Recyclable Tough Adhesive Sheets with Movable Cross-Links for Sustainable Use.

Acrylic adhesive sheets have been used for many applications, from popular seal materials to high-end electrical devices. One of the basic and critical design features of adhesives is effective covalent cross-linking for superior adhesive properties. On the other hand, covalent cross-linking prevents reuse or recycling of the adhesive. This makes the adhesive sheets insoluble and poorly workable. For development of sustainable adhesives, we investigated the adhesive sheets based on acrylic elastomers with "Movable Cross-links" (M-PEA-CD (0.5)) copolymerized with 0.5 mol % cyclodextrin monomers. The peel strength and creep resistance of M-PEA-CD (0.5) were greater than those of adhesives (N-PEA) without any cross-links. M-PEA-CD (0.5) was recyclable via dissolution in ethyl acetate. Furthermore, the recycled M-PEA-CD (0.5) from solution exhibited the same adhesion properties as virgin M-PEA-CD (0.5). Spectroscopic and mechanical measurements indicated that topological cross-linking with Cyclodextrin (CD) moieties generated novel recyclable adhesive sheets without restricting the polymer main chains, unlike covalent cross-linking (CC-PEA). The movable cross-links were maintained in both the solid state and in solution, which allowed recycling of the elastomer via simple methods.

LIGHT regulated gene expression in rheumatoid synovial fibroblasts.

BACKGROUND: Synovial hyperplasia caused by rheumatoid arthritis (RA), an autoimmune inflammatory disease, leads to the destruction of the articular cartilage and bone. A member of the tumor necrosis factor superfamily, Lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) has been shown to correlate with the pathogenesis of RA. METHODS: We used cDNA microarray analysis to compare the expression of genes in rheumatoid fibroblast-like synoviocytes with and without LIGHT stimulation. RESULTS: Significant changes in gene expression (P-values < 0.05 and fold change ≥ 2.0) were associated mainly with biological function categories of glycoprotein, glycosylation site as N-linked, plasma membrane part, integral to plasma membrane, intrinsic to plasma membrane, signal, plasma membrane, signal peptide, alternative splicing, and topological domain as extracellular. CONCLUSIONS: Our results indicate that LIGHT may regulate the expression in RA-FLS of genes which are important in the differentiation of several cell types and in cellular functions.

Improvement in Cohesive Properties of Adhesion Systems Using Movable Cross-Linked Materials with Stress Relaxation Properties.

A strong, tough, and stable adhesion system used in various environments must be developed. A long-lasting adhesion system should effectively perform in the following five aspects: adhesion strength, toughness, energy dissipation property, self-restoration property, and creep resistance property. However, these properties are difficult to balance using conventional adhesives. Here, a new topological adhesion system using single-movable cross-network (SC) materials [SC(DMAAm) Adh] was designed. 3-(Trimethoxysilyl) propyl acrylate was used as the anchor, N,N-dimethyl acrylamide (DMAAm) was used as the main chain monomer, and γ-cyclodextrin (γ-CD) units acted as movable cross-links. The movable cross-links provided SC(DMAAm) Adh with energy dissipation properties, thereby improving its toughness. The γ-CD units also acted as bulky stoppers that provided a high adhesion strength and self-restoration properties. Moreover, the combination of the movable cross-links and bulky stoppers provided creep resistance to SC(DMAAm) Adh. The performance of the adhesion systems under different mobilities of the polymer chains was examined by adjusting the water content. In proper water-containing states, all mechanical properties of SC(DMAAm) Adh were better than those of the adhesion systems using homopolymers [P(DMAAm) Adh] and polymers with covalent cross-linking points [CP(DMAAm) Adh].

Reversible Host-Guest Crosslinks in Supramolecular Hydrogels for On-Demand Mechanical Stimulation of Human Mesenchymal Stem Cells.

