and differentiation for improved osseointegration of dental implants
- The presence of specific functional groups, such as amine (-NH2), carboxyl (-COOH), or hydroxyl (-OH), can selectively bind proteins and influence cell behavior
- Example: Carboxyl-functionalized surfaces can promote the adsorption of , an ECM protein that facilitates cell adhesion through integrin binding
Bioactive Molecules and Stiffness
- Immobilization of bioactive molecules, such as ECM proteins (fibronectin, ), peptides (), or growth factors, on surfaces can provide specific biochemical cues to guide cell fate
- Example: RGD peptide-functionalized surfaces can selectively promote the adhesion and spreading of cells expressing integrin receptors
- Surface stiffness, as determined by the underlying material's elastic modulus, can direct stem cell lineage commitment. Softer surfaces often promote neuronal differentiation, while stiffer surfaces favor osteogenic differentiation
- Example: Mesenchymal stem cells (MSCs) cultured on soft hydrogels (0.1-1 kPa) tend to differentiate into neurons, while MSCs on stiff substrates (25-40 kPa) prefer osteogenic differentiation
Surface Modification for Cell Growth
Physical and Chemical Modification
- Physical surface modification techniques, such as plasma treatment or UV irradiation, can alter surface wettability, roughness, and introduce functional groups to enhance cell adhesion and proliferation
- Example: Oxygen plasma treatment can increase the hydrophilicity and introduce oxygen-containing functional groups on polymer surfaces, promoting cell attachment and growth
- Chemical surface modification methods, including self-assembled monolayers (SAMs), silanization, and polymer grafting, allow precise control over surface chemistry and the presentation of bioactive molecules
- Example: Silanization with 3-aminopropyltriethoxysilane (APTES) can introduce amine groups on glass or silicon surfaces, enabling the covalent immobilization of biomolecules or subsequent functionalization
- Biochemical surface modification, through the immobilization of ECM proteins, peptides, or growth factors, can selectively enhance cell adhesion and proliferation by engaging specific cell surface receptors
- Example: Covalent immobilization of () on biomaterial surfaces can promote endothelial cell proliferation and angiogenesis
Patterning and Stability
- Micro- and nano-patterning techniques, such as photolithography, soft lithography, or electron beam lithography, can create controlled topographical features to guide cell alignment, adhesion, and proliferation
- Example: Microcontact printing of ECM proteins in specific patterns can spatially control cell adhesion and guide the formation of organized cell monolayers or co-cultures
- The stability and durability of surface modifications should be considered, as degradation or delamination of the modified layer can affect long-term cell behavior and device performance
- Example: The use of stable covalent bonding or cross-linking strategies can improve the long-term stability of immobilized biomolecules or polymer coatings on surfaces
Surface Design for Tissue Organization
Anisotropic Topographies and Gradients
- Anisotropic surface topographies, such as grooves, ridges, or aligned fibers, can guide cell alignment and orient cytoskeletal organization through contact guidance
- The dimensions of topographical features, including width, depth, and spacing, should be optimized for specific cell types and desired alignment
- Aligned topographies can direct cell migration and promote the formation of oriented tissues, such as neurites in nerve regeneration or myotubes in muscle tissue engineering
- Gradient surfaces, with gradual changes in surface chemistry, stiffness, or topography, can guide cell migration and spatially control tissue organization
- Chemical gradients can be created using microfluidic devices or diffusion-based methods to generate concentration profiles of biomolecules or signaling factors
- Stiffness gradients, produced by varying the crosslinking density or composition of hydrogels or polymers, can direct cell migration and differentiation
Micropatterning and Hierarchical Designs
- Micropatterned surfaces, with controlled geometries and sizes of adhesive islands, can regulate cell shape, spreading, and differentiation
- The size and spacing of micropatterned features can influence cell-cell interactions, polarization, and the formation of multicellular structures, such as vascular networks or epithelial tissues
- Example: Micropatterned islands of fibronectin on non-adhesive backgrounds can control the size and shape of single cells or multicellular clusters, influencing their differentiation and function
- Hierarchical surface designs, combining micro- and nano-scale features, can mimic the complex hierarchical structure of native ECM and provide multiscale cues for tissue organization
- Example: Electrospun scaffolds with aligned nanofibers and microgrooves can guide the orientation and alignment of cells and ECM deposition, recapitulating the hierarchical organization of native tissues like tendons or ligaments
- Surface features can be dynamically modulated using stimuli-responsive materials, such as temperature-sensitive polymers or light-responsive molecules, to control cell behavior and tissue remodeling over time
- Example: Thermoresponsive polymers like poly(N-isopropylacrylamide) (PNIPAAm) can switch between hydrophobic and hydrophilic states, allowing the dynamic control of cell adhesion and detachment for cell sheet engineering or regenerative medicine applications
Key Terms to Review (29)
3D printing: 3D printing, also known as additive manufacturing, is a process that creates three-dimensional objects layer by layer from digital models. This technology allows for the precise fabrication of complex geometries, making it particularly useful in the development of customized medical devices and scaffolds using both natural and synthetic biomaterials.
