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Cancer radio-immunotherapy, integrating external/internal radiation therapy with immuno-oncology treatments, emerges in the current management of cancer. A growing number of pre-clinical studies and clinical trials have recently validated the synergistic antitumor effect of radio-immunotherapy, far beyond the "abscopal effect", but it suffers from a low response rate and toxicity issues. To this end, nanomedicines with an optimized design have been introduced to improve cancer radio-immunotherapy. Specifically, these nanomedicines are elegantly prepared by incorporating tumor antigens, immuno- or radio-regulators, or biomarker-specific imaging agents into the corresponding optimized nanoformulations. Moreover, they contribute to inducing various biological effects, such as generating

Signal enhancement of magnetic resonance imaging (MRI) in the diseased region is dependent on the molecular structure of the MRI contrast agent. In this study, a macromolecular contrast agent, Branched-LAMA-DOTA-Cy5.5-Gd (BLDCGd), was prepared to target liver cancer. Due to the affinity of lactose to the Asialoglycoprotein receptor (ASGPR) over-expressed on the surface of liver cancer cells, lactose was selected as the targeting moiety in the contrast agent. A cathepsin B-sensitive tetrapeptide, GFLG, was used as a linkage moiety to construct a cross-linked macromolecular structure of the contrast agent, and the contrast agent could be degraded into fragments for clearance. A small-molecular-weight molecule, DOTA-Gd, and a fluorescent dye, Cy5.5, were conjugated to the macromolecular structure

Nanoprobes that offer both fluorescence imaging (FI) and magnetic resonance imaging (MRI) can provide supplementary information and hold synergistic advantages. However, synthesis of such dual-modality imaging probes that simultaneously exhibit tunability of functional groups, high stability, great biocompatibility and desired dual-modality imaging results remains challenging. In this study, we used an amphiphilic block polymer from (ethylene glycol) methyl ether methacrylate (OEGMA) and

Despite the extensive explorations of nanoscale metal-organic frameworks (nanoMOFs) in drug delivery, the intrinsic bioactivity of nanoMOFs, such as anticancer activity, is severely underestimated owing to the overlooked integration of the hierarchical components including nanosized MOFs and molecular-level organic ligands and metal-organic complexes. Herein, we propose a de novo design of multifunctional bioactive nanoMOFs ranging from molecular to nanoscale level, and demonstrate this proof-of-concept by a copper-olsalazine (Olsa, a clinically approved drug for inflammatory bowel disease, here as a bioactive linker and DNA hypomethylating agent) nanoMOF displaying a multifaceted anticancer mechanism: (1) Cu-Olsa nanoMOF-mediated redox dyshomeostasis for enhanced catalytic tumor therapy, (2) targeting downregulation of cyclooxygenase-2 by the organic complex of Cu

Microenvironment-responsive drug delivery systems (DDSs) can achieve targeted drug delivery, reduce drug side effects and improve drug efficacies. Among them, pH-responsive DDSs have gained popularity since the pH in the diseased tissues such as cancer, bacterial infection and inflammation differs from a physiological pH of 7.4 and this difference could be harnessed for DDSs to release encapsulated drugs specifically to these diseased tissues. A variety of synthetic approaches have been developed to prepare pH-sensitive DDSs, including introduction of a variety of pH-sensitive chemical bonds or protonated/deprotonated chemical groups. A myriad of nano DDSs have been explored to be pH-responsive, including liposomes, micelles, hydrogels, dendritic macromolecules and organic-inorganic hybrid nanoparticles, and micron level microspheres. The prodrugs from drug-loaded pH-sensitive nano DDSs have been applied in research on anticancer therapy and diagnosis of cancer, inflammation, antibacterial infection, and neurological diseases. We have systematically summarized synthesis strategies of pH-stimulating DDSs, illustrated commonly used and recently developed nanocarriers for these DDSs and covered their potential in different biomedical applications, which may spark new ideas for the development and application of pH-sensitive nano DDSs.