Stem cells are regulated not only by biochemical signals but also by biophysical properties of extracellular matrix (ECM). The ECM is constantly monitored and remodeled because the fate of stem cells can be misdirected when the mechanical interaction between cells and ECM is imbalanced. A well-defined ECM model for bone marrow-derived human mesenchymal stem cells (hMSCs) based on supramolecular hydrogels containing reversible host-guest crosslinks is fabricated. The stiffness (Young's modulus E) of the hydrogels can be switched reversibly by altering the concentration of non-cytotoxic, free guest molecules dissolved in the culture medium. Fine-adjustment of substrate stiffness enables the authors to determine the critical stiffness level E* at which hMSCs turn the mechano-sensory machinery on or off. Next, the substrate stiffness across E* is switched and the dynamic adaptation characteristics such as morphology, traction force, and YAP/TAZ signaling of hMSCs are monitored. These data demonstrate the instantaneous switching of traction force, which is followed by YAP/TAZ signaling and morphological adaptation. Periodical switching of the substrate stiffness across E* proves that frequent applications of mechanical stimuli drastically suppress hMSC proliferation. Mechanical stimulation across E* level using dynamic hydrogels is a promising strategy for the on-demand control of hMSC transcription and proliferation.

Enhancement of the mechanical properties of organic-inorganic hybrid elastomers by introducing movable and reversible crosslinks.

Organic-inorganic materials have been widely utilized in various fields as multifunctional materials. Poly(dimethyl siloxane) (PDMS), a typical inorganic polymer, has industrially appealing functions, such as transparency, biocompatibility, and gas permeability; however, it has poor mechanical properties. We incorporated organic-inorganic hybrid elastomers (PDMS-γCD-AAl⊃P(EA-HEMA) (x)) with movable crosslinks, and we utilized hydrogen bonds as reversible crosslinks. The organic polymer poly ethyl acrylate-r-hydroxy ethyl methacrylate (P(EA-HEMA)) penetrated the cavity of triacetylated γ-cyclodextrin (γCD), which was introduced into the side chains of PDMS, and it compounded with PDMS at the nanoscale. Structural studies involving visual and X-ray scattering measurements revealed that movable crosslinks improved the compatibility levels of PDMS and acrylate copolymers. However, macroscopic phase separation occurred when the number of reversible crosslinks increased. Furthermore, studies on the mobility levels of acrylate copolymers and movable crosslinks indicated that the relaxation behaviour of PDMS-γCD-AAl⊃P(EA-HEMA) (x) changed with changing numbers of reversible crosslinks. Introducing reversible crosslinks improved the Young's modulus and toughness values. The movable and reversible crosslinks between the organic and inorganic polymers contributed to the high elongation properties. The design of PDMS-γCD-AAl⊃P(EA-HEMA) (x) incorporated cooperatively movable and reversible crosslinks to achieve high compatibility of immiscible polymers and to control the mechanical properties.

Highly Stretchable Stress-Strain Sensor from Elastomer Nanocomposites with Movable Cross-links and Ketjenblack.

Practical applications like very thin stress-strain sensors require high strength, stretchability, and conductivity, simultaneously. One of the approaches is improving the toughness of the stress-strain sensing materials. Polymeric materials with movable cross-links in which the polymer chain penetrates the cavity of cyclodextrin (CD) demonstrate enhanced strength and stretchability, simultaneously. We designed two approaches that utilize elastomer nanocomposites with movable cross-links and carbon filler (ketjenblack, KB). One approach is mixing SC (a single movable cross-network material), a linear polymer (poly(ethyl acrylate), PEA), and KB to obtain their composite. The electrical resistance increases proportionally with tensile strain, leading to the application of this composite as a stress-strain sensor. The responses of this material are stable for over 100 loading and unloading cycles. The other approach is a composite made with KB and a movable cross-network elastomer for knitting dissimilar polymers (KP), where movable cross-links connect the CD-modified polystyrene (PSCD) and PEA. The obtained composite acts as a highly sensitive stress-strain sensor that exhibits an exponential increase in resistance with increasing tensile strain due to the polymer dethreading from the CD rings. The designed preparations of highly repeatable or highly responsive stress-strain sensors with good mechanical properties can help broaden their application in electrical devices.

Stem-like CD4+ T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis.

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4+ T cell population with stem cell-like features. CD4+ T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES)+ cytotoxic T cells and B cell lymphoma 6 (BCL6)+ T follicular helper-like cells. TCF1hiCD4+ T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1hiCD4+ T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4+ T cells instead of only effector T cells.

Water-Content-Dependent Switching of the Bending Behavior of Photoresponsive Hydrogels Composed of Hydrophilic Acrylamide-Based Main Chains and Hydrophobic Azobenzene.

