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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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Scheme illustrating the hypothetical induction of antioxidant defenses by PB-DOPA. Reproduced with permission from [45]. Copyright © Elsevier, 2007.
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marinedrugs-13-06792-f011: Scheme illustrating the hypothetical induction of antioxidant defenses by PB-DOPA. Reproduced with permission from [45]. Copyright © Elsevier, 2007.

Mentions: Yang et al. [10] recently developed injectable citrate-based mussel-inspired bioadhesives in the form of a biodegradable strong wet-tissue adhesive that can effectively close a bleeding wound, thus stopping the bleeding and helping with tissue regeneration without the aid of surgical tools. The injectable citrate-based mussel-inspired bioadhesives can be used for topical and non-topical applications across all disciplines of surgical practice, ranging from a suture/staple replacement; tissue grafts to treat hernias, ulcers, and burns; hemostatic wound dressings for laparoscopic partial nephrectomy; waterproof sealants for vascular anastomoses; and for the treatment of gastrointestinal fistulas, leaks, mucosal oozing or bleeding, and perforations (Figure 10) [10]. Inspired by a mussels byssus secretion through a pH jump, Holten-Andersen et al. [43] developed a simple method to control catechol-Fe3+ interpolymer cross-linking via changing the pH. The Raman resonance signature of catechol-Fe3+ cross-linked polymer gels at high pH levels is similar to that of natural adhesives secreted by mussels. These gels display elastic moduli (G′) that approach those of covalently cross-linked gels as well as self-healing properties [43]. There is an urgent need for medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory responses. To address these performance characteristics, Brubaker et al. [44] generated a synthetic adhesive material inspired by mussels. The in vivo performance of the material was assessed in a mouse extra-hepatic syngeneic islet transplantation model. They designed the adhesive polymer with a branched PEG core whose end groups were derivatized with catechol, a functional group inspired by mussels adhesive proteins. In an oxidizing environment, the adhesive forms within a minute from catechol-derivatized PEG (cPEG) solutions. The cPEG adhesive elicited minimal inflammatory responses in mice and maintained a bond with supporting tissue for up to one year upon implantation. The synthesized cPEG adhesive was shown to immobilize transplanted islets at epididymal fat pads and external liver surfaces efficiently, permitting normoglycemic recovery and graft revascularization. The findings by Messersmith et al. [44] established the use of mussel-inspired adhesives for islet transplantation. Nelson et al. [45] developed protein hydroperoxides and protein-bound 3,4-dihydroxyphenylalinine as the key redox-active products during free radical attacks on proteins. Protein-bound 3,4-dihydroxyphenylalinine forms a redox cycle between the catechol and quinone forms and binds transition metals, while hydroperoxides are converted to stable hydroxides. The free amino acid 3,4-dihydroxy phenylalinine, an oxidation product of tyrosine, is a normal metabolite which is involved in the pathways of dopamine and melanin production. On the other hand, the physiological levels of protein-bound 3,4-dihydroxy-phenylalinine are very low, though remarkably elevated levels occur in some pathologic conditions. Unlike free 3,4-dihydroxyphenylalinine, protein-bound 3,4-dihydroxyphenylalinine has been proposed as a signal for the activation of cellular defenses against both oxidative fluxes during oxidative stress and oxidative damage, which occasionally develop. For distinctly free 3,4-dihydroxyphenylalinine, the levels of protein-bound 3,4-dihydroxyphenylalinine can change by five to ten times during oxidative damage in vivo, which can serve as an appropriate property for signaling molecules. Several mechanisms by which protein-bound 3,4-dihydroxyphenylalinine may trigger oxidative defenses via NF-κB and other transcription factors have been suggested (Figure 11). Many effects of 3,4-dihydroxyphenylalinine in these situations may be mediated by the production and actions of protein-bound 3,4-dihydroxyphenylalinine [45].


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)

Scheme illustrating the hypothetical induction of antioxidant defenses by PB-DOPA. Reproduced with permission from [45]. Copyright © Elsevier, 2007.
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-06792-f011: Scheme illustrating the hypothetical induction of antioxidant defenses by PB-DOPA. Reproduced with permission from [45]. Copyright © Elsevier, 2007.
Mentions: Yang et al. [10] recently developed injectable citrate-based mussel-inspired bioadhesives in the form of a biodegradable strong wet-tissue adhesive that can effectively close a bleeding wound, thus stopping the bleeding and helping with tissue regeneration without the aid of surgical tools. The injectable citrate-based mussel-inspired bioadhesives can be used for topical and non-topical applications across all disciplines of surgical practice, ranging from a suture/staple replacement; tissue grafts to treat hernias, ulcers, and burns; hemostatic wound dressings for laparoscopic partial nephrectomy; waterproof sealants for vascular anastomoses; and for the treatment of gastrointestinal fistulas, leaks, mucosal oozing or bleeding, and perforations (Figure 10) [10]. Inspired by a mussels byssus secretion through a pH jump, Holten-Andersen et al. [43] developed a simple method to control catechol-Fe3+ interpolymer cross-linking via changing the pH. The Raman resonance signature of catechol-Fe3+ cross-linked polymer gels at high pH levels is similar to that of natural adhesives secreted by mussels. These gels display elastic moduli (G′) that approach those of covalently cross-linked gels as well as self-healing properties [43]. There is an urgent need for medical adhesives that function reliably on wet tissue surfaces with minimal inflammatory responses. To address these performance characteristics, Brubaker et al. [44] generated a synthetic adhesive material inspired by mussels. The in vivo performance of the material was assessed in a mouse extra-hepatic syngeneic islet transplantation model. They designed the adhesive polymer with a branched PEG core whose end groups were derivatized with catechol, a functional group inspired by mussels adhesive proteins. In an oxidizing environment, the adhesive forms within a minute from catechol-derivatized PEG (cPEG) solutions. The cPEG adhesive elicited minimal inflammatory responses in mice and maintained a bond with supporting tissue for up to one year upon implantation. The synthesized cPEG adhesive was shown to immobilize transplanted islets at epididymal fat pads and external liver surfaces efficiently, permitting normoglycemic recovery and graft revascularization. The findings by Messersmith et al. [44] established the use of mussel-inspired adhesives for islet transplantation. Nelson et al. [45] developed protein hydroperoxides and protein-bound 3,4-dihydroxyphenylalinine as the key redox-active products during free radical attacks on proteins. Protein-bound 3,4-dihydroxyphenylalinine forms a redox cycle between the catechol and quinone forms and binds transition metals, while hydroperoxides are converted to stable hydroxides. The free amino acid 3,4-dihydroxy phenylalinine, an oxidation product of tyrosine, is a normal metabolite which is involved in the pathways of dopamine and melanin production. On the other hand, the physiological levels of protein-bound 3,4-dihydroxy-phenylalinine are very low, though remarkably elevated levels occur in some pathologic conditions. Unlike free 3,4-dihydroxyphenylalinine, protein-bound 3,4-dihydroxyphenylalinine has been proposed as a signal for the activation of cellular defenses against both oxidative fluxes during oxidative stress and oxidative damage, which occasionally develop. For distinctly free 3,4-dihydroxyphenylalinine, the levels of protein-bound 3,4-dihydroxyphenylalinine can change by five to ten times during oxidative damage in vivo, which can serve as an appropriate property for signaling molecules. Several mechanisms by which protein-bound 3,4-dihydroxyphenylalinine may trigger oxidative defenses via NF-κB and other transcription factors have been suggested (Figure 11). Many effects of 3,4-dihydroxyphenylalinine in these situations may be mediated by the production and actions of protein-bound 3,4-dihydroxyphenylalinine [45].

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