Targeting metabolic vulnerability of tumor cells is a promising anti-cancer strategy. However, the therapeutic efficacy of existing metabolism-regulating agents is often compromised due to tolerance resulting from tumor metabolic plasticity, as well as their poor bioavailability and tumor-targetability. Inspired by the inhibitive effect of N-ethylmaleimide on the mitochondrial function, we developed a dendronized polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating N-ethylmaleimide-modified doxorubicin (Mal-DOX) to enable improvement in the overall delivery efficiency and inhibition of the tumor metabolism via multiple pathways. We observe that Mal-DOX and its derived nanomedicine induce energy depletion of CT26 colorectal cancer cells more efficiently than doxorubicin, and shifts the balance of programmed cell death from apoptosis toward necroptosis. Notably, pOEG-b-D-SH@NP simultaneously inhibits cellular oxidative phosphorylation and glycolysis, thus potently suppressing cancer growth and peritoneal intestinal metastasis in mouse models. Overall, the study provides a promising dendronized polymer-derived nano-platform for the treatment of cancers through impairing metabolic plasticity. This article is protected by copyright. All rights reserved.

Interaction between carcinoma-associated fibroblasts (CAFs) and tumor cells leads to the invasion and metastasis of breast cancer. Herein, we prepared a redox-responsive chondroitin sulfate (CS)-based nanomedicine, in which hydrophobic cabazitaxel (CTX) was conjugated to the backbone of CS via glutathione (GSH)-sensitive dithiomaleimide (DTM) to form an amphipathic CS-DTM-CTX (CDC) conjugate, and dasatinib (DAS) co-assembled with the CDC conjugate to obtain DAS@CDC. After CD44 receptor-mediated internalization by CAFs, the nanomedicine could reverse CAFs to normal fibroblasts, blocking their crosstalk with tumor cells and reducing synthesis of major tumor extracellular matrix proteins, including collagen and fibronectin. Meanwhile, the nanomedicine internalized by tumor cells could effectively inhibit tumor proliferation and metastasis, leading to shrinkage of the tumor volume and inhibition of lung metastasis in a subcutaneous 4T1 tumor model with low side effects. Collectively, the nanomedicine showed a remarkably synergistic therapy effect against breast cancer by modulating tumor-stromal crosstalk.

The proposed photoclick HC–HN bioink expands the palette of available polysaccharide-based bioinks and greatly extends the biofabrication window to broaden the application opportunities of 3D bioprinting.

Due to their inherent and tunable biomechanical and biochemical performances, bioactive hydrogels based on polysaccharides and peptides have shown attractive potential for wound management. In this review, the recent progress of bioactive hydrogels prepared by polysaccharides and peptides for soft tissue wound management is overviewed. Meanwhile, we focus on the elaboration of the relationship between chemical structures and inherent bioactive functions of polysaccharides and peptides, as well as the strategies that are taken for achieving multiple wound repairing effects including hemostasis, adhesion, wound contraction and closure, anti-bacteria, anti-oxidation, immunomodulation, molecule delivery

Three-dimensional (3D) bioprinting has played an increasingly crucial role in the manufacturing of organized complex tissues and organs, which has shown tremendous potential in the field of tissue engineering. Extrusion-based bioprinting takes advantage of its competitive pricing and flexibility to print various biomaterials, and it has now developed into one of the most used printing techniques. However, extruding soft hydrogels, also known as bioinks, often leads to poor fidelity when printed in air. As an emerging printing approach, 3D embedded bioprinting deposits bioinks not on a platform but into a support bath, preventing constructs from settling and collapsing. This review discusses the challenges faced in the traditional 3D bioprinting of soft or low-viscosity bioinks and the changes brought by embedded bioprinting as an emerging solution. Particular focus is given to the progress of hydrogels used as bioinks and support baths. Finally, we highlight the challenges involved in this process and look forward to the prospects of this technology.

Tumor cells are dominant in the nutritional competition in the tumor microenvironment (TME), and their metabolic abnormalities often lead to microenvironmental acidosis and nutrient deprivation, thereby impairing the function of immune cells and diminishing the anti-tumor therapeutic effect. Herein, we report a branched polymeric conjugate and its efficacy in attenuating the metabolic competition of tumor cells. Compared with the control nanoparticles prepared from its linear counterpart, the branched conjugate-based nanoparticles (branched NPs) could more efficiently accumulate in the tumor tissue and interfere with the metabolic processes of tumor cells to increase the concentration of essential nutrients and reduce the level of immunosuppressive metabolites in the TME, thus creating a favorable environment for infiltrated immune cells. Its combined treatment with an immune checkpoint inhibitor (ICI) achieved an enhanced anti-tumor effect. Our work presents a promising approach for targeting the metabolic competition in the TME to enhance the chemo-immunotherapeutic effect against cancers. This article is protected by copyright. All rights reserved.