Photoresponsiveness is a promising characteristic of stimulus-responsive materials. Photoresponsiveness can be achieved by incorporating photoresponsive molecules into polymeric materials. In addition, multiple-stimuli-responsive materials have attracted scientists' interest. Among the numerous multiple-stimuli-responsive materials, moisture- and photoresponsive materials are the focus of this report. These stimuli-responsive materials responded to the stimuli synergistically or orthogonally. Unlike most stimulus-responsive materials utilizing moisture and light as stimuli, the materials studied herein switch their photoresponsiveness in the presence of moisture. Appropriate copolymers consisting of hydrophilic acrylamide-based monomers for the main chain and hydrophobic azobenzene moieties switched their bending behaviors at 6-9 wt% water contents. At water contents lower than 6 wt%, the polymeric materials bent away from the light source, while they bent toward the light source at water contents higher than 10 wt%. At a low water content, the bending behaviors can be described on the molecular scale. At a high water content, the bending behavior requires consideration of the phase scale, not only the molecular scale. By controlling the balance between hydrophilicity and hydrophobicity, the switching behavior was achieved. This switching behavior may inspire additional strategies for the application of polymeric material as actuators.

Leaf-Inspired Host-Guest Complexation-Dictating Supramolecular Gas Sensors.

We report unique conductive leaf-inspired (in particular, stomata-inspired) supramolecular gas sensors in which acetylated cyclodextrin derivatives rule the electric output. The gas sensors consist of polymers bearing acetylated cyclodextrin, adamantane, and carbon black. Host-guest complexes between acetylated cyclodextrin and adamantane corresponding to the closed stomata realize a flexible polymeric matrix. Effective recombination of the cross-links contributes to the robustness. As gas sensors, the supramolecular materials detect ammonia as well as various other gases at 1 ppm in 10 min. The free acetylated cyclodextrin corresponding to open stomata recognized the guest gases to alter the electric resistivity. Interestingly, the conductive device failed to detect ammonia gases at all without acetylated cyclodextrin. The molecular recognition was studied by molecular dynamics simulations. The gas molecules existed stably in the cavity of free acetylated cyclodextrin. These findings show the potential for developing wearable gas sensors.

Heterogeneous Cells as well as Adipose-Derived Stromal Cells in Stromal Vascular Fraction Contribute to Enhance Anabolic and Inhibit Catabolic Factors in Osteoarthritis.

The stromal-vascular fraction (SVF), comprising heterogeneous cell populations and adipose-derived stromal cells (ADSCs), has therapeutic potential against osteoarthritis (OA); however, the underlying mechanism remains elusive. This study aimed to investigate the therapeutic effects of heterogeneous cells in rabbit SVF on rabbit chondrocytes. Rabbit SVF and ADSCs were autografted into knees at OA onset. The SVF (1 × 105) and low-dose ADSCs (lADSC; 1 × 104) groups adjusted for their stromal cell content were compared. Animals were euthanized 8 and 12 weeks after OA onset for macroscopic and histological analyses of OA progression and synovitis. Immunohistochemical and real-time polymerase chain reaction assessments were conducted. In vitro, immune-fluorescent double staining was performed for SVF to stain macrophages with F4/80, CD86(M1), and CD163(M2). OA progression was markedly suppressed, and synovitis was reduced in the SVF groups (OARSI histological score 8 W: 6.8 ± 0.75 vs. 3.8 ± 0.75, p = 0.001; 12 W: 8.8 ± 0.4 vs. 5.4 ± 0.49, p = 0.0002). The SVF groups had higher expression of collagen II and SOX9 in cartilage and TGF-ß and IL-10 in the synovium, lower expression of MMP-13, and lower macrophage M1/M2 ratio than the lADSC groups. Immunofluorescent double staining revealed a markedly higher number of M2 than that of M1 macrophages in the SVF. The therapeutic effects of SVF on chondrocytes were superior than those of lADSCs, with enhanced anabolic and inhibited catabolic factors. Heterogeneous cells, mainly M2 macrophages in the SVF, enhanced growth factor secretion and chondrocyte-protective cytokines, thus benefiting chondrocytes and knee joint homeostasis. Overall, the SVF is a safe, relatively simple, and a useful treatment option for OA.

A Transformable and Bulky Methacrylate Monomer That Enables the Synthesis of an MMA-nBA Alternating Copolymer: Sequence-Dependent Self-Healing Properties.

