The role of FERMT2 in the tumor microenvironment and immunotherapy in pan-cancer using comprehensive single-cell and bulk sequencing.

FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.

Zinc hybrid polyester barrier membrane accelerates guided tissue regeneration.

Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.

Copper Nanodrugs by Atom Transfer Radical Polymerization.

In this study, some copper catalysts used for atom transfer radical polymerization (ATRP) were explored as efficient anti-tumor agents. The aqueous solution of copper-containing nanoparticles with uniform spheric morphology was in situ prepared through a copper-catalyzed activator generated by electron transfer (AGET) ATRP in water. Nanoparticles were then directly injected into tumor-bearing mice for antitumor chemotherapy. The copper nanodrugs had prolonged blood circulation time and enhanced accumulation at tumor sites, thus showing potent antitumor activity. This work provides a novel strategy for precise and large-scale preparation of copper nanodrugs with high antitumor activity.

Click-based injectable bioactive PEG-hydrogels guide rapid craniomaxillofacial bone regeneration by the spatiotemporal delivery of rhBMP-2.

Craniomaxillofacial bone defects result in physical and psychological dual injuries making the promotion or acceleration of bone regeneration imperative. In this work, a fully biodegradable hydrogel is facilely prepared via thiol-ene "click" reactions under human physiological conditions using multifunctional poly(ethylene glycol) (PEG) derivatives as precursors. This hydrogel shows excellent biological compatibility, enough mechanical strength, a low swelling rate and an appropriate degradation rate. Rat bone marrow mesenchymal stem cells (rBMSCs) can survive and proliferate on/in the PEG hydrogel and differentiate into osteogenic cells. The PEG hydrogel can also effectively load rhBMP-2 through the above "click" reaction. Under the physical barrier of the chemically crosslinked hydrogel network, the spatiotemporal release of rhBMP-2 effectively promotes the proliferation and osteogenic differentiation of rBMSCs at a loading concentration of 1 µg ml-1. Finally, based on a rat calvarial critical-size defect model, the rhBMP-2 immobilized hydrogel loaded with rBMSCs basically accomplishes the repair and regeneration within 4 weeks featured by remarkably enhanced osteogenesis and angiogenesis. The click-based injectable bioactive PEG hydrogel developed in the present study is a new type of bone substitute with great expectations in future clinical applications.

Catalytic Amounts of an Antibacterial Monomer Enable the Upcycling of Poly(Ethylene Terephthalate) Waste.

Poly(ethylene terephthalate) (PET) is an important polymer with an annual output second only to polyethylene. The development of PET recycling technologies is therefore necessary to not only eliminate the harm associated with white pollution and microplastics, but also to reduce carbon emissions. Antibacterial PET, one of the most high-value advanced materials, has improved the ability to treat bacterial infections. However, current methods of manufacturing commercial antibacterial PET require blending with an excess of metal-based antibacterial agents, which leads to biotoxicity and a nonpersistent antibacterial activity. In addition, high-efficiency organic antibacterial agents have yet to be employed in antibacterial PET due to their poor thermal stabilities. Herein, a solid-state reaction for the upcycling of PET waste using a novel hyperthermostable antibacterial monomer is described. This reaction is catalyzed by the residual catalyst present in the PET waste. It is found that a catalytic amount of the antibacterial monomer enabled the low-cost upcycling of PET waste to produce high-value recycled PET with a strong and persistent antibacterial activity, as well as similar thermal properties to the virgin PET. This work provides a feasible and economic strategy for the large-scale upcycling of PET waste and exhibits potential for application in the polymer industry.

Construction of an antibacterial low-defect hybrid layer by facile PEI electrostatic assembly promotes dentin bonding.

Dentin bonding is the most common form of human tissue repair among tissue-biomaterial adhesions, concerning billions of people's oral health worldwide. However, insufficient adhesive infiltration in the demineralized dentin matrix (DDM) always produces numerous defects in the bonding interface termed the hybrid layer, which causes high levels of bacteria-related secondary dental diseases, and less than 50% of the bonding lasts more than 5 years. Therefore, it is urgent and vital to construct an antibacterial low-defect hybrid layer to solve the durability-related problems. A DDM with a hydrogel-like surface formed by the hydration of highly-anionic non-collagenous proteins (NCPs) is firstly used as a template to electrostatically assemble polyethyleneimine (PEI). The formation of a stable antibacterial polyelectrolyte complex of PEI/NCPs rapidly eliminates NCP hydration capacity and significantly improves the infiltration of various adhesives. Simultaneously, both the PEI during the assembly and the PEI-assembled DDM can directly destroy a biofilm of S. Mutans on the DDM. Consequently, a long-term antibacterial and low-defect hybrid layer is successfully created, which greatly improves the bonding effectiveness. This helps to improve the clinical treatment of bacteria-based dental diseases and the tooth-restoration repair effect and prevent secondary dental diseases, having significance in clinical dentistry and providing insights for other tissue-biomaterial adhesions.

