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Polymer adhesives play an important role in many medical, consumer, and industrial products. Polymers of α-lipoic acid (αLA) have the potential to fulfill the need for versatile and environmentally friendly adhesives, but their performance is plagued by spontaneous depolymerization. We report a family of stabilized αLA polymer adhesives that can be tailored for a variety of medical or nonmedical uses and sustainably sourced and recycled in a closed-loop manner. Minor changes in monomer composition afforded a pressure-sensitive adhesive that functions well in dry and wet conditions, as well as a structural adhesive with strength equivalent to that of conventional epoxies. αLA surgical superglue successfully sealed murine amniotic sac ruptures, increasing fetal survival from 0 to 100%.

Purpose: Gene therapy using adeno-associated virus (AAV) vector-mediated gene delivery has undergone substantial growth in recent years with promising results in both preclinical and clinical studies, as well as emerging regulatory approval. However, the inability to quantify the efficacy of gene therapy from cellular delivery of gene-editing technology to specific functional outcomes is an obstacle for efficient development of gene therapy treatments. Building on prior works that used the CEST reporter gene lysine rich protein, we hypothesized that AAV viral capsids may generate endogenous CEST contrast from an abundance of surface lysine residues., Methods: NMR experiments were performed on isolated solutions of AAV serotypes 1-9 on a Bruker 800-MHz vertical scanner. In vitro experiments were performed for testing of CEST-NMR contrast of AAV2 capsids under varying pH, density, biological transduction stage, and across multiple serotypes and mixed biological media. Reverse transcriptase-polymerase chain reaction was used to quantify virus concentration. Subsequent experiments at 7 T optimized CEST saturation schemes for AAV contrast detection and detected AAV2 particles encapsulated in a biocompatible hydrogel administered in the hind limb of mice., Results: CEST-NMR experiments revealed CEST contrast up to 52% for AAV2 viral capsids between 0.6 and 0.8 ppm. CEST contrast generated by AAV2 demonstrated high levels of CEST contrast across a variety of chemical environments, concentrations, and saturation schemes. AAV2 CEST contrast displayed significant positive correlations with capsid density (R 2  > 0.99, p < 0.001), pH (R 2  = 0.97, p = 0.01), and viral titer per cell count (R 2  = 0.92, p < 0.001). Transition to a preclinical field strength yielded up to 11.8% CEST contrast following optimization of saturation parameters. In vivo detection revealed statistically significant molecular contrast between viral and empty hydrogels using both mean values (4.67 ± 0.75% AAV2 vs. 3.47 ± 0.87% empty hydrogel, p = 0.02) and quantile analysis., Conclusion: AAV2 viral capsids exhibit strong capacity as an endogenous CEST contrast agent and can potentially be used for monitoring and evaluation of AAV vector-mediated gene therapy protocols., (© 2024 International Society for Magnetic Resonance in Medicine.)

This research evolves into a comparative study of three different phenolic composites as coatings for rigid contact lenses, with a particular emphasis on enhancing their antifouling properties and hydrophobicity. The primary layer, comprised of diverse phenolic compounds, serves as a sturdy foundation. An exclusive secondary layer, featuring synthetic peptoids, is introduced to further minimize biofouling. Validated through X-ray photoelectron spectroscopy, the surface analysis confirms the successful integration of the polyphenolic layers and the subsequent grafting of peptoids onto the lens surface. The efficacy of the proposed coatings is substantiated through protein adsorption tests, providing definitive evidence of their antifouling capabilities. This research employs a nuanced assessment of coating performance, utilizing the quantification of fluorescence intensity to gauge effectiveness. Additionally, contact angle measurements offer insights into wettability and surface characteristics, contributing to a comprehensive understanding of the coating's practicality.

Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia-inducible factor one-alpha (HIF-1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self-assembly of PEG-DPCA conjugates. Pre-treatment of mice with PEG-DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)-induced colitis. Surprisingly, a single subcutaneous dose of PEG-DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA-induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF-1α and associated targets leading to an epithelial-to-mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand-alone restorative treatment to combat active IBD is warranted., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Polyethylene is a commodity material that is widely used because of its low cost and valuable properties. However, the lack of functional groups in polyethylene limits its use in applications that include adhesives, gas barriers, and plastic blends. The inertness of polyethylene makes it difficult to install groups that would enhance its properties and enable programmed chemical decomposition. To overcome these deficiencies, the installation of pendent functional groups that imbue polyethylene with enhanced properties is an attractive strategy to overcome its inherent limitations. Here, we describe strategies to derivatize oxidized polyethylene that contains both ketones and alcohols to monofunctional variants with bulk properties superior to those of unmodified polyethylene. Iridium-catalyzed transfer dehydrogenation with acetone furnished polyethylenes with only ketones, and ruthenium-catalyzed hydrogenation with hydrogen furnished polyethylenes with only alcohols. We demonstrate that the ratio of these functional groups can be controlled by reduction with stoichiometric hydride-containing reagents. The ketones and alcohols serve as sites to introduce esters and oximes onto the polymer, thereby improving surface and bulk properties over those of polyethylene. These esters and oximes were removed by hydrolysis to regenerate the original oxygenated polyethylenes, showing how functionalization can lead to materials with circularity. Waste polyethylenes were equally amenable to oxidative functionalization and derivatization of the oxidized material, showing that this low- or negative-value feedstock can be used to prepare materials of higher value. Finally, the derivatized polymers with distinct solubilities were separated from mechanically mixed plastic blends by selective dissolution, demonstrating that functionalization can lead to novel approaches for distinguishing and separating polymers from a mixture.

Functional polyethylenes possess valuable bulk and surface properties, but the limits of current synthetic methods narrow the range of accessible materials and prevent many envisioned applications. Instead, these materials are often used in composite films that are challenging to recycle. We report a Cu-catalyzed amination of polyethylenes to form mono- and bifunctional materials containing a series of polar groups and substituents. Designed catalysts with hydrophobic moieties enable the amination of linear and branched polyethylenes without chain scission or cross-linking, leading to polyethylenes with otherwise inaccessible combinations of functional groups and architectures. The resulting materials possess tunable bulk and surface properties, including toughness, adhesion to metal, paintability, and water solubility, which could unlock applications for functional polyethylenes and reduce the need for complex composites.