In this study, we designed a methacrylate molecule with an alkyl-substituted trichloro salicylic acid pendant as a transformable bulky monomer to enable the synthesis of an alternating copolymer of methyl methacrylate (MMA) and n-butyl acrylate (nBA). The adamantyl-substituted methacrylate monomer (1-Ad) showed very low homopolymerization propensity in radical polymerizations, but afforded the alternating copolymer with nBA via copolymerization. The 1-Ad units in the resultant copolymer were quantitatively and selectively transformed into MMA via transesterification with methanol to yield the alternating copolymer of MMA and nBA. Its alternating sequence was clearly demonstrated by a structural analysis via 13 C NMR spectroscopy as well as the low reactivity ratios for the 1-Ad and nBA pair. Finally, we verified the superior self-healing ability of the alternating copolymer compared to that of the corresponding 1 : 1 statistical copolymer.

The influence of ruptured scar pattern of human anterior cruciate ligament remnant tissue on tendon-bone healing in vivo.

The purpose of this study was to determine whether the transplantation of human cells from a non-reattached injured anterior cruciate ligament (ACL) remnant could enhance tendon-bone healing. Human ACL remnant tissue was classified into two groups based on the morphologic pattern as per Crain's classification: (1) non-reattachment group (Crain Ⅳ) and (2) reattachment group (Crain Ⅰ-Ⅲ). Seventy-five 10-week-old immunodeficient rats underwent ACL reconstruction followed by intracapsular administration of one of the following: (1) ACL-derived cells from the non-reattached remnant (non-reattachment group) (n = 5), (2) ACL-derived cells from the reattached tissue (reattachment group) (n = 5), or (3) phosphate-buffered saline (PBS) only (PBS group) (n = 5). Histological (Weeks 2, 4, and 8), immunohistochemical (Week 2), radiographic (Weeks 0, 2, 4, and 8), and biomechanical (Week 8) assessments were performed. Histological evaluation showed high and early healing, induction of endochondral ossification-like integration, and mature bone ingrowth at Week 4 in the non-reattachment group. Microcomputed tomography at Week 4 showed that the tibial bone tunnels in the non-reattachment group were significantly reduced compared to those in the reattachment and PBS groups. Moreover, biomechanical testing showed that ultimate load-to-failure in the non-reattachment group tended to be larger than that in the reattachment group, though not statistically significant. The enhanced healing potential in the non-reattachment group was explained by the increase in intrinsic angiogenesis/osteogenesis. In the subacute phase, the ACL-derived cells with the non-reattached morphologic pattern showed greater and earlier tendon bone healing compared with the cells obtained from the reattached morphologic pattern.

The Effect of Prosthesis Type on Intraoperative Soft-Tissue Balance and Clinical Outcomes in Modified Kinematically Aligned Cruciate-Retaining Total Knee Arthroplasty.

INTRODUCTION: Kinematically aligned total knee arthroplasty (KA-TKA) has gained interest for achieving more favorable clinical outcomes than mechanically aligned TKA. One of the advantages of KA-TKA is reported to be an easy acquisition of intraoperative soft-tissue balance without excessive medial release for varus osteoarthritis. However, we hypothesized that the prosthesis type affects intraoperative soft-tissue balance even in the KA-TKA. The present study aimed to compare intraoperative soft-tissue balance and clinical outcomes of KA-TKAs using single-radius (SR) or multiradius (MR) prostheses. MATERIALS: AND METHODS: Consecutive 70 cruciate-retaining modified KA-TKAs (31 SR and 39 MR) were performed in patients with varus-type osteoarthritis using a navigation system. Intraoperative soft-tissue balance including joint component gap and varus/valgus balance was measured with femoral component placement and patellofemoral joint reduction throughout the range of motion using offset-type tensor and compared between the two groups. Two years postoperatively, the range of motion and 2011 Knee Society Scores were compared between the two groups. RESULTS AND CONCLUSION: Joint component gaps showed no significant differences between the two groups from 0 to 30 degrees of flexion. However, during 60 to 120 degrees of flexion, joint component gaps of SR group showed significantly larger values than those of MR group (p < 0.05). There were no significant differences in varus/valgus balance throughout the range of motion between the two groups. The postoperative clinical outcomes showed no significant differences between the two groups. INTERPRETATION: Despite no difference in clinical outcomes, joint component gap showed different patterns due to the prosthesis type in modified KA-TKAs.

Polyarthritis presented in a patient with untreated chronic hepatitis B infection.

