Automated BigSMILES conversion workflow and dataset for homopolymeric macromolecules.

The simplified molecular-input line-entry system (SMILES) has been utilized in a variety of artificial intelligence analyses owing to its capability of representing chemical structures using line notation. However, its ease of representation is limited, which has led to the proposal of BigSMILES as an alternative method suitable for the representation of macromolecules. Nevertheless, research on BigSMILES remains limited due to its preprocessing requirements. Thus, this study proposes a conversion workflow of BigSMILES, focusing on its automated generation from SMILES representations of homopolymers. BigSMILES representations for 4,927,181 records are provided, thereby enabling its immediate use for various research and development applications. Our study presents detailed descriptions on a validation process to ensure the accuracy, interchangeability, and robustness of the conversion. Additionally, a systematic overview of utilized codes and functions that emphasizes their relevance in the context of BigSMILES generation are produced. This advancement is anticipated to significantly aid researchers and facilitate further studies in BigSMILES representation, including potential applications in deep learning and further extension to complex structures such as copolymers.

Mechanically Robust Cellulose-Based Piezoelectric Elastomer Formed by Slidable Polyrotaxane Cross-Linker.

Cellulose has great potential in the field of piezoelectricity owing to its high crystallinity; however, it exhibits low processability and poor mechanical robustness. In this study, to enhance the applicability of cellulose-based piezoelectric materials, a robust cellulose-based piezoelectric elastomer with excellent piezoelectric properties was developed by cross-linking cellulose with polyrotaxane (PR). The effects of cross-linking on the mechanical properties and crystalline structures of the resulting elastomers were investigated. The ferroelectric and piezoelectric properties were evaluated from their polarization hysteresis loops and voltage generation characteristics. eHPC25PR75 exhibited 2.7 times higher toughness (20.4 MJ m-3) than eHPC100 (7.57 MJ m-3). It also shows a power density 4.2 times higher (1.34 µW cm-2) than eHPC100 (0.321 µW cm-2). As a result, eHPC25PR75 demonstrated piezosensitivity to mechanical vibrations in a variety of devices that require mechanical robustness. These results can inform the design and development of high-performance piezoelectric devices.

Physical Properties of Poly(ether-thiourea)-Based Elastomer Formed by Zigzag Hydrogen Bonding and Slidable Cross-Linking.

In this study, the effects of zigzag hydrogen bonding and slidable cross-linking on the design of stretchable elastomers were explored. Poly(ether-thiourea) (TU), capable of generating strong zigzag hydrogen bonds without crystallization, was introduced as the main chain in the non-cross-linked region of the developed elastomer. Consequently, the toughness of the TU-based elastomer was 14 times higher than that of elastomers formed using linear poly(ethylene glycol), despite the relatively low molecular weight of TU (∼3k). When a slidable polyrotaxane cross-linker was introduced into the TU-based elastomer, its flexibility became twice as high as that of the rigid polymer cross-linker. Moreover, the mechanical properties of the elastomer were prevented from deterioration against repeated deformation under the limited strain condition of 150%.

Slidable Cross-Linking Effect on Liquid Crystal Elastomers: Enhancement of Toughness, Shape-Memory, and Self-Healing Properties.

The network structures of liquid crystal elastomers (LCEs) are crucial to impart rubbery behavior to LCEs and enable reversible actuation. Most LCEs developed to date are covalently linked, implying that the cross-links are fixed at a particular position. Herein, we report a new class of LCEs integrating polyrotaxanes (PRs) as slidable cross-links (PR-LCEs). Interestingly, the incorporation of a low loading (0.3-2.0 wt %) of the PR cross-linkers to the LCE causes a significant impact on various properties of the resulting PR-LCEs due to the pulley effect. The optimum PR loading is determined to be 0.5 wt %, at which point the toughness and damping behavior are maximized. The robust mechanical properties of the PR-LCE offers a superior actuation performance to that of the pristine LCE along with an excellent quadruple shape-memory effect. Furthermore, the incorporation of PR is useful to enhance the efficiency of shape-memory-assisted self-healing when heating above the nematic-isotropic transition.

Enhanced osteogenic differentiation of mesenchymal stem cells by surface lithium modification in a sandblasted/acid-etched titanium implant.

