Sprayable hydrogels have emerged as a transformative innovation in biomedical technology, offering a versatile, efficient, and minimally invasive platform for various clinical applications. They form gels in situ upon tissue contact, enabling seamless application on even complex surfaces. This property is especially useful in wound care, drug delivery, and tissue engineering, where localized and sustained release of therapeutics is essential. Formulations can be customized to include various bioactive compounds, such as growth factors, antibiotics, and anti-inflammatory agents, thereby enhancing targeted treatment outcomes. This review delves into the fundamental principles governing sprayable hydrogels, emphasizing critical mechanisms such as in situ cross-linking, shear-thinning properties, and thermoresponsive behavior. Furthermore, it highlights recent advancements since 2020, including the strategic incorporation of bioactive agents to augment therapeutic efficacy. By examining these core mechanisms and design strategies, this review provides a comprehensive perspective on the engineering of sprayable hydrogels for modern medical applications.

Biomolecular motors are dynamic systems found in organisms with high energy conversion efficiency. F_OF₁-ATPase is a rotary biomolecular motor known for its near 100% energy conversion efficiency. It utilizes the synthesis and hydrolysis of ATP to induce conformational changes in motor proteins, thereby converting chemical energy into mechanical motion. Given their high efficiency, autonomous propulsion capability, and modifiable structures, F_OF₁-ATPase motors have attracted significant attention for potential biomedical applications. This Review aims to introduce the detailed structure of F_OF₁-ATPase, explore various motility manipulation strategies, and summarize its applications in biological detection and cargo delivery. Additionally, innovative research methods are proposed to analyze the motion mechanism of F_OF₁-ATPase more comprehensively, with the goal of advancing its biomedical applications. Finally, this Review concludes with key insights and future perspectives.

The rapid development of flexible electronics has led to unprecedented social and economic improvements. But conventional power devices cannot adapt to the advances of flexible electronics. Triboelectric nanogenerators (TENGs) have been used as robust power sources to transform ambient mechanical energy into electricity, thus meeting the power requirements of flexible electronics. Hydrogels are widely used for soft bioelectronics owing to the decent stretchability and biocompatibility. This Review presents the recent progress in the use of hydrogels for TENGs and self-powered hydrogel bioelectronics, including hydrogel synthesis, hydrogel TENGs fabrication, and their applications in wearable electricity generation, self-powered active sensing, and therapeutics. Hydrogel-enabled TENGs are emerging as a novel form of soft bioelectronics. We provided a critical analysis of hydrogel TENGs and insights into future opportunities and directions of this rapidly evolving field. These advancements will push the boundaries of hydrogel bioelectronics and contribute to the development of personalized healthcare solutions.

Small molecules are frontline therapeutics for many diseases; however, they are often limited by their poor solubility. Therefore, hydrophobic small molecules are often encapsulated or prepared as pure drug nanoparticles. Navitoclax, used to eliminate senescent cells, is one such small molecule that faces challenges in translation due to its hydrophobicity and toxic side effects. Further, as senescent cells exhibit context-dependent pathologic or beneficial properties, it is preferable to eliminate senescent cells locally. To formulate navitoclax and enable local treatment, we designed an injectable hydrogel loaded with navitoclax nanoparticles as a senolytic delivery vehicle. Navitoclax nanoparticles (Ø ∼ 110 nm) were prepared via solvent–antisolvent nanoprecipitation and formulated in an injectable polymer–nanoparticle (PNP) hydrogel to create a local senolytic depot. Navitoclax-loaded PNP hydrogels selectively cleared senescent cells in vitro in senescent endothelial monolayers. This work demonstrates the value of formulating lipophilic small molecules and the potential of localized drug delivery strategies to improve senolytic therapies.

In situ polymerization on cell membranes can decrease cell mobility, which may inhibit tumor growth and invasion. However, the initiation of radical polymerization traditionally requires exogenous catalysts or free radical initiators, which might cause side effects in normal tissues. Herein, we synthesized a Y-type diacetylene-containing lipidated peptide amphiphile (TCDA-KFFFFK(GRGDS)-YIGSR, Y-DLPA) targeting integrins and laminin receptors on murine mammary carcinoma 4T1 cells, which underwent nanoparticle-to-nanofiber morphological transformation and in situ polymerization on cell membranes. Specifically, the polymerized Y-DLPA induced 4T1 cell apoptosis and disturbed the substance exchange and metabolism. In vitro assays demonstrated that the polymerized Y-DLPA nanofibers decreased the migration capacity of 4T1 cells, potentially suppressing tumor invasion and metastasis. When administered locally to 4T1 tumor-bearing mice, the Y-DLPA nanoparticles formed a biomimetic extracellular matrix that effectively suppressed tumor growth. This study provides an in situ polymerization strategy that can serve as an effective drug-free biomaterial with low side effects for antitumor therapy.

Traditional polymer systems often rely on toxic initiators or catalysts for cross-linking, posing significant safety risks. For bone tissue engineering, another issue is that the scaffolds often take a longer time to degrade, inconsistent with bone formation pace. Here, we developed an enzyme-responsive biodegradable poly(propylene fumarate) (PPF) and polycaprolactone (PCL) polyphosphoester (PPE) dendrimer cross-linked utilizing click chemistry (EnzDeg-click-PFCLPE scaffold) for enhanced biocompatibility and degradation. The strain-promoted alkyne–azide cycloaddition (SPAAC) offers high efficiency and biocompatibility without harmful agents. The polyphosphoesters render polymer cleavage responsive to alkaline phosphatase (ALP) enzyme in bone formation, ensuring facilitated scaffold biodegradation. The in vitro testing confirmed biocompatibility, enzyme-responsive degradation, and capability to support stem cell differentiation. Further in vivo implantation in rat demonstrated bone regeneration and scaffold integration. In summary, this polymer system combining click chemistry with ALP-responsive biodegradation ensures initial bone support and facilitates scaffold degradation synchronized with the natural bone healing process.