Hepatitis B virus (HBV) infection can cause arthritis, but it is rarely reported. In the current report, we present a case of chronic polyarthritis in a patient with untreated HBV infection. A 63-year-old woman suffering from polyarthritis in her fingers visited our institution. She had experienced exacerbations and remissions of polyarthritis for more than 20 years. She had been diagnosed with rheumatoid arthritis and had been treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and nonsteroidal anti-inflammatory drugs by her primary care doctor, but the csDMARDs were discontinued at the request of the patient 10 years before the first visit to our hospital. The blood test showed negative for rheumatoid factor and anticyclic citrullinated peptides antibody but positive for hepatitis B surface antigen. Hepatitis B surface antigen and HBV-Deoxyribo Nucleic Acid (DNA) were increased to 312.6 (IU/ml) and 4.6 (log copies/ml), respectively. Based on the results of abdominal computed tomography and echography, she was diagnosed with liver cirrhosis. Treatment for HBV infection was begun with oral tenofovir at 25 mg/day. The polyarthritis in her fingers gradually disappeared and has not relapsed for 6 months after the initiation of treatment for HBV infection. When polyarthritis is diagnosed, the possibility that chronic HBV infection can be one of the causes of polyarthritis should be considered.

Effects of Femoral Component Design on the Deepest Point Position of the Trochlear Grove in Kinematically Aligned Total Knee Arthroplasty: A Comparison of Four Prothesis Designs.

The aim of the study is to explore and compare the differences in trochlear shape and knee anatomy between four types of prostheses and preoperative native knee matched with preoperative computed tomography (CT). Thirty patients were scheduled for primary kinematically aligned total knee arthroplasty (TKA) for varus knee osteoarthritis at our hospital and the region between their pelvis to ankle joint was simulated using a CT-based three-dimensional planning software. The axial plane containing the transepicondylar axis was set as Slice A, and the 10-mm distal plane from Slice A was set as Slice B. The distances to the deepest trochlear groove between the native knee and each prosthesis and the medial and lateral facet heights were compared among the four groups. The deepest femoral trochlear groove of the prostheses was located 1.6 to 3.0 mm more medial than that of the native knee, and in the Persona group, it was significantly more medial than in the e-motion or Triathlon groups on both Slices A and B. The native knee and the medial and lateral facet heights of the four prostheses on both Slices A and B were significantly lower than those of preoperative native knees when femoral prostheses were set in the kinematically aligned (KA)-TKA position. The deepest point of the trochlear groove of the Persona group was the most medial among the four prostheses studied, and the deepest points differed depending on the prosthesis design in KA-TKA. Thus, surgeons should carefully select the type of prostheses used in KA-TKA.

Simultaneous control of the mechanical properties and adhesion of human umbilical vein endothelial cells to suppress platelet adhesion on a supramolecular substrate.

The demand for artificial blood vessels to treat vascular disease will continue to increase in the future. To expand the application of blood-compatible poly(2-methoxyethyl acrylate) (pMEA) to artificial blood vessels, control of the mechanical properties of pMEA is established using supramolecular cross-links based on inclusion complexation of acetylated cyclodextrin. The mechanical properties, such as Young's modulus and toughness, of these pMEA-based elastomers change with the amount of cross-links, maintaining tissue-like behavior (J-shaped stress-strain curve). Regardless of the cross-links, the pMEA-based elastomers exhibit low platelet adhesion properties (approximately 3% platelet adherence) compared with those of poly(ethylene terephthalate), which is one of the commercialized materials for artificial blood vessels. Contact angle measurements imply a shift of supramolecular cross-links in response to the surrounding environment. When immersed in water, hydrophobic supramolecular cross-links are buried within the interior of the materials, thereby exposing pMEA chains to the aqueous environment; this is why supramolecular cross-links do not affect the platelet adhesion properties. In addition, the elastomers exhibit stable adhesion to human umbilical vein endothelial cells. This report shows the potential of combining supramolecular cross-links and pMEA.

A genome-wide association study identifying single nucleotide polymorphisms in the PPFIBP2 gene was predictive for interstitial lung disease in rheumatoid arthritis patients.

