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Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials.

Kaushik NK, Kaushik N, Pardeshi S, Sharma JG, Lee SH, Choi EH - Mar Drugs (2015)

Bottom Line: However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion.We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation.The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.

View Article: PubMed Central - PubMed

Affiliation: Plasma Bioscience Research Center, Kwangwoon University, Seoul 139701, Korea. kaushik.nagendra@kw.ac.kr.

ABSTRACT
The substance secreted by mussels, also known as nature's glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via mussel adhesive proteins (MAPs), a group of proteins containing 3,4-dihydroxyphenylalanine (DOPA) and catecholic amino acid. Several aspects of this adhesion process have inspired the development of various types of synthetic materials for biomedical applications. Further, there is an urgent need to utilize biologically inspired strategies to develop new biocompatible materials for medical applications. Consequently, many researchers have recently reported bio-inspired techniques and materials that show results similar to or better than those shown by MAPs for a range of medical applications. However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion. In this review, various strategies are discussed to provide an option for DOPA/metal ion chelation and to compensate for the limitations imposed by facile 3,4-dihydroxyphenylalanine autoxidation. We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation. The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.

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Proposed pH dependence of covalent and coordination-bond formation in catechol-polymer hydrogels containing Fe3+. The reaction of the catechol-terminated branched PEG with Fe3+ at an acidic pH results in covalently cross-linked hydrogels. Subsequent equilibration of these gels at a pH of 5, 7, or 9 introduces varying number of Fe3+-catechol coordination bonds that mechanically enhance the covalent network. Under the influence of a mechanical force, these coordination bonds reversibly rupture and re-form, acting as a mechanism for energy dissipation. Both oligomeric and monomeric (unreacted) catechols are believed to participate in the coordination network. Adapted with permission from [22]. Copyright © WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim, 2013.
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marinedrugs-13-06792-f006: Proposed pH dependence of covalent and coordination-bond formation in catechol-polymer hydrogels containing Fe3+. The reaction of the catechol-terminated branched PEG with Fe3+ at an acidic pH results in covalently cross-linked hydrogels. Subsequent equilibration of these gels at a pH of 5, 7, or 9 introduces varying number of Fe3+-catechol coordination bonds that mechanically enhance the covalent network. Under the influence of a mechanical force, these coordination bonds reversibly rupture and re-form, acting as a mechanism for energy dissipation. Both oligomeric and monomeric (unreacted) catechols are believed to participate in the coordination network. Adapted with permission from [22]. Copyright © WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim, 2013.

Mentions: Mussel-inspired adhesive hydrogels represent novel candidates for medical sealants or glues. Brubaker and Messersmith [21] described an enzyme-degradable mussel-inspired adhesive hydrogel formulation which was achieved by incorporating the minimal-elastase substrate-peptide Ala-Ala into a branched polyethyleneglycol (PEG) structure. This system takes advantage of the neutrophil elastase expression up-regulation and secretion from neutrophils upon recruitment on wounded tissue. The degradation of the adhesive hydrogel was not observed during short-term trials involving in vitro treatments with elastase, though in vivo degradation proceeded over several months following implantation in mice. The work of Brubaker and Messersmith [21] represents the first model of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of these materials. Barrett et al. [22] demonstrated a novel bio-inspired approach for designing extremely tough hydrogels. By regulating the pH of the reaction between catechol-terminated branched PEG and Fe3+, a covalently cross-linked network was prepared by the Messersmith research group with a series of coordination bonds which undertake reversible interactions to dissipate energy during the deformation process (Figure 6) [22]. Their findings show the richness of the cross-linking chemical and physical properties accessible in synthetic mussel-inspired biomaterials, which were achieved through the simple manipulation of the pH, composition, and processing method. Cautious administration of these variables provides access to a wide variety of physical properties, reflecting the stability of covalent and coordination cross-linking in the gel network. These biologically inspired hydrogels, with a viscoelastic response and water content reminiscent of hydrated natural soft tissues, represent a new set of biomaterials [22]. Previously developed synthetic polymer hydrogel tissue adhesives and sealants swell greatly under physiologic conditions, which can result in mechanical weakening and adverse medical complications. A recent report described the synthesis and characterization of mechanically hard zero- or negative-swelling mussel-inspired surgical adhesives based on catechol-modified amphiphilic poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymers [23]. Catechol oxidation at or less than room temperature resulted in a chemically cross-linked network, with subsequent warming to physiological temperatures inducing a thermal hydrophobic transition in the PPO domains and providing a mechanism for mechanical toughening. This designed approach can be easily adapted for other heat-sensitive copolymers and cross-linking strategies, representing a typical approach that can be used to manage swelling and improve the mechanical properties of hydrogels for new medical applications. Transient network hydrogels, cross-linked through histidine-divalent cation coordination bonds, were studied by Fullenkamp et al., using histidine-modified star PEG polymers [24]. These biomaterials were inspired by the mussel, which utilizes histidine-metal coordination bonds to impart self-healing properties in its byssal threads. Fullenkamp et al. calculated pH-dependent speciation curves using equilibrium constants determined by potentiometric titration, providing insight into the pH-dependence of the histidine-metal ion coordination. It was also demonstrated that the new mussel-inspired catecholamine polymer can be used for DNA immobilization via a simple surface modification. One-step immersion of the substrate (noble metals, oxides, and polymer) in a polymer solution forms a substrate that allows the immobilization of DNA strands [25]. This method will be useful for developing DNA microarrays in various types of substrate materials with a simple preparation process. This strategy can be used for the immobilization of various types of other biomolecules, such as probes for cDNA, peptides, aptamers, or direct polymerase chain reaction (PCR) products. This method can also be used in various biomedical assays. Recently, the immobilization of trypsin on a silica and titanium support was achieved via a mussel-inspired adhesion strategy [26]. The method involves the fabrication of titanium substrates with catechol-containing biomimetic PD followed by the fabrication of trypsin on a PD layer. The immobilized enzyme maintains its catalytic activity after being coated onto PD in a wide variety of monolithic substrates.