Smart materials have great potential in many biomedical applications, in which biodegradable shape memory polymers (SMPs) can be used as surgical sutures, implants, and stents. Poly(dl-lactide

Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics., Graphical abstract Image 1, Highlights • Cancer immunotherapy is an emerging antitumor approach but with drawbacks. • Polysaccharides can interact with the immune system to enhance immune response. • Polysaccharides can be applied as nano-carriers for cancer immunotherapeutics with enhanced anti-tumor efficacy. • Polysaccharide-based nanomedicines can relieve the toxic and side effect of cancer immunotherapy.

Users of wearable services are different in age, occupation, income, education, personality, values and lifestyle, which also determine their different consumption patterns. Therefore, for the trust of wearable services, the influencing factors or strength may not be the same for different users. This article starts with the resource and motivation dimensions of VALSTM model, and the clustering model and questionnaire scale for consumers of wearable services were constructed. And then the users and potential users of wearable service are clustered by an improved clustering algorithm based on adaptive chaotic particle swarm optimization. Through clustering analysis of 535 valid questionnaires, users are grouped into three types of consumers with different lifestyles, respectively named: trend-following users, fashion-leading users and economic-rational users. Finally, this paper analyzes and compares the trust subgroup models of three clusters, and draws some conclusions.

Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstract

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd3+) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer., Highlights • A cathepsin B-responsive theranostic nanomedicine (glycopolymer-PTX-DOTA-Gd) based on a branched glycopolymer was prepared. • Glycopolymer-PTX-DOTA-Gd can be specifically degradated and release drug at tumor enviornment. • Glycopolymer-PTX-DOTA-Gd enhance the contrast of magnetic resonance imaging (MRI) at tumor sites. • The nanomedicine have good biocompatibility, excellent tumor targeting and anti-tumor efficacy., Graphical abstract Cathepsin B-responsive biodegradable branched glycopolymer-based prodrug was designed and prepared as theranostic nanomedicine for cancer treatments, resulting in significantly enhanced therapeutic indexes and strengthened contrast of magnetic resonance imaging (MRI) at tumor sites.Image 1

Dendron-polymer-based nanoscale and stimuli-responsive drug delivery systems have shown great promise in tumor-targeting accumulation without significant toxicity. Here we report a dendronized polymer-doxorubicin (DOX) hybrid (DPDH) with an improved in vivo drug delivery efficiency for cancer therapy compared with a linear polymer-DOX conjugate (LPDC). The in vitro drug release profile of DOX indicates that DPDH displays pH-responsive drug release due to cleavage of hydrazone bonds since a greater amount of DOX is released at pH 5.2 at a faster rate than at pH 7.4. DPDH efficiently enters 4T1 cells and releases DOX to induce cytotoxicity and apoptosis. Owing to the dendronzied structure, DPDH has a significantly longer blood circulation time than LPDC. DPDH substantially enhances the therapeutic efficacy to suppress tumor growth in a 4T1 mammary cancer model than LPDC as well as free drug, evidenced from tumor growth inhibition, TUNEL assessment and histological analysis. Biosafety of DPDH is also confirmed from hemolysis, body weight shifts during treatment and pathological analysis. This study demonstrates the use of dendronized polymer-DOX hybrids for specific drug molecules is a promising approach for drug delivery.

