Biomimetic materials
Encyclopedia
Biomimetic materials are materials developed using inspiration from nature
. This may be useful in the design of composite materials, or material structures. Natural structures have evolved many inspiring examples that have been used by man. Common examples are the honeycombe structure of the beehive, the fibre structure of wood, spider silks, nacre, bone, hedgehog quills.
Biomimetic materials in tissue engineering are materials that have been designed such that they elicit specified cellular responses mediated by interactions with scaffold-tethered peptides from extracellular matrix
(ECM) protein
s; essentially, the incorporation of cell-binding peptides into biomaterial
s via chemical or physical modification .
Such peptides include both native long chains of ECM proteins as well as short peptide sequences derived from intact ECM proteins. The idea is that the biomimetic material will mimic some of the roles that an extracellular matrix plays in neural tissue. In addition to promoting cellular growth and mobilization, the incorporated peptides could also mediate material degradation by specific protease enzymes or initiate cellular responses not present in a local native tissue . In the beginning, long chains of ECM proteins including fibronectin
(FN), vitronectin
(VN), and laminin
(LN) were used, but more recently the advantages of using short peptides have been discovered. Short peptides are more advantageous because, unlike the long chains that fold randomly upon adsorption causing the active protein domains to be sterically unavailable, short peptides remain stable and do not hide the receptor binding domains when adsorbed. Another advantage to short peptides is that they can be replicated more economically due to the smaller size. A bi-functional cross-linker with a long spacer arm is used to tether peptides to the substrate
surface. If a functional group
is not available for attaching the cross-linker, photochemical immobilization may be used . In addition to modifying the surface, biomaterials can be modified in bulk, meaning that the cell signaling
peptides and recognition sites are present not just on the surface but also throughout the bulk of the material. The strength of cell attachment, cell migration rate, and extent of cytoskeletal organization formation is determined by the receptor binding to the ligand
bound to the material; thus, receptor-ligand affinity, the density of the ligand, and the spatial distribution of the ligand must be carefully considered when designing a biomimetic material .
growth guidance. Its primary functional site for bioactivity is its core protein domain isoleucine
-lysine
-valine
-alanine
-valine
(IKVAV), which is located in the α-1 chain of laminin . A recent study by Wu, Zheng et al., synthesized a self-assembled IKVAV peptide nanofiber and tested its effect on the adhesion of neuron-like pc12 cells
. Early cell adhesion is very important for preventing cell degeneration; the longer cells are suspended in culture, the more likely they are to degenerate. The purpose was to develop a biomaterial
with good cell adherence and bioactivity with IKVAV, which is able to inhibit differentiation and adhesion of glial cells in addition to promoting neuronal cell adhesion
and differentiation . The IKVAV peptide domain is on the surface of the nanofibers so that it is exposed and accessible for promoting cell contact interactions. The IKVAV nanofibers promoted stronger cell adherence than the electrostatic attraction induced by poly-L-lysine, and cell adherence increased with increasing density of IKVAV until the saturation point was reached. IKVAV does not exhibit time dependent effects because the adherence was shown to be the same at 1 hour and at 3 hours .
Laminin is known to stimulate neurite
outgrowth and it plays a role in the developing nervous system. It is known that gradients are critical for the guidance of growth cones to their target tissues in the developing nervous system
. There has been much research done on soluble gradients; however, little emphasis has been placed on gradients of substratum bound substances of the extracellular matrix such as laminin . Dodla and Bellamkonda, fabricated an anisotropic 3D agarose gel with gradients of coupled laminin-1 (LN-1). Concentration gradients of LN-1 were shown to promote faster neurite extension than the highest neurite growth rate observed with isotropic LN-1 concentrations. Neurites grew both up and down the gradients, but growth was faster at less steep gradients and was faster up the gradients than down the gradients .
Biomimicry
Biomimicry or biomimetics is the examination of nature, its models, systems, processes, and elements to emulate or take inspiration from in order to solve human problems. The term biomimicry and biomimetics come from the Greek words bios, meaning life, and mimesis, meaning to imitate...
. This may be useful in the design of composite materials, or material structures. Natural structures have evolved many inspiring examples that have been used by man. Common examples are the honeycombe structure of the beehive, the fibre structure of wood, spider silks, nacre, bone, hedgehog quills.
Biomimetic materials in tissue engineering are materials that have been designed such that they elicit specified cellular responses mediated by interactions with scaffold-tethered peptides from extracellular matrix
Extracellular matrix
In biology, the extracellular matrix is the extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions. The extracellular matrix is the defining feature of connective tissue in animals.Extracellular...
(ECM) protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s; essentially, the incorporation of cell-binding peptides into biomaterial
Biomaterial
A biomaterial is any matter, surface, or construct that interacts with biological systems. The development of biomaterials, as a science, is about fifty years old. The study of biomaterials is called biomaterials science. It has experienced steady and strong growth over its history, with many...
s via chemical or physical modification .