Reduction-Responsive Anticancer Nanodrug Using a Full Poly(ethylene glycol) Carrier.

Poly(ethylene glycol) (PEG) is applied extensively in biomedical fields because of its nontoxic, nonimmunogenic, and protein resistance properties. However, the strong hydrophilicity of PEG prevents it from self-assembling into an amphiphilic micelle in water, making it a challenge to fabricate a full-PEG carrier to deliver hydrophobic anticancer drugs. Herein, a paclitaxel (PTX)-loaded nanodrug was readily prepared through self-assembly of PTX and an amphiphilic PEG derivative, which was synthesized via melt polycondensation of two PEG diols (i.e., PEG200 and PEG10k) and mercaptosuccinic acid. The full PEG component endows the nanocarrier with good biocompatibility. Furthermore, because of the core cross-linked structure via the oxidation of mercapto groups, the nanodrug can be selectively disassociated under an intratumor reductive microenvironment through the reduction of disulfide bonds to release the loaded PTX and kill the cancer cells while maintaining high stability under the extratumor physiological condition. Additionally, it was confirmed that the nanodrug not only prolongs the biocirculation time of PTX but also possesses excellent in vivo antitumor efficacy while avoiding side effects of free PTX, for example, liver damage, which is promising for delivering clinical hydrophobic drugs to treat a variety of malignant tumors.

A simple hydrogel scaffold with injectability, adhesivity and osteogenic activity for bone regeneration.

Numerous efforts have been made to prepare hydrogels with injectability, adhesivity and osteogenic activity for bone regeneration. However, current hydrogels with these characteristics have limited application in clinical translation due to their complex chemical compositions, which causes difficulty in batch production. In this study, a multifunctional hydrogel with a binary component is prepared for bone regeneration. Dopamine (DA) is first grafted to alginate (Alg) by amidation reaction to give Alg-DA. Then an injectable hydrogel is facilely prepared by mixing strontium ions with the Alg-DA aqueous solution, utilizing the dynamic ionic bonds between the strontium ions and carboxyl groups of Alg-DA. Under the simulated oxidation conditions in vivo, the injectable hydrogel can form stable chemical crosslinkages owing to the presence of catechol groups on Alg-DA. In addition, the catechol groups endow the hydrogel with significant tissue adhesivity. More importantly, the strontium ions endow the hydrogel with osteogenic activity. As indicated by animal experiments, the strontium containing hydrogel scaffolds help to treat rat bone defects within 8 weeks compared to hydrogels without strontium and control groups. This simple hydrogel constructed by using a binary component has achieved several necessary functions, and is expected to be used as a scaffold for bone tissue engineering in clinical applications.

Full Poly(ethylene glycol) Hydrogels with High Ductility and Self-Recoverability.

Energy dissipation is a common mechanism to improve the ductility of polymeric hydrogels. However, for poly(ethylene glycol) (PEG) hydrogels, it is not easy to dissipate energy, as polymer chains are dispersed in water without strong interchain interactions or decent entanglement. The brittleness limits the real applications of PEG hydrogels, although they are promising candidates in biomedical fields, as PEG has been approved by the U.S. Food and Drug Administration. Herein, we chemically introduced a center for energy dissipation in the PEG hydrogel system. Amphiphilic segmented PEG derivatives were designed through the melt polycondensation of triethylene glycol (PEG150) and high molecular weight PEG in the presence of succinic acid and mercaptosuccinic acid as dicarboxylic acids. Full PEG hydrogels with elastic nanospheres as giant cross-linkers were facilely prepared by the self-assembly of esterified PEG150 segments and the oxidation of mercapto groups. The resultant full PEG hydrogels can dissipate energy by the deformation of elastic nanospheres with outstanding ductility and self-recoverability while maintaining the excellent biocompatibility owing to their full PEG components. This work provides an original strategy to fabricate full PEG hydrogels with high ductility and self-recoverability, potentially applicable in biomedical fields.

A biodegradable CO2-based polymeric antitumor nanodrug via a one-pot surfactant- and solvent-free miniemulsion preparation.