Although tissue adhesives have potential advantages over traditional sutures, existing ones suffer from several limitations: slow adhesion kinetic, low mechanical strength, and poor interfacial bonding with wet biological tissues. Herein, a cooperative mussel/slug double-bioinspired hydrogel adhesive (DBHA) composed of a robust adhesive interface and a stretchable dissipative matrix is developed. The DBHA is formed by a cationic polysaccharide (chitosan), an anionic polysaccharide (carboxymethyl cellulose), and a barbell-like dendritic lysine grafted with catechol groups (G3KPCA). Compared to various commercial bio-glues and traditional adhesives, the DBHA has significantly stronger tissue adhesion and enhanced toughness both ex vivo and in vivo. Meanwhile, the DBHA exhibits fast, strong, tough, and durable adhesion to diverse ex vivo tissue surfaces with blood. The adhesion energy between the adhesive and porcine skin can reach 200-900 J m

Shape memory polymers (SMPs) have a wide range of potential applications in many fields. In particular, electrically driven SMPs have attracted increasing attention due to their unique electrical deformation behaviors. Carbon nanotubes (CNTs) are often used as SMP conductive fillers because of their excellent electrical conductivities. However, raw CNTs do not disperse into the polymer matrix well. This strictly limits their use. In this study, to improve their dispersion performance characteristics in the polymer matrix, hydroxylated multi-walled carbon nanotubes (MWCNT-OHs) were functionalized with octadecyl isocyanate (i-MWCNTs). Polyurethane with shape memory properties (SMPU) was synthesized using polycaprolactone diol (PCL-diol), hexamethylene diisocyanate (HDI), and 1,4-butanediol (BDO) at a 1:5:4 ratio. Then, electroactive shape memory composites were developed by blending SMPU with i-MWCNTs to produce SMPU/i-MWCNTs. The functionalized i-MWCNTs exhibited better dispersibility characteristics in organic solvents and SMPU composites than the MWCNT-OHs. The addition of i-MWCNTs reduced the crystallinity of SMPU without affecting the original chemical structure. In addition, the hydrogen bond index and melting temperature of the SMPU soft segment decreased significantly, and the thermal decomposition temperatures of the composites increased. The SMPU/i-MWCNT composites exhibited conductivity when the i-MWCNT content was 0.5 wt%. This conductivity increased with the i-MWCNT content. In addition, when the i-MWCNT content exceeded 1 wt%, the composite temperature could increase beyond 60°C within 140 s and the temporary structure could be restored to its initial state within 120 s using a voltage of 30 eV. Therefore, the functionalized CNTs exhibit excellent potential for use in the development of electroactive shape memory composites, which may be used in flexible electronics and other fields.

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as "eat me" signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Cancer theranostics is a new strategy for combating cancer that integrates cancer imaging and treatment through theranostic agents to provide an efficient and safe way to improve cancer prognosis. Design and synthesis of these cancer theranostic agents are crucial since these agents are required to be biocompatible, tumor-specific, imaging distinguishable and therapeutically efficacious. In this regard, several types of gadolinium (Gd)-based nanomaterials have been introduced to combine different therapeutic agents with Gd to enhance the efficacy of therapeutic agents. At the same time, the entire treatment procedure could be monitored via imaging tools due to incorporation of Gd ions, Gd chelates and Gd/other imaging probes in the theranostic agents. This review aims to overview recent advances in the Gd-based nanomaterials for cancer theranostics and perspectives for Gd nanomaterial-based cancer theranostics are provided.

The controllable synthesis and customized design of micro/nanomotors represents a highly desired paradigm in the field of intelligent nanovehicles. Exploiting asymmetrical structures and geometry-dependent propulsion are the two main strategies for achieving light-driven micro/nanomotors. However, inherent crystal-structure differences in a single colloidal motor have rarely been explored. Here, we propose the first surface-heterojunction-induced propulsion methodology for cuprous oxide (Cu2O) nanomotors, by tailoring the crystal morphology of a Cu2O crystalloid from a sphere into a truncated octahedron and preserving the controllable-index crystal facets of {100} and {111} in a single colloid. Due to the high crystallinity and distinct activity of the exposed crystal facets, a surface heterojunction between the {100} and {111} facets is formed to enhance electron-hole separation, as confirmed by density functional theory (DFT) calculations, thus endowing the truncated octahedral Cu2O nanomotors with autonomous and vigorous movement in biocompatible fuels under visible light. These Cu2O nanomotors can reach a propulsion speed in water of over two times faster than that of polycrystalline spherical motors with low crystallinity. The efficient Cu2O nanomotors offer a promising guideline not only for the synthesis of novel light-driven motors with desired structures, but also for potential applications in biocompatible environments.

