Cellulose nanofibrils (CNFs) have been studied extensively over the past decade. Their applications, e.g., as fillers for nanocomposites, stabilizers for Pickering emulsions, and scaffolds for cell culture, are mostly dictated by interfacial adhesion. In general, the individual surface free energy values of the constituents of a material correlate with its adsorption and desorption behaviors. In the present study, we estimated the surface free energy values of thin films composed of CNFs using traditional contact angle methods based on the Wenzel equation and van Oss–Chaudhury–Good theory. The accuracy and utility of the estimated surface free energy values were verified by close matching between the obtained adhesion energy values and the actual interfacial adsorption behaviors of the CNFs. Therefore, the evaluated surface energy values are expected to be a feasible tool for designing of interfacial interactions between CNF surfaces and other materials.

Core cross-linked polymeric micelles (CCPMs) are designed to improve the therapeutic profile of hydrophobic drugs, reduce or completely avoid protein corona formation, and offer prolonged circulation times, a prerequisite for passive or active targeting. In this study, we tuned the CCPM stability by using bifunctional or trifunctional cross-linkers and varying the cross-linkable polymer block length. For CCPMs, amphiphilic thiol-reactive polypept(o)ides of polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) [pSar-b-pCys(SO2Et)] were employed. While the pCys(SO2Et) chain lengths varied from Xn = 17 to 30, bivalent (derivatives of dihydrolipoic acid) and trivalent (sarcosine/cysteine pentapeptide) cross-linkers have been applied. Asymmetrical flow field-flow fraction (AF4) displayed the absence of aggregates in human plasma, yet for non-cross-linked PM and CCPMs cross-linked with dihydrolipoic acid at [pCys(SO2Et)]17, increasing the cross-linking density or the pCys(SO2Et) chain lengths led to stable CCPMs. Interestingly, circulation time and biodistribution in mice of non-cross-linked and bivalently cross-linked CCPMs are comparable, while the trivalent peptide cross-linkers enhance the circulation half-life from 11 to 19 h.

Photo electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) has emerged as a powerful reversible-deactivation radical polymerization technique, enabling oxygen-tolerant polymerizations with exquisite spatiotemporal control through irradiation with visible light. In contrast to traditional free radical photo-polymerization, which often requires the use of DNA-damaging UV irradiation, PET-RAFT offers a more cytocompatible alternative for the preparation of polymeric materials in cell culture environments. Herein, we report the use of PET-RAFT for the fabrication of self-healing hydrogels using commercially available monomers, reaching high monomer conversions and cell encapsulation efficiencies. Our hydrogels showed the expected rheological and mechanical properties for the systems considered, together with excellent cytocompatibility and spatiotemporal control over the polymerization process. Moreover, hydrogels prepared through this method could be cut and healed again by simply adding further monomer and irradiating the system with visible light, even in the presence of mammalian cells. This study demonstrates for the first time the potential of PET-RAFT polymerization as a viable methodology for the synthesis of self-healing hydrogel scaffolds for cell encapsulation.

Oral defects lead to a series of function disorders, severely threatening the patients’ health. Although injectable hydrogels are widely studied in tissue regeneration, their mechanical performance is usually stationary after implant, without further self-adaption toward the microenvironment. Herein, an injectable hydrogel with programmed mechanical kinetics of instant gelation and gradual self-strengthening along with outstanding biodegradation ability is developed. The fast gelation is realized through rapid Schiff base reaction between biodegradable chitosan and aldehyde-modified sodium hyaluronate, while self-strengthening is achieved via slow reaction between redundant amino groups on chitosan and epoxy-modified hydroxyapatite. The resultant hydrogel also possesses multiple functions including (1) bio-adhesion, (2) self-healing, (3) bactericidal, (4) hemostasis, and (5) X-ray in situ imaging, which can be effectively used for oral jaw repair. We believe that the strategy illustrated here will provide new insights into dynamic mechanical regulation of injectable hydrogels and promote their application in tissue regeneration.