Atomic Force Microscopy: Atomic force microscopy (AFM) is a high-resolution imaging technique that uses a cantilever with a sharp tip to scan surfaces at the atomic level, allowing for the measurement of surface topography and mechanical properties. This technique is essential for understanding how cells respond to mechanical stimuli, characterizing materials, and analyzing surface chemistry, making it a pivotal tool in various scientific fields.
Bioactive molecules: Bioactive molecules are naturally occurring compounds that have an effect on living organisms, particularly in terms of influencing biological processes. These molecules can interact with biological systems and play critical roles in cellular signaling, immune responses, and tissue regeneration, making them essential in the field of regenerative medicine. Their incorporation into biomaterials and their influence on surface chemistry and topography significantly enhance the functionality and performance of these materials.
Biomolecule immobilization: Biomolecule immobilization refers to the process of attaching biomolecules, such as proteins, enzymes, or antibodies, onto solid supports or surfaces in a way that maintains their biological activity. This technique is crucial in various applications, including biosensors, drug delivery systems, and tissue engineering. By effectively immobilizing biomolecules, researchers can enhance the stability, functionality, and reusability of these important biological agents.
Cell Adhesion: Cell adhesion refers to the process by which cells interact and attach to neighboring cells or the extracellular matrix (ECM) through specific proteins known as cell adhesion molecules (CAMs). This process is crucial for tissue formation, maintenance, and repair, as well as for cell signaling and communication.
Chemical Grafting: Chemical grafting is a process that involves the covalent bonding of molecules onto a surface to modify its chemical properties. This technique enhances the functionality and compatibility of materials, especially in biomedical applications where surface characteristics can significantly influence cellular behavior. By altering surface chemistry through grafting, it's possible to create tailored environments that promote desired interactions between materials and biological systems.
Collagen: Collagen is a primary structural protein that provides strength and support to various tissues in the body, including skin, bones, cartilage, and tendons. It plays a crucial role in the composition of the extracellular matrix, influencing the behavior of stem cells and their microenvironments, as well as facilitating the remodeling and repair of tissues.
Electron beam lithography: Electron beam lithography is a highly precise technique used to create nanostructures by utilizing a focused beam of electrons to write custom patterns onto a substrate coated with an electron-sensitive film. This process is significant for its ability to produce complex designs with high resolution, making it ideal for applications in semiconductor manufacturing and nanotechnology. The technique’s effectiveness is largely influenced by surface chemistry and topography, which impact how the electron beam interacts with the material.
Fibronectin: Fibronectin is a high-molecular-weight glycoprotein of the extracellular matrix that plays a crucial role in cell adhesion, growth, migration, and differentiation. It serves as a bridge between cells and the surrounding matrix, influencing how cells interact with their environment, including stem cell niches and biomaterials.
Focal adhesion complexes: Focal adhesion complexes are dynamic, multi-protein assemblies that form at the interface between cells and the extracellular matrix (ECM). They play a crucial role in connecting the actin cytoskeleton of cells to ECM proteins, enabling cells to sense and respond to their environment, facilitating processes such as migration, proliferation, and differentiation. The properties of surface chemistry and topography greatly influence the formation and function of these complexes.
Hydrophilicity: Hydrophilicity refers to the affinity of a substance for water, meaning that hydrophilic materials can interact favorably with water molecules. This property is crucial in biomaterials as it significantly influences how cells adhere to surfaces and how biomaterials interact with their surrounding biological environment. Materials with high hydrophilicity tend to promote better cell adhesion, which is essential for tissue integration and healing.
Hydrophobicity: Hydrophobicity refers to the property of a molecule or surface that repels water. This characteristic is vital in understanding how materials interact with biological fluids, affecting processes like adhesion, cell behavior, and material compatibility. Hydrophobic surfaces can hinder the wetting process, influencing how cells and proteins behave in regenerative medicine applications.
Joseph DeSimone: Joseph DeSimone is a prominent scientist and engineer known for his groundbreaking work in the field of biomaterials, particularly in the development of innovative natural and synthetic materials for medical applications. His research emphasizes the importance of surface chemistry and topography in determining how biomaterials interact with biological systems, making significant contributions to regenerative medicine and tissue engineering.
Mechanotransduction: Mechanotransduction is the process by which cells convert mechanical stimuli from their environment into biochemical signals that can influence cellular behavior. This key mechanism is vital for understanding how cells interact with their extracellular matrix (ECM), migrate, and adapt to various physical forces, playing a crucial role in tissue engineering and regenerative medicine.
Plasma treatment: Plasma treatment is a surface modification technique that uses ionized gas (plasma) to enhance the properties of materials, such as adhesion, wettability, and biocompatibility. This process involves creating a plasma environment that interacts with the surface of a material, effectively altering its chemical and physical properties without significantly changing its bulk characteristics. The benefits of plasma treatment extend to applications in regenerative medicine, where improved surface characteristics can influence cell behavior and tissue integration.
Polymer grafting: Polymer grafting is a process where polymer chains are chemically bonded to a substrate or another polymer to enhance surface properties or modify the material's characteristics. This technique is crucial for improving biocompatibility, adhesion, and mechanical strength, especially in regenerative medicine applications. By strategically modifying the surface chemistry and topography, polymer grafting can create tailored materials that interact better with biological systems.