Hybrid hydrogels are promising for wound dressing, tissue engineering, and drug delivery due to their exceptional biocompatibility and mechanical stability. This study synthesized hybrid hydrogels for photodynamic therapy using electron beam-initiated polymerization with varying PEGDA/gelatin ratios and irradiation doses to evaluate their effectiveness as uptake and release systems for five photosensitizers. Toluidine blue, O (TBO); methylene blue (MB); eosin, Y; indocyanine, green; and sodium meso-tetraphenylporphine-4,4′,4″,4‴-tetrasulfonate were studied for their uptake and release dynamics in relation to their structural properties and the hydrogels’ composition. Uptake was influenced by the gelatin ratio and ionic properties, with anionic photosensitizers achieving over 80% uptake while cationic ones remained below 45%. Increased irradiation doses highlighted the roles of ionic interactions, hydrophilicity, and surface polarity. Cationic photosensitizers produced singlet oxygen 9–10 times more efficiently. Nontoxic PEGDA/gelatin hydrogels demonstrated photosensitizer-dependent cytotoxicity, with TBO and MB consistent with previous findings. These results confirm their potential in photodynamic therapy.

Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline-co-2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule. These polymers were successfully used to stabilize (solid) lipid nanoparticles ((S)LNP) consisting of tetradecan-1-ol and cholesterol with their hydrophobic anchor. While the pure polymers interacted with GLUT1-expressing cell lines mainly based on their physicochemical properties, especially via interactions of the hydrophobic anchor with membranous compartments of the cells, LNP-cell interactions hinted toward an influence of the glucosylation on particle–cell interactions. The presented LNP are therefore promising systems for the delivery of drugs into GLUT1-expressing cell lines.

As an abundant renewable natural material, starch has attracted unprecedented interest in the biomedical field. Carboxylated starch particles have been investigated for topical hemostasis, but the powder may not provide physical protection or support for wounds. Here, we prepared macroporous cryogel sponges of methacrylated carboxymethyl starch (CM-ST-MA) containing a covalent and a calcium ionic double network. The second ionic cross-linking network enhanced the compressive strength and toughness dramatically but reduced the swelling ratios. Cryogels and sponges exhibited excellent compressive elasticity at low Ca²⁺ concentrations (0.01 M). Cryogels became more plastic and dry sponges became rigid and brittle at high Ca²⁺ concentrations. The cryogels have outstanding wet-thermal stability but are still degradable via enzymatic hydrolysis. All CM-ST-MA sponges showed excellent biocompatibility, hemocompatibility, and outstanding hemostasis in in vitro assays. In the in vivo mouse tail amputation model, both CM-ST-MA cryogels without or with Ca²⁺ (0.01 M) reduced the blood loss and bleeding time significantly.

Wood modification using low molecular weight thermosetting resins improves the biological durability and dimensional stability of wood while avoiding increasingly regulated biocides. During the modification process, resin monomers diffuse from the cell lumen to the cell wall, occupying micropore spaces before in situ curing at 150 °C. This study investigated the mechanism of cell wall diffusion at multiple scales, comparing two test groups where diffusion was either facilitated or restricted. Antiswelling efficiency tests demonstrated improved dimensional stability when diffusion was facilitated. Differential scanning calorimetry showed that bound water was excluded more effectively from the cell wall if cell wall diffusion was enabled. Solid-state NMR spectroscopy (¹H MAS and ¹³C MAS) with relaxation time analysis indicated that resin migrated to distinct locations within the cell wall, influenced by diffusion and drying conditions. These findings highlight how optimizing cell wall diffusion can significantly improve the performance of wood modification processes using thermosetting resins.

Various polycations and polyanions were sequentially adsorbed onto the gold electrode of a quartz crystal microbalance with dissipation monitoring. The study focused on determining the adsorption kinetics, viscoelastic properties, and electroresponsivity of polyelectrolyte layers. For the first time, it was demonstrated that the structure (compact or expanded) of the layers can be determined by electroresponsivity. Viscoelastic modeling alone did not provide a conclusive answer as to whether the layers were compact or expanded. The study was further enriched by streaming potential and contact angle measurements, where polyelectrolyte multilayers were formed on mica. It was found that successive adsorption of layers led to periodic inversion of the zeta potential. Systematic differences were observed between the different top layers, which were explained by intermixing between layers. The presence or absence of interpenetration, as determined by the measurements of streaming potential and contact angles, correlated well with electroresponsivity.

To understand xylan–cellulose interactions in softwood, the adsorption behavior of hexameric softwood xylan proxies with various substitutions was analyzed on the three surfaces of a hexagonal cellulose microfibril. The study found that all surfaces could bind xylan motifs, showing equally high affinity for the hydrophilic (110) and hydrophobic (100) surfaces and significantly lower affinity for the hydrophilic (11̅0) surface. Unsubstituted xylose hexamers had the highest affinity and most ordered adsorption structures, while substitutions generally reduced the affinity and regularity. An exception was a motif with two glucuronic acids two residues apart, which displayed high affinity and increased tendency to adopt a 2-fold screw on hydrophilic surfaces. Surface affinity correlated with the tightness of xylan–cellulose associations and the ratio of the xylan–cellulose to xylan–water interaction energies. Novel methods to quantify backbone conformations were proposed. Future work should address differences in simulation models and explore the competition between xylan and glucomannan for cellulose surfaces.

The development of biobased polyesters with the combination of high UV shielding and degradability is a significant challenge. Herein, three 4-membered cyclic monomers containing two pyrrolidone and two furan rings were prepared by the aza-Michael addition of biobased bifuran diamine and dimethyl itaconate (DMI). They were available in melt polycondensation reactions with various diols to synthesize biobased polyesters. The bifuran structure endowed the polyesters with ultrahigh UV-shielding cutoff values of up to 443 nm, which achieved the highest UV-shielding results among the commercial polyesters. The bipyrrolidone structure conferred high hydrolysis sensitivity to the polyesters, which facilitated hydrolytic degradation of the polyester in an aqueous environment. The variability of the link structure between the multirings of the three monomers can regulate the various properties of the polyesters. Overall, the 4-membered cyclic monomers are promising precursors for sustainable biobased materials in providing high UV shielding and hydrolysis sensitivity.