Hierarchical organization is one of the fundamental features observed in biological systems that allows for efficient and effective functioning. Virus-like particles (VLPs) are elegant examples of a hierarchically organized supramolecular structure, where many subunits are self-assembled to generate the functional cage-like architecture. Utilizing VLPs as building blocks to construct two- and three-dimensional (3D) higher-order structures is an emerging research area in developing functional biomimetic materials. VLPs derived from P22 bacteriophages can be repurposed as nanoreactors by encapsulating enzymes and modular units to build higher-order catalytic materials via several techniques. In this study, we have used coiled-coil peptide interactions to mediate the P22 interparticle assembly into a highly stable, amorphous protein macromolecular framework (PMF) material, where the assembly does not depend on the VLP morphology, a limitation observed in previously reported P22 PMF assemblies. Many encapsulated enzymes lose their optimum functionalities under the harsh conditions that are required for the P22 VLP morphology transitions. Therefore, the coiled-coil-based PMF provides a fitting and versatile platform for constructing functional higher-order catalytic materials compatible with sensitive enzymes. We have characterized the material properties of the PMF and utilized the disordered PMF to construct a biocatalytic 3D material performing single- and multistep catalysis.

To achieve osteogenesis, angiogenesis, and neurogenesis for repairing bone defects, we constructed an anisotropic microspheres–cryogel composite loaded with magnesium l-threonate (MgT). These composites were prepared by the photo-click reaction of norbornene-modified gelatin (GB) in the presence of MgT-loaded microspheres through the bidirectional freezing method. The composites possessed an anisotropic macroporous (around 100 μm) structure and sustained release of bioactive Mg2+, which facilitate vascular ingrowth. These composites could significantly promote osteogenic differentiation of bone marrow mesenchymal stem cells, tubular formation of human umbilical vein vessel endothelial cells, and neuronal differentiation in vitro. Additionally, these composites significantly promoted early vascularization and neurogenesis as well as bone regeneration in the rat femoral condyle defects. In conclusion, owing to the anisotropic macroporous microstructure and bioactive MgT, these composites could simultaneously promote bone, blood vessel, and nerve regeneration, showing great potential for bone tissue engineering.

A series of cellulose-graft-diblock bottlebrush copolymer elastomers (cellulose-graft-poly(n-butyl acrylate)-block-poly(methyl methacrylate) (Cell-g-PBA-b-PMMA)) with short side chains were synthesized via successive atom transfer radical polymerization (ATRP) to study the influence of varying compositions and lengths of the graft diblock side chains on microphase morphologies and properties. The microphase-separated morphologies from misaligned spheres to cylinders were observed by atomic force microscopy (AFM) and small-angle X-ray scattering (SAXS) measurements. These bottlebrush copolymer elastomers possessed thermal stability and enhanced mechanical properties because the PMMA outer block could self-assemble into hard microdomains, which served as physical cross-links. The viscoelastic responses of these bottlebrush copolymers within the linear viscoelastic (LVE) regime were carried out by the oscillatory shear rheology. The time–temperature superposition (tTs) principle was applied to construct the master curves of the dynamic moduli, and the sequential relaxation of dense bottlebrush copolymers with different PMMA hard outer block lengths was analyzed. The rheological behaviors in this work could be utilized to build up the connection of microstructures and properties for the application of these bottlebrush copolymers as high-performance thermoplastic elastomers.