Hyaluronic acid (HA) and chitosan (CHI) are biopolyelectrolytes which are interesting for both the medical and polymer physics communities due to their biocompatibility and semi-flexibility, respectively. In this work, we demonstrate by rheology experiments that the linear viscoelasticity of HA/CHI coacervates depends strongly on the molecular weight of the polymers. Moduli for coacervates were found significantly higher than those of individual HA and CHI physical gels. A remarkable 1.5-fold increase in moduli was noted when catechol-conjugated HA and CHI were used instead. This was attributed to the conversion of coacervates to chemical gels by oxidation of 3,4-dihydroxyphenylalanine (DOPA) groups in HA and CHI to di-DOPA crosslinks. These rheological results put HA/CHI coacervates in the category of strong candidates as injectable tissue scaffolds or medical adhesives.

Supramolecular self-assemblies of hydrophilic macromolecules functionalized with hydrophobic, structure-directing components have long been used for drug delivery. In these systems, loading of poorly soluble compounds is typically achieved through physical encapsulation during or after formation of the supramolecular assembly, resulting in low encapsulation efficiencies and limited control over release kinetics, which are predominately governed by diffusion and carrier degradation. To overcome these limitations, amphiphilic prodrugs that leverage a hydrophobic drug as both the therapeutic and structure-directing component can be used to create supramolecular materials with higher loading and controlled-release kinetics using biodegradable or enzymatically cleavable linkers. Here, we report the design, synthesis, and characterization of a library of supramolecular polymer prodrugs based on poly(ethylene glycol) (PEG) and the proregenerative drug 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA). Structure-property relationships were elucidated through experimental characterization of prodrug behavior in both the wet and dry states using scattering techniques and electron microscopy and corroborated by coarse-grained modeling. Molecular architecture and the hydrophobic-to-hydrophilic ratio of PEG-DPCA conjugates strongly influenced their physical state in water, ranging from fully soluble to supramolecular spherical assemblies and nanofibers. Molecular design and supramolecular structure, in turn, were shown to dramatically alter hydrolytic and enzymatic release and cellular transport of DPCA. In addition to potentially expanding therapeutic options for DPCA through control of supramolecular assemblies, the design principles elaborated here may inform the development of other supramolecular prodrugs based on hydrophobic small-molecule compounds.

Macrophages (Mφs) are characterized by remarkable plasticity, an essential component of chronic inflammation. Thus, an appropriate and timely transition from proinflammatory (M1) to anti-inflammatory (M2) Mφs during wound healing is vital to promoting resolution of acute inflammation and enhancing tissue repair. Herein, exosomes derived from M2-Mφs (M2-Exos), which contain putative key regulators driving Mφ polarization, are used as local microenvironmental cues to induce reprogramming of M1-Mφs toward M2-Mφs for effective wound management. As an injectable controlled release depot for exosomes, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogels (Exogels) are designed and employed for encapsulating M2-Exos to maximize their therapeutic effects in cutaneous wound healing. The degradation time of the hydrogels is adjustable from 6 days or up to 27 days by controlling the crosslinking density and tightness. The localization of M2-Exos leads to a successful local transition from M1-Mφs to M2-Mφs within the lesion for more than 6 days, followed by enhanced therapeutic effects including rapid wound closure and increased healing quality in an animal model for cutaneous wound healing. Collectively, the hydrolytically degradable PEG hydrogel-based exosome delivery system may serve as a potential tool in regulating local polarization state of Mφs, which is crucial for tissue homeostasis and wound repair., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Translating fundamental studies of marine mussel adhesion into practical mussel-inspired wet adhesives remains an important technological challenge. To adhere, mussels secrete adhesive proteins rich in the catecholic amino acid 3,4-dihydroxyphenylalanine (Dopa) and positively charged lysine. Consequently, numerous synthetic adhesives incorporating catecholic and cationic functionalities have been designed. However, despite widespread research, uncertainties remain about the optimal design of synthetic mussel-inspired adhesives. Here, we present a study of the adhesion of mussel-inspired pressure-sensitive adhesives. We explore the effects of catechol content, molecular architecture, and solvent quality on pressure-sensitive adhesive (PSA) adhesion and cohesion measured in a surface forces apparatus. Our findings demonstrate that the influence of catechol content depends on the choice of solvent and that adhesive performance is dictated by film composition rather than molecular architecture. Our results also highlight the importance of electrostatic and hydrophobic interactions for adhesion and cohesion in aqueous environments. Together, our findings contribute to an improved understanding of the interplay between materials chemistry, environmental conditions, and adhesive performance to facilitate the design of bioinspired wet adhesives.

Bone injuries and fractures reliably heal through a process of regeneration with restoration to original structure and function when the gap between adjacent sides of a fracture site is small. However, when there is significant volumetric loss of bone, bone regeneration usually does not occur. In the present studies, we explore a particular case of volumetric bone loss in a mouse model of human periodontal disease (PD) in which alveolar bone surrounding teeth is permanently lost and not replaced. This model employs the placement a ligature around the upper second molar for 10 days leading to inflammation and bone breakdown and faithfully replicates the bacterially-induced inflammatory etiology of human PD to induce bone degeneration. After ligature removal, mice are treated with a timed-release formulation of a small molecule inhibitor of prolylhydroxylases (PHDi; 1,4-DPCA) previously shown to induce epimorphic regeneration of soft tissue in non-regenerating mice. This PHDi induces high expression of HIF-1α and is able to shift the metabolic state from OXPHOS to aerobic glycolysis, an energetic state used by stem cells and embryonic tissue. This regenerative response was completely blocked by siHIF1a . In these studies, we show that timed-release 1,4-DPCA rapidly and completely restores PD-affected bone and soft tissue with normal anatomic fidelity and with increased stem cell markers due to site-specific stem cell migration and/or de-differentiation of local tissue, periodontal ligament (PDL) cell proliferation, and increased vascularization. In-vitro studies using gingival tissue show that 1,4-DPCA indeed induces de-differentiation and the expression of stem cell markers but does not exclude the role of migrating stem cells. Evidence of metabolic reprogramming is seen by the expression of not only HIF-1a, its gene targets, and resultant de-differentiation markers, but also the metabolic genes Glut-1, Gapdh, Pdk1, Pgk1 and Ldh-a in jaw periodontal tissue., Competing Interests: Competing Interests: EHK and PBM are co-inventors on US Patents 9,675,607, 10,307,415, and 11,033, 541 for 1,4-DPCA drug delivery systems. Conflict of Interest: The authors have declared that no conflict of interest exists.

