Precisely Programmable Degradation and Drug Release Profiles in Triblock Copolyether Hydrogels with Cleavable Acetal Pendants.

Hydrogels hold significant promise as drug delivery systems due to their distinct advantage of sustained localized drug release. However, the challenge of regulating the initial burst release while achieving precise control over degradation and drug-release kinetics persists. Herein, we present an ABA-type triblock copolymer-based hydrogel system with precisely programmable degradation and release kinetics. The resulting hydrogels were designed with a hydrophilic poly(ethylene oxide) midblock and a hydrophobic end-block composed of polyethers with varying ratios of ethoxyethyl glycidyl ether and tetrahydropyranyl glycidyl ether acetal pendant possessing different hydrolysis kinetics. This unique side-chain strategy enabled us to achieve a broad spectrum of precise degradation and drug-release profiles under mildly acidic conditions while maintaining the cross-linking density and viscoelastic modulus, which is unlike the conventional polyester-based backbone degradation system. Furthermore, programmable degradation of the hydrogels and release of active therapeutic agent paclitaxel loaded therein are demonstrated in an in vivo mouse model by suppressing tumor recurrence following surgical resection. Tuning of the fraction of two acetal pendants in the end-block provided delicate tailoring of hydrogel degradation and the drug release capability to achieve the desired therapeutic efficacy. This study not only affords a facile means to design hydrogels with precisely programmable degradation and release profiles but also highlights the critical importance of aligning the drug release profile with the target disease.

Anisotropic Liesegang pattern for the nonlinear elastic biomineral-hydrogel complex.

The Liesegang pattern is a beautiful natural anisotropic patterning phenomenon observed in rocks and sandstones. This study reveals that the Liesegang pattern can induce nonlinear elasticity. Here, a Liesegang-patterned complex with biomineral-hydrogel repetitive layers is prepared. This Liesegang-patterned complex is obtained only when the biomineralization is performed under the supersaturated conditions. The Liesegang-patterned complex features a nonlinear elastic response, whereas a complex with a single biomineral shell shows a linear behavior, thus demonstrating that the Liesegang pattern is essential in achieving nonlinear elasticity. The stiff biomineral layers have buffered the concentrated energy on behalf of soft hydrogels, thereby exposing the hydrogel components to reduced stress and, in turn, enabling them to perform the elasticity continuously. Moreover, the nonlinear elastic Liesegang-patterned complex exhibits excellent stress relaxation to the external loading, which is the biomechanical characteristic of cartilage. This stress relaxation allows the bundle of fiber-type Liesegang-patterned complex to endure greater deformation.

Coordinative Double Hydrophilic All-Polyether Micelles for pH-Responsive Delivery of Cisplatin.

Despite its widespread use in the treatment of numerous cancers, the use of cisplatin still raises concerns about its high toxicity and limited selectivity. Consequently, the necessity arises for the development of an effective drug delivery system. Here, we present an effective approach that introduces a double hydrophilic block copolyether for the controlled delivery of cisplatin. Specifically, poly(ethylene glycol)-block-poly(glycidoxy acetic acid) (mPEG-b-PGA) was synthesized via anionic ring-opening polymerization using the oxazoline-based epoxide monomer 4,4-dimethyl-2-oxazoline glycidyl ether, followed by subsequent acidic deprotection. The coordinative metal-ligand interaction between cisplatin and the carboxylate group within the PGA block facilitated the formation of micelles from the double hydrophilic mPEG-b-PGA copolyether. Cisplatin-loaded polymeric micelles had a high loading capacity, controlled pH-responsive release kinetics, and high cell viability. Furthermore, in vitro biological assays revealed cellular apoptosis induced by the cisplatin-loaded micelles. This study thus successfully demonstrates the potential use of double hydrophilic block copolyethers as a versatile platform for biomedical applications.

Effect of Transcranial Direct Current Stimulation with Balance Training in a Middle-Aged Population: Randomized Double-Blind Sham-Controlled Trial.