The application of conductive hydrogels in flexible electronics has attracted much interest in recent years due to their excellent mechanical properties and conductivity. However, the development of conductive hydrogels combining with superior self-adhesion, mechanical properties, antifreeze, and antibacterial activity is still a challenge. Herein, inspired by the structure of the ligament, a multifunctional conductive hydrogel is constructed to address the issue by introducing collagen into the polyacrylamide. The obtained conductive hydrogel exhibits outstanding conductivity (52.08 mS/cm), ultra-stretchability (>2000%), self-adhesion, and antibacterial properties. More significantly, the supercapacitor based on this hydrogel electrolyte achieves a desirable capacitance (514.7 mF·cm–2 at 0.25 mA·cm–2 current density). As a wearable strain sensor, the obtained hydrogel can rapidly detect different movements of the body such as finger, wrist, elbow, and knee joints. It is conceived that this study would provide a potential approach for the preparation of conductive hydrogels in the application of flexible electronics.

Polymeric surface coatings capable of effectively integrating desired functional molecules and ligands are attractive for fabricating bio-interfaces necessary for various applications. Herein, we report the design of a polymeric platform amenable to such modifications in a modular fashion through host–guest chemistry. Copolymers containing adamantane (Ada) moieties, diethylene glycol (DEG) units, and silyloxy groups to provide functionalization handles, anti-biofouling character, and surface attachment, respectively, were synthesized. These copolymers were employed to modify silicon/glass surfaces to enable their functionalization using beta-cyclodextrin (βCD) containing functional molecules and bioactive ligands. Moreover, surface functionalization could be spatially controlled using a well-established technique like microcontact printing. Efficient and robust functionalization of polymer-coated surfaces was demonstrated by immobilizing a βCD-conjugated fluorescent rhodamine dye through the specific noncovalent binding between Ada and βCD units. Furthermore, biotin, mannose, and cell adhesive peptide-modified βCD were immobilized onto the Ada-containing polymer-coated surfaces to direct noncovalent conjugation of streptavidin, concanavalin A (ConA), and fibroblast cells, respectively. It was demonstrated that the mannose-functionalized coating could selectively bind to the target lectin ConA, and the interface could be regenerated and reused several times. Moreover, the polymeric coating was adaptable for cell attachment and proliferation upon noncovalent modification with cell-adhesive peptides. One can envision that the facile synthesis of the Ada-based copolymers, mild conditions for coating surfaces, and their effective transformation to various functional interfaces in a modular fashion offers an attractive approach to engineering functional interfaces for several biomedical applications.

Nanocellulose is emerging as a sustainable building block in materials science. Surface modification via polymer grafting has proven to be effective in tuning diverse material properties of nanocellulose, including wettability of films and the reinforcement effect in polymer matrices. Despite its widespread use in various environments, the structure of a single polymer-grafted nanocellulose remains poorly understood. Here, we investigate the morphologies of polymer-grafted CNFs at water–mica and air–mica interfaces by using all-atom molecular dynamics simulation and atomic force microscopy. We show that the morphologies of the polymer-grafted CNFs undergo a marked change in response to the surrounding environment due to variations in the conformation of the surface polymer chains. Our results provide novel insights into the molecular structure of polymer-grafted CNFs and can facilitate the design and development of innovative biomass-based nanomaterials.

Rapid and specific assaying of molecules that report on a pathophysiological condition, environmental pollution, or drug concentration is pivotal for establishing efficient and accurate diagnostic systems. One of the main components required for the construction of these systems is the recognition element (receptor) that can identify target analytes. Oligonucleotide switching structures, or aptamers, have been widely studied as selective receptors that can precisely identify targets in different analyzed matrices with minimal interference from other components in an antibody-like recognition process. These aptasensors, especially when integrated into sensing platforms, enable a multitude of sensors that can outperform antibody-based sensors in terms of flexibility of the sensing strategy and ease of deployment to areas with limited resources. Research into compounds that efficiently enhance signal transduction and provide a suitable platform for conjugating aptamers has gained huge momentum over the past decade. The multifaceted nature of conjugated polymers (CPs), notably their versatile electrical and optical properties, endows them with a broad range of potential applications in optical, electrical, and electrochemical signal transduction. Despite the substantial body of research demonstrating the enhanced performance of sensing devices using doped or nanostructure-embedded CPs, few reviews are available that specifically describe the use of conjugated polymers in aptasensing. The purpose of this review is to bridge this gap and provide a comprehensive description of a variety of CPs, from a historical viewpoint, underpinning their specific characteristics and demonstrating the advances in biosensors associated with the use of these conjugated polymers.