Introduction: The benefits of fetal surgery are impaired by the high incidence of iatrogenic preterm prelabor rupture of the fetal membranes (iPPROM), for which chorioamniotic separation has been suggested as a potential initiator. Despite the urgent need to prevent iPPROM by sealing the fetoscopic puncture site after intervention, no approach has been clinically translated., Methods: A mussel-inspired biomimetic glue was tested in an ovine fetal membrane (FM) defect model. The gelation time of mussel glue (MG) was first optimized to make it technically compatible with fetal surgery. Then, the biomaterial was loaded in polytetrafluoroethylene-coated nitinol umbrella-shaped receptors and applied on ovine FM defects (N = 10) created with a 10 French trocar. Its sealing performance and tissue response were analyzed 10 days after implantation by amniotic fluid (AF) leakage and histological methods., Results: All ewes and fetuses recovered well after the surgery, and 100% ewe survival and 91% fetal survival were observed at explantation. All implants were tight at explantation, and no AF leakage was observed in any of them. Histological analysis revealed a mild tissue response to the implanted glue., Conclusion: MG showed promising properties for the sealing of FM defects and thereby the prevention of preterm birth. Studies to analyze the long-term tissue response to the sealant should be performed., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Phenolics are ubiquitous in nature and have gained immense research attention because of their unique physiochemical properties and widespread industrial use. In recent decades, their accessibility, versatile reactivity, and relative biocompatibility have catalysed research in phenolic-enabled nanotechnology (PEN) particularly for biomedical applications which have been a major benefactor of this emergence, as largely demonstrated by polydopamine and polyphenols. Therefore, it is imperative to overveiw the fundamental mechanisms and synthetic strategies of PEN for state-of-the-art biomedical applications and provide a timely and comprehensive summary. In this review, we will focus on the principles and strategies involved in PEN and summarize the use of the PEN synthetic toolkit for particle engineering and the bottom-up synthesis of nanohybrid materials. Specifically, we will discuss the attractive forces between phenolics and complementary structural motifs in confined particle systems to synthesize high-quality products with controllable size, shape, composition, as well as surface chemistry and function. Additionally, phenolic's numerous applications in biosensing, bioimaging, and disease treatment will be highlighted. This review aims to provide guidelines for new scientists in the field and serve as an up-to-date compilation of what has been achieved in this area, while offering expert perspectives on PEN's use in translational research.

Biomimetic surface coatings based on plant polyphenols and catecholamines have been used broadly in a variety of applications. However, the lack of a rational cost-effective platform for screening these coatings and their properties limits the true potential of these functional materials to be unleashed. Here, we investigated the oxidation behavior and coating formation ability of a library consisting of 45 phenolic compounds and catecholamines. UV-vis spectroscopy demonstrated significant acceleration of oxidation and polymerization under UV irradiation. We discovered that several binary mixtures resulted in non-additive behavior (synergistic or antagonistic effect) yielding much thicker or thinner coatings than individual compounds measured by ellipsometry. To investigate the properties of coatings derived from new combinations, we used a miniaturized high-throughput strategy to screen 2,532 spots coated with single, binary, and ternary combinations of coating precursors in one run. We evaluated the use of machine learning models to learn the relation between the chemical structure of the precursors and the thickness of the nanocoatings. Formation and stability of nanocoatings were investigated in a high-throughput manner via discontinuous dewetting. 30 stable combinations (hits) were used to tune the surface wettability and to form water droplet microarray and spot size gradients of water droplets on the coated surface. No toxicity was observed against eukaryotic HeLa cells and Pseudomonas aeruginosa (strain PA30) bacteria after 24 h incubation at 37 °C. The strategy introduced here for high-throughput screening of nanocoatings derived from combinations of coating precursors enables the discovery of new functional materials for various applications in science and technology in a cost-effective miniaturized manner., Competing Interests: The authors declare that they have no financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Historically, the field of regenerative medicine has aimed to heal damaged tissue through the use of biomaterials scaffolds or delivery of foreign progenitor cells. Despite 30 years of research, however, translation and commercialization of these techniques has been limited. To enable mammalian regeneration, a more practical approach may instead be to develop therapies that evoke endogenous processes reminiscent of those seen in innate regenerators. Recently, investigations into tadpole tail regrowth, zebrafish limb restoration, and the super-healing Murphy Roths Large (MRL) mouse strain, have identified ancient oxygen-sensing pathways as a possible target to achieve this goal. Specifically, upregulation of the transcription factor, hypoxia-inducible factor one alpha (HIF-1α) has been shown to modulate cell metabolism and plasticity, as well as inflammation and tissue remodeling, possibly priming injuries for regeneration. Since HIF-1α signaling is conserved across species, environmental or pharmacological manipulation of oxygen-dependent pathways may elicit a regenerative response in non-healing mammals. In this review, we will explore the emerging role of HIF-1α in mammalian healing and regeneration, as well as attempts to modulate protein stability through hyperbaric oxygen treatment, intermittent hypoxia therapy, and pharmacological targeting. We believe that these therapies could breathe new life into the field of regenerative medicine., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A modular approach to synthesizing functional pressure sensitive adhesives (PSAs) was introduced, wherein a modifiable acrylic PSA copolymer was synthesized by copolymerizing common PSA monomers with 6 mol % glycidyl methacrylate, allowing for subsequent functional group modification via the pendant epoxide functionality. This postmodification technique has the advantage of allowing the installation of a variety of functional groups relevant to adhesion, without variation of molecular weight. Because comparisons of cohesive and adhesive performance of candidate PSAs can be complicated by molecular weight differences, this strategy simplifies direct comparisons of the effects of functional groups on performance. As a proof of concept, a mussel-inspired catecholic PSA was synthesized by postreaction of the epoxide scaffold polymer with a thiol-modified catechol, allowing the effect of catechol on underlying structure-property relationships to be determined without variation in molecular weight. The mechanical performance of catecholic PSA was compared to relevant control PSAs by using industry-standard 180° peel and static shear tests, revealing an increase in peel strength achieved through catechol modification. Moreover, we observed an unexpected enhancement in PSA cohesive strength attributed to oxidation of catechol, which cannot be attributed to differences in molecular weight, a common source of changes in PSA cohesive strength.

Here we introduce a tissue-adhesive patch with orthogonal cohesive and adhesive chemistries; supramolecular ureido-4-pyrimidinone (UPy) cross-links provide cohesive strength, and catechols provide mussel-inspired tissue adhesion. In the development of tissue-adhesive biomaterials, prior research has focused on forming strong adhesive interfaces in wet conditions, leaving the use of supramolecular cross-links for cohesive strength underexplored. In developing this adhesive patch, the influence of the comonomers' composition and amphiphilicity on adhesion was investigated by lap shear adhesion to wet tissue. We determined failed lap joints' failure mechanism using catechol-specific Arnow's stain and identified formulations with improved cohesive strength. The adhesive materials were cytocompatible in mammalian cell conditioned media viability studies. We found that using orthogonal motifs to independently control adhesives' cohesive and adhesive strengths resulted in stronger tissue adhesion. The design principles presented here advance the development of wet tissue adhesives and could allow for the future design of biomaterials with desirable stimuli-responsive properties.

