Catechol-Functionalized Chitosan: Optimized Preparation Method and Its Interaction with Mucin.

Chitosan is one of the most popular biopolymers used for biomedical applications with its unique properties of blood clotting and adhesion to tissues. Catechol-functionalized chitosan (CatChit) has shown a significant improvement of those properties of chitosan as biomaterials. However, some well-cited methods of CatChit preparation in existing literature, repeatedly followed by numerous research groups in the past decades, have not stressed the importance of the vulnerability of catechol to oxidation, which resulted in many priceless in vivo studies that used wrong materials, i.e., partially oxidized forms of CatChit. Since some key synthesis parameters were erroneous in those previous reports, it is a challenge to reproduce the published results. To avoid the loss of critical details with these repeated citations, it is essential that we re-establish the critical parameters in these methods. In this study, we examined the accuracy of existing protocols, and optimized one of the protocols to synthesize CatChit. We have confirmed that a notable degree of catechol oxidation is inevitable with the inaccurate synthetic protocols and the maintenance of pH < 5 throughout the preparation of CatChit is essential. We have also re-evaluated interaction between CatChit and mucin, which is widely present in the gastrointestinal (GI) tract, at different pH values using CatChit prepared via our optimized synthetic protocol. Turbidimetric titrations suggested that regardless of the reaction pH, the association between CatChit and mucin increased with increasing concentration of polymer with respect to mucin. The decrease in the average size of the aggregated particles observed by Dynamic Light Scattering (DLS) studies was attributed to the formation of a large number of aggregations with increasing polymer to mucin ratio. ζ potential (ZP) measurements suggested that at acidic reaction pH, the average particle size was dictated by electrostatic interactions, while at a physiological pH, consolidation of covalent and charge-based interactions contributed to the overall surface charge.

Rapidly responsive smart adhesive-coated micropillars utilizing catechol-boronate complexation chemistry.

Smart adhesive hydrogels containing 10 mol% each of dopamine methacrylamide (DMA) and 3-acrylamido phenylboronic acid (APBA) were polymerized in situ onto polydimethylsiloxane (PMDS) micropillars with different aspect ratios (AR = 0.4, 1 and 2). Using Johnson-Kendall-Roberts (JKR) contact mechanics tests, the adhesive-coated pillars demonstrated strong wet adhesion at pH 3 (Wadh = 420 mJ m-2) and can be repeatedly deactivated and reactivated by changing the pH value (pH 9 and 3, respectively). When compared to the bulk adhesive hydrogel of the same composition, the adhesive-coated pillars exhibited a significantly faster rate of transition (1 min) between strong and weak adhesion. This was attributed to an increased surface area to volume ratio of the adhesive hydrogel-coated pillars, which permitted rapid diffusion of ions into the adhesive matrix to form or break the catechol-boronate complex.

Incorporation of Anionic Monomer to Tune the Reversible Catechol-Boronate Complex for pH-Responsive, Reversible Adhesion.

Up to 30 mol % of acrylic acid (AAc) was incorporated into a pH-responsive smart adhesive consisting of dopamine methacrylamide and 3-acrylamido phenylboronic acid. Fourier transform infrared spectroscopy and rheometry confirmed that the incorporation of AAc shifted the pH of catechol-boronate complexation to a more basic pH. Correspondingly, adhesive formulations with elevated AAc contents demonstrated strong adhesion to quartz substrate at a neutral to mildly basic pH (7.5-8.5) based on Johnson-Kendall-Roberts contact mechanics test. When pH was further increased to 9.0, there was a drastic reduction in the measured work of adhesion (18- and 7-fold reduction compared to values measured at pHs 7.5 and 8.5, respectively) due to the formation of catechol-boronate complex. The complex remained reversible, and the interfacial binding property of the adhesive was successfully tuned with changing pH in successive contact cycles. However, an acidic pH (3.0) was required to break the catechol-boronate complex to recover the elevated adhesive property. Adding AAc enables the smart adhesive to function in physiological or marine pH ranges.

Effect of Ionic Functional Groups on the Oxidation State and Interfacial Binding Property of Catechol-Based Adhesive.

Adhesive hydrogels were prepared by copolymerizing dopamine methacrylamide with either acrylic acid (AAc) or N-(3-aminopropyl)methacrylamide hydrochloride (APMH). The effect of incorporating the anionic and cationic side chains on the oxidation state of catechol was characterized using the FOX assay to track the production of hydrogen peroxide byproduct generated during the autoxidation of catechol, and the interfacial binding property of the adhesive was determined by performing Johnson-Kendall-Roberts contact mechanics tests tested over a wide range of pH values (pH 3.0-9.0). The ionic species contributed to interfacial binding to surfaces with the opposite charge with measured work of adhesion values that were comparable to or in some cases higher than those of catechol. Addition of AAc minimized the oxidation of catechol even at a pH of 8.5 and correspondingly preserved the elevated adhesive property of catechol to both quartz and amine-functionalized surfaces. However, AAc lost its buffering capacity at pH 9.0, and catechol was oxidized at this pH. On the other hand, catechol formed a cohesive covalent bond with the network-bound amine side chain of APMH at basic pH, which interfered with the interfacial binding capability of APMH and the catechol.

Thermally and Photothermally Triggered Cytocompatible Triple-Shape-Memory Polymer Based on a Graphene Oxide-Containing Poly(ε-caprolactone) and Acrylate Composite.