The development of dynamic covalent chemistry opens the way to the design of materials able to be reprocessed by an internal exchange reaction under thermal stimulus. Imine exchange differs from other exchange reactions by its relatively low temperature of activation. In this study, amine-functionalized star-shaped PEG–PLA and an aldehyde-functionalized hydroxyurethane modifier were combined to produce PEG–PLA/hydroxyurethane networks incorporating imine bonds. The thermal and mechanical properties of these new materials were evaluated as a function of the initial ratio of amine/aldehyde used during synthesis. Rheological analyses highlighted the dynamic behavior of these vitrimers at moderate temperature (60–85 °C) and provided the flow activation energies. Additionally, the reprocessability of these PEG–PLA/hydroxyurethane vitrimers was assessed by comparing the material properties before reshaping and after three reprocessing cycles (1 ton, 1 h, 70 °C). Hence, these materials can easily be designed to satisfy a specific medical application without properties loss. This work opens the way to the development of a new generation of dynamic materials combining degradable PEG–PLA copolymers and hydroxyurethane modifiers, which could find applications in the shape of medical devices on-demand under mild conditions.

Protein fouling is a critical issue in the development of electrochemical sensors for medical applications, as it can significantly impact their sensitivity, stability, and reliability. Modifying planar electrodes with conductive nanomaterials that possess a high surface area, such as carbon nanotubes (CNTs), has been shown to significantly improve fouling resistance and sensitivity. However, the inherent hydrophobicity of CNTs and their poor dispersibility in solvents pose challenges in optimizing such electrode architectures for maximum sensitivity. Fortunately, nanocellulosic materials offer an efficient and sustainable approach to achieving effective functional and hybrid nanoscale architectures by enabling stable aqueous dispersions of carbon nanomaterials. Additionally, the inherent hygroscopicity and fouling-resistant nature of nanocellulosic materials can provide superior functionalities in such composites. In this study, we evaluate the fouling behavior of two nanocellulose (NC)/multiwalled carbon nanotube (MWCNT) composite electrode systems: one using sulfated cellulose nanofibers and another using sulfated cellulose nanocrystals. We compare these composites to commercial MWCNT electrodes without nanocellulose and analyze their behavior in physiologically relevant fouling environments of varying complexity using common outer- and inner-sphere redox probes. Additionally, we use quartz crystal microgravimetry with dissipation monitoring (QCM-D) to investigate the behavior of amorphous carbon surfaces and nanocellulosic materials in fouling environments. Our results demonstrate that the NC/MWCNT composite electrodes provide significant advantages for measurement reliability, sensitivity, and selectivity over only MWCNT-based electrodes, even in complex physiological monitoring environments such as human plasma.

Tethering nanoparticles (NPs) onto the cell surface is critical to cellular hitchhiking applications, such as targeted NP delivery and enhanced cell therapy. While numerous methods have been developed to achieve NP attachment onto the cell membrane, they often face limitations such as the use of complicated cell surface modifications or low-efficiency NP attachment. The purpose of this work was to explore a DNA-based synthetic ligand–receptor pair for NP attachment to the surface of live cells. Polyvalent ligand mimics were used to functionalize NPs, while the cell membrane was functionalized with DNA-based cell receptor mimics. Base pair-directed polyvalent hybridization allowed the NPs to bind to the cells quickly and efficiently. Notably, the process of attaching NPs to cells did not require sophisticated chemical conjugation on the cell membrane or involve any cytotoxic cationic polymers. Therefore, DNA-based polyvalent ligand–receptor binding is promising to various applications ranging from cell surface engineering to NP delivery.