Polypeptoid-coated surfaces and many surface-grafted hydrophilic polymer brushes have been proven efficient in antifouling-the prevention of nonspecific biomolecular adsorption and cell attachment. Protein adsorption, in particular, is known to mediate subsequent cell-surface interactions. However, the detailed antifouling mechanism of polypeptoid and other polymer brush coatings at the molecular level is not well understood. Moreover, most adsorption studies focus only on measuring a single adsorbed mass value, and few techniques are capable of characterizing the hydrated in situ layer structure of either the antifouling coating or adsorbed proteins. In this study, interfacial assembly of polypeptoid brushes with different chain lengths has been investigated in situ using neutron reflection (NR). Consistent with past simulation results, NR revealed a common two-step structure for grafted polypeptoids consisting of a dense inner region that included a mussel adhesive-inspired oligopeptide for grafting polypeptoid chains and a highly hydrated upper region with very low polymer density (molecular brush). Protein adsorption was studied with human serum albumin (HSA) and fibrinogen (FIB), two common serum proteins of different sizes but similar isoelectric points (IEPs). In contrast to controls, we observed higher resistance by grafted polypeptoid against adsorption of the larger FIB, especially for longer chain lengths. Changing the pH to close to the IEPs of the proteins, which generally promotes adsorption, also did not significantly affect the antifouling effect against FIB, which was corroborated by atomic force microscopy imaging. Moreover, NR enabled characterization of the in situ hydrated layer structures of the polypeptoids together with proteins adsorbed under selected conditions. While adsorption on bare SiO 2 controls resulted in surface-induced protein denaturation, this was not observed on polypeptoids. Our current results therefore highlight the detailed in situ view that NR may provide for characterizing protein adsorption on polymer brushes as well as the excellent antifouling behavior of polypeptoids.

The hypoxia-inducible factor 1α (HIF-1α) is critically involved in tissue regeneration. Hence, the pharmacological prevention of HIF-1α degradation by prolyl hydroxylase (PHD) under normoxic conditions is emerging as a promising option in regenerative medicine. Using a mouse model of ligature-induced periodontitis and resolution, we tested the ability of an injectable hydrogel-formulated PHD inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA/hydrogel), to promote regeneration of alveolar bone lost owing to experimental periodontitis. Mice injected subcutaneously with 1,4-DPCA/hydrogel at the onset of periodontitis resolution displayed significantly increased gingival HIF-1α protein levels and bone regeneration, as compared to mice treated with vehicle control. The 1,4-DPCA/hydrogel-induced increase in bone regeneration was associated with elevated expression of osteogenic genes, decreased expression of pro-inflammatory cytokine genes, and increased abundance of FOXP3 + T regulatory (Treg) cells in the periodontal tissue. The enhancing effect of 1,4-DPCA/hydrogel on Treg cell accumulation and bone regeneration was reversed by AMD3100, an antagonist of the chemokine receptor CXCR4 that mediates Treg cell recruitment. In conclusion, the administration of 1,4-DPCA/hydrogel at the onset of periodontitis resolution promotes CXCR4-dependent accumulation of Treg cells and alveolar bone regeneration, suggesting a novel approach for regaining bone lost due to periodontitis., (© 2020 Federation of American Societies for Experimental Biology.)

Polydopamine (PDA) is a simple and versatile conformal coating material that has been proposed for a variety of uses; however in practice its performance is often hindered by poor mechanical properties and high roughness. Here, we show that blue-diode laser annealing dramatically improves mechanical performance and reduces roughness of PDA coatings. Laser-annealed PDA (LAPDA) was shown to be >100-fold more scratch resistant than pristine PDA and even better than hard inorganic substrates, which we attribute to partial graphitization and covalent coupling between PDA subunits during annealing. Moreover, laser annealing provides these benefits while preserving other attractive properties of PDA, as demonstrated by the superior biofouling resistance of antifouling polymer-grafted LAPDA compared to PDA modified with the same polymer. Our work suggests that laser annealing may allow the use of PDA in mechanically demanding applications previously considered inaccessible, without sacrificing the functional versatility that is so characteristic of PDA.

The outstanding adhesive performance of mussel byssal threads has inspired materials scientists over the past few decades. Exploiting the amino-catechol synergy, polymeric pressure-sensitive adhesives (PSAs) have now been synthesized by copolymerizing traditional PSA monomers, butyl acrylate and acrylic acid, with mussel-inspired lysine- and aromatic-rich monomers. The consequences of decoupling amino and catechol moieties from each other were compared (that is, incorporated as separate monomers) against a monomer architecture in which the catechol and amine were coupled together in a fixed orientation in the monomer side chain. Adhesion assays were used to probe performance at the molecular, microscopic, and macroscopic levels by a combination of AFM-assisted force spectroscopy, peel and static shear adhesion. Coupling of catechols and amines in the same monomer side chain produced optimal cooperative effects in improving the macroscopic adhesion performance., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The mussel byssus has long been a source of inspiration for the adhesion community. Recently, adhesive synergy between flanking lysine (Lys, K) and 3,4-Dihydroxyphenylalanine (DOPA, Y) residues in the mussel foot proteins (Mfps) has been highlighted. However, the complex topological relationship of DOPA and Lys as well as the interfacial adhesive roles of other amino acids have been understudied. Herein, we study adhesion of Lys and DOPA-containing peptides to organic and inorganic substrates using single-molecule force spectroscopy (SMFS). We show that a modest increase in peptide length, from KY to (KY) 3 , increases adhesion strength to TiO 2. Surprisingly, further increase in peptide length offers no additional benefit. Additionally, comparison of adhesion of dipeptides containing Lys and either DOPA (KY) or phenylalanine (KF) shows that DOPA is stronger and more versatile. We furthermore demonstrate that incorporating a nonadhesive spacer between (KY) repeats can mimic the hidden length in the Mfp and act as an effective strategy to dissipate energy.