Emerging techniques of additive manufacturing, such as vat-based three-dimensional (3D) bioprinting, offer novel routes to prepare personalized scaffolds of complex geometries. However, there is a need to develop bioinks suitable for clinical translation. This study explored the potential of bacterial-sourced methacrylate levan (LeMA) as a bioink for the digital light processing (DLP) 3D bioprinting of bone tissue scaffolds. LeMA was successfully synthesized, characterized, and used to fabricate 3D-bioprinted scaffolds with excellent printability and physicochemical properties. In vitro studies demonstrated superior cytocompatibility of 15% w/v LeMA gels compared to 20% gels. 15% LeMA gels supported osteogenic differentiation , as evidenced by alkaline phosphatase activity and mineral deposition by MC3T3 pre-osteoblasts. Importantly, the LeMA hydrogels positively modulated the macrophage phenotype, promoting the expression of the anti-inflammatory marker CD206. These findings suggest that 3D-printed LeMA scaffolds can create a favorable microenvironment for bone regeneration, highlighting their potential for tissue repair and regeneration applications.

The present investigation aims to develop a reactive oxygen species (ROS) and esterase-responsive biodegradable mannosylated polyurethane to effectively deliver the encapsulated antileishmanial drug amphotericin B (AmB) selectively to infected macrophage cells. Owing to suitable amphiphilic balance, the as-synthesized glycosylated polyurethane (PU2M) with aryl boronic ester-based diol (M2) moiety as ROS-trigger, water-soluble mannose pendants, and fluorescent 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) chain ends for bioimaging formed nanoaggregates in an aqueous medium as confirmed by ¹H NMR spectroscopy, dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), and critical aggregation concentration (CAC) measurements. Aided by two endogenous stimuli present in phagolysosome, ROS and esterase, AmB-encapsulated polymeric nanoaggregates as drug delivery vehicles achieved an efficient reduction of both L. donovani and L. major intracellular amastigote burden compared to the free AmB. Overall, this work illustrated a promising therapeutic application of dual endogenous stimuli-triggered degradable theranostic polyurethane for target-specific drug delivery of AmB, to mitigate leishmaniasis.

Polyamide (PA) has notable physical and chemical properties and is one of the most versatile synthetic materials in the industrial sector. However, its hydrophobicity creates significant challenges in its beneficiation and modification. Modifications of PA with chitosan nanoparticles (CNPs) can improve its undesired properties but are rarely found in the literature due to the weak interaction between the chemical groups of both structures. Surface hydrolysis mediated by enzymes can mildly improve the PA properties and create reactive sites. These sites can react with CNPs to confer enhanced properties to the fabrics, such as antimicrobial activity and flame retardancy. This study investigated the action of 14 hydrolases in the surface hydrolysis of 100% polyamide 6 (PA 6) fabric. Such an extensive study applying several enzymes for this process is uncommon. Under the optimum conditions, the hydrolyzed fabric was covalently bonded to the CNPs, generating material with reduced bacterial proliferation and flame retardancy properties. The uncommon covalent bond attachment achieved high material durability, even after five washing cycles.

Recently, polyamides have been widely used in various fields due to their excellent durability, thermal stability, and other advantageous properties. However, polyamide products that end up in oceans have become a source of microplastics. For this reason, the development of highly degradable polyamides is greatly desired. We here focused on polyamide 4 (PA4), which has a high density of amide groups in its main chain. As model samples, two types of PA4 thin film, thermally annealed at different temperatures, were prepared, and their aggregation states and biodegradation behavior were examined. The results revealed that the swelling properties of the PA4 thin films in underwater environments play a crucial role in their degradation. It was also found that the crystal polymorph of the PA4 thin films significantly influences their biodegradation behavior. This fundamental understanding of PA4 degradation behavior will contribute to the further development of PA4-based devices.

Nanosecond pulsed electric fields (nsPEFs) can induce protein-mediated electroporation (PMEP) in voltage-gated ion channels. However, their effects on the tetrameric structure of voltage-gated potassium (Kv) channels remain unexplored. Our study pioneered the molecular dynamics (MD) investigation of the open-state (O) Kv channel to understand the effects of PMEP under unipolar and bipolar pulses (UP and BP). Our findings revealed that BP induces pore formation more effectively than UP. Additionally, the frequency of pore formation shows a more consistent decline with increased pulse interval under BP. We further examined three other distinct functional states─intermediate (C*), inactivated (I), and resting closed (C)─of Kv channels under BP. SF pores formed exclusively in the O state, while complex pores formed only in the O and C states. In conclusion, our study highlights BP’s role in enhancing pore formation and specificity, offering insights into Kv channel PMEP and its therapeutic potential.

Chitosan is a versatile bioactive polysaccharide in various industries, such as pharmaceuticals and environmental applications, owing to its abundance, biodegradability, biocompatibility, and antibacterial properties. To effectively harness its potential for various purposes, it is crucial to understand the mechanisms of its interaction in water. This study investigates the interactions between high molecular weight (HMW, >150 kDa) chitosan and four different functionalized self-assembled monolayers (SAMs) at three different pHs (3.0, 6.5, and 8.5) using a surface forces apparatus (SFA). We report that HMW chitosan exhibits the strongest adhesion to methyl-terminated SAM (CH₃–SAM) at all pHs, showing potential for strong hydrophobic interactions against other molecules containing hydrophobic moieties. Noting that hydrogen bonding has been considered the dominating interaction mechanism of chitosan, the consequence of this study provides valuable insights into its applications in developing chitosan-based eco-friendly materials.