Biomedical and Clinical Importance of Mussel-Inspired Polymers and Materials.

Kaushik NK, Kaushik N, Pardeshi S, Sharma JG, Lee SH, Choi EH - Mar Drugs (2015)

Proposed pH dependence of covalent and coordination-bond formation in catechol-polymer hydrogels containing Fe3+. The reaction of the catechol-terminated branched PEG with Fe3+ at an acidic pH results in covalently cross-linked hydrogels. Subsequent equilibration of these gels at a pH of 5, 7, or 9 introduces varying number of Fe3+-catechol coordination bonds that mechanically enhance the covalent network. Under the influence of a mechanical force, these coordination bonds reversibly rupture and re-form, acting as a mechanism for energy dissipation. Both oligomeric and monomeric (unreacted) catechols are believed to participate in the coordination network. Adapted with permission from [22]. Copyright © WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim, 2013.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663554&req=5

marinedrugs-13-06792-f006: Proposed pH dependence of covalent and coordination-bond formation in catechol-polymer hydrogels containing Fe3+. The reaction of the catechol-terminated branched PEG with Fe3+ at an acidic pH results in covalently cross-linked hydrogels. Subsequent equilibration of these gels at a pH of 5, 7, or 9 introduces varying number of Fe3+-catechol coordination bonds that mechanically enhance the covalent network. Under the influence of a mechanical force, these coordination bonds reversibly rupture and re-form, acting as a mechanism for energy dissipation. Both oligomeric and monomeric (unreacted) catechols are believed to participate in the coordination network. Adapted with permission from [22]. Copyright © WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim, 2013.
Mentions: Mussel-inspired adhesive hydrogels represent novel candidates for medical sealants or glues. Brubaker and Messersmith [21] described an enzyme-degradable mussel-inspired adhesive hydrogel formulation which was achieved by incorporating the minimal-elastase substrate-peptide Ala-Ala into a branched polyethyleneglycol (PEG) structure. This system takes advantage of the neutrophil elastase expression up-regulation and secretion from neutrophils upon recruitment on wounded tissue. The degradation of the adhesive hydrogel was not observed during short-term trials involving in vitro treatments with elastase, though in vivo degradation proceeded over several months following implantation in mice. The work of Brubaker and Messersmith [21] represents the first model of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of these materials. Barrett et al. [22] demonstrated a novel bio-inspired approach for designing extremely tough hydrogels. By regulating the pH of the reaction between catechol-terminated branched PEG and Fe3+, a covalently cross-linked network was prepared by the Messersmith research group with a series of coordination bonds which undertake reversible interactions to dissipate energy during the deformation process (Figure 6) [22]. Their findings show the richness of the cross-linking chemical and physical properties accessible in synthetic mussel-inspired biomaterials, which were achieved through the simple manipulation of the pH, composition, and processing method. Cautious administration of these variables provides access to a wide variety of physical properties, reflecting the stability of covalent and coordination cross-linking in the gel network. These biologically inspired hydrogels, with a viscoelastic response and water content reminiscent of hydrated natural soft tissues, represent a new set of biomaterials [22]. Previously developed synthetic polymer hydrogel tissue adhesives and sealants swell greatly under physiologic conditions, which can result in mechanical weakening and adverse medical complications. A recent report described the synthesis and characterization of mechanically hard zero- or negative-swelling mussel-inspired surgical adhesives based on catechol-modified amphiphilic poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymers [23]. Catechol oxidation at or less than