This study investigated the osteogenesis-related cell functions of osteoprogenitor cells modulated by surface chemistry modification using lithium (Li) ions in a current clinical oral implant surface in order to gain insights into the future development of titanium (Ti) implants with enhanced osteogenic capacity. Wet chemical treatment was performed to modify a sandblasted/acid-etched (SLA) Ti implant surface using Li ions. The osteogenesis-related cell response to the surface Li ion-modified SLA sample was evaluated using two kinds of murine bone marrow stem cells, bipotent ST2 cells and primary multipotent mesenchymal stem cells (MSCs). The modified surface exhibited the formation of an Li-containing Ti oxide layer with plate-like nanostructures. The Li-incorporated surface enhanced early cellular events, including spreading, focal adhesion formation and integrin mRNA expression (α2, α5, αv and ß3), and accelerated osteogenic differentiation of bipotent ST2 cells compared with unmodified SLA surface. Surface Li modification significantly increased GSK-3ß phosphorylation and suppressed ß-catenin phosphorylation, and promoted the subsequent osteogenic differentiation of primary MSCs. These results indicate that surface chemistry modification of SLA implants by wet chemical treatment with Li ions induces a more favorable osseointegration outcome through the promotion of the osteogenic differentiation of bone marrow MSCs via the positive regulation of GSK-3ß and ß-catenin activity.

Preclinical testing of an anal bulking agent coated with a zwitterionic polymer in a fecal incontinence rat model.

Fecal incontinence is a disabling condition in which the passage of fecal material cannot be controlled. Although the condition is not life-threatening, it can seriously reduce the quality of life of a patient by isolating them from others. Though various surgical treatments are available for moderate to severe symptoms, a bulking agent is a minimally invasive technique that has attracted attention because of its safety and simple treatment process. However, the biocompatibility of bulking agent materials remains a central issue, with their durability questioned because immune responses and/or the circulatory system may remove the bulking agent in vivo. This study investigated a bulking agent composed of polydimethylsiloxane and hyaluronic acid as a microfiller and carrier gel, respectively. To improve the injectability of the bulking agent, the filler size was tuned using a suspension-based fabrication technique. To evade immune responses, the filler surface was treated with a zwitterionic polymer that simultaneously functionalized and stabilized the material interfaces. The resulting bulking agent exhibited good injectability and biocompatibility in vitro, with 58% lower protein adsorption and no cytotoxicity, leading to an improved bulking effect in a preclinical rat model compared with a bulking agent without surface treatment. These results illustrate the promising potential of bulking agents as a therapy for fecal incontinence with reduced foreign body reactions and long-lasting efficacy.

Injectable polydimethylsiloxane microfiller coated with zwitterionic polymer for enhanced biocompatibility.

Silicone-based fillers have been applied in several branches of medicine, such as soft tissue augmentation, because of their stability and durability. However, the inherently hydrophobic surfaces of silicone occasionally cause excessive deposition of the fibrous matrix in vivo, leading to severe fibrosis. In this study, we evaluated the use of a zwitterionic copolymer to offer a facile surface treatment method for silicone-based fillers and performed a preclinical trial of the formulation as-prepared. The copolymer has amphiphilic moieties, which act as macromolecular surfactants that can functionalize and stabilize the silicone particles during fabrication. The effectiveness and safety of the particle filler were evaluated histologically by scoring the peri-implant tissues into previously defined categories. Our results suggest that zwitterion-coated silicone fillers can inhibit protein adsorption, and thus, help attenuate foreign body reactions in a rat model. This demonstrates their potential for wide application in different fields within the discipline of medicine.

Scratch Properties of Clear Coat for Automotive Coating Comprising Molecular Necklace Crosslinkers with Silane Functional Groups for Various Environmental Factors.

