A Biodegradable Janus Sponge for Negative Pressure Wound Therapy.

Negative pressure wound therapy (NPWT) is effective in repairing serious skin injury. The dressing used in the NPWT is important for wound healing. In this paper, we develop biodegradable amphiphilic polyurethanes (PUs) and fabricate the PUs into sponges as wound dressings (Bi@e) with Janus pore architectures for NPWT. The Bi@e is adaptive to all the stages of the wound healing process. The Janus Bi@e sponge consists of two layers: the dense hydrophobic upper layer with small pores provides protection and support during negative pressure drainage, and the loose hydrophilic lower layer with large pores absorbs large amounts of wound exudate and maintains a moist environment. Additionally, antibacterial agent silver sulfadiazine (SSD) is loaded into the sponge against Escherichia coli and Staphylococcus aureus with a concentration of 0.50 wt%. The Janus sponge exhibits a super absorbent capacity of 19.53 times its own water weight and remarkable resistance to compression. In a rat skin defect model, the Janus Bi@e sponge not only prevents the conglutination between regenerative skin and dressing but also accelerates wound healing compared to commercially available NPWT dressing. The Janus Bi@e sponge is a promising dressing for the NPWT.

A pH-sensitive imidazole grafted polymeric micelles nanoplatform based on ROS amplification for ferroptosis-enhanced chemodynamic therapy.

Highly toxic reactive oxygen species (ROS), crucial in inducing apoptosis and ferroptosis, are pivotal for cell death pathways in cancer therapy. However, the effectiveness of ROS-related tumor therapy is impeded by the limited intracellular ROS and substrates, coupled with the presence of abundant ROS scavengers like glutathione (GSH). In this research, we developed acid-responsive, iron-coordinated polymer nanoparticles (PPA/TF) encapsulating a mitochondrial-targeting drug alpha-tocopheryl succinate (α-TOS) for enhanced synergistic tumor treatment. The imidazole grafted micelles exhibit prolonged blood circulation and improve the delivery efficiency of the hydrophobic drug α-TOS. Additionally, PPA's design aids in delivering Fe3+, supplying ample iron ions for chemodynamic therapy (CDT) and ferroptosis through the attachment of imidazole groups to Fe3+. In the tumor's weakly acidic intracellular environment, PPA/TF facilitates pH-responsive drug release. α-TOS specifically targets mitochondria, generating ROS and replenishing those depleted by the Fenton reaction. Moreover, the presence of Fe3+ in PPA/TF amplifies ROS upregulation, promotes GSH depletion, and induces oxidative damage and ferroptosis, effectively inhibiting tumor growth. This research presents an innovative ROS-triggered amplification platform that optimizes CDT and ferroptosis for effective cancer treatment.

Copper-dependent control of uptake, translocation and accumulation of cadmium in hyperaccumlator Sedum alfredii.

Cadmium (Cd) is detrimental to plant growth and threatens human health. Here, we investigated the potential for remediation of Cd-contaminated soil with high copper (Cu) background using Cd hyperaccumulator ecotype (HE) Sedum alfredii. We assessed effects of Cu on Cd accumulation, compartmentation and translocation in HE S. alfredii, and compared with those in a related non-accumulator ecotype (NHE). We found that Cu supply significantly induced Cd accumulation in roots and shoots of long-term soil-cultivated HE S. alfredii. A large fraction of root Cd was accumulated in the organelles, but a small fraction was stored in the cell wall. Importantly, Cu addition reduced Cd accumulation in the cell wall and the organelles in root cells. Furthermore, leaf cell capacity to sequestrