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Abstract Catechol is an oft‐used crosslinking precursor and adhesive molecule for designing in situ curable biomaterials and adhesives and the addition of chemical or enzymatic oxidants is required to initiate fast curing. Here, the feasibility for 6‐hydroxydopamine (6‐OHDA)‐modified 8‐armed polyethylene glycol (PEG) (8‐arm PEG‐DA‐OH) to cure through autoxidation is evaluated. The modification of catechol side chain with an electron‐donating hydroxyl group at the six‐position drastically increased the rate of oxidation and the adhesive cured in just over 1 min through autoxidation. The cure time is decreased to under 40 s with the addition of branched polyethyleneimine (PEI). UV–vis spectra revealed that the deprotonated quinone of 6‐OHDA is a key oxidation intermediate for chemical crosslinking between 6‐OHDA and with primary amine. PEG functionalized with unmodified catechol do not solidify through autoxidation, which highlights the contribution of the electron‐donating hydroxyl group in promoting fast oxidation and crosslinking. Eight‐arm PEG‐DA‐OH and PEI mixture also demonstrated significantly higher adhesion strength to pericardium tissues when compared to a commercial PEG‐based adhesive, DuraSeal. This report highlights 6‐OHDA as an effective crosslinking precursor and adhesive molecule for designing injectable adhesives that do not require externally added oxidants and the adhesive is activated by simple dissolution in an aqueous solution. 

Hemorrhage is one of the leading preventable causes of death associated with trauma, which is often complicated by wound infection. Current hemostatic materials are not ideal and lack antimicrobial properties needed for infection prevention. Here, we tested the feasibility for 6-chlorodopamine-functionalized gelatin (GDC) nanoparticles to function as a hemostatic powder with strong tissue adhesion and antibacterial properties. 6-Chlorodopamine contains a catechol sidechain that is further modified with an electron withdrawing chlorine atom, and provides strong tissue adhesion and antimicrobial property. These gelatin nanoparticles are not covalently crosslinked, which enablde them to rapidly transition into an adhesive film when hydrated with an aqueous solution or blood. The chlorination of catechol significantly increased structural integrity, interfacial bonding to tissue surface, and the rate of film formation. Additionally, GDC nanoparticles are noncytotoxic and nonhemolytic, and effectively killed Gram-positive (Staphylococcus epidermidis, Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. Finally, GDC nanoparticles achieved significantly faster hemostasis and reduced blood loss when compared to a commercial fibrin glue, Tisseel, in tail transection and liver hemorrhage models performed in mice. These findings highlight the potential of GDC nanoparticle as a versatile, multifunctional hemostatic agent capable of both rapid hemorrhage control and infection prevention. 

Physically crosslinked gelatin microgels were functionalized with a bioadhesive molecule, catechol, to study the effect of in situ generated H2O2 on full-thickness wound repair in diabetic mice. Due to the physically crosslinked nature of the microgels, they transition into a hydrogel film upon hydration. The formation of a hydrogel film was confirmed by the changes in their morphology and viscoelastic properties. Additionally, these microgels released up to 86 μM of H2O2 as a result of catechol autoxidation. The generated H2O2 completely eradicated Staphylococcus epidermidis with an initial concentration of 103 CFU mL−1. These microgels were not cytotoxic and promoted VEGF upregulation in immortalized human keratinocytes (HaCaT) in vitro. When the microgels were applied to a full-thickness dermal wound in diabetic mice, dermal wound closure was accelerated over 14 days, achieving a wound closure of 90% based on the wound area. Microgel-treated wounds also resulted in complete re-epithelialization and regeneration of new dermal tissues with morphology and structure resembling those of native tissues. These results indicate that the release of micromolar concentrations of H2O2 can accelerate wound healing in a healing-impaired animal. 

An SHAM-containing adhesive was combined with PVDF to form a novel structural adhesive. SHAM provides interfacial bonding capability while PVDF increases cohesion through hydrogen bonding with the adhesive polymer backbone. 

A coating that can be activated by moisture found in respiratory droplets could be a convenient and effective way to control the spread of airborne pathogens and reduce fomite transmission. Here, the ability of a novel 6-hydroxycatechol-containing polymer to function as a self-disinfecting coating on the surface of polypropylene (PP) fabric was explored. Catechol is the main adhesive molecule found in mussel adhesive proteins. Molecular oxygen found in an aqueous solution can oxidize catechol and generate a known disinfectant, hydrogen peroxide (H2O2), as a byproduct. However, given the limited amount of moisture found in respiratory droplets, there is a need to enhance the rate of catechol autoxidation to generate antipathogenic levels of H2O2. 6-Hydroxycatechol contains an electron donating hydroxyl group on the 6-position of the benzene ring, which makes catechol more susceptible to autoxidation. 6-Hydroxycatechol-coated PP generated over 3000 μM of H2O2 within 1 h when hydrated with a small amount of aqueous solution (100 μL of PBS). The generated H2O2 was three orders of magnitude higher when compared to the amount generated by unmodified catechol. 6-Hydroxycatechol-containing coating demonstrated a more effective antimicrobial effect against both Gram-positive (Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria when compared to unmodified catechol. Similarly, the self-disinfecting coating reduced the infectivity of both bovine viral diarrhea virus and human coronavirus 229E by as much as a 2.5 log reduction value (a 99.7% reduction in viral load). Coatings containing unmodified catechol did not generate sufficient H2O2 to demonstrate significant virucidal effects. 6-Hydroxycatechol-containing coating can potentially function as a self-disinfecting coating that can be activated by the moisture present in respiratory droplets to generate H2O2 for disinfecting a broad range of pathogens. 

A pair of alkyne- and thiol-functionalized polyesters are designed to engineer elastomeric scaffolds with a wide range of tunable material properties (e.g., thermal, degradation, and mechanical properties) for different tissues, given their different host responses, mechanics, and regenerative capacities. The two prepolymers are quickly photo-cross-linkable through thiol-yne click chemistry to form robust elastomers with small permanent deformations. The elastic moduli can be easily tuned between 0.96 ± 0.18 and 7.5 ± 2.0 MPa, and in vitro degradation is mediated from hours up to days by adjusting the prepolymer weight ratios. These elastomers bear free hydroxyl and thiol groups with a water contact angle of less than 85.6 ± 3.58 degrees, indicating a hydrophilic nature. The elastomer is compatible with NIH/3T3 fibroblast cells with cell viability reaching 88 ± 8.7% relative to the TCPS control at 48 h incubation. Differing from prior soft elastomers, a mixture of the two prepolymers without a carrying polymer is electrospinnable and UV-cross-linkable to fabricate elastic fibrous scaffolds for soft tissues. The designed prepolymer pair can thus ease the fabrication of elastic fibrous conduits, leading to potential use as a resorbable synthetic graft. The elastomers could find use in other tissue engineering applications as well. 

Strong adherence to underwater or wet surfaces for applications like tissue adhesion and underwater robotics is a significant challenge. This is especially apparent when switchable adhesion is required that demands rapid attachment, high adhesive capacity, and easy release. Nature displays a spectrum of permanent to reversible attachment from organisms ranging from the mussel to the octopus, providing inspiration for underwater adhesion design that has yet to be fully leveraged in synthetic systems. Here, we review the challenges and opportunities for creating underwater adhesives with a pathway to switchability. We discuss key material, geometric, modeling, and design tools necessary to achieve underwater adhesion similar to the adhesion control demonstrated in nature. Through these interdisciplinary efforts, we envision that bioinspired adhesives can rise to or even surpass the extraordinary capabilities found in biological systems.