Automotive coatings, which comprise multiple layers, i.e., primer, base coating, and clear coat layers, are exposed to various environmental conditions that pose various types of damages to them. In particular, the outer layer of the automotive coating, i.e., the clear coat, is affected significantly by such damages. Therefore, a reliable and durable clear coat must be developed to improve the appearance of automobiles. In this study, a new clear coat based on an acrylic-based clear coat modified using polyrotaxane crosslinkers, which are necklace-shaped supramolecules composed of ring-shaped host molecules, is developed and characterized. The effects of polyrotaxane and silane on the scratch properties and mechanisms of the clear coating are analyzed. It is observed that the critical loads of the clear coat from scratch tests can be improved by adding optimal molecular necklace crosslinkers comprising silane functional groups. The improvement in the scratch properties of the modified acrylic-based clear coat may be attributed to the crosslinking characteristics and dynamic molecular movements of the polyrotaxane. In addition, the effects of environmental factors on the scratch characteristics of the modified acrylic-based clear coat are investigated by addressing the scratch durability of the clear coat.

Mechanical Durability of Flexible Printed Circuit Boards Containing Thin Coverlays Fabricated with Poly(Amide-Imide-Urethane)/Epoxy Interpenetrating Networks.

Because electronics are becoming flexible, the demand for techniques to manufacture thin flexible printed circuit boards (FPCBs) has increased. Conventional FPCBs are fabricated by attaching a coverlay film (41 µm) onto copper patterns/polyimide (PI) film to produce the structure of coverlay/Cu patterns/PI film. Given that the conventional coverlay consists of two layers of polyimide film and adhesive, its thickness must be reduced to generate thinner FPCBs. In this study, we fabricated 25-µm-thick poly(amide-imide-urethane)/epoxy interpenetrating networks (IPNs) to replace the thick conventional coverlay. Poly(amide-imide-urethane) (PAIU) was synthesized by reacting isocyanate-capped polyurethane with trimellitic anhydride and then mixed with epoxy resin to produce PAIU/epoxy IPNs after curing. Thanks to the soft segments of polyurethane, the elongation of PAIU/epoxy IPNs increased with increasing PAIU content and reached over 200%. After confirming the excellent thermal stability and chemical resistance of the PAIU/epoxy IPNs, we fabricated FPCBs by equipping them as coverlays. The mechanical durability of the FPCBs was evaluated through an MIT folding test, and the FPCB fabricated with PAIU/ep-2 was stable up to 164 folding cycles because of the balanced mechanical properties.

Optimization of Anisotropic Crystalline Structure of Molecular Necklace-like Polyrotaxane for Tough Piezoelectric Elastomer.

While piezoelectric materials are applied in various fields, they generally exhibit poor mechanical toughness. To increase the applicability of these, their mechanical properties need to be improved. In this study, a tough piezoelectric polyrotaxane (PRX) elastomer was developed by blending PRX samples of two different lengths, formed using 10K and 35K poly(ethylene glycol), to align dipole moments for optimization of the piezoelectricity characteristics. The effects of the blending ratio on the crystalline structure of the obtained PRX elastomer were investigated by X-ray diffraction analysis and transmission electron microscopy. In addition, the ferroelectric and piezoelectric properties of the PRX elastomer were evaluated based on its polarization hysteresis loop and voltage generation characteristics, respectively. The PRX elastomer formed by using a ratio of 3:1 (ePR10k7535k25) exhibited a long-range-ordered anisotropic crystalline structure, resulting in a large polarization (Pr) value. As a result, ePR10k7535k25 showed greatly enhanced piezosensitivity against the mechanical vibrations generated by respiratory signals.

Phosphorylcholine-based encoded hydrogel microparticles with enhanced fouling resistance for multiplex immunoassays.

Due to the growing interest in multiplex protein detection, encoded hydrogel microparticles have received attention as a possible path to high performance multiplex immunoassays through a combination of high multiplexing capability and enhanced binding kinetics. However, their practical operation in real complex samples is still limited because polyethylene glycol, which is the main component of hydrogel particles, suffers from oxidative damage and relatively high fouling properties in biochemical solutions. Here, we introduce poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-based encoded hydrogel microparticles to perform fouling-resistant multiplex immunoassays, where the anti-fouling characteristics are attributed to the zwitterionic PMPC. By applying a newly developed molding lithography technique, viscous PMPCs with low reactivity were successfully incorporated into the hydrogel network while maintaining uniformity and rigidity for use in multiplex immunoassays. Non-specific protein adsorption on the PMPC particles was reduced by about 37.5% compared to that of conventional PEG particles, which leads to better assay sensitivity. We also validate the multiplex capability of the PMPC particles by performing multiplex detection of two target proteins. Furthermore, we verify that the PMPC particles have a 70% enhancement in anti-fouling characteristics compared to PEG particles in human platelet-rich plasma, potentiating a practical immunoassay platform for clinical diagnosis.