Objective: Genetic polymorphisms might serve as useful prognostic markers for the timely diagnosis of RA. The purpose of this study was to identify genomic factors predictive of the occurrence of interstitial lung disease (ILD) in RA by performing a genome-wide association study of genetic variants, including single nucleotide polymorphisms (SNPs). Methods: The study population included 306 RA patients. All patients were treated with conventional DMARDs, including 6-16 mg MTX per week. Clinical data and venous blood samples were collected from all patients before administration of DMARDs. A total of 278 347 SNPs were analysed to determine their association with ILD occurrence. Results: Several SNPs were strongly associated with ILD occurrence (P < 10-5). rs6578890, which is located on chromosome 11 in the intronic region of the gene encoding tyrosine phosphatase receptor type F polypeptide-interacting protein-binding protein 2 (PPFIBP2), showed the strongest association with ILD occurrence (odds ratio 4.32, P = 10-7.93). Conclusion: PPFIBP2 could be a useful genetic marker for occurrence of interstitial pneumonia in RA patients and might help to identify the risk of ILD occurrence before RA treatment, thereby improving patient outcomes.

Comparison of the inhibitory effect of tocilizumab and etanercept on the progression of joint erosion in rheumatoid arthritis treatment.

We compared the efficacy of tocilizumab and etanercept in inhibiting radiographic progression of joint destruction in rheumatoid arthritis. Overall, 187 patients treated with etanercept or tocilizumab were selected. To adjust for baseline patient characteristics between the tocilizumab and etanercept treatment groups, a propensity score matching was performed. Radiographic progression of joint destruction was compared between patients treated with tocilizumab or etanercept. Clinical disease activity index (CDAI) and modified health assessment questionnaire (mHAQ) scores at the administration of biologic treatment and after 12 months of tocilizumab and etanercept therapy were measured and compared to radiographical parameters between the groups. Levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), CDAI, and mHAQ scores improved after 12 months of treatment in the two groups. Proportion of patients with no Sharp erosion score progression was significantly higher with tocilizumab treatment than with etanercept treatment (p = 0.032). Multivariate analysis demonstrated that Sharp erosion score was significantly associated with baseline CDAI (odds ratio, 1.05; 95% confidence interval, 1.003-1.099, p = 0.037). Tocilizumab treatment suppressed joint erosion progression compared to etanercept, and the progression correlated with baseline CDAI.

Stimulus-Responsive, Gelatin-Containing Supramolecular Nanofibers as Switchable 3D Microenvironments for Cells.

Polymer- and/or protein-based nanofibers that promote stable cell adhesion have drawn increasing attention as well-defined models of the extracellular matrix. In this study, we fabricated two classes of stimulus-responsive fibers containing gelatin and supramolecular crosslinks to emulate the dynamic cellular microenvironment in vivo. Gelatin enabled cells to adhere without additional surface functionalization, while supramolecular crosslinks allowed for the reversible switching of the Young's modulus through changes in the concentration of guest molecules in culture media. The first class of nanofibers was prepared by coupling the host-guest inclusion complex to gelatin before electrospinning (pre-conjugation), while the second class of nanofibers was fabricated by coupling gelatin to polyacrylamide functionalized with host or guest moieties, followed by conjugation in the electrospinning solution (post-conjugation). In situ AFM nano-indentation demonstrated the reversible switching of the Young's modulus between 2-3 kPa and 0.2-0.3 kPa under physiological conditions by adding/removing soluble guest molecules. As the concentration of additives does not affect cell viability, the supramolecular fibers established in this study are a promising candidate for various biomedical applications, such as standardized three-dimensional culture matrices for somatic cells and the regulation of stem cell differentiation.

Multi-energy dissipation mechanisms in supramolecular hydrogels with fast and slow relaxation modes.

Reversible cross-links by non-covalent bonds have been widely used to produce supramolecular hydrogels that are both tough and functional. While various supramolecular hydrogels with several kinds of reversible cross-links have been designed for many years, a universal design that would allow control of mechanical and functional properties remains unavailable. The physical properties of reversible cross-links are usually quantified by thermodynamics, dynamics, and bond energies. Herein, we investigated the relationship between the molecular mobility and mechanical toughness of supramolecular hydrogels consisting of two kinetically distinct reversible cross-links via host-guest interactions. The molecular mobility was quantified as the second-order average relaxation time (〈τ〉w) of the reversible cross-links. We discovered that hydrogels combining fast (〈τ〉w = 1.8 or 18 s) and slowly (〈τ〉w = 6.6 × 103 or 9.5 × 103 s) reversible cross-links showed increased toughness compared to hydrogels with only one type of cross-link because relaxation processes in the former occurred with wide timescales.