Microbial surface attachment negatively impacts a wide range of devices from water purification membranes to biomedical implants. Mimics of antimicrobial peptides (AMPs) constituted from poly(N-substituted glycine) "peptoids" are of great interest as they resist proteolysis and can inhibit a wide spectrum of microbes. We investigate how terminal modification of a peptoid AMP-mimic and its surface immobilization affect antimicrobial activity. We also demonstrate a convenient surface modification strategy for enabling alkyne-azide "click" coupling on amino-functionalized surfaces. Our results verified that the N- and C-terminal peptoid structures are not required for antimicrobial activity. Moreover, our peptoid immobilization density and choice of PEG tether resulted in a "volumetric" spatial separation between AMPs that, compared to past studies, enabled the highest AMP surface activity relative to bacterial attachment. Our analysis suggests the importance of spatial flexibility for membrane activity and that AMP separation may be a controlling parameter for optimizing surface anti-biofouling., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

We report a versatile method to form bacterial cellulose coatings through simple dip-coating of 3D objects in suspensions of cellulose-producing bacteria. The adhesion of cellulose-secreting bacteria on objects was promoted through surface roughness and chemistry. Immobilized bacteria secreted highly porous hydrogels with high water content directly from the surface of a variety of materials. The out-of-plane orientation of cellulose fibers present in this coating leads to high mechanical stability and energy dissipation with minimal cellulose concentration. The conformal, biocompatible, and lubricious nature of the in situ grown cellulose surfaces makes the coated 3D objects attractive for biomedical applications.

Inspired by the catechol and amine-rich adhesive proteins of mussels, polydopamine (pDA) has become one of the most widely employed methods for functionalizing material surfaces, powered in part by the versatility and simplicity of pDA film deposition that takes place spontaneously on objects immersed in an alkaline aqueous solution of dopamine monomer. Despite the widespread adoption of pDA as a multifunctional coating for surface modification, it exhibits poor mechanical performance. Attempts to modify the physical properties of pDA by incorporation of oxidizing agents, cross-linkers, or carbonization of the films at ultrahigh temperatures have been reported; however, improving mechanical properties with mild post-treatments without sacrificing the functionality and versatility of pDA remains a challenge. Here, we demonstrate thermal annealing at a moderate temperature (130 °C) as a facile route to enhance mechanical robustness of pDA coatings. Chemical spectroscopy, X-ray scattering, molecular force spectroscopy, and bulk mechanical analyses indicate that monomeric and oligomeric species undergo further polymerization during thermal annealing, leading to fundamental changes in molecular and bulk mechanical behavior of pDA. Considerable improvements in scratch resistance were noted in terms of both penetration depth (32% decrease) and residual depth (74% decrease) for the annealed pDA coating, indicating the enhanced ability of the annealed coating to resist mechanical deformations. Thermal annealing resulted in significant enhancement in the intermolecular and cohesive interactions between the chains in the pDA structure, attributed to cross-linking and increased entanglements, preventing desorption and detachment of the chains from the coating. Importantly, improvements in pDA mechanical performance through thermal annealing did not compromise the ability of pDA to support secondary coating reactions as evidenced by electroless deposition of a metal film adlayer on annealed pDA.

A synthetic strategy to incorporate catechol functional groups into benzoxazine thermoset monomers was developed, leading to a family of bioinspired small-molecule resins and main-chain polybenzoxazines derived from biologically available phenols. Lap-shear adhesive testing revealed a polybenzoxazine derivative with greater than 5 times improved shear strength on aluminum substrates compared to a widely studied commercial benzoxazine resin. Derivative synthesis identified the catechol moiety as an important design feature in the adhesive performance and curing behavior of this bioinspired thermoset. Favorable mechanical properties comparable to commercial resin were maintained, and glass transition temperature and char yield under nitrogen were improved. Blending of monomers with bioinspired main-chain polybenzoxazine derivatives provided formulations with enhanced shear adhesive strengths up to 16 MPa, while alloying with commercial core-shell particle-toughened epoxy resins led to shear strengths exceeding 20 MPa. These results highlight the utility of bioinspired design and the use of biomolecules in the preparation of high-performance thermoset resins and adhesives with potential utility in transportation and aerospace industries and applications in advanced composites synthesis., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The byssus-mediated adhesion of marine mussels is a widely mimicked system for robust adhesion in both dry and wet conditions. Mussel holdfasts are fabricated from proteins that contain a significant amount of the unique catecholic amino acid dihydroxyphenylalanine, which plays a key role in enhancing interfacial adhesion to organic and inorganic marine surfaces and contributes to cohesive strength of the holdfast. In this work, pressure-sensitive adhesives (PSAs) were synthesized by copolymerization of dopamine methacrylamide (DMA) with common PSA monomers, butyl acrylate and acrylic acid, with careful attention paid to the effects of catechol on adhesive and cohesive properties. A combination of microscopic and macroscopic adhesion assays was used to study the effect of catechol on adhesion performance of acrylic PSAs. Addition of only 5% DMA to a conventional PSA copolymer containing butyl acrylate and acrylic acid resulted in 6-fold and 2.5-fold increases in work required to separate the PSA from silica and polystyrene, respectively, and a large increase in 180° peel adhesion against stainless steel after 24 h storage in both ambient and underwater conditions. Moreover, the holding power of the catechol PSAs on both steel and high-density polyethylene under shear load continuously increased as a function of catechol concentration, up to a maximum of 10% DMA. We also observed stark increases in shear and peel adhesion for the catecholic adhesives over PSAs with noncatecholic aromatic motifs, further underlining the benefits of catechols in PSAs. Overall, catechol PSAs perform extremely well on polar and metallic surfaces. The advantage of incorporating catechols in PSA formulations, however, is less straightforward for peel adhesion in nonpolar, organic substrates and tackiness of the PSAs.

Fetal surgery and fetal therapy involve surgical interventions on the fetus in utero to correct or ameliorate congenital abnormalities and give a developing fetus the best chance at a healthy life. Historical use of biomaterials in fetal surgery has been limited, and most biomaterials used in fetal surgeries today were originally developed for adult or pediatric patients. However, as the field of fetal surgery moves from open surgeries to minimally invasive procedures, many opportunities exist for innovative biomaterials engineers to create materials designed specifically for the unique challenges and opportunities of maternal-fetal surgery. Here, we review biomaterials currently used in clinical fetal surgery as well as promising biomaterials in development for eventual clinical translation. We also highlight unmet challenges in fetal surgery that could particularly benefit from novel biomaterials, including fetal membrane sealing and minimally invasive myelomeningocele defect repair. Finally, we conclude with a discussion of the underdeveloped fetal immune system and opportunities for exploitation with novel immunomodulating biomaterials.