In the present study, low molecular weight poly(propylene carbonate) (PPC, Mn = 3500), a biodegradable liquid polymer easily prepared from carbon dioxide (CO2), was modified into poly(propylene carbonate)diacrylate (PPC-DA) by acylation, and methoxy poly(ethylene glycol) (mPEG) was modified into methoxy poly(ethylene glycol) acrylate (mPEG-A). Using PPC-DA as the dispersant to dissolve hydrophobic doxorubicin (DOX) and the initiator, and with mPEG-A as the co-monomer and polymerisable surfactant, a biodegradable nanodrug with excellent biocompatibility was prepared by shear emulsification polymerization without surfactants or organic solvent residues. The nanodrug can be efficiently endocytosed by tumor cells and can rapidly release doxorubicin triggered by the acidic endosomal pH. As evidenced by experiments in tumor-bearing mice, such a nanodrug is stealthy during blood circulation, and targets tumor sites with high efficiency. Moreover, this nanodrug is more effective and less toxic than free doxorubicin. This study provides a green and versatile approach for preparing biodegradable nanodrugs via a simple and efficient process. Moreover, this study extends the applications of CO2 based polymers in the biomedical field, promoting the development of CO2 polymerization fixation.

A shear-thinning electrostatic hydrogel with antibacterial activity by nanoengineering of polyelectrolytes.

Injectable shear-thinning hydrogels can be prepared by the non-covalent interactions between hydrophilic polymers. Although electrostatic force is a typical non-covalent interaction, direct mixing of two oppositely charged polyelectrolytes usually leads to a complex coacervate rather than an injectable hydrogel. Herein, a facile approach is proposed to prepare a shear-thinning hydrogel by nanoengineering of polyelectrolytes. Nanosized cationic micelles with electroneutral shells were prepared by mixing methoxyl poly(ethylene glycol)-block-poly(ε-caprolactone) and poly(ε-caprolactone)-block-poly(hexamethylene guanidine) hydrochloride-block-poly(ε-caprolactone) in an aqueous solution. When sodium carboxymethyl cellulose was added into the micellar solution, the outer poly(ethylene glycol) shell of mixed micelles prevented the instant electrostatic interaction between poly(hexamethylene guanidine) hydrochloride segments and sodium carboxymethyl cellulose, resulting in a homogenous shear-thinning electrostatic (STES) hydrogel. Because of the cationic poly(hexamethylene guanidine) hydrochloride segments, this hydrogel exhibits strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, the poly(ε-caprolactone) core of the mixed micelles can efficiently encapsulate a hydrophobic drug. In this work, curcumin-loaded STES hydrogel prepared by this method was used as wound dressing material that can promote wound healing even in infected wounds by further reducing bacterial infection via releasing curcumin. The present study provides a facile strategy to prepare shear-thinning antibacterial hydrogels from polyelectrolytes, which has great potential in biomedical application.

Facile and Versatile Modification of Cotton Fibers for Persistent Antibacterial Activity and Enhanced Hygroscopicity.

Natural fibers with functionalities have attracted considerable attention. However, developing facile and versatile strategies to modify natural fibers is still a challenge. In this study, cotton fibers, the most widely used natural fibers, were partially oxidized by sodium periodate in aqueous solution, to give oxidized cotton fibers containing multiple aldehyde groups on their surface. Then poly(hexamethylene guanidine) was chemically grafted onto the oxidized cotton fibers forming Schiff bases between the terminal amines of poly(hexamethylene guanidine) and the aldehyde groups of oxidized cotton fibers. Finally, carbon-nitrogen double bonds were reduced by sodium cyanoborohydride, to bound poly(hexamethylene guanidine) covalently to the surface of cotton fibers. These functionalized fibers show strong and persistent antibacterial activity: complete inhibition against Escherichia coli and Staphylococcus aureus was maintained even after 1000 consecutive washing in distilled water. On the other hand, cotton fibers with only physically adsorbed poly(hexamethylene guanidine) lost their antibacterial activity entirely after a few washes. According to Cell Counting Kit-8 assay and hemolytic analysis, toxicity did not significantly increase after chemical modification. Attributing to the hydrophilicity of poly(hexamethylene guanidine) coatings, the modified cotton fibers were also more hygroscopic compared to untreated cotton fibers, which can improve the comfort of the fabrics made of modified cotton fibers. This study provides a facile and versatile strategy to prepare modified polysaccharide natural fibers with durable antibacterial activity, biosecurity, and comfortable touch.