Atom transfer radical polymerization (ATRP) is a leading method for creating polymers with precise control over molecular weight, yet its reliance on metal catalysts limits its application in metal-sensitive and environmental contexts. Addressing these limitations, we have developed a recyclable, biocompatible, robust, and tunable ATRP catalyst composed of a protein–polymer-copper conjugate, synthesized by polymerizing an L-proline-based monomer onto bovine serum albumin and complexing with Cu(II). The use of this conjugate catalyst maintains ATRP’s precision while ensuring biocompatibility with bothEscherichia coli and HEK 293 cells, and its high molecular weight allows for easy recycling through dialysis. Therefore, our efforts extend ATRP’s applicability across diverse fields, including biotechnology and green chemistry, marking a significant advance toward environmentally friendly and safe polymerization technologies.

Amphiphilic polymers with distinct polarity differences, known as sharp polarity contrast polymers (SPCPs), have gained much attention for their ability to form micelles with low critical micelle concentrations (CMCs) and potential in anticancer drug delivery. This study addresses the limited research on structure–property relationships of SPCPs by developing various SPCPs and exploring their physicochemical properties and biological applications. Specifically, the superhydrophobic aliphatic palmitoyl (Pal) was coupled to the superhydrophilic zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (pMPC) to form Pal-pMPC diblock copolymers. Adjusting the lengths of hydrophilic chains allowed the creation of structures with varying hydrophilic–hydrophobic ratios for micelle formation. Comprehensive evaluations were carried out, including particle size, CMC, chain exchange rates, cellular uptake efficiency, and anticancer effectiveness. Our findings indicate that micelles with optimal hydrophilic–hydrophobic ratios significantly enhanced cellular uptake and cytotoxicity in both two-dimensional (2D) and three-dimensional (3D) tumor models, offering valuable insights for designing SPCPs for anticancer drug delivery.

Silk fibroin (SF) hydrogel has been proven to have excellent applications in the field of pressure sensors, but its sensing performance still needs improvement. A flexible hydrogel prepared from natural macromolecular materials was developed, and lignin nanoparticles (LNPs) were introduced during the preparation of the SF hydrogel. When LNPs account for 3% of SF, the sensing unit of the SF-LNPs_3% hydrogel exhibits high stress sensitivity (1.32 kPa^–1), fast response speed (<0.1 s), and superior cycle stability (≥8000 cycles). The sensor can detect human motion information, such as finger bending, elbow bending, and pulse signals. When worn at the vocal cord position, it can detect the peak value of the characteristic signal during the wearer speaks. This work demonstrates that the SF-LNPs_3% hydrogel has high sensitivity and shows great potential in the field of pressure sensors.

Silk fiber, produced by the silkworm Bombyx mori, is a protein fiber with an excellent mechanical strength and broad biocompatibility. Multiple approaches, including genetic and chemical methods, must be combined to tailor silk fiber properties for wide applications, such as textiles and biomaterials. Genetic code expansion (GCE) is an alternative method to alter proteins’ chemical and physical properties by incorporating synthetic amino acids into their primary structures. Here, we report an efficient system for selecting variants of B. mori tyrosyl-tRNA synthetase (BmTyrRS) used for GCE in silkworms. Four BmTyrRS variants with expanded substrate recognition toward halogenated tyrosine (Tyr) derivatives were selected, and transgenic silkworms expressing these variants were generated. The silkworms incorporated halogenated Tyr derivatives into silk fibroin to produce halogenated silk fiber with improved thermal stability. These results demonstrate the power of GCE to create protein materials with improved physical properties.

Wood-degrading brown-rot fungi primarily target carbohydrates, leaving the lignin modified and potentially valuable for valorization. Here, we report a comprehensive comparison of how Gloeophyllum trabeum in vitro degrades hardwood and softwood, which have fundamentally different lignin structures. By harnessing the latest advancements in analytical methodologies, we show that G. trabeum removes more lignin from wood (up to 36%) than previously reported. The brown-rot decayed lignin appeared substantially C_α-oxidized, O-demethylated, with a reduction in interunit linkages, leading to formation of substructures indicative of C_α-C_β, β-O, and O-4 cleavage. Our work shows that the G. trabeum conversion of hardwood and softwood lignin results in similar modifications, despite the structural differences. Furthermore, lignin modification by G. trabeum enhances the antioxidant capacity of the lignin and generates an extractable lower molecular weight fraction. These findings improve our understanding of lignin conversion by brown-rot fungi and highlight their biotechnological potential for the development of lignin-based products.

This study proposes fluorenylmethoxycarbonyl (Fmoc)-protected single amino acids (Fmoc-AAs) as a minimalistic model system to investigate liquid–liquid phase separation (LLPS) and the elusive liquid-to-solid transition of condensates. We demonstrated that Fmoc-AAs exhibit LLPS depending on the pH and ionic strength, primarily driven by hydrophobic interactions. Systematic examination of the conditions under which each Fmoc-AA undergoes LLPS revealed distinct residue-dependent trends in the critical concentrations and phase behavior. Importantly, we elucidated the liquid-to-solid transition process, suggesting that it may be driven by a molecular mechanism different from that of LLPS. Fmoc-AA condensates showed promise for biomolecular enrichment and catalytic applications. This work provides significant insights into the molecular mechanisms of LLPS and the subsequent liquid-to-solid transition, offering a robust platform for future studies related to protocells and protein aggregation diseases.

