생체모방형 공중합체를 갖는 접착 소재의 제조 및 특성

Abstract

Tissue adhesives, hemostatic agents and tissue sealants are used as bio-adhesives for wound closure, hemostasis, and tissue sealants. Bio-adhesives have been intensively studied and developed as an alternative to sutures and staples for wound closure and hemostasis due to potential advantages including ease of use, and minimal tissue damage. However, there are many challenges that still must be overcome, and as such there are no bio-adhesives that are suitable for practical applications. Because it has many problems such as leaving scars and difficult to maintain adhesion on wet surfaces, cytotoxic, and probability for infection. Recently, several bio-adhesives have been studied to overcome these problems, including mussel-inspired adhesives, nanoparticle solutions, tough-adhesive hydrogel, ultraviolet(UV)-curable tissue adhesive glues. Marine mussels are mediated by the byssus, a proteinaceous holdfast that is formed by secretion and solidification of unique adhesive proteins. One of the unique structural differences of mussel foot proteins(Mfps), is the presence of L-3,4-dihyrdoxyphenylalanine(DOPA), that contains two hydroxy groups, called catechol. The catechol groups can physically interact with various substrates through π-π stacking, cation-π interaction, and hydrogen bonding. These are recognized for their properties of adhesion and cohesion. Generally, it is well known that the complex coacervate can form on mixing oppositely charged polyelectrolytes in aqueous solutions, due to electrostatic attraction between the oppositely charged polymers. However, the strong short-range cation–π interactions induce the like-charged coacervate by overcoming repulsive electrostatic interactions. This often leads to liquid–liquid phase separation, called complex coacervation, that is the appearance of a dense polyelectrolyte-rich liquid phase (coacervate phase) and a more dilute solution phase (aqueous phase) without dissolving. Interestingly, the cation-π interaction could serve as a driving force for the formation of complex coacervate in mussel adhesion proteins, which aromatic and cationic residues coexist. The cation–π interactions can lead to complex coacervation with low interfacial energy underwater, it is due to this that they have been studied and applied in biomedical applications such as cell encapsulant, emulsifiers, and bio-adhesives. The objection of this study is to prepare and characterize the bio-adhesion materials based on DOPA biomimetic copolymers in relation to the adhesive mechanics of marine mussels. In this study, the DOPA-modified derivatives are chemically synthesized by various acrylic monomers, which methacrylate, 2-ethylcyanoacrylate, and 2-hydroxyethyl methacrylate, via free radical polymerization for improving their adhesion properties. Cation-π interaction was induced by blending with different types and different blend ratio of cations (Mg2+, Ca2+, Fe3+, V5+) into the synthesized DOPA derivatives copolymer and PEO-PPO-PEO triblock copolymers solutions. They have been prepared by solution blending in order to induce the formation of complex coacervate. The complex coacervate was characterized and evaluated by various analytical methods such as FT-IR, Universal technical machine(UTM), Contact angle, and SEM. Considering the results from these studies, the complex coacervate between DOPA derivatives and various type of cation showed that adhesion strength is effectively increased even in wet conditions.

Hydrogels are three-dimensional network structures, which consists hydrophilic polymer networks with high water content without dissolving and a structural resemblance to extra matrix cellular(ECM). Therefore, hydrogel is used as scaffolds for tissue engineering such as drug delivery vehicles, actuators, and wound healing. However, most hydrogels do not exhibit with both adequate high stretchability and adhesive properties. Numerous attempts have been made to overcome the problems of poor mechanical properties and adhesive property, such as nanocomposite hydrogels, macromolecular microsphere composite hydrogels, polyampholyte hydrogels, and interpenetrating polymer network(IPN) hydrogel. Among them, IPN hydrogel is known to be the most promising. The IPN have been studied extensively to improve the mechanical properties of general hydrogels. IPN hydrogels brought distinct benefits compared to single network hydrogels like more widely controllable physical properties, and it provides better thermal stability, mechanical properties, and chemical resistance. Also, it consists of two (or more) polymer networks, at least one of them being synthesized physciallly/chemically crosslinked. In this work, bio-inspired adhesive IPN hydrogels were prepared by the L-3,4-dihydroxyphenylalanine derivatives and Polyacrylamide(PAAm) that can be efficiently and rapidly activated with an initiator and a cross-linker without the external stimuli such as UV, pH, and temperature. Also, the high elasticity and adhesive hydrogels were prepared with Polyacrylamide(PAAm) and bio mimetic copolymers, that catechol moieties can form strong covalent bonds in the hydrogel networks via the IPN. The IPN hydrogels were characterized and evaluated by various analytical methods such as FT-IR, UTM, Thermal gravimetric analysis(TGA), Contact angle, and SEM. IPN hydrogels based on PAAm with DOPA derivative copolymers endow the hydrogel with strong adhesion on various substrates including rough surfaces, smooth surfaces, and porcine skin even wet condition. The cytotoxicity of IPN hydrogels were evaluated by the CCK-8 assay. The results of cell viability of IPN hydrogels were over 100%. These results suggest that the IPN-structred PAAm/DOPA inspired copolymer hydrogels are promising functional materials in the field of biomedical engineering. This study not only offers a promising adhesive materials for bio-material with superior performances but also, advances the understanding of adhesion mechanism of DOPA for the development of future bio-adhesives underwater.