Covalently Grafted 2-Methacryloyloxyethyl Phosphorylcholine Networks Inhibit Fibrous Capsule Formation around Silicone Breast Implants in a Porcine Model.

The surface of human silicone breast implants is covalently grafted at a high density with a 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer. Addition of cross-linkers is essential for enhancing the density and mechanical durability of the MPC graft. The MPC graft strongly inhibits not only adsorption but also the conformational deformation of fibrinogen, resulting in the exposure of a buried amino acid sequence, γ377-395, which is recognized by inflammatory cells. Furthermore, the numbers of adhered macrophages and the amounts of released cytokines (MIP-1α, MIP-1ß, IL-8, TNFα, IL-1α, IL-1ß, and IL-10) are dramatically decreased when the MPC network is introduced at a high density on the silicone surface (cross-linked PMPC-silicone). We insert the MPC-grafted human silicone breast implants into Yorkshire pigs to analyze the in vivo effect of the MPC graft on the capsular formation around the implants. After 6 month implantation, marked reductions of inflammatory cell recruitment, inflammatory-related proteins (TGF-ß and myeloperoxidase), a myoblast marker (α-smooth muscle actin), vascularity-related factors (blood vessels and VEGF), and, most importantly, capsular thickness are observed on the cross-linked PMPC-silicone. We propose a mechanism of the MPC grafting effect on fibrous capsular formation around silicone implants on the basis of the in vitro and in vivo results.

Enhanced Mechanical Strength, Flexibility, and Shape-Restoring Rate of a Drug-Eluting Shape-Memory Polymer by Incorporation of Supramolecular Cross-Linkers.

The purpose of this study is to develop mechanically robust soybean oil and polycaprolactone (PC)-based drug-eluting shape memory polymers (SMPs) containing polyrotaxane (PRX) cross-linkers. Essentially, the dynamic PRX cross-linker-containing methacrylate group is introduced to increase the cross-linking density and flexibility of the SMP to overcome its mechanical limitations. It was confirmed that the elongation and cross-linking density of the PRX-incorporated SMP were increased by 2-4 times compared to neat SMP. In addition, those high mechanical properties of the PRX-incorporated SMP could be maintained after the degradation of the PC by the drug-eluting process.

Mechanically Reinforced Gelatin Hydrogels by Introducing Slidable Supramolecular Cross-Linkers.

Tough mechanical properties are generally required for tissue substitutes used in regeneration of damaged tissue, as these substitutes must be able to withstand the external physical force caused by stretching. Gelatin, a biopolymer derived from collagen, is a biocompatible and cell adhesive material, and is thus widely utilized as a component of biomaterials. However, the application of gelatin hydrogels as a tissue substitute is limited owing to their insufficient mechanical properties. Chemical cross-linking is a promising method to improve the mechanical properties of hydrogels. We examined the potential of the chemical cross-linking of gelatin hydrogels with carboxy-group-modified polyrotaxanes (PRXs), a supramolecular polymer comprising a poly(ethylene glycol) chain threaded into the cavity of α-cyclodextrins (α-CDs), to improve mechanical properties such as stretchability and toughness. Cross-linking gelatin hydrogels with threading α-CDs in PRXs could allow for freely mobile cross-linking points to potentially improve the mechanical properties. Indeed, the stretchability and toughness of gelatin hydrogels cross-linked with PRXs were slightly higher than those of the hydrogels with the conventional chemical cross-linkers 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS). In addition, the hysteresis loss of gelatin hydrogels cross-linked with PRXs after repeated stretching and relaxation cycles in a hydrated state was remarkably improved in comparison with that of conventional cross-linked hydrogels. It is considered that the freely mobile cross-linking points of gelatin hydrogels cross-linked with PRXs attenuates the stress concentration. Accordingly, gelatin hydrogels cross-linked with PRXs would provide excellent mechanical properties as biocompatible tissue substitutes exposed to a continuous external physical force.