Medical adhesives that are strong, easy to apply and biocompatible are promising alternatives to sutures and staples in a large variety of surgical and clinical procedures. Despite progress in the development and regulatory approval of adhesives for use in the clinic, adhesion to wet tissue remains challenging. Marine organisms have evolved a diverse set of highly effective wet adhesive approaches that have inspired the design of new medical adhesives. Here we provide an overview of selected marine animals and their chemical and physical adhesion strategies, the state of clinical translation of adhesives inspired by these organisms, and target applications where marine-inspired adhesives can have a significant impact. We will focus on medical adhesive polymers inspired by mussels, sandcastle worms, and cephalopods, emphasize the history of bioinspired medical adhesives from the peer reviewed and patent literature, and explore future directions including overlooked sources of bioinspiration and materials that exploit multiple bioinspired strategies., Competing Interests: Competing financial interests The authors declare no competing financial interests.

Supramolecular polymers self-assemble into nanofibers, micelles, and other nanostructures through weak noncovalent interactions between subunits. Such systems possess attractive properties for use in a variety of practical settings such as energy, sustainability, and healthcare. In regenerative medicine, a common approach involves implanting a supramolecular material containing cell and growth factor binding motifs directly into a diseased or traumatized tissue defect, whereupon it interacts with and/or recruits components of the biological system to induce tissue healing. Here we introduce a supramolecular therapeutic in which tissue regeneration is orchestrated by a supramolecular polymer prodrug implanted subcutaneously in a remote tissue. Our approach exploits a hydrophobic small-molecule inhibitor of prolyl hydroxylase enzyme as both a regeneration-inducing therapeutic and a structure-directing agent in a supramolecular polymer that forms shear-thinning nanofiber hydrogels. Subcutaneous injection of the supramolecular hydrogel in the back of mice wounded with a critical-sized defect in the ear led to transient upregulation of hypoxia inducible factor-1α and regeneration of ear tissue in a manner reminiscent of epimorphic regeneration. This drug-induced regeneration strategy utilizes a simple and translatable supramolecular design, eliminates the need for delivery of biologics ( e. g., growth factors, cells), and avoids implantation of a foreign material directly in a tissue defect.

Robust, biocompatible, and facile coatings are promising for improving the in vivo performance of medical implants and devices. Here, we demonstrate the formation of nanothin silk coatings by leveraging the biomimetic self-assembly of eADF4(C16), an amphiphilic recombinant protein based on the Araneus diadematus dragline spidroin ADF4. These coatings result from concurrent adsorption and supramolecular assembly of eADF4(C16) induced by KH2PO4, thereby providing a mild one-pot coating strategy in which the coating rate can be controlled by protein and KH2PO4 concentration. The thickness of the coatings ranges from 2-30 nm depending on the time immersed in the aqueous coating solution. Coatings can be formed on hydrophobic and hydrophilic substrates regardless of surface chemistry and without requiring specialized surface activation. Moreover, coatings appear to be stable through vigorous rinsing and prolonged agitation in water. Grazing incidence wide angle X-ray scattering, single-molecule force spectroscopy, and Congo red staining techniques confirm the formation of β-sheet nanocrystals within the eADF4(C16) coating, which contributes to the cohesive and adhesive stability of the material. Coatings are exceptionally smooth in the dry state and are hydrophilic regardless of substrate hydrophobicity. Under aqueous conditions, nanothin silk coatings exhibit the properties of a hydrogel material.

Inspired by the adhesive proteins of mussels, polydopamine (pDA) has emerged as one of the most widely employed materials for surface functionalization. Despite numerous attempts at characterization, little consensus has emerged regarding whether pDA is a covalent polymer or a noncovalent aggregate of low molecular weight species. Here, we employed single-molecule force spectroscopy (SMFS) to characterize pDA films. Retraction of a pDA-coated cantilever from an oxide surface shows the characteristic features of a polymer with contour lengths of up to 200 nm. pDA polymers are generally weakly bound to the surface through much of their contour length, with occasional "sticky" points. Our findings represent the first direct evidence for the polymeric nature of pDA and provide a foundation upon which to better understand and tailor its physicochemical properties., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Plant phenolic compounds and catecholamines have been widely used to obtain substrate-independent precursor nanocoatings and adhesives. Nevertheless, there are downsides in using such phenolic compounds for surface modification such as formation of nonuniform coatings, need for multistep modification, and restricted possibilities for postfunctionalization. In this study, inspired by a strong binding ability of natural polyphenols found in plants, we used three different macrocyclic polyphenols, known as resorcin[4]arenes, to modify the surface of different substrates by simple dip-coating into the dilute solution of these compounds. Eight hydroxyl groups on the large rim of these resorcin[4]arenes provide multiple anchoring points to the surface, whereas the lower rim decorated with different appending groups introduces the desired chemical and physical functionalities to the substrate's surface. Deposition of a uniform and transparent resorcinarene layer on the surface was confirmed by several surface characterization techniques. Incubation of the modified substrates in different environments indicated that the stability of the resorcinarene layer was dependent on the type of substrate and the pH value. The most stable resorcinarene layer was formed on amine-functionalized substrates. The surface was modified with alkenyl functional groups in one step using a resorcinarene compound possessing four alkenyl appending groups on its small rim. Thiol-ene photoclick chemistry was used to site-selectively postfunctionalize the surface with hydrophilic and hydrophobic micropatterns, which was confirmed by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. Thus, we demonstrate that resorcin[4]arenes extend the scope of applications of plant polyphenol and mussel-inspired precursors to tailor-made multifunctional nanocoatings, suitable for a variety of potential applications in biotechnology, biology, and material science.

Nanocapsules can be designed for applications including drug delivery, catalysis, and biological imaging. The mussel-inspired material polydopamine is a promising shell layer for nanocapsules because of its free radical scavenging capacity, ability to react with a broad range of functional molecules, lack of toxicity, and biodegradability. Previous reports of polydopamine nanocapsule formation have relied on a templating approach. Herein, we report a template-free approach to polydopamine nanocapsule formation in the presence of resveratrol, a naturally occurring anti-inflammatory and antioxidant compound found in red wine and grapes. Synthesis of nanocapsules occurs spontaneously in an ethanolic resveratrol/dopamine·HCl solution at pH 8.5. UV-vis absorbance spectroscopy and X-ray photoelectron spectroscopy indicate that resveratrol is incorporated into the nanocapsules. We also observed the formation of a soluble fluorescent dopamine-resveratrol adduct during synthesis, which was identified by high-performance liquid chromatography, UV-vis spectroscopy, and electrospray ionization mass spectrometry. Using transmission electron microscopy and dynamic light scattering, we studied the influence of solvent composition, dopamine concentration, and resveratrol/dopamine ratio on the nanocapsule diameter and shell thickness. The resulting nanocapsules have excellent free radical scavenging activity as measured by a 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. Our work provides a convenient pathway by which resveratrol, and possibly other hydrophobic bioactive compounds, may be encapsulated within polydopamine nanocapsules.