Combination therapy has exhibited crucial potential in the treatment of cancers, especially in drug-resistant cancers. In this work, a novel tumor-targeted, redox dual-responsive and paclitaxel (PTX) loaded nanoparticle based on multifunctional dendrimer and lentinan was developed for combinational chemo-photodynamic therapy of PTX-resistant cancers. The nanoparticles exhibited enhanced cellular uptake and tumor penetration based on phenylboronic acid-sialic acid interactions, and had the ability to control drug release in response to intracellular high concentration of glutathione and H2O2. Specifically, light irradiation not only triggered the photodynamic effect of the nanoparticles for prominent photodynamic cytotoxicity, but also resulted in increased internalization and accelerated release of PTX into cytoplasm through the lysosome disruption, as well as the obvious damage to microtubules and actin microfilaments, for drug resistance reversal of A549/T cells. Meanwhile, PTX treatment would arrest cells in G2/M phase, thereby prolonging the period when nuclear membrane is broken down, which further facilitated photosensitizer accumulation in nuclei and improved DNA damage response. Consequently, the combination of PTX and photodynamic treatment lead to excellent antitumor effects to drug-resistant A549/T cells in vitro and in vivo, which provides a new strategy for the design of co-delivery system to overcome drug resistance.

A hypoxic environment in tumors hampers the therapeutic efficacy of radiotherapy. Moreover, radiotherapy, a localized treatment technique, can barely control tumor metastases. Herein, poly(lactic-co-glycolic acid) was used to encapsulate perfluorocarbon (PFC) for increasing the oxygen level and a lignan-derived compound (Q1) for enhancing IL-25 secretion from fibroblasts, thereby boosting the radiotherapeutic effect on local and distant tumors. The prepared co-delivery nanoplatform, PFC-Q1@PLGA, has a nano-scale size of around 160 nm and a negative zeta potential (about -13 mV). PFC-Q1@PLGA treatment leads to an arrest of the G2 phase (4n) in the cell cycle and reduces the mitochondria membrane potential. A high expression level of IL-25 in fibroblasts is detected after the cells are treated with PFC-Q1@PLGA, which increases the late apoptosis percentage of 4T1 cells after treatment with IL-25-containing conditional medium from fibroblasts. The oxygen level in tumors is significantly promoted to about 52.3% after injection of oxygen-saturated PFC-Q1@PLGA (O2), which is confirmed from the functional magnetic resonance images of the tumor site in mice. The in vivo study demonstrates that the injection of PFC-Q1@PLGA (O2) into local tumors significantly enhances the radiotherapeutic effect on local tumors and also inhibits the growth of remote tumors by an enhanced abscopal effect. This study presents a novel radiotherapy strategy to enable synergistic whole-body therapeutic responses after localized treatment with PFC-Q1@PLGA (O2).

The architecture of multivalent polymers exerts an amplified interaction between attached ligands and targets. In current research, we reveal that a dendronized polymer augments the efficacy of an oncolytic peptide (OP; KKWWKKWDipK) for immunotherapy by exploiting (i) "flexible" linear polymer backbone to facilitate interactions with biomembrane systems, and (ii) "rigid" dendronized side chains to enhance the membrane lytic property. We show that a dendronized N-(2-hydroxypropyl)methacrylamide (HPMA) polymer-OP conjugate (PDOP) adopts α-helix secondary structure and induces robust immunogenic cell death (ICD) in cancer cells as characterized by multiple damage-associated molecular patterns (DAMPs) which include intracellular formation of reactive oxygen species (ROS) and surface exposure of calreticulin (CRT). These events convert immunosuppressive 4T1 tumor to an immunoresponsive one by recruiting CD8+ cytotoxic T cells into tumor beds. Combination of PDOP with anti-PD-L1 immune checkpoint blockade (ICB) increases the number of effector memory T cells and completely eradicates 4T1 tumors in mice. Our findings suggest that PDOP is a promising platform for oncolytic immunotherapy.

