No abstract

Exploitation of unique biochemical and biophysical properties of marine organisms has led to the development of functional biomaterials for various biomedical applications. Recently, ascidians have received great attention, owing to their extraordinary properties such as strong underwater adhesion and rapid self-regeneration. Specific polypeptides containing 3,4,5-trihydroxyphenylalanine (TOPA) in the blood cells of ascidians are associated with such intrinsic properties generated through complex oxidative processes. In this study, a bioinspired hydrogel platform is developed, demonstrating versatile applicability for tissue engineering and drug delivery, by conjugating pyrogallol (PG) moiety resembling ascidian TOPA to hyaluronic acid (HA). The HA-PG conjugate can be rapidly crosslinked by dual modes of oxidative mechanisms using an oxidant or pH control, resulting in hydrogels with different mechanical and physical characteristics. The versatile utility of HA-PG hydrogels formed via different crosslinking mechanisms is tested for different biomedical platforms, including microparticles for sustained drug delivery and tissue adhesive for noninvasive cell transplantation. With extraordinarily fast and different routes of PG oxidation, ascidian-inspired HA-PG hydrogel system may provide a promising biomaterial platform for a wide range of biomedical applications.

Serotonin-conjugated hyaluronic acid hydrogel inspired by platelet coagulation provides a multifunctional hemostatic adhesive mediating highly effective hemostasis and preventing abnormal tissue adhesion.

polymers, but they are water-insoluble, organic-solvent basis glues. [10,11] Despite recent novel approaches in adhesives using nanoparticles, [12] stretchable gels, [13] and numerous bioadhesive studies summarized in reviews, [3,4] bioinspired waterborne and biocompatible adhesives showing superglue-like adhesion strength have not been reported. Phenol-amine synergy is also found in insect exoskeletons in which aminerich polymer backbones are cross-linked by phenolic compounds by N-acetyldopamine, N-β-alanyl-dopamine, and dopamine. [14,15] The key biochemistry in sclerotization (i.e., hardening) processes is crosslinking of amine-rich polymers via phenol-quinone involved oxidative reactions. Being different from mechanically weak adhesive materials inspired by marine organisms mentioned above, Young's moduli of exoskeletons are extremely high exhibiting 1-20 GPa, [16] which is similar to ones of common plastics including nylon (2-4 GPa), poly(ethylene terephthalate) (PET) (2-2.7 GPa), and polystyrene (3-3.5 GPa). So far, no studies attempting uses of insect sclerotization process as a new curing strategy in adhesives are reported. We hypothesized that combining: 1) adhesive properties originated from phenols and 2) insect exoskeleton-like hard material properties inspired by phenol-amine phenolamine crosslinking would result in biomimetic superglues. To achieve this goal, the Exoskeletons of insects formed by sclerotization processes exhibit superstrong properties in moduli. Here, it is demonstrated that mimicking the sclerotization process using phenol and polyamine molecules unexpectedly results in a 100% ecofriendly, biocompatible waterborne superglue. Oxygen presented in air and dissolved in water acts as an initiator producing phenolic radical/quinone for superglue curing. Despite synthesis-free uses of water, phenol, and polyamine, its adhesion strength is comparable to commercial epoxy glue showing >6 MPa in lap shear strength. The phenol-amine superglue bonds to various substrates including ceramics, woods, fabrics, plastics, metals, and importantly biological tissues. Due to strong adhesion, the superglue effectively seals wounds within a few seconds, and, due to its waterborne nature, no harmful respiratory effect is observed because of any release of volatile organic compounds. The easy, cost-effective preparation of the phenol-amine superglue can revolutionize varieties of industrial, biomedical, daily life processes. Phenol-amine synergy found in marine mussels or tunicates inspires researchers to develop material-independent surface chemistry and medical soft adhesives. [1] Examples include polydopamine coatings in surface chemistry [2] and catechol-and gallol-tethered soft adhesives. [3-9] Adhesion forces observed from bioinspired adhesive polymers are generally weak in the range of kPa: hyaluronic acid-catechol (0.8 kPa), [5] poly(glutamic acid)-catechol (26.1-58.2 kPa), [6] poly(methacrylamide)-catechol (10-300 kPa), [7] and chitin-gallol (215 kPa). [8] A few studies reported adhesion in MPa ord...

Chondroitin sulfate (CS), the main component of cartilage extracellular matrix, has attracted attention as a biomaterial for cartilage tissue engineering. However, current CS hydrogel systems still have limitations for application in successful cartilage tissue engineering owing to their unsuitable degradation kinetics, insufficient mechanical similarity, and lack of integration with the native cartilage tissue. In this study, using mussel adhesive-inspired catechol chemistry, we developed a functional CS hydrogel that exhibits tunable physical and mechanical properties as well as excellent tissue adhesion for efficient integration with native tissues. Various properties of the developed catechol-functionalized CS (CS-CA) hydrogel, including swelling, degradation, mechanical properties, and adhesiveness, could be tailored by varying the conjugation ratio of the catechol group to the CS backbone and the concentration of the CS-CA conjugates. CS-CA hydrogels exhibited significantly increased modulus (∼10 kPa) and superior adhesive properties (∼3 N) over conventional CS hydrogels (∼hundreds Pa and ∼0.05 N). In addition, CS-CA hydrogels incorporating decellularized cartilage tissue dice promoted the chondrogenic differentiation of human adipose-derived mesenchymal stem cells by providing a cartilage-like microenvironment. Finally, the transplantation of autologous cartilage dice using tissue-adhesive CS-CA hydrogels enhanced cartilage integration with host tissue and neo-cartilage formation owing to favorable physical, mechanical, and biological properties for cartilage formation. In conclusion, our study demonstrated the potential utility of the CS-CA hydrogel system in cartilage tissue reconstruction.