Such peptides include both native long chains of ECM proteins as well as short peptide sequences derived from intact ECM proteins. The idea is that the biomimetic material will mimic some of the roles that an extracellular matrix plays in neural tissue. In addition to promoting cellular growth and mobilization, the incorporated peptides could also mediate material degradation by specific protease enzymes or initiate cellular responses not present in a local native tissue . In the beginning, long chains of ECM proteins including fibronectin
Fibronectin
Fibronectin is a high-molecular weight glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. In addition to integrins, fibronectin also binds extracellular matrix components such as collagen, fibrin and heparan sulfate proteoglycans...
(FN), vitronectin
Vitronectin
Vitronectin also known as VTN is a protein that in humans is encoded by the VTN gene.The protein encoded by this gene is a member of the pexin family...
(VN), and laminin
Laminin
Laminins are major proteins in the basal lamina , a protein network foundation for most cells and organs...
(LN) were used, but more recently the advantages of using short peptides have been discovered. Short peptides are more advantageous because, unlike the long chains that fold randomly upon adsorption causing the active protein domains to be sterically unavailable, short peptides remain stable and do not hide the receptor binding domains when adsorbed. Another advantage to short peptides is that they can be replicated more economically due to the smaller size. A bi-functional cross-linker with a long spacer arm is used to tether peptides to the substrate
Substrate (biochemistry)
In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
surface. If a functional group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
is not available for attaching the cross-linker, photochemical immobilization may be used . In addition to modifying the surface, biomaterials can be modified in bulk, meaning that the cell signaling
Cell signaling
Cell signaling is part of a complex system of communication that governs basic cellular activities and coordinates cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue...
peptides and recognition sites are present not just on the surface but also throughout the bulk of the material. The strength of cell attachment, cell migration rate, and extent of cytoskeletal organization formation is determined by the receptor binding to the ligand
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...
bound to the material; thus, receptor-ligand affinity, the density of the ligand, and the spatial distribution of the ligand must be carefully considered when designing a biomimetic material .
Extracellular matrix proteins
Many studies utilize laminin-1 when designing a biomimetic material. Laminin is a component of the extracellular matrix that is able to promote neuron attachment and differentiation, in addition to axonAxon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
growth guidance. Its primary functional site for bioactivity is its core protein domain isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....
-lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
-valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
-alanine
Alanine
Alanine is an α-amino acid with the chemical formula CH3CHCOOH. The L-isomer is one of the 20 amino acids encoded by the genetic code. Its codons are GCU, GCC, GCA, and GCG. It is classified as a nonpolar amino acid...
-valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
(IKVAV), which is located in the α-1 chain of laminin . A recent study by Wu, Zheng et al., synthesized a self-assembled IKVAV peptide nanofiber and tested its effect on the adhesion of neuron-like pc12 cells
PC12 cells
PC12 is a cell line derived from a pheochromocytoma of the rat adrenal medulla. PC12 cells stop dividing and terminally differentiate when treated with nerve growth factor...
. Early cell adhesion is very important for preventing cell degeneration; the longer cells are suspended in culture, the more likely they are to degenerate. The purpose was to develop a biomaterial
Biomaterial
A biomaterial is any matter, surface, or construct that interacts with biological systems. The development of biomaterials, as a science, is about fifty years old. The study of biomaterials is called biomaterials science. It has experienced steady and strong growth over its history, with many...
with good cell adherence and bioactivity with IKVAV, which is able to inhibit differentiation and adhesion of glial cells in addition to promoting neuronal cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
and differentiation . The IKVAV peptide domain is on the surface of the nanofibers so that it is exposed and accessible for promoting cell contact interactions. The IKVAV nanofibers promoted stronger cell adherence than the electrostatic attraction induced by poly-L-lysine, and cell adherence increased with increasing density of IKVAV until the saturation point was reached. IKVAV does not exhibit time dependent effects because the adherence was shown to be the same at 1 hour and at 3 hours .
Laminin is known to stimulate neurite
Neurite
A neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
outgrowth and it plays a role in the developing nervous system. It is known that gradients are critical for the guidance of growth cones to their target tissues in the developing nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. There has been much research done on soluble gradients; however, little emphasis has been placed on gradients of substratum bound substances of the extracellular matrix such as laminin . Dodla and Bellamkonda, fabricated an anisotropic 3D agarose gel with gradients of coupled laminin-1 (LN-1). Concentration gradients of LN-1 were shown to promote faster neurite extension than the highest neurite growth rate observed with isotropic LN-1 concentrations. Neurites grew both up and down the gradients, but growth was faster at less steep gradients and was faster up the gradients than down the gradients .