Introduction: The first signs of deteriorated balance impairment begin during middle age. Early intervention could delay the fall risk in older populations; hence, addressing balance deficits during this age is crucial. The authors aimed to determine the effects of transcranial direct current stimulation (tDCS) combined with balance training (BT) on the improvement of static and dynamic balance in a middle-aged population, along with the participants' safety and satisfaction. Methods: Participants (n = 28) were randomized into two groups: active tDCS (active tDCS + BT) and sham tDCS (sham tDCS + BT). Both groups received the intervention thrice a week for 6 weeks. Dynamic and static balance were assessed by sway rate changes with eyes open and closed, and the functional reach test and a postintervention survey were conducted to assess participants' safety and satisfaction. Results: The active tDCS group showed significantly greater static and dynamic balance improvements in sway scores. The surveys demonstrated the safety of the program and satisfaction of 80% of the participants with the combined intervention. Conclusion: tDCS could be used in a middle-aged population as part of regular BT to improve balance and minimize the risk of balance deficits in older populations while ensuring patient safety and satisfaction. This study is a subanalysis of a larger clinical trial that included young adults as well (Clinical trial number: KCT0007414).

Effect of tDCS Combined With Physical Training on Physical Performance in a Healthy Population.

Purpose: The effectiveness of transcranial direct current stimulation (tDCS) combined with physical training has shown inconsistent results through research. Hence, a study utilizing a long-term tDCS application over the primary motor cortex and a large sample size is required to determine whether tDCS combined with physical training can increase physical performance (muscular strength, endurance, and explosive strength) in healthy adults. Material and methods: Fifty-six healthy adults were randomly distributed into two groups: active (active tDCS+ physical training) and sham (sham tDCS + physical training) and received the intervention three times per week for six weeks. Muscle strength was assessed using maximal isometric muscle strength (MIMS) by a digital dynamometer. Muscular endurance and lower limb explosive strength were assessed by using muscle fitness testing (MFT), and the Sargent jump test. Results: The active and sham groups exhibited significant improvement in all measured parameters in intragroup analyses. However, intergroup analyses revealed no significant difference between the groups. Conclusion: Our findings suggest that only physical training improved MIMS in the upper and lower extremities, MFT endurance scores, and lower limb explosive power. Thus, tDCS failed to demonstrate its effectiveness in a healthy population according to the protocol used in this study.

Anionic ring-opening polymerization of functional epoxide monomers in the solid state.

Despite recent advancements in mechanochemical polymerization, understanding the unique mechanochemical reactivity during the ball milling polymerization process still requires extensive investigations. Herein, solid-state anionic ring-opening polymerization is used to synthesize polyethers from various functional epoxide monomers. The critical parameters of the monomers are investigated to elucidate the unique reactivity of ball milling polymerization. The controllable syntheses of the desired polyethers are characterized via NMR, GPC, and MALDI-ToF analyses. Interestingly, bulky monomers exhibit faster conversions in the solid-state in clear contrast to that observed for solution polymerization. Particularly, a close linear correlation is observed between the conversion of the ball milling polymerization and melting point of the functional epoxide monomers, indicating melting point as a critical predictor of mechanochemical polymerization reactivity. This study provides insights into the efficient design and understanding of mechanochemical polymerization.

Cu(triNHC)-catalyzed polymerization of glycidol to produce ultralow-branched polyglycerol.