Engineered natural killer (NK) cells eliminate cancer cells by overexpressing a chimeric antigen receptor, producing highly efficient and safe NK cell therapies. This study investigated the polyplex formulation for the fusion protein GreenLantern-natural killer group 2D (NKG2D) mRNA to evaluate its ex vivo delivery efficacy into NK cells, wherein NKG2D on the surface of NK cells recognized its counterpart NKG2D ligands on cancer cells. Amphiphilic polyaspartamide derivatives Chol-PAsp(DET/CHE) were prepared by adding cyclohexylethylamine (CHE) and diethylenetriamine (DET) in the side chains and cholesterol (Chol) at the α-terminus to enhance endosomal escapability and optimize hydrophobicity. Chol-PAsp(DET/CHE) significantly improved mRNA delivery efficacy into NK-92mi cells, explained by increased polyplex stability and improved cellular uptake of mRNA. The NKG2D-overexpressing NK-92mi cells exhibited high anticancer efficacy against human colon cancer cells without affecting the viability of fibroblasts. Therefore, Chol-PAsp(DET/CHE) could be a promising mRNA delivery carrier for the ex vivo engineering of NK cells.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense extracellular matrix (ECM) exhibiting high stiffness and fast stress relaxation. In this work, gelatin-based viscoelastic hydrogels were developed to mimic the compositions, stiffness, and fast stress relaxation of PDAC tissues. The hydrogels were cross-linked by gelatin-norbornene-boronic acid (GelNB-BA), thiolated macromers, and a 1,2-diol-containing linear synthetic polymer PHD. Controlling the thiol–norbornene cross-linking afforded tunable stiffness, whereas increasing PHD content led to hydrogels with PDAC-mimicking fast stress relaxation. In vitro studies, including proliferation, morphology, and mRNA-sequencing, showed that fast-relaxing hydrogels supported PDAC cell proliferation, epithelial–mesenchymal transition (EMT), and integrin β1 activation. Blocking integrin β1 in vitro led to upregulating EMT markers in both slow and fast-relaxing hydrogels. However, this strategy profoundly impacted tumor growth rate and reduced tumor size but did not alter metastasis patterns in an orthotopic mouse model. This suggests a need to further evaluate the antitumor effect of integrin β1 blockade.

Terpene-based amphiphilic copolymers have been designed as biobased stabilizers for waterborne latex synthesized by miniemulsion or emulsion polymerization of 1,3-diene terpene monomers. The pH-responsive P(AA-co-My) amphiphilic copolymers were synthesized by nitroxide-mediated radical copolymerization of β-myrcene (My) and acrylic acid (AA) with reactivity ratios of r_My = 0.24 ± 0.06 and r_AA = 0.05 ± 0.10. Polymerization was controlled for My-rich monomer feed ratios (f_My,0 > 0.3). Though AA NMP exhibited reasonable control, a low fraction of My (f_My,0 ≤ 0.3) produced branched structures with higher molar masses. P(AA_0.80-co-My_0.20) was the most efficient copolymer to stabilize monomodal PMy latexes (D_h ∼ 150–350 nm) synthesized by miniemulsion or emulsion polymerization. P(AA-co-My) copolymers with a higher hydrophobic PMy fraction (>35 mol %) were less efficient stabilizers. The more hydrophobic β-farnesene monomer was successfully polymerized by miniemulsion polymerization, whereas emulsion polymerization failed. The biobased waterborne latexes are pH-responsive with pH-triggered flocculation at low pH.

Chitosan (CHT) is a known piezoelectric biomacromolecule; however, its usage is limited due to rapid degradation in an aqueous system. Herein, we prepared CHT film via a solvent casting method and cross-linked in an alkaline solution. Sodium hydroxide facilitated deprotonation, leading to increased intramolecular hydrogen bonding and mechanical properties. The CHT film remained intact for 30 days in aqueous environments. A systematic study revealed a gradual increase in the output voltage from 0.9 to 1.8 V under external force (1–16 N). In addition, the CHT film showed remarkable antibacterial and anti-inflammatory activities under ultrasound stimulation and inhibition of inflammatory cytokines. The CHT films also displayed enhanced cellular proliferation and ∼5-fold faster migration of NIH3T3 cells under US stimulation. Overall, this work presents a robust, biocompatible, and wearable CHT device that can transform biomechanical energy into electrical pulses for the modulation of cell fate processes and other bioactivities.

Chitosan is one of the most abundant biopolymers on earth. It is used as a nontoxic alternative in a wide range of medicines, packaging, adhesives, and flame retardants. Chitosan is poorly soluble in neutral or alkaline solutions, but it dissolves in solutions of weak acids, such as acetic acid or citric acid, both of which occur naturally. As a replacement for formaldehyde-containing resins in engineered wood, a chitosan-acid mixture acts as a low-cost, nontoxic adhesive for natural wood that also offers fire protection by forming a char barrier. Pentaerythritol was studied as an additive due to its similarity to glycerol (a common plasticizer for chitosan) and its potential flame retardant benefit. The properties of chitosan adhesives produced with acetic acid and citric acid are compared, and moderate thermal treatment is applied to facilitate covalent bonding (e.g., Maillard reaction) that improves water resistance. Tensile shear strengths of >1 MPa are obtained on lap joints. The unique combination of fire protection and adhesion for wood makes these low cost, biobased systems very appealing.

Cerebral ischemic stroke, neuronal death, and inflammation bring difficulties in neuroprotection and rehabilitation. In this study, we developed and designed the ability of natural lactoferrin-polyethylene glycol-polyphenylalanine-baicalein nanomicelles (LF-PEG-PPhe-Bai) to target and reduce these pathological processes, such as neurological damage and cognitive impairment in the stages of poststroke. Nanomicelles made from biocompatible materials have improved bioavailability and targeted distribution to afflicted brain areas. The results showed that LF-PEG-PPhe-Bai greatly improved the antioxidation, antiapoptosis, and anti-inflammation activity in vitro. Meanwhile, LF-PEG-PPhe-Bai improved the behavioral and cognitive impairment of 2-VO model mice, protected nerve cells in the hippocampus, and reduced inflammation at the brain injury site in vivo. In conclusion, LF-PEG-PPhe-Bai nanomicelles are employed for enhancing neuroprotection and poststroke rehabilitation. The development of this technology might provide a new technique for neural repair after ischemia in the future.