Protection of opening lids: very high catalytic activity of lipase immobilized on core-shell nanoparticles.

Various hydrophobic supports have been used for lipase immobilization since the active site of lipase can be opened in a hydrophobic environment. Nevertheless, the increase of lipase activity is still limited. This study demonstrates a hyperactivation-protection strategy of lipase after immobilization on poly(n-butyl acrylate)-polyaldehyde dextran (PBA-PAD) core-shell nanoparticles. The inner hydrophobic PBA domain helps to rearrange lipase conformation to a more active form after immobilization into the PAD shell. More importantly, the outer PAD shell with dense polysaccharide chains prevents the immobilized lipase from contact with outside aqueous medium and revert its conformation back to an inactive form. As a result, under optimal conditions the activity of lipase immobilized in PBA-PAD nanoparticles was enhanced 40 times over the free one, much higher than in any previous report. Furthermore, the immobilized lipase retained more than 80 % of its activity after 10 reaction cycles.

Phase separation behavior of poly(methyl methacrylate)/poly(styrene-co-maleic anhydride) in the presence of hollow silica nanotubes.

The phase separation behavior of poly(methyl methacrylate) (PMMA)/poly(styrene-co-maleic anhydride) (SMA) blends with and without one-dimensional hollow silica nanotubes (HSNTs) was investigated using time-resolved small-angle laser light scattering. During isothermal annealing over a range of 100 °C above the glass transition temperature, the Arrhenius equation is applicable to describe the temperature dependence of phase separation behavior at the early and late stages of spinodal decomposition (SD) for unfilled and filled PMMA/SMA systems. The mechanical barrier effect of HSNTs on the macromolecular chain diffusion of the blend matrix may retard the concentration fluctuation at the early stage and slow down the domain coarsening at the late stage of SD phase separation for the blend matrix to result in the decrease of apparent diffusion coefficient D app, the postponement of the relaxation time and the decline of temperature sensitivity for the phase separation rate.

An injectable drug-loaded hydrogel based on a supramolecular polymeric prodrug.

We reported a novel injectable doxorubicin-loaded hydrogel based on host-guest interaction and Schiff's base reaction. A supramolecular polymeric prodrug was prepared through the inclusion of adamantane-modified doxorubicin into the ß-cyclodextrin cavity on the polyaldehyde dextran chain, which was in situ crosslinked by carboxymethyl chitosan.

Topography-dependent antibacterial, osteogenic and anti-aging properties of pure titanium.

After nearly half a century of development under the guidance of the osseointegration theory, the major dilemmas for current implant dentistry are the implant associated infection and insufficient osseointegration. Moreover, biological aging of titanium (Ti) implants also brings great uncertainty to clinical results. In the present study, a novel nano-micro-hierarchical topography pattern is created by sandblasting and dual acid-etching on a Ti surface. The physico-chemical properties of the surfaces were characterized by scanning electron microscopy, contact angle measurement, X-ray photoelectron spectroscopy and X-ray diffraction. The effects of the hierarchical surfaces on osteoprogenitor cell growth and bacterial activities were separately evaluated. The optimized nano-micro-hierarchical Ti surface exhibits surprisingly topography-dependent antibacterial capacity via inhibiting bacterial adhesion of several species in the early stage and better osteogenesis ability than the microscaled surface. Aging studies demonstrate that, compared with the surface with a microscale structure, the nano-micro-hierarchical Ti surface has greater anti-aging ability manifested as being more capable to retain hydrophilicity and bioactivity during aging. Furthermore, the present study reveals that the biological aging of the Ti implant is attributed to two decisive factors during the aging period: the progressively thickened amorphous TiO2 layer by autoxidation and the unavoidable accumulation of hydrocarbons on the Ti implant surface.

Reduction-triggered release of paclitaxel from in situ formed biodegradable core-cross-linked micelles.

Paclitaxel-loaded reduction-responsive core-crosslinked micelles were prepared in situ in aqueous media via"click" chemistry. An amphiphilic block copolymer with multiple pendant azide groups was first synthesized through the controlled ring-opening copolymerization of ε-caprolactone (CL) and 5,5-dibromomethyl trimethylene carbonate (DBTC) in the presence of methoxy poly(ethylene glycol) (mPEG) as a macroinitiator, followed by azidation. This amphiphilic block copolymer could self-assemble into micelles and paclitaxel (PTX) could be encapsulated into the micellar core to form PTX-loaded micelles, which were core-crosslinked in situ by propargyl dithiopropionate via"click" chemistry, to develop a reduction-responsive polymeric drug delivery system. The in vitro release studies revealed the minimized release of PTX under physiological conditions, whereas a burst release of PTX was observed in response to reductive conditions. The core-crosslinked micelles displayed efficient cell-uptake and reduction-responsive drug release due to the nanoscale diameter and splitting of disulfide bonds under a reductive environment, which was confirmed by confocal laser scanning microscopy using Nile red as a fluorescent probe. This kind of polymeric nano-carrier with excellent biocompatibility and quick reduction-response opens a new avenue to intracellular anticancer drug delivery.