We have successfully synthesized a novel form of polyglycerol with an unprecedentedly low degree of branching (DB = 0.08-0.18), eliminating the need for glycidol protection. Leveraging the remarkable efficiency and selectivity of our Cu(triNHC) catalyst, comprising copper(i) ions and NHC ligands, we achieved a highly selective polymerization process. The proposed Cu-coordination mechanisms presented the formation of linear L1,3 units while effectively suppressing dendritic units. Consequently, our pioneering approach yielded polyglycerol with an ultralow DB and exceptional yields. To comprehensively assess the physical properties and topology of the synthesized polyglycerol, we employed 1H diffusion-ordered spectroscopy, size-exclusion chromatography, and matrix-assisted laser desorption/ionization-time of flight spectrometry. Remarkably, the ultralow-branched cyclic polyglycerol (DB = 0.08) synthesized at 0 °C showcased extraordinary characteristics, exhibiting the lowest diffusion coefficient and the highest molecular weight. This achievement establishes the significant potential of our polyglycerol with a low degree of branching, revolutionizing the field of biocompatible polymers.

Acid-sensitive stable polymeric micelle-based oxidative stress nanoamplifier as immunostimulating anticancer nanomedicine.

Oxidative stress amplifying compounds could elicit selective killing of cancer cells with minimal toxicity to normal cells and also induce immunogenic cell death (ICD). However, compared to conventional anticancer drugs, oxidative stress amplifying compounds have inferior therapeutic efficacy. It can be postulated that the anticancer therapeutic efficacy and immunostimulating activity of oxidative stress amplifying hybrid prodrug (OSamp) could be fully maximized by employing ultrastable polymeric micelles as drug carriers. In this work, we developed tumour-targeted oxidative stress nanoamplifiers, composed of OSamp, amphiphilic poly(ethylene glycol) methyl ether-block-poly(cyclohexyloxy ethyl glycidyl ether)s (mPEG-PCHGE) and a lipopeptide containing Arg-Gly-Asp (RGD). Tumour targeted OSamp-loaded mPEG-PCHGE (T-POS) micelles exhibited excellent colloidal stability and significant cytotoxicity to cancer cells with the expression of DAMPs (damage-associated molecular patterns). In the syngeneic mouse tumour model, T-POS micelles induced significant apoptotic cell death to inhibit tumour growth without noticeable body weight changes. T-POS micelles also induced ICD and activated adaptive immune responses by increasing the populations of cytotoxic CD4+ and CD8+ T cells. Therefore, these results suggest that T-POS micelles hold great translational potential as immunostimulating anticancer nanomedicine.

Unlocking the Potential of Colloidal Quantum Dot/Organic Hybrid Solar Cells: Band Tunable Interfacial Layer Approach.

Hybrid colloidal quantum dot (CQD)/organic architectures are promising candidates for emerging optoelectronic devices having high performance and inexpensive fabrication. For unlocking the potential of CQD/organic hybrid devices, enhancing charge extraction properties at electron transport layer (ETL)/CQD interfaces is crucial. Hence, we carefully adjust the interface properties between the ETL and CQD layer by incorporating an interfacial layer for the ETL (EIL) using several types of cinnamic acid ligands. The EIL having a cascading band offset (ΔEC) between the ETL and CQD layer suppresses the potential barrier and the local charge accumulation at ETL/CQD interfaces, thereby reducing the bimolecular recombination. An optimal EIL effectively expands the depletion region that facilitates charge extraction between the ETL and CQD layer while preventing the formation of shallow traps. Representative devices with an EIL exhibit a maximum power conversion efficiency of 14.01% and retain over 80% of initial performances after 300 h under continuous maximum power point operation.

Pain Reduction and Posture Alignment Improvement in Older Adults with Chronic Low Back Pain: A Novel Approach Using Spinal Thermal Massage Bed and Calf Pneumatic Cell Compression.