The development of natural polymer-based hydrogels, combining outstanding injectability, self-healing, and tissue adhesion, with mechanical performance, able to facilitate full-thickness skin wound healing, remains challenging. We have developed an injectable micellar hydrogel (AF127/HA-ADH/OHA-Dop) with outstanding adhesive and self-healing properties able to accelerate full-thickness skin wound healing. Dopamine-functionalized oxidized hyaluronic acid (OHA-Dop), adipic acid dihydrazide-modified HA (HA-ADH), and aldehyde-terminated Pluronic F127 (AF127) were employed as polymer backbones. They were cross-linked in situ using Schiff base dynamic covalent bonds (AF127 micelle/HA-ADH network and HA-ADH/OHA-Dop network), hydrogen bonding, and π-π stacking interactions. The resulting multicross-linked double-network design forms a micellar hydrogel. The unique multicross-linked double-network structure endows the hydrogel with both improved injection abilities and mechanical performance while self-healing faster than single-network hydrogels. Inspired by mussel foot adhesive protein, OHA-Dop mimics the catechol groups seen in mussel proteins, endowing hydrogels with robust adhesion properties. We also demonstrate the potential of our hydrogels to accelerate full-thickness cutaneous wound closure and improve skin regeneration with reduced scarring. We anticipate that our hydrogel platform based on a novel multicross-linked double-network design will transform the future development of multifunctional wound dressings.

Background Recent interest in Populus as a source of renewable energy, combined with its numerous available pretreatment methods, has enabled further research on structural modification and hydrolysis. To improve the biodegradation efficiency of biomass, a better understanding of the relationship between its macroscopic structures and enzymatic process is important. Results This study investigated mutant cell wall structures compared with wild type on a molecular level. Furthermore, a novel insight into the structural dynamics occurring on mutant biomass was assessed in situ and in real time by functional Atomic Force Microscopy (AFM) imaging. High-resolution AFM images confirmed that genetic pretreatment effectively inhibited the production of irregular lignin. The average roughness values of the wild type are 78, 60, and 30 nm which are much higher than that of the mutant cell wall, approximately 10 nm. It is shown that the action of endoglucanases would expose pure crystalline cellulose with more cracks for easier hydrolysis by cellobiohydrolase I (CBHI). Throughout the entire CBHI hydrolytic process, when the average roughness exceeded 3 nm, the hydrolysis mode consisted of a peeling action. Conclusion Functional AFM imaging is helpful for biomass structural characterization. In addition, the visualization of the enzymatic hydrolysis process will be useful to explore the cell wall structure–activity relationships.

3D bioprinting has been developed as a promising technology in a wide variety of biomedical applications. However, the successful implementation of bioprinting is still heavily restricted by the relatively narrow range of printable and biocompatible materials. Recently, many comprehensive reviews of the main bioprinting methods, commonly used bioprinting materials and the trending bioprinting applications have been carried out. In this review, we focused on the trends in the development of materials for 3D bioprinting. The significance and recent advances of ECM-based materials, multi-material and stimuli-responsive materials for bioprinting were summarized successively. Moreover, the challenges in current studies and future perspectives of materials for 3D bioprinting were discussed.

Multiple sclerosis (MS) is a neurological disorder characterized by loss of the myelin sheath. Since the myelin sheath could insulate nerve fibers from the surrounding environment, its loss would result in dysfunction of the affected neurons in transmitting electrical signals, thus leading to sensation and motor disabilities. The treatment of MS is accompanied by a low treatment efficacy due to the existence of the blood-brain barrier (BBB) and occurrence of side effects due to a poor targeting efficacy. To overcome these obstacles of traditional MS treatment methods, nanomedicines have recently been employed to deliver MS therapeutic agents to the lesions. With deep BBB penetration and specific targeting, these nano-based interventions have received positively encouraging results and become another potential MS treatment method with better therapeutic outcomes. This review will focus on recent advances in nanomedicines for the treatment of MS by critically analyzing their strengths and weaknesses. We will propose perspectives on the development of these MS therapeutic nanomaterials.

Product characteristics of wearable devices have large impacts on users’ initial trust as users intend to adopt wearable devices, which further impacts wearable devices' use intention. This paper a...