The construction of hierarchical structure on Ti substrate with superior osteogenic activity and intrinsic antibacterial capability.

The deficient osseointegration and implant-associated infections are pivotal issues for the long-term clinical success of endosteal Ti implants, while development of functional surfaces that can simultaneously overcome these problems remains highly challenging. This study aimed to fabricate sophisticated Ti implant surface with both osteogenic inducing activity and inherent antibacterial ability simply via tailoring surface topographical features. Micro/submciro/nano-scale structure was constructed on Ti by three cumulative subtractive methods, including sequentially conducted sandblasting as well as primary and secondary acid etching treatment. Topographical features of this hierarchical structure can be well tuned by the time of the secondary acid treatment. Ti substrate with mere micro/submicro-scale structure (MS0-Ti) served as a control to examine the influence of hierarchical structures on surface properties and biological activities. Surface analysis indicated that all hierarchically structured surfaces possessed exactly the same surface chemistry as that of MS0-Ti, and all of them showed super-amphiphilicity, high surface free energy, and high protein adsorption capability. Biological evaluations revealed surprisingly antibacterial ability and excellent osteogenic activity for samples with optimized hierarchical structure (MS30-Ti) when compared with MS0-Ti. Consequently, for the first time, a hierarchically structured Ti surface with topography-induced inherent antibacterial capability and excellent osteogenic activity was constructed.

Cooperative, reversible self-assembly of covalently pre-linked proteins into giant fibrous structures.

We demonstrate a simple bioconjugate polymer system that undergoes reversible self-assembling into extended fibrous structures, reminiscent of those observed in living systems. It is comprised of green fluorescent protein (GFP) molecules linked into linear oligomeric strands through click step growth polymerization with dialkyne poly(ethylene oxide) (PEO). Confocal microscopy, atomic force microscopy, and dynamic light scattering revealed that such strands form high persistence length fibers, with lengths reaching tens of micrometers, and uniform, sub-100 nm widths. We ascribe this remarkable and robust form of self-assembly to the cooperativity arising from the known tendency of GFP molecules to dimerize through localized hydrophobic patches and from their covalent pre-linking with flexible PEO. Dissipative particle dynamics simulations of a coarse-grained model of the system revealed its tendency to form elongated fibrous aggregates, suggesting the general nature of this mode of self-assembly.

Acid-triggered drug release from micelles based on amphiphilic oligo(ethylene glycol)-doxorubicin alternative copolymers.

We report a facile strategy to synthesize pH-sensitive amphiphilic oligo(ethylene glycol) (OEG)-doxorubicin (DOX) alternative conjugates. Poly[oligo(ethylene glycol) malicate] (POEGM) with numerous pendent hydroxyl groups was first synthesized by the direct polycondensation of oligo(ethylene glycol) (OEG) with malic acid under mild conditions. Then, benzaldehyde groups were introduced into the POEGM backbone via esterification between the pendant hydroxyl groups and 4-formylbenzoic acid. DOX moieties were finally attached to the polymeric backbone via benzoic imine linkages to obtain the OEG-DOX conjugates. Because of the high molecular weight and alternate architecture, this type of amphiphilic OEG-DOX alternative conjugates can form stable micelles in aqueous solution with a high DOX loading content (38.2 wt%) and low critical micelle concentrations (0.021 mg mL-1). Due to the pH-sensitive benzoic imine linkages between the DOX moieties and polymeric backbone, DOX could be rapidly released from the micelles at pH 5.8, whereas only a minimal amount of DOX was released at pH 7.4 under the same conditions. The cytotoxicity assay indicates that the OEG-DOX conjugates show cytotoxic effects to MCF-7 tumor cells, while the corresponding polymer material POEGM-CHO exhibits a great biocompatibility for MCF-7 tumor cells. These pH-sensitive and high drug loading nano-carriers based on the OEG-DOX alternative conjugates provide a promising platform for targeted cancer therapy.