BACKGROUND Chronic low back pain (CLBP) significantly affects the well-being of older adults, leading to diminished quality of life and heightened stress. Existing treatments have limited effectiveness and potential side effects. This study aimed to explore an integrative approach, employing a combination of spinal thermal massage bed (STMB) and intermittent pneumatic calf compression, as an alternative strategy for managing CLBP, improving body posture, reducing stress, and enhancing quality of life. MATERIAL AND METHODS Twenty-three participants aged 65-80 years completed a 4-week intervention involving eight sessions (2 per week) with the STMB device. Outcome measures included pain level assessed by the visual analog scale, trunk and pelvic tilting angles indicating spine curvature, stress level of the autonomic nervous system, Oswestry Disability Index, and EuroQol five-dimensions QoL questionnaire. RESULTS The study revealed significant reductions in pain intensity between baseline and mid-term scores (p=0.002) and between baseline and post-test scores (p=0.001). Moreover, notable improvements were observed in trunk and pelvic tilting angles (p<0.001) and stress scores between baseline and mid-term scores (p=0.037) and between baseline and post-test scores (p=0.019). However, no significant changes were observed in disability level or QoL. Participants expressed high satisfaction with the intervention, and no serious side effects were reported CONCLUSIONS This study provides compelling evidence supporting the safety and efficacy of combining STMB with intermittent pneumatic calf compression in reducing pain intensity and stress levels and improving trunk and pelvic tilting angles. Clinical trial number: KCT0008212.

Quantum Dot-Siloxane Anchoring on Colloidal Quantum Dot Film for Flexible Photovoltaic Cell.

Lead sulfide (PbS) colloidal quantum dots (CQDs) are promising materials for next-generation flexible solar cells because of near-infrared absorption, facile bandgap tunability, and superior air stability. However, CQD devices still lack enough flexibility to be applied to wearable devices owing to the poor mechanical properties of CQD films. In this study, a facile approach is proposed to improve the mechanical stability of CQDs solar cells without compromising the high power conversion efficiency (PCE) of the devices. (3-aminopropyl)triethoxysilane (APTS) is introduced on CQD films to strengthen the dot-to-dot bonding via QD-siloxane anchoring, and as a result, crack pattern analysis reveals that the treated devices become robust to mechanical stress. The device maintains 88% of the initial PCE under 12 000 cycles at a bending radius of 8.3 mm. In addition, APTS forms a dipole layer on CQD films, which improves the open circuit voltage (VOC ) of the device, achieving a PCE of 11.04%, one of the highest PCEs in flexible PbS CQD solar cells.

Mechanochemical Degradation of Poly(vinyl chloride) into Nontoxic Water-Soluble Products via Sequential Dechlorination, Heterolytic Oxirane Ring-Opening, and Hydrolysis.

As one of the most widely used commodity plastics, poly(vinyl chloride) (PVC) is extensively used worldwide, yet is difficult to recycle and is often discarded immediately after use. Its end-of-life treatment often generates toxic hydrogen chloride and dioxins that pose a critical threat to ecosystems. To address this challenge, the mechanochemical degradation of PVC into water-soluble biocompatible products is presented herein. Oxirane mechanophores are strategically introduced into the polymeric backbone via sequential dechlorination followed by epoxidation. The oxirane mechanophore in the polymer backbone undergoes a force-induced heterolytic ring-opening to carbonyl ylide intermediates, which eventually generates acetals during the course of the reaction. The subsequent hydrolysis of the backbone acetals affords the scission of the polymeric chain into water-soluble low-molecular-weight fragments. Combined with its low cytotoxicity and phytotoxicity, this solvent-free mechanochemical degradation process offers a green alternative for the degradation of PVC.

Tailoring the Interplay between Two Monomers in the Properties of Degradable Polyesters Synthesized via Ring-Opening Alternating Copolymerization.

Ring-opening alternating copolymerization (ROAC) of cyclic anhydrides and epoxides has emerged as a powerful strategy to produce degradable polyesters with a diverse array of structures from the combination of two distinct building blocks. In this work, we exploited the organocatalytic ROAC of cyclic anhydrides and a functional epoxide, t-butyl glycidoxy acetate, followed by acidic deprotection to access degradable polyesters with carboxylic acid pendants. To study the interplay between monomers, diglycolic anhydride and glutaric anhydride were used as cyclic anhydrides to prepare two polyesters. In particular, the effects of the oxygen heteroatom in the cyclic anhydrides on the properties of the carboxylic acid-containing polyesters were investigated. The introduction of the oxygen heteroatom into the cyclic anhydrides significantly influenced their thermal properties and pH-dependent self-association behavior in an aqueous solution. Furthermore, molecular dynamics simulations elucidate that the number and type of hydrogen bonds play a crucial role in the self-association behavior between the polymers both in the solution and bulk states. The findings of this study highlight the importance of the interplay between monomers in the design of functional polyesters with tunable properties.