Mussel byssi form a robust underwater adhesive system, anchoring to various surfaces in harsh marine environments. Central to byssus is foot protein type 4 (fp-4), a junction protein connecting collagenous threads to proteinaceous plaque. This study investigated an anionic plaque-binding domain of fp-4 (fp-4a) and its interactions with cationic foot proteins (fp-1, fp-5, and fp-151 as model substitutes for fp-2) and metal ions (Ca²⁺, Fe³⁺, and V³⁺). Aggregation, a liquid–solid phase transition, was confirmed for recombinant fp-4a (rfp-4a) with rfp-5, rfp-151, and metal ions using turbidity measurements and microscopy. Molecular cohesion forces were measured by the surface forces apparatus, while dynamic light scattering, circular dichroism spectroscopy, and chaotropic agent assay clarified the aggregation mechanisms. Collectively, we discovered that rfp-4a formed aggregates with cationic rfps through electrostatic interactions and hydrogen bonding, further stabilized by metal ion incorporation, emphasizing its critical role in mussel adhesion systems and its potential for bioadhesive applications.

The study of the phase behavior of polyelectrolyte complex coacervates has attracted significant attention in recent years due to their potential use as membrane-less organelles, microreactors, and drug delivery platforms. In this work, we investigate the mechanism of protein loading in chain-length asymmetric complex coacervates composed of a polyelectrolyte and an oppositely charged multivalent ion. Unlike the symmetric case (polycation + polyanion), we show that protein loading is highly selective based on the protein’s net charge: only proteins with charges opposite to the polyelectrolyte can be loaded. Through a series of systematic experiments, we identified that the protein loading process relies on the formation of a neutral three-component coacervate in which both the protein and the multivalent ion serve as complexing agents for the polyelectrolyte. Lastly, we demonstrated that this mechanism extends to the sequestration of other charged small molecules, offering valuable insights into designing functional multicomponent coacervates.

Herein, an eco-friendly and degradable poly(lactic acid) aerogel was prepared by combining a poly(ethylene glycol) template material with thermally induced phase separation. Due to the tailored pore size introduced by the template material, the aerogel exhibits high solar reflectance (92.0%), excellent thermal emittance (90.5%), low thermal conductivity (52.0 mW m^–1 K^–1), and high compressive strength (0.15 MPa). Cooling tests demonstrate that the aerogel can achieve temperature drops of 3.7 °C during the day and of 6.2 °C at night. Furthermore, simulations of building cooling energy systems reveal that the aerogel can reduce energy consumption by 2.2 to 10.2 MJ m^–2 per year in various cities, achieving energy savings ranging from 8.2 to 24.3%. Meanwhile, the aerogel cooler demonstrates excellent self-cleaning performance (WCA = 149.1°) and cyclic compression performance. This research will promote the field of passive radiative cooling toward a greener and more sustainable direction.

Enzymes are attractive as catalysts due to their specificity and biocompatibility; however, their use in industrial and biomedical applications is limited by stability. Here, we present a facile approach for enzyme immobilization within “all-enzyme” hydrogels by forming photochemical covalent cross-links between the enzyme glucose oxidase. We demonstrate that the mechanical properties of the enzyme hydrogel can be tuned with enzyme concentration and the data suggests that the dimeric nature of glucose oxidase results in unusual gel formation behavior which suggests a degree of forced induced dimer dissociation and unfolding. We confirm and quantify the enzyme activity of the hydrogel using the Trinder assay and a 1D modeling approach and show that 50% enzymatic activity is retained upon hydrogel formation. These observed effects may be due to the forces experienced by the individual nanoscale enzymes during mesoscale network formation. We have therefore demonstrated that photochemical cross-linking can be readily employed to produce functional all-enzyme glucose oxidase hydrogels with easily tunable mechanical properties and specific catalytic activity. This approach provides enormous potential for producing biocatalytic materials with tunable mechanical properties, responsive biological functionality and high volumetric productivity which may inform the future design of biomedical devices with enhanced sensitivity and activity.

Hemostasis is the initial step in wound healing, yet significant challenges, such as massive bleeding and infection, often arise. In this study, we developed amphiphilic biodegradable polyester-based segmented polyurethane (SPU) microspheres modified with epigallocatechin gallate (EGCG)-Ag nanoparticles and calcium-alginate cross-linking shell, combining blood absorption with the pro-coagulation properties of Ca²⁺ and the negative charge of EGCG for synergistic hemostatic effects across various stages of the coagulation cascade. The in vitro blood clotting time of the SPU@EAg@CaAlg microsphere (328.7 s) was reduced by half compared to the SPU microsphere (685.0 s). SPU@EAg@CaAlg exhibited a reduced hemostatic time and blood loss in three rat hemostatic models. Additionally, EGCG-Ag nanoparticles imparted strong antibacterial and anti-inflammatory properties both in vitro and in vivo. In vivo infected wound model demonstrated that SPU@EAg@CaAlg effectively eliminated bacteria and reduced the levels of pro-inflammatory factors, thereby promoting wound healing. Thus, the modified SPU microspheres present a promising candidate for effective hemostatic applications.

Antioxidant hydrogels that can provide a moist environment and scavenge reactive oxygen species have emerged as highly potential wound dressing materials. In situ-forming and good tissue adhesiveness will make them more desirable, as they can fill the irregular wound defect, stick to the wound, and offer intimate contact with the wound. Herein, a hydrogel dressing combining in situ-forming, good tissue adhesiveness, and excellent antioxidant capabilities was developed by simply conjugating dopamine onto carboxymethyl chitosan. The introduction of dopamine allows in situ gelation of the polymer under mild conditions using an HRP-catalyzed cross-linking reaction. The introduction of dopamine also endows the hydrogels with suitable tissue-adhesion properties. Excellent antioxidant properties were also imparted as a result of the introduction of dopamine. Thanks to the favorable moist environment provided by the hydrogel and the effectively mitigated oxidative stress at wound sites, accelerated healing and reduced scar formation were observed in a rat full-thickness skin wound model.