room temperature resulted in a chemically cross-linked network, with subsequent warming to physiological temperatures inducing a thermal hydrophobic transition in the PPO domains and providing a mechanism for mechanical toughening. This designed approach can be easily adapted for other heat-sensitive copolymers and cross-linking strategies, representing a typical approach that can be used to manage swelling and improve the mechanical properties of hydrogels for new medical applications. Transient network hydrogels, cross-linked through histidine-divalent cation coordination bonds, were studied by Fullenkamp et al., using histidine-modified star PEG polymers [24]. These biomaterials were inspired by the mussel, which utilizes histidine-metal coordination bonds to impart self-healing properties in its byssal threads. Fullenkamp et al. calculated pH-dependent speciation curves using equilibrium constants determined by potentiometric titration, providing insight into the pH-dependence of the histidine-metal ion coordination. It was also demonstrated that the new mussel-inspired catecholamine polymer can be used for DNA immobilization via a simple surface modification. One-step immersion of the substrate (noble metals, oxides, and polymer) in a polymer solution forms a substrate that allows the immobilization of DNA strands [25]. This method will be useful for developing DNA microarrays in various types of substrate materials with a simple preparation process. This strategy can be used for the immobilization of various types of other biomolecules, such as probes for cDNA, peptides, aptamers, or direct polymerase chain reaction (PCR) products. This method can also be used in various biomedical assays. Recently, the immobilization of trypsin on a silica and titanium support was achieved via a mussel-inspired adhesion strategy [26]. The method involves the fabrication of titanium substrates with catechol-containing biomimetic PD followed by the fabrication of trypsin on a PD layer. The immobilized enzyme maintains its catalytic activity after being coated onto PD in a wide variety of monolithic substrates.

Bottom Line: However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion.We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation.The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.

View Article: PubMed Central - PubMed

Affiliation: Plasma Bioscience Research Center, Kwangwoon University, Seoul 139701, Korea. kaushik.nagendra@kw.ac.kr.

ABSTRACT
The substance secreted by mussels, also known as nature's glue, is a type of liquid protein that hardens rapidly into a solid water-resistant adhesive material. While in seawater or saline conditions, mussels can adhere to all types of surfaces, sustaining its bonds via mussel adhesive proteins (MAPs), a group of proteins containing 3,4-dihydroxyphenylalanine (DOPA) and catecholic amino acid. Several aspects of this adhesion process have inspired the development of various types of synthetic materials for biomedical applications. Further, there is an urgent need to utilize biologically inspired strategies to develop new biocompatible materials for medical applications. Consequently, many researchers have recently reported bio-inspired techniques and materials that show results similar to or better than those shown by MAPs for a range of medical applications. However, the susceptibility to oxidation of 3,4-dihydroxyphenylalanine poses major challenges with regard to the practical translation of mussel adhesion. In this review, various strategies are discussed to provide an option for DOPA/metal ion chelation and to compensate for the limitations imposed by facile 3,4-dihydroxyphenylalanine autoxidation. We discuss the anti-proliferative, anti-inflammatory, anti-microbial activity, and adhesive behaviors of mussel bio-products and mussel-inspired materials (MIMs) that make them attractive for synthetic adaptation. The development of biologically inspired adhesive interfaces, bioactive mussel products, MIMs, and arising areas of research leading to biomedical applications are considered in this review.

Show MeSH
Related in: MedlinePlus