One-dimensional (1D) nanomaterials of conductive polypyrrole (PPy) are competitive biomaterials for constructing bioelectronics to interface with biological systems. Synergistic synthesis using lignocellulose nanofibrils (LCNF) as a structural template in chemical oxidation of pyrrole with Fe(III) ions facilitates surface-confined polymerization of pyrrole on the nanofibril surface within a submicrometer- and micrometer-scale fibril length. It yields a core–shell nanocomposite of PPy@LCNF, wherein the surface of each individual fibril is coated with a thin nanoscale layer of PPy. A highly positive surface charge originating from protonated PPy gives this 1D nanomaterial a durable aqueous dispersity. The fibril–fibril entanglement in the PPy@LCNFs facilely supported versatile downstream processing, e.g., spray thin-coating on glass, flexible membranes with robust mechanics, or three-dimensional cryogels. A high electrical conductivity in the magnitude of several to 12 S·cm–1 was confirmed for the solid-form PPy@LCNFs. The PPy@LCNFs are electroactive and show potential cycling capacity, encompassing a large capacitance. Dynamic control of the doping/undoping process by applying an electric field combines electronic and ionic conductivity through the PPy@LCNFs. The low cytotoxicity of the material is confirmed in noncontact cell culture of human dermal fibroblasts. This study underpins the promises for this nanocomposite PPy@LCNF as a smart platform nanomaterial in constructing interfacing bioelectronics.

Antibody drug conjugates (ADCs) are poised to have an enormous impact on targeted nanomedicine, especially in many cancer pathologies. The reach of the current format of ADCs is limited by their low drug-to-antibody ratio (DAR) because of the associated physiochemical instabilities. Here, we design antibody polymer conjugates (APCs) as a modular strategy to utilize polymers to address ADC’s shortcomings. We show here that conjugation of polymer-based therapeutic molecules to antibodies helps increase the DAR, owing to the hydrophilic comonomer in the polymer that helps in masking the increased hydrophobicity caused by high drug loading. We show that the platform exhibits cell targetability and selective cell killing in multiple cell lines expressing disease-relevant antigens, viz., HER2 and EGFR. The ability to use different functionalities in the drug as the handle for polymer attachment further demonstrates the platform nature of APCs. The findings here could serve as an alternative design strategy for the next generation of active targeted nanomedicine.

In this study, selective photo-oxidation (SPO) is proposed as a simple, fast, and scalable one-stop strategy that enables simultaneous self-patterning and sensitivity adjustment of ultrathin stretchable strain sensors. The SPO of an elastic substrate through irradiation time-controlled ultraviolet treatment in a confined region enables precise tuning of both the surface energy and the elastic modulus. SPO induces the hydrophilization of the substrate, thereby allowing the self-patterning of silver nanowires (AgNWs). In addition, it promotes the formation of nonpermanent microcracks of AgNWs/elastomer nanocomposites under the action of strain by increasing the elastic modulus. This effect improves sensor sensitivity by suppressing the charge transport pathway. Consequently, AgNWs are directly patterned with a width of 100 μm or less on the elastic substrate, and AgNWs/elastomer-based ultrathin and stretchable strain sensors with controlled sensitivity work reliably in various operating frequencies and cyclic stretching. Sensitivity-controlled strain sensors successfully detect both small and large movements of the human hand.