Mechanochemical solid-state vinyl polymerization with anionic initiator.

Mechanochemistry has been extended to various polymer syntheses to achieve efficiency, greenness, and new products. However, many fundamental polymerization reactions have not been explored, although anionic polymerization of vinyl compounds has been pursued under mechanochemical conditions. Two solid monomers, 4-biphenyl methacrylate and 4-vinyl biphenyl, representing methacrylate and styrenic classes, respectively, were reacted with secondary butyl lithium under high-speed ball-milling. The alkyl-anion-promoted polymerization process was established by excluding radical initiation and producing the expected polymers with good efficiency. However, the generally expected features of anionic polymerization, such as molecular weight control and narrow dispersity, were not observed. Analysis of the milling parameters, reaction monitoring, and microstructural analysis revealed that the mechanism of the mechanochemical process differs from that of conventional anionic polymerizations. The mechanical force fractured the newly formed polymer chains via anionic initiation and generated macroradicals, which participated in the polymerization process. The anionic process governs the initiation step and the radical process becomes dominant during the propagation step.

Redox-active polyimides for energy conversion and storage: from synthesis to application.

As the demand for next-generation electronics is increasing, organic and polymer-based semiconductors are in the spotlight as suitable materials owing to their tailorable structures along with flexible properties. Especially, polyimide (PI) has been widely utilised in electronics because of its outstanding mechanical and thermal properties and chemical resistance originating from its crystallinity, conjugated structure and π-π interactions. PI has recently been receiving more attention in the energy storage and conversion fields due to its unique redox activity and charge transfer complex structure. In this review, we focus on the design of PI structures with improved electrochemical and photocatalytic activities for use as redox-active materials in photo- and electrocatalysts, batteries and supercapacitors. We anticipate that this review will offer insight into the utilisation of redox-active PI-based polymeric materials for the development of future electronics.

Janus regulation of ice growth by hyperbranched polyglycerols generating dynamic hydrogen bonding.

In this study, a new phenomenon describing the Janus effect on ice growth by hyperbranched polyglycerols, which can align the surrounding water molecules, has been identified. Even with an identical polyglycerol, we not only induced to inhibit ice growth and recrystallization, but also to promote the growth rate of ice that is more than twice that of pure water. By investigating the polymer architecture and population, we found that the stark difference in the generation of quasi-structured H2O molecules at the ice/water interface played a crucial role in the outcome of these opposite effects. Inhibition activity was induced when polymers at nearly fixed loci formed steady hydrogen bonding with the ice surface. However, the formation-and-dissociation dynamics of the interfacial hydrogen bonds, originating from and maintained by migrating polymers, resulted in an enhanced quasi-liquid layer that facilitated ice growth. Such ice growth activity is a unique property unseen in natural antifreeze proteins or their mimetic materials.

Dual-Modulated Release of a Cytotoxic Photosensitizer Using Photogenerated Reactive Oxygen Species and Glutathione.

Reversible thiol-disulfide exchange chemistry is of particular interest in drug delivery systems. However, high levels of glutathione (GSH) in cancer cells are hard to distinguish from GSH in normal cells, resulting in unmanageable cytotoxic drug release. This study investigates the spatiotemporally-controlled irreversible degradation of Ir-based photosensitizer (TIr3)-encapsulating nanogels (IrNG) through the hyperoxidation of resulting intracellular thiols using reactive oxygen species (ROS). A highly cytotoxic TIr3 was stably encapsulated within IrNG through hydrophobic interactions and reversible crosslinking between its disulfide bonds and thiols in the absence of light, resulting in high biocompatibility under normal cellular conditions. However, upon photoirradiation, TIr3 generated high levels of ROS, irreversibly oxidizing the thiols to induce electrostatic repulsion between the polymer molecules, resulting in the TIr3 release and induction of cancer cell apoptosis.