Nanoparticle-mediated drug delivery has demonstrated great potential to treat various diseases especially cancer. However, there is an unmet need for the scalable synthesis of multifunctional nanoparticles to meet the complex challenges of drug delivery. Here we show that we can synthesize nanoparticles from the polyphenol quercetin, which can be conveniently functionalized with ligands and drug molecules by simple mixing under ambient conditions. Nanoparticles (∼30-40 nm in diameter) were formed by oxidative self-polymerization of quercetin in alkaline buffer (pH 9). The reactivity of oxidized polyphenols was exploited to immobilize amine-terminated methoxy poly(ethylene glycol) on the nanoparticles' surface for steric stability, followed by loading with doxorubicin as a model drug. Surface modification of the nanoparticles was confirmed by X-ray Photoelectron Spectroscopy. An antioxidant assay showed that the nanoparticles retained some antioxidant activity. The nanoparticles were readily internalized by KB cells via an endo-lysosomal pathway. Doxorubicin-loaded nanoparticles showed a drug loading of 35.6 ± 4.9% w/w with a loading efficiency of 88.9 ± 12.4%, sustained drug release, and potent cytotoxicity in vitro. Our findings demonstrate a promising new application for naturally occurring polyphenols as a renewable source of drug delivery nanocarriers that can be synthesized at low cost with minimal equipment.

We report here the development of hydrogels formed at physiological conditions using PEG (polyethylene glycol) based polymers modified with boronic acids (BAs) as backbones and the plant derived polyphenols ellagic acid (EA), epigallocatechin gallate (EGCG), tannic acid (TA), nordihydroguaiaretic acid (NDGA), rutin trihydrate (RT), rosmarinic acid (RA) and carminic acid (CA) as linkers. Rheological frequency sweep and single molecule force spectroscopy (SMFS) experiments show that hydrogels linked with EGCG and TA are mechanically stiff, arising from the dynamic covalent bond formed by the polyphenol linker and boronic acid functionalized polymer. Stability tests of the hydrogels in physiological conditions revealed that gels linked with EA, EGCG, and TA are stable. We furthermore showed that EA- and EGCG-linked hydrogels can be formed via in situ gelation in pH 7.4 buffer, and provide long-term steady state release of bioactive EA. In vitro experiments showed that EA-linked hydrogel significantly reduced the viability of CAL-27 human oral cancer cells via gradual release of EA.

Developing adhesives that can function underwater remains a major challenge for bioengineering, yet many marine creatures, exemplified as mussels and barnacles, have evolved their unique proteinaceous adhesives for strong wet adhesion. The mechanisms underlying the strong adhesion of these natural adhesive proteins provide rich information for biomimetic efforts. Here, combining atomic force microscopy (AFM) imaging and force spectroscopy, we examine the effects of pH on the self-assembly and adhesive properties of cp19k, a key barnacle underwater adhesive protein. For the first time, we confirm that the bacterial recombinant Balanus albicostatus cp19k (rBalcp19k), which contains no 3,4-dihydroxyphenylalanine (DOPA) or any other amino acids with post-translational modifications, can self-assemble into aggregated nanofibers at acidic pHs. Under moderately acidic conditions, the adhesion strength of unassembled monomeric rBalcp19k on mica is only slightly lower than that of a commercially available mussel adhesive protein mixture, yet the adhesion ability of rBalcp19k monomers decreases significantly at increased pH. In contrast, upon preassembly at acidic and low-salinity conditions, rBalcp19k nanofibers keep stable in basic and high-salinity seawater and display much stronger adhesion and thus show resistance to its adverse impacts. Besides, we find that the adhesion ability of Balcp19k is not impaired when it is combined with an N-terminal Thioredoxin (Trx) tag, yet whether the self-assembly property will be disrupted is not determined. Collectively, the self-assembly-enhanced adhesion presents a previously unexplored mechanism for the strong wet adhesion of barnacle cement proteins and may lead to the design of barnacle-inspired adhesive materials.

Polydopamine is one of the simplest and most versatile approaches to functionalizing material surfaces, having been inspired by the adhesive nature of catechols and amines in mussel adhesive proteins. Since its first report in 2007, a decade of studies on polydopamine molecular structure, deposition conditions, and physicochemical properties have ensued. During this time, potential uses of polydopamine coatings have expanded in many unforeseen directions, seemingly only limited by the creativity of researchers seeking simple solutions to manipulating surface chemistry. In this review, we describe the current state of the art in polydopamine coating methods, describe efforts underway to uncover and tailor the complex structure and chemical properties of polydopamine, and identify emerging trends and needs in polydopamine research, including the use of dopamine analogs, nitrogen-free polyphenolic precursors, and improvement of coating mechanical properties.

The excessive volume changes during cell cycling of Si-based anode in lithium ion batteries impeded its application. One major reason for the cell failure is particle isolation during volume shrinkage in delithiation process, which makes strong adhesion between polymer binder and anode active material particles a highly desirable property. Here, a biomimetic side-chain conductive polymer incorporating catechol, a key adhesive component of the mussel holdfast protein, was synthesized. Atomic force microscopy-based single-molecule force measurements of mussel-inspired conductive polymer binder contacting a silica surface revealed a similar adhesion toward substrate when compared with an effective Si anode binder, homo-poly(acrylic acid), with the added benefit of being electronically conductive. Electrochemical experiments showed a very stable cycling of Si-alloy anodes realized via this biomimetic conducting polymer binder, leading to a high loading Si anode with a good rate performance. We attribute the ability of the Si-based anode to tolerate the volume changes during cycling to the excellent mechanical integrity afforded by the strong interfacial adhesion of the biomimetic conducting polymer.

Fluorescent carbon dots have received considerable attention as a result of their accessibility and potential applications. Although several prior studies have demonstrated that nearly any organic compound can be converted into carbon dots by chemical carbonization processes, mechanisms explaining the formation of carbon dots still remain unclear. Herein, we propose a seed-growth mechanism of carbon dot formation facilitated by ferulic acid, a widespread and naturally occurring phenolic compound in the seeds of Ocimum basilicum (basil). Ferulic acid triggers the local condensation of polysaccharide chains and forms catalytic core regions resulting in nanoscale carbonization. Our study indicates that carbon dots generated from natural sources might share the similar mechanism of phenolic compound mediated nanoscale condensation followed by core carbonization.