The α-helical coiled coil (CC) is one of the best-characterized folding motifs in the protein world. In this context, fluorinated amino acids have been shown to be capable of tuning the properties of CC assemblies, and especially fluorinated derivatives of aliphatic amino acids can significantly increase the stability of this folding motif when placed in the hydrophobic a and d positions. However, it has not been shown yet whether fluorinated amino acids, by means of rational design, can be used as an orthogonal tool to control CC assembly processes. In the current work, we approached this question by creating a combinatorial peptide library based on a VPE/VPK heteromeric CC system previously established and characterized in our group. This CC model allowed us to screen fluorinated amino acids for interaction with different potential binding partners in position a of the VPE/VPK model with a particular emphasis on studying the impact of stereochemistry within the side chain of α-branched aliphatic fluorinated amino acids on CC properties such as oligomerization state, thermodynamic stability, and orientation. 28 combinations of library members were characterized regarding structure, oligomerization, and thermal stability utilizing circular dichroism, size exclusion chromatography, and Förster resonance energy transfer measurements. This detailed approach showed that the stability and oligomerization state of the motif were not only dependent on the steric demand and the fluorination of corresponding amino acids but also on the stereochemistry within the side chain. The results were applied for a rational design of the fluorine-driven orthogonal assembly, and we could show that CC dimer formation occurred based on specific interactions between fluorinated amino acids. These results demonstrate the potential of fluorinated amino acids as an orthogonal tool besides classical electrostatic and hydrophobic interactions for the fine-tuning and direction of peptide–peptide interactions. Furthermore, within the space of fluorinated amino acids, we could demonstrate the specificity of interactions between differently fluorinated side chains.

Injectable hydrogels have demonstrated advantages in cartilage repair by enabling the delivery of cells through a minimally invasive approach. However, several injectable hydrogels suffer from rapid degradation and low mechanical strength. Moreover, higher mechanical stiffness in hydrogels can have a detrimental effect on post-implantation cell viability. To address these challenges, we developed an in situ forming bioinspired double network hydrogel (BDNH) that exhibits temperature-dependent stiffening after implantation. The BDNH mimics the microarchitecture of aggrecan, with hyaluronic acid-conjugated poly(N-isopropylacrylamide) providing rigidity and Schiff base crosslinked polymers serving as the ductile counterpart. BDNHs exhibited self-healing property and enhanced stiffness at physiological temperature. Excellent cell viability, long time cell proliferation, and cartilage specific matrix production were observed in the chondrocytes cultured in the BDNH hydrogel. Evidence of cartilage regeneration in a rabbit cartilage defect model using chondrocyte-laden BDNH has suggested it to be a potential candidate for cartilage tissue engineering.

Dynamic G-quadruplex supramolecular hydrogels have aroused great interest in a broad range of bioapplications. However, neither the development of native extracellular matrix (ECM)-derived natural biopolymer-functionalized G-quadruplex hydrogels nor their use to create perfusable self-supporting hydrogels has been explored to date, despite their intrinsic potential as carrier vehicles of therapeutic agents, or even living cells in advanced regenerative therapies, or as platforms to enable the diffusion of nutrients and oxygen to sustain long-term cell survival. Herein, we developed a dynamic co-assembling multicomponent system that integrates guanosine (G), 3-aminophenylboronic acid functionalized hyaluronic acid (HA-PBA), and potassium chloride to bioengineer strong, homogeneous, and transparent HA-functionalized G-quadruplex hydrogels with injectable, thermo-reversible, conductive, and self-healing properties. The supramolecular polymeric hydrogels were developed by hydrogen bonding and π–π stacking interactions between G coupled via dynamic covalent boronate ester bonds to HA-PBA and stabilized by K+ ions, as demonstrated by a combination of experiments and molecular dynamics simulations. The intrinsic instability of the self-assembled G-quadruplex structures was used to bioengineer self-supporting perfusable multicomponent hydrogels with interconnected size and shape-tunable hollow microchannels when embedded in 3D methacrylated gelatin supporting matrices. The microchannel-embedded 3D constructs have shown enhanced cell viability when compared to the bulk hydrogels, holding great promise for being use as artificial vessels for enabling the diffusion of nutrients and oxygen essential for cell survival. The proposed approach opens new avenues on the use of ECM-derived natural biopolymer-functionalized dynamic G-quadruplex hydrogels to design next-generation smart systems for being used in tissue regeneration, drug screening, or organ-on-a-chip.