In recent years, with the emergence of various kinds of drug-resistant bacteria, existing antibiotics have become inefficient in killing these bacteria, and the formation of biofilms has further weakened the therapeutic effect. More problematically, the massive use and abuse of antibiotics have caused severe side effects. Thus, the development of ultra-efficient and safe antibacterial systems is urgently needed. Herein, a photodynamic therapy (PDT)-driven CO-controlled delivery system (Ce6&CO@FADP) is developed for synergistic antibacterial and ablation biofilms. Ce6&CO@FADP is constructed using a fluorinated amphiphilic dendritic peptide (FADP) and physically loaded with Ce6 and CORM-401. After efficiently entering the bacteria, Ce6&CO@FADP can rapidly release CO intracellularly by the massive consumption of the H2O2 generated during the PDT process, without affecting the generation of singlet oxygen (1O2). As such, the combination of CO and 1O2 exerts notable synergistic antibacterial and biofilm ablation effects both in vitro and in vivo (including subcutaneous bacterial infection and biofilm catheter models) experiments. More importantly, all biosafety assessments suggest the good biocompatibility of Ce6&CO@FADP. Together, these results reveal that Ce6&CO@FADP is an efficient and safe antibacterial system, which has essential application prospects for the treatment of bacterial infections and ablation of biofilms in vivo.

Corneal blindness is a common phenomenon, and corneal transplantation is an effective treatment for corneal defects. However, there is usually a mismatch between the corneal repair material and the degree of the patient’s corneal defect. Therefore, patients with different corneal defects need suitable corneal repair materials with a specific microstructure for personalized treatment. In this research, collagen films with bionic structures were fabricated through ethanol evaporation technique by regulating the volume ratios of collagen solution: ethanol = 10:0(Col)/9:1(CC91)/8:2(CC82)/CC73(CC73). Under various preparation conditions, the obtained collagen films contain layered structures of different density. SEM photos show that the CC73 film with a dense layer arrangement has a microstructure similar to that of the corneal epithelial layer, whereas the Col film has a loose layered structure similar to that of the corneal stroma layer. Four kinds of collagen films showed different optical properties and water absorption ability. A more ordered arrangement of internal layer structure leads to better mechanical properties of the collagen film. In view of this, we think that these collagen films with different microstructures and different interlayer spacing may have huge potential applications for personalized corneal repair.

Rapid development of stimuli-responsive drug delivery systems (DDSs) for tumor therapy has raised increasing interest in recent decades, and many nanomedicines are prepared to achieve accurate or sustained drug release. However, the fabrication process for these nanomedicines has been far too intricate and their potential biosafety has not been fully understood, which has hampered their clinical translation. Challenges for developing DDSs remain on balancing the complexity of the fabrication process with their translational feasibility. Owing to water-solubility, biocompatibility, biodegradability and CD44-targetability, hyaluronic acid (HA) as a versatile building block has gained great popularity due to a simplified fabrication process and unique characteristics of HA for DDSs. In this review, we overviewed the biological function and multiple chemical modifications of HA, and discussed the fabrication of HA-based drug delivery systems (HA-DDSs) with specific tumor microenvironmental stimuli-responsive linkers. We systemically surveyed the applications of HA-DDSs for chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, gene delivery and combination therapy.

Combination therapy is a promising approach for effective treatment of tumors through synergistically regulating pathways. However, the synergistic effect is limited, likely by uncontrolled co-delivery of different therapeutic payloads in a single nanoparticle. Herein, a combination nanotherapeutic is developed by using two amphiphilic conjugates, hyperbranched poly(ethylene glycol)-pyropheophorbide-a (Ppa) (HP-P) and hyperbranched poly(ethylene glycol)-doxorubicin (DOX) (HP-D) to construct co-assembly nanoparticles (HP-PD NPs) for controllably co-loading and co-delivering Ppa and DOX. In vitro and in vivo antitumor studies confirm the synergistic effect of photodynamic therapy and chemotherapy from HP-PD NPs. Metabolic variations reveal that tumor suppression is associated with disruption of metabolic homeostasis, leading to reduced protein translation. This study uncovers the manipulation of metabolic changes in tumor cells through disruption of cellular homeostasis using HP-PD NPs and provides a new insight into the rational design of synergistic nanotherapeutics for combination therapy.