Porous silica is an attractive biomaterial in many applications, including drug-delivery systems, bone-graft fillers and medical devices. The issue with porous silica biomaterials is the rate at which they resorb and the significant role played by interfacial chemistry on the host response in vivo. This paper explores the potential of diatom-biosilica as a model tool to assist in the task of mapping and quantifying the role of surface topography and chemical cues on cell fate. Diatoms are unicellular microalgae whose cell walls are composed of, amorphous nanopatterned biosilica that cannot be replicated synthetically. Their unique nanotopography has the potential to improve understanding of interface reactions between materials and cells. This study used Cyclotella meneghiniana as a test subject to assess cytotoxicity and pro-inflammatory reactions to diatom-biosilica. The results suggest that diatom-biosilica is non-cytotoxic to J774.2 macrophage cells, and supports cell proliferation and growth. The addition of amine and thiol linkers have shown a significant effect on cytotoxicity, growth and cytokine response, thus warranting further investigation into the interfacial effects of small chemical modifications to substrate surfaces. The overall findings suggest diatom-biosilica offers a unique platform for in-depth investigation of the role played by nanotopography and chemistry in biomedical applications.

As synthetic analogs of the natural pigment melanin, polydopamine nanoparticles (NPs) are under active investigation as non-toxic anticancer photothermal agents and as free radical scavenging therapeutics. By analogy to the widely adopted polydopamine coatings, polydopamine NPs offer the potential for facile aqueous synthesis and incorporation of (bio)functional groups under mild temperature and pH conditions. However, clear procedures for the convenient and reproducible control of critical NP properties such as particle diameter, surface charge, and loading with functional molecules have yet to be established. In this work, we have synthesized polydopamine-based melanin-mimetic nanoparticles (MMNPs) with finely controlled diameters spanning ≈25 to 120 nm and report on the pH-dependence of zeta potential, methodologies for PEGylation, and the incorporation of fluorescent organic molecules. A comprehensive suite of complementary techniques, including dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), X-ray photoelectron spectroscopy (XPS), zeta-potential, ultraviolet-visible (UV-Vis) absorption and fluorescence spectroscopy, and confocal microscopy, was used to characterize the MMNPs and their properties. Our PEGylated MMNPs are highly stable in both phosphate-buffered saline (PBS) and in cell culture media and exhibit no cytotoxicity up to at least 100 μg mL -1 concentrations. We also show that a post-functionalization methodology for fluorophore loading is especially suitable for producing MMNPs with stable fluorescence and significantly narrower emission profiles than previous reports, suggesting they will be useful for multimodal cell imaging. Our results pave the way towards biomedical imaging and possibly drug delivery applications, as well as fundamental studies of MMNP size and surface chemistry dependent cellular interactions., Competing Interests: Conflicts of Interest The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Star-shaped poly(ethylene glycol) (PEG) chain termini were functionalized with alendronate to create transient networks with reversible crosslinks upon addition of calcium ions. The gelation ability of alendronate-functionalized PEG was greatly dependent on the number of arms and arm molecular weight. After mixing polymer and calcium solutions, the formed hydrogels could be cut and then brought back together without any visible interface. After 2 minutes of contact, their connection was strong enough to allow for stretching without tearing through the previous fracture surface. Oscillatory rheology showed that the hydrogels recovered between 70 and 100% of the original storage and loss modulus after rupture. Frequency sweep measurements revealed a liquid-like behavior at lower frequencies and solid-like at high frequencies. Shifting frequency curves obtained at different calcium and polymer concentrations, all data collapsed in a single common master curve. This time-concentration superposition reveals a common relaxation mechanism intrinsically connected to the calcium-bisphosphonate complexation equilibrium., Competing Interests: Note The authors declare no competing financial interest.

We present a platform strategy that offers diverse flexibility in tailoring the structure and properties of core-shell plasmonic nanoparticles with built-in nanogaps. Our results have demonstrated that polydopamine serves multiple concerted functions as a nanoscale spacer to afford controllable nanogap sizes, a redox-active coating to promote metal shell growth, and a reactive scaffold to exclusively lock molecular probes inside the nanogap for surface-enhanced Raman scattering (SERS). More interestingly, the universal adhesion of polydopamine on diverse colloidal substrates allows for customized synthesis of multishell plasmonic nanogapped nanoparticles (NNPs) and multifunctional hybrid NNPs containing different cores (i.e., magnetic nanoparticles), which are not readily accessible by conventional methods. Internally coupled plasmonic NNPs with broadly tunable spectroscopic properties, highly active SERS, and multifunctionality hold great promise for emerging fields, such as sensing, optoelectronics, and theranostics, as demonstrated by the ultrasensitive SERS detection and efficient photothermal killing of food-borne pathogens here.

Unlabelled: Collagen cross-linkings are determinant of biological tissue stability and function. Plant-derived proanthocyanidins (PACs) mimic different hierarchical levels of collagen cross-links by non-enzymatic interactions resulting in the enhancement to the biomechanics and biostability of collagen-rich tissues such as dentin. This study investigated the interaction of PACs from Vitis vinifera grape seed extract with type I collagen in solubilized form and in the demineralized dentin matrix (DDM) by fluorescence spectral analysis; collagen-collagen binding forces in presence of cross-linking solutions by atomic force microscopy (AFM); and spectroscopic analysis of the DDM using attenuated total reflectance Fourier transform-infrared spectroscopy (ATR-FTIR). Glutaraldehyde (GA) and carbodiimide hydrochloride (EDC) with known cross-linking mechanisms were selected for comparative analyses. Changes in fluorescence upon interaction of solubilized type I collagen with PACs, EDC and GA reflected pronounced modifications in collagen conformation. PACs also promoted stronger collagen-collagen fibrils interaction than EDC and GA. A new feature was observed using ATR-FTIR spectroscopic analysis in PACs-treated collagen and DDM. The findings suggest covalent interactions between collagen and PACs. The mechanisms of interaction between PACs-collagen hold attractive and promising tissue-tailored biomedical applications and the binding forces that potentially drive such interaction were characterized., Statement of Significance: Connective tissues such as skin, bone and dentin are mainly composed of type I collagen, which is cross-linked to promote tissue stability, strength and function. Novel therapies using substances that mimic cross-links have been proposed to promote repair of collagen-based-tissues. In dentistry, naturally occurring proanthocyanidins (PACs) have the potential to enhance dentin mechanical properties and reduce its enzymatic degradation, but their mechanisms of cross-linking are unclear. The present study investigated the specific interactions between PACs-type I collagen in purified and dentin collagen and compared to the well described cross-linking mechanisms promoted by synthetic chemical substances. Findings reveal that covalent-like bonds are induced by plant PACs in type I collagen as well as in complex dental native tissue, promoting strong collagen-collagen interactions., (Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)