Porosity: Porosity refers to the measure of void spaces in a material, typically expressed as a percentage of the total volume. In regenerative medicine, porosity is crucial as it influences nutrient and cell migration, scaffold design, and tissue integration within biological systems. A well-designed porous structure can support the growth of cells and tissues by allowing for the exchange of nutrients and waste products.
Porous Scaffolds: Porous scaffolds are three-dimensional structures designed to support cell attachment and tissue growth, featuring interconnected voids that allow for the diffusion of nutrients and waste products. These scaffolds play a critical role in regenerative medicine by mimicking the extracellular matrix, providing mechanical support while facilitating cellular activities and tissue formation. The surface chemistry and topography of these scaffolds significantly influence cellular behavior, including adhesion, proliferation, and differentiation.
Protein adsorption: Protein adsorption refers to the process by which proteins adhere to surfaces, particularly in the context of biomaterials and tissue engineering. This phenomenon is critical as it influences cellular responses, biocompatibility, and the overall performance of medical devices. Understanding protein adsorption helps in designing surfaces that can either promote or inhibit specific biological interactions.
Rgd: RGD is a tripeptide sequence made up of the amino acids arginine, glycine, and aspartic acid, which plays a crucial role in cell adhesion to biomaterials. This sequence is vital for promoting interactions between cells and their extracellular environment, especially in tissue engineering and regenerative medicine applications. The presence of RGD on biomaterial surfaces can enhance cell attachment, migration, and proliferation, making it a key feature in the design of scaffolds for tissue regeneration.
Robert Langer: Robert Langer is a prominent biomedical engineer known for his pioneering work in drug delivery systems and biomaterials. His innovative research has significantly advanced the fields of tissue engineering and regenerative medicine, impacting how therapies are developed and delivered. Langer's contributions to surface chemistry, immunology, skeletal muscle engineering, and growth factor application have led to new treatments and technologies that enhance healing and tissue regeneration.
Roughness: Roughness refers to the texture and irregularities on the surface of a material, which can significantly influence its physical and chemical properties. This surface texture can affect interactions such as adhesion, wettability, and biological response, making it a crucial factor in applications involving biomaterials and tissue engineering.
Scanning Electron Microscopy: Scanning electron microscopy (SEM) is a powerful imaging technique that uses a focused beam of electrons to create high-resolution images of the surface morphology and composition of samples. This method provides detailed three-dimensional images and is essential in studying materials at the microscopic level, including biological specimens and engineered materials.
Self-assembled monolayers: Self-assembled monolayers (SAMs) are thin films formed spontaneously when molecules organize themselves into a single layer on a surface. This process occurs due to specific interactions such as van der Waals forces, hydrogen bonding, and electrostatic interactions, leading to a stable and well-ordered arrangement. SAMs play a crucial role in surface chemistry, influencing properties like wettability, adhesion, and biocompatibility, thereby impacting various applications in regenerative medicine and materials science.
Silanization: Silanization is a chemical process that involves the application of silanes to modify the surface properties of materials, typically enhancing their hydrophobicity or promoting adhesion. This technique is crucial in surface chemistry as it allows for the creation of functionalized surfaces that can interact favorably with biological systems, influencing cell behavior and material compatibility in regenerative medicine applications.
Soft lithography: Soft lithography is a technique used to create micro- and nanostructures on surfaces by using a flexible stamp, often made from polydimethylsiloxane (PDMS). This method allows for high-resolution patterning and is widely employed in the fabrication of biomaterials, microfluidic devices, and in various applications in regenerative medicine. It connects to surface chemistry through the manipulation of surface properties for enhanced adhesion and functionality, and plays a crucial role in vascularization strategies by enabling the creation of precise channels and structures that mimic biological tissues.
Vascular endothelial growth factor: Vascular endothelial growth factor (VEGF) is a signaling protein that plays a crucial role in the formation of blood vessels, also known as angiogenesis. It promotes the growth and survival of endothelial cells, which line the inside of blood vessels, and is vital for processes such as wound healing and the development of new tissues. VEGF is linked to various medical applications, including regenerative therapies, engineered blood vessel design, and understanding how surface chemistry can affect cellular responses.
VEGF: Vascular Endothelial Growth Factor (VEGF) is a signaling protein that plays a crucial role in angiogenesis, the formation of new blood vessels from existing ones. It is essential for various physiological processes, including development, wound healing, and tissue repair, and it significantly impacts stem cell niches, surface chemistry interactions, biomolecule immobilization techniques, bone regeneration, and strategies for promoting vascularization.
Wettability: Wettability refers to the ability of a liquid to maintain contact with a solid surface, influenced by intermolecular interactions between the liquid and the solid. It is quantified by the contact angle formed at the interface of the liquid and solid, which determines whether a surface is hydrophilic (water-attracting) or hydrophobic (water-repelling). Understanding wettability is essential for various applications, such as coating technologies, adhesion, and the interaction of biomaterials with biological fluids.