Triple-shape-memory polymers (triple-SMPs) are a class of polymers capable of fixing two temporary shapes and recovering sequentially from the first temporary shape to the second temporary shape and, last, to the permanent shape. To accomplish a sequential shape change, a triple-SMP must have two separate shape-fixing mechanisms triggerable by distinct stimuli. Despite the biomedical potential of triple-SMPs, a triple-SMP that with cells present can undergo two different shape changes via two distinct cytocompatible triggers has not previously been demonstrated. Here, we report the design and characterization of a cytocompatible triple-SMP material that responds separately to thermal and light triggers to undergo two distinct shape changes under cytocompatible conditions. Tandem triggering was achieved via a photothermally triggered component, comprising poly(ε-caprolactone) (PCL) fibers with graphene oxide (GO) particles physically attached, embedded in a thermally triggered component, comprising a tert-butyl acrylate-butyl acrylate (tBA-BA) matrix. The material was characterized in terms of thermal properties, surface morphology, shape-memory performance, and cytocompatibility during shape change. Collectively, the results demonstrate cytocompatible triple-shape behavior with a relatively larger thermal shape change (an average of 20.4 ± 4.2% strain recovered for all PCL-containing groups) followed by a smaller photothermal shape change (an average of 3.5 ± 0.8% strain recovered for all PCL-GO-containing groups; samples without GO showed no recovery) with greater than 95% cell viability on the triple-SMP materials, establishing the feasibility of triple-shape memory to be incorporated into biomedical devices and strategies.

Smart biomaterial platforms: Controlling and being controlled by cells.

Across diverse research and application areas, dynamic functionality-such as programmable changes in biochemical property, in mechanical property, or in microscopic or macroscopic architecture-is an increasingly common biomaterials design criterion, joining long-studied criteria such as cytocompatibility and biocompatibility, drug release kinetics, and controlled degradability or long-term stability in vivo. Despite tremendous effort, achieving dynamic functionality while simultaneously maintaining other desired design criteria remains a significant challenge. Reversible dynamic functionality, rather than one-time or one-way dynamic functionality, is of particular interest but has proven especially challenging. Such reversible functionality could enable studies that address the current gap between the dynamic nature of in vivo biological and biomechanical processes, such as cell traction, cell-extracellular matrix (ECM) interactions, and cell-mediated ECM remodeling, and the static nature of the substrates and ECM constructs used to study the processes. This review assesses dynamic materials that have traditionally been used to control cell activity and static biomaterial constructs, experimental and computational techniques, with features that may inform continued advances in reversible dynamic materials. Taken together, this review presents a perspective on combining the reversibility of smart materials and the in-depth dynamic cell behavior probed by static polymers to design smart bi-directional ECM platforms that can reversibly and repeatedly communicate with cells.

Femtosecond Laser Densification of Hydrogels to Generate Customized Volume Diffractive Gratings.

Inspired by nature's ability to shape soft biological materials to exhibit a range of optical functionalities, we report femtosecond (fs) laser-induced densification as a new method to generate volume or subsurface diffractive gratings within ordinary hydrogel materials. We characterize the processing range in terms of fs laser power, speed, and penetration depths for achieving densification within poly(ethylene glycol) diacrylate (PEGDA) hydrogel and characterize the associated change in local refractive index (RI). The RI change facilitates the fabrication of custom volume gratings (parallel line, grid, square, and ring gratings) within PEGDA. To demonstrate this method's broad applicability, fs laser densification was used to generate line gratings within the phenylboronic acid (PBA) hydrogel, which is known to be responsive to changes in pH. In the future, this technique can be used to convert ordinary hydrogels into multicomponent biophotonic systems.

pH Responsive and Oxidation Resistant Wet Adhesive based on Reversible Catechol-Boronate Complexation.

A smart adhesive capable of binding to a wetted surface was prepared by copolymerizing dopamine methacrylamide (DMA) and 3-acrylamido phenylboronic acid (AAPBA). pH was used to control the oxidation state and the adhesive property of the catechol side chain of DMA and to trigger the catechol-boronate complexation. FTIR spectroscopy confirmed the formation of the complex at pH 9, which was not present at pH 3. The formation of the catechol-boronate complex increased the cross-linking density of the adhesive network. Most notably, the loss modulus values of the adhesive were more than an order of magnitude higher for adhesive incubated at pH 9 when compared to those measured at pH 3. This drastic increase in the viscous dissipation property is attributed to the introduction of reversible complexation into the adhesive network. Based on the Johnson Kendall Roberts (JKR) contact mechanics test, adhesive containing both DMA and AAPBA demonstrated strong interfacial binding properties (work of adhesion (Wadh) = 2000 mJ/m2) to borosilicate glass wetted with an acidic solution (pH 3). When the pH was increased to 9, Wadh values (180 mJ/m2) decreased by more than an order of magnitude. During successive contact cycles, the adhesive demonstrated the capability to transition reversibly between its adhesive and nonadhesive states with changing pH. Adhesive containing only DMA responded slowly to repeated changes in pH and became progressively oxidized without the protection of boronic acid. Although adhesive containing only AAPBA also demonstrated strong wet adhesion (Wadh ∼ 500 mJ/m2), its adhesive properties were not pH responsive. Both DMA and AAPBA are required to fabricate a smart adhesive with tunable and reversible adhesive properties.