Foldable and Extremely Scratch-Resistant Hard Coating Materials from Molecular Necklace-like Cross-Linkers.

A flexible hard coating material displaying extreme scratch resistance and foldable flexibility was developed via the design of an organic-inorganic hybrid coating material employing an alkoxysilyl-functionalized polyrotaxane cross-linker (PRX_Si1). PRX_Si1 has a molecular necklace-like structure that can form organic-inorganic cross-linking points and provide large molecular movements. It was postulated that the scratch resistance and flexibility could be simultaneously increased because of the hybrid cross-linking points and dynamic molecular movements. To confirm this hypothesis, the crystalline structure and mechanical properties of the PRX_Si1-based hard coating material were analyzed via transmission electron microscopy, small-angle X-ray diffraction, tensile, pencil hardness, and scratch tests. Finally, the PRX_Si1-based hard coating material could form homogeneously dispersed nanoscale siloxane crystalline domains, and the strain at the break point was 3 times higher than that of a commercial hard coating material, resulting in no defect formation even after 5000 folding test runs. Moreover, the material displayed extremely high pencil hardness (9H) and scratch resistance.

Calcium-Binding Polymer-Coated Poly(lactide- co-glycolide) Microparticles for Sustained Release of Quorum Sensing Inhibitors to Prevent Biofilm Formation on Hydroxyapatite Surfaces.

Quorum sensing (QS) inhibitor-based therapy is an attractive strategy to inhibit bacterial biofilm formation without excessive induction of antibiotic resistance. Thus, we designed Ca2+-binding poly(lactide- co-glycolide) (PLGA) microparticles that can maintain a sufficient concentration of QS inhibitors around hydroxyapatite (HA) surfaces in order to prevent biofilm formation on HA-based dental or bone tissues or implants and, therefore, subsequent pathogenesis. Poly(butyl methacrylate- co-methacryloyloxyethyl phosphate) (PBMP) contains both Ca2+-binding phosphomonoester groups and PLGA-interacting butyl groups. The PBMP-coated PLGA (PLGA/PBMP) microparticles exhibited superior adhesion to HA surfaces without altering the sustained release properties of uncoated PLGA microparticles. PLGA/PBMP microparticle-encapsulating furanone C-30, a representative QS inhibitor, effectively inhibited the growth of Streptococcus mutans and its ability to form biofilms on HA surface for prolonged periods of up to 100 h, which was much longer than either furanone C-30 in its free form or when encapsulated in noncoated PLGA microparticles.

One-Pot Synthesis of a Zwitterionic Small Molecule Bearing Disulfide Moiety for Antibiofouling Macro- and Nanoscale Gold Surfaces.

The goal of this study is to develop a simple one-pot method for the synthesis of a zwitterionic small molecule bearing disulfide moiety, which can effectively inhibit nonspecific protein adsorption on macroscopic and nanoscopic gold surfaces. To this end, the optimal molecular structure of a pyridine disulfide derivative was explored and a zwitterionic small molecule was successfully synthesized from the tertiary amine residue on the pyridine ring through a one-pot method. The coating conditions of the synthesized zwitterionic molecules on the gold surface were optimized through contact angle measurements, and the strong interactions between the gold surface and the disulfide moiety of the zwitterion small molecule were confirmed by surface plasmon resonance (SPR) analysis and X-ray photoelectron spectroscopy. The antibiofouling properties of the coated gold surface were analyzed by fluorescence microscopic observations after contacting with FITC-labeled bovine serum albumin (BSA) and SPR sensor as contacting with BSA solution. In addition, the effect of zwitterion-coating on the salt stability of and protein adsorption on nanoscopic gold surfaces were examined through a NaCl stability test and BSA adsorption test, respectively. From the obtained results, it was confirmed that the simply synthesized zwitterionic small molecule was effective in inhibiting nonspecific protein adsorption on macroscopic and nanoscopic gold surfaces; further, it enhanced the salt stability of gold nanoparticle surfaces.

Developing a thermal grafting process for zwitterionic polymers on cross-linked polyethylene with geometry-independent grafting thickness.