Injectable biomaterials play a vital role in modern medicine, offering tailored functionalities for diverse therapeutic and diagnostic applications. In ophthalmology, for instance, viscoelastic materials are crucial for procedures such as cataract surgery but often leave residues, increasing postoperative risks. This study introduces injectable fluorescent viscoelastics (FluoVs) synthesized via one-step controlled radical copolymerization of oligo(ethylene glycol) acrylate and fluorescein acrylate. These bottlebrush-shaped polymers exhibit enhanced fluorescence intensity for improved traceability and facile removal postsurgery. To prevent aggregation, charged terpolymers were synthesized, ensuring intra- and intermolecular electrostatic repulsion. Dynamic light scattering and energy-conserved dissipative particle dynamics simulations revealed how the fluorescein content and monomer sequence affect the hydrodynamic size of these copolymers. Biocompatibility assessments showed that FluoVs maintained cell viability comparable to commercial hydroxypropyl methylcellulose and nonfluorescent poly(oligo(ethylene glycol) acrylate) controls. The FluoVs combine high fluorescence intensity, low viscosity, and excellent biocompatibility, offering intraoperative traceability and significant advancements for ocular and bioimaging applications.

Polymer-based photosensitizers have found various applications in photodynamic therapy (PDT). However, the absence of targeting ability commonly results in a substantial reduction in photosensitizer accumulation at the tumor site, significantly limiting the therapeutic efficacy of the system. In addition, the development of biodegradable polymeric photosensitizers is of critical importance for biological applications. In this work, we present the development of guanidine-functionalized biodegradable photosensitizers based on poly(trimethylene carbonate) (PTMC) block copolymers, which can self-assemble into polymersomes. The presence of guanidine groups on the surface of polymersomes can significantly enhance the cellular uptake efficiency of photosensitizers, thereby improving the intracellular production of reactive oxygen species (ROS). The in vitro study demonstrates that the guanidinylated polymersome photosensitizers can promote the killing of cancer cells compared to unfunctionalized polymersomes in the presence of light irradiation. The guanidine-functionalized PTMC-based polymersome photosensitizers, with the integration of cell-targeting ability and biodegradability, are anticipated to provide a novel strategy for developing advanced biomedical polymer systems for PDT.

2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) structures possess potent antioxidant activities for biomedical applications. TEMPO immobilization on hydrophilic polymers is a powerful strategy to improve its properties; however, it is mostly limited to reversible-deactivation radical polymerizations or postpolymerization approaches. Here, we immobilized TEMPO units on a hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) backbone through cationic ring-opening polymerization (CROP) of a new 2-oxazoline monomer bearing a methoxy-protected TEMPO 2-substituent with 2-ethyl-2-oxazoline (EtOx). The ratios of EtOx/TempOx were adjusted to optimize the nitroxide content while maintaining suitable water solubility of the resulting P(EtOx_x-stat-TempOx-O_y^•) copolymers upon deprotection. P(EtOx₄₀-stat-TempOx-O₁₀^•) and P(EtOx₃₃-stat-TempOx-O₁₇^•) showed a dual stimuli-responsive behavior and demonstrated significant radical-trapping activities in aqueous media. Particularly, a meaningful augmentation in the activity of TempOx-O^• was observed when it was immobilized as P(EtOx_x-stat-TempOx-O_y^•). The P(EtOx₄₀-stat-TempOx-O₁₀^•) system exhibited a longer-lasting activity in water, statistically comparable to that of the antioxidant ferrostatin-1 (Fer-1). Overall, this study introduces a biocompatible polymeric platform for TEMPO immobilization that augments its radical-trapping activity and offers controllable stimuli-responsive properties.

Green separation of protein (e.g., bovine serum albumin (BSA)) by low-melting mixture solvents (LoMMSs) depends on the underlying mechanism between BSA and LoMMSs. Here, we for the first time find that eco-friendly biomass-derived LoMMSs could be potentially used for the efficient and green purification of BSA protein by enthalpy-driven interactions. Biomass-derived LoMMSs possess the merits of high biocompatibility, high degradability, high abundance, and low cost. A single high-affinity binding site via hydrogen bonding and van der Waals forces is observed between BSA and LoMMSs by fluorescence and thermodynamic analysis. Experimental results from circular dichroism and infrared spectra demonstrate that the addition of LoMMSs stabilizes the secondary structure of the BSA protein. This work provides a valuable indication for the design of eco-friendly and cost-effective LoMMSs for the purification of protein.

Managing uncontrolled and noncompressible bleeding presents a major challenge in emergency trauma care. Methods to halt bleeding quickly and efficiently, without applying direct pressure on the wound, have become a key focus of research. Herein, a novel fructose-modified chitosan/gelatin composite sponge has been developed, exhibiting high elasticity, low rebound pressure, and excellent cell compatibility. This material can rapidly return to its original form in around 1.5 s after being compressed by 80% upon contact with water. Additionally, experimental results from a rat liver wound model demonstrated that it exhibited a clear hemostatic effect. The hemostatic time was shortened from 204 ± 15.35 s to 53.3 ± 6.54 s, and the blood loss was reduced from 867 ± 153.15 mg to 187 ± 61.06 mg. Moreover, it can promote tissue healing by inhibiting the production of inflammatory factors including TNF-α, MCP-1, and IL-6. This material offers an effective solution for noncompressible tissue injuries.

Hydroxypropyl cellulose (HpC) forms a liquid crystalline phase and is thought to have a rod-like shape in aqueous solution. The viscoelastic behaviors of aqueous solutions of HpC samples with average molar substitution numbers (MS ∼ 3.8) and weight-average molar masses (M_w = 36–740 kg mol^–1) were examined over a wide concentration (c) range, and the results were discussed based on a concept of rod particle suspension rheology. The c and M_w dependencies of viscoelastic parameters determined in the frequency range showing flow behavior, such as the zero-shear viscosity, the average relaxation time, and the steady-state compliance in the c range for HpC molecules to fully entangle, were considered by using the number density (ν = cN_A/M_w, where N_A is the Avogadro constant), the intrinsic viscosity, and the average rod particle length of HpC molecules determined via dilute solution properties. The obtained relationships were successfully understood with the rod particle suspension rheology.

Silk fibroin (SF) hydrogels are widely used in three-dimensional (3D) cell culture and tissue repair. Despite their importance, few studies have focused on regulating their degradation and further revealing the effects of the degradation process on encapsulated cell behaviors. Herein, SF hydrogels with equivalent initial properties and different degradation rates were prepared by adjusting the ratios between the hydrogel-encapsulated normal SF microspheres (MS_N) and enzyme-loaded SF microspheres (MS_E). Further, cell experiments revealed that moderately accelerating the hydrogel degradation obviously improved the proliferation of MSCs during 7 days of culture. Slightly accelerating the hydrogel degradation promoted MSC chondrogenesis. However, too rapid of a hydrogel degradation was unfavorable for these cell behaviors. The relevant studies are expected to provide useful strategies for regulating SF hydrogel degradation and also afford new references for the development of excellent SF hydrogels and other protein-based biomaterials for cartilage regeneration.

Decoration of proteins and enzymes with well-defined polymeric structures allows precise decoration of protein surfaces, enabling controlled modulation of activity. Here, the impact of dendronization on the interaction between avidin and biotin was investigated. A series of generation 3–7 bis(2,2-hydroxymethyl)propionic acid (bis-MPA) dendrons were coupled to either biotin or avidin to yield a library of dendronized avidin and biotin structures. The thermodynamics of binding each biotinylated generation to a library of avidin conjugates was probed with isothermal titration calorimetry (ITC). Dissociation constants of high-generation biotin-dendrons (G5 and G6) with higher-generation avidin-dendron conjugates (Av-G6) increased from ∼10^–15 M (for the native structures) to ∼10^–6 M, and binding was found to be weaker than that of the Avidin-HABA complex. Avidin-G5 and Avidin-G6 were highly size-selective for biotinylated ligands; both prevented the binding of aprotinin (6.9 kDa), bovine serum albumin (BSA), and PEG₃₄₀₀ while forming fractional complexes with smaller biotinylated dendrons.

Three chondroitin sulfate (CS) analogues with predominant subtypes (A, C, and E) were prepared from engineered Escherichia coli K4 combined with regioselective sulfation. CS with the designed sulfates as the main components was characterized by nuclear magnetic resonance spectroscopy, elementary analysis, and disaccharide analysis. CS prepared from the native or degraded capsular polysaccharide had molecular weights of 1.55 × 10⁴–1.90 × 10⁴ and 5.6 × 10³–7.4 × 10³, respectively. We found that CS with dual sulfates promoted the outgrowth and survival of hippocampal neurons, whereas CS with monosulfate had an inhibitory effect. CS interacted with the nerve growth factor (NGF) and tyrosine kinase (TrkA), which activated the extracellular signal-regulated kinase (ERK) signaling pathway to modulate the outgrowth of hippocampal neurons. This work clarified the multiple effects of CS on neurite outgrowth based on nonanimal-sourced glycosaminoglycans, which would benefit efforts in discovering their novel functions and therapeutic applications.

Friction is the trigger cause for excessive exogenous adhesion, leading to the poor self-repair of the tendon. To address this problem, we developed electrospun dual-functional nanofibers with surface robust superlubricated performance and bioactive agent delivery to regulate healing balance by reducing exogenous adhesion and promoting endogenous healing. Coaxial electrospinning and our previous developed in situ robust nanocoating growth techniques were employed to create the lubricative/repairable core–shell structured nanofibrous membrane (L/R-NM). The L/R-NM shell featured a robust coating of the zwitterionic PMPC polymer for strong hydration lubrication to resist exogenous healing. The core could achieve sustained platelet-rich plasma release to promote endogenous healing. Friction tests and cell experiments confirmed L/R-NM’s prominent lubricating properties and antiadhesive performance in vitro. Rat tendon injury model evaluation indicated that L/R-NM effectively promotes high-quality tendon repair by inhibiting friction-induced exogenous adhesion and promoting endogenous healing. Therefore, we believe that L/R-NM will open a unique novel horizon for tendon repair.

Reactive oxygen species (ROS)-sensitive polymers are extensively used in cancer therapies. However, the ROS levels in the tumor microenvironment are often insufficient to trigger an adequate therapeutic response. Herein, we report a cinnamaldehyde (CA)-based ROS-responsive cationic polymer (PCA) and demonstrate its high efficiency in gene delivery and tumor cell growth inhibition. CA could be released from the polymer via a ROS-sensitive thioacetal bond by endogenous ROS. The released CA successively induced more ROS accumulation through GSH depletion, and the positive feedback helped PCA to achieve self-accelerating degradation. Results proved that PCA/p53 complexes were efficient in depleting GSH, upregulating ROS levels, and gene transfection. Besides, PCA was also shown to be effective in delivering the therapeutic gene p53. More importantly, PCA/p53 complexes could significantly induce tumor cell growth suppression by a synergistic effect of PCA and p53, providing valuable insights into the design of self-amplifying ROS-responsive polymeric gene vectors.

This study reports the preparation of cellulose nanocrystals (CNCs) from commercial bleached eucalyptus Kraft pulp (BEKP) using a hydrothermal treatment in the presence of maleic acid (MA), followed by high-pressure homogenization. Compared with conventional hydrolysis methods, this approach offers significant advantages, including lower acid concentration, higher yield, and milder processing conditions. CNCs were produced with a high yield (70–85 wt %) by high-pressure homogenization of hydrothermally treated BEKP fibers with 10–20 wt % maleic acid at 150 °C, giving rise to a stable translucent gel of CNCs with a rod-like morphology (200–400 nm length and 10–40 nm width). The reinforcing potential of the CNCs was also assessed by preparing nanocomposite films with CNC contents of up to 15 wt %, and the results were compared to commercial CNCs from CelluForce. Additionally, their biodegradability in aquatic media was assessed using biological oxygen demand, with results compared to those of neat cellulose fibers. The MA-assisted hydrothermal process is an environmentally friendly alternative to conventional CNC production methods, offering higher yields and enhanced thermal stability while preserving a strong reinforcing property.