Singlet Oxygen Generation from Polyaminoglycerol by Spin-Flip-Based Electron Transfer.

Reactive oxygen species have drawn attention owing to their strong oxidation ability. In particular, the singlet oxygen (1O2) produced by energy transfer is the predominant species for controlling oxidation reactions efficiently. However, conventional 1O2 generators, which rely on enhanced energy transfer, frequently suffer from poor solubility, low stability, and low biocompatibility. Herein, we introduce a hyperbranched aliphatic polyaminoglycerol (hPAG) as a 1O2 generator, which relies on spin-flip-based electron transfer. The coexistence of a lone pair electron on the nitrogen atom and a hydrogen-bonding donor (the protonated form of nitrogen and hydroxyl group) affords proximity between hPAG and O2. Subsequent direct electron transfer after photo-irradiation induces hPAG•+-O2 •- formation, and the following spin-flip process generates 1O2. The spin-flip-based electron transfer pathway is analyzed by a series of photophysical, electrochemical, and computational studies. The 1O2 generator, hPAG, is successfully employed in photodynamic therapy and as an antimicrobial reagent.

Peptidomimetic Wet-Adhesive PEGtides with Synergistic and Multimodal Hydrogen Bonding.

The remarkable underwater adhesion of mussel foot proteins has long been an inspiration in the design of peptidomimetic materials. Although the synergistic wet adhesion of catechol and lysine has been recently highlighted, the critical role of the polymeric backbone has remained largely underexplored. Here, we present a peptidomimetic approach using poly(ethylene glycol) (PEG) as a platform to evaluate the synergistic compositional relation between the key amino acid residues (i.e., DOPA and lysine), as well as the role of the polyether backbone in interfacial adhesive interactions. A series of PEG-based peptides (PEGtides) were synthesized using functional epoxide monomers corresponding to catechol and lysine via anionic ring-opening polymerization. Using a surface force apparatus, highly synergistic surface interactions among these PEGtides with respect to the relative compositional ratio were revealed. Furthermore, the critical role of the catechol-amine synergy and diverse hydrogen bonding within the PEGtides in the superior adhesive interactions was verified by molecular dynamics simulations. Our study sheds light on the design of peptidomimetic polymers with reduced complexity within the framework of a polyether backbone.

Stress Dissipation Encoded Silk Fibroin Electrode for the Athlete-Beneficial Silk Bioelectronics.

The kinetic body motions have guided the core-shell fabrics of wearable bioelectronics to be elastoplastic. However, the polymeric electrodes follow the trade-off relationship between toughness and stretchability. To this end, the stress dissipation encoded silk fibroin electrode is proposed as the core electrode of wearable bioelectronics. Significantly, the high degree of intrinsic stress dissipation is realized via an amino acid crosslink. The canonical phenolic amino acid (i.e., tyrosine) of silk fibroin is engineered to bridge the secondary structures. A sufficient crosslink network is constructed when tyrosine is exposed near the amorphous strand. The stress dissipative tyrosine crosslink affords 12.5-fold increments of toughness (4.72 to 58.9 MJ m-3 ) and implements the elastoplastic silk fibroin. The harmony of elastoplastic core electrodes with shell fabrics enables the wearable bioelectronics to employ mechanical performance (elastoplasticity of 750 MJ m-3 ) and stable electrical response. The proposed wearable is capable of assisting the effective workouts via triboelectricity. In principle, active mobility with suggested wearables potentially relieves muscular fatigues and severe injuries during daily fitness.