To overcome the drawbacks of the UV grafting method, an alternative, thermal grafting process is suggested. The uniform and geometry-independent grafting of zwitterionic polymers on curved cross-linked polyethylene (CLPE), which is used in artificial hip joints, surface was successfully achieved. Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly(2-(methacryloyloxy)ethyl)dimethyl(3-sulfopropyl)ammonium hydroxide) (PMEDSAH) were grafted on the CLPE by two methods: a UV-based process and a thermal process. The thermal method yielded zwitterionic surfaces with similar hydrophilicities and graft layer thicknesses to those prepared via the UV grafting method. The X-ray photoelectron spectra and surface zeta potential results showed that the PMPC and PMEDSAH layers were successfully grafted onto the CLPE surface. In addition, 3-D confocal microscopy, as well as friction and wear volume tests, confirmed that there was a significant decrease in the friction coefficient and wear, which indicates that the thermal grafting method can successfully substitute the UV grafting method. The thermally grafted polymer showed uniform graft layer thickness on the curved CLPE surface, whereas the UV-grafted polymer showed a geometry-dependent heterogeneous graft layer thickness. Thus, we confirmed that the thermal grafting method is advantageous for the preparation of uniform grafting layers on artificial joint surfaces with complicated shapes. STATEMENT OF SIGNIFICANCE: Formation of uniform grafting thickness of the zwitterionic polymers on the implant materials is a very important issue in the field of biomaterials. In this study, a thermal grafting process was developed for the formation of the uniform grafting thickness of the zwitterionic polymers on the curved cross-linked polyethylene (CLPE) surface used in artificial hip-joint. This method yielded zwitterionized CLPE surfaces with similar hydrophilicities and friction coefficient to those prepared via the UV grafting method which has been widely used process to modify the implant surfaces. Furthermore, the thermally grafted CLPE surface showed geometry-independent uniform grafting thickness on the curved CLPE surface while UV-grafted one showed uneven grafting thickness. This grafting method could help the development of complex, personalized, and biocompatible artificial liner surfaces.

Surface-Restructuring Differences between Polyrotaxanes and Random Copolymers in Aqueous Environment.

In the present study, we investigated the surface reorganization behaviors and adsorption conformations of fibrinogen on the surface of polyrotaxanes containing different amounts of α-cyclodextrin (α-CD) by using surface-sensitive vibrational spectroscopy sum frequency generation (SFG). For comparison, behaviors of the surface restructuring and fibrinogen adsorption on the random copolymers containing similar terminal groups were also investigated. It was found that larger amounts of BMA moieties of polyrotaxanes form ordered surface structures after immersion in water for 48 h. Furthermore, the polyrotaxane surfaces exhibit a much higher capability of fibrinogen adsorption than the random copolymer surfaces. The water-induced surface restructuring of the polyrotaxane films slightly affects the adsorption structure of the fibrinogen molecules.

Fabrication of an Anti-Biofouling Plasma-Filtration Membrane by an Electrospinning Process Using Photo-Cross-linkable Zwitterionic Phospholipid Polymers.

The goal of this study is to fabricate a stable plasma filtration membrane with antibiofouling properties via an electrospinning process. To this end, a random-type copolymer consisting of zwitterionic phosphorylcholine (PC) groups and ultraviolet (UV)-cross-linkable phenyl azide groups was synthesized. The zwitterionic PC group provides antibiofouling properties, and the phenyl azide group enables the stable maintenance of the fibrous nanostructure of hydrophilic zwitterion polymers in aqueous medium via a simple UV curing process. To demonstrate the antibiofouling nature of the PC group, a polymer without antibiofouling PC groups was also prepared for comparison. The successful synthesis of the random-type copolymers containing phenyl azide groups was proven by 1H nuclear magnetic resonance and Fourier transform infrared spectroscopy, and the fibrous structure of the prepared membranes was observed by field emission scanning electron microscopy. The antibiofouling properties were analyzed by fluorescein isothiocyanate-labeled bovine serum albumin adsorption and platelet adhesion tests. The experimental results show that membranes containing zwitterionic PC groups exhibited obvious decreases in platelet adhesion and protein adsorption. Platelet-rich plasma solution was filtered using the prepared membranes to test their filtration properties. The sequential filtration process removed 80% and almost 98% of the platelets. This finding confirmed that the membrane retained its blood-inert biomaterial surface in a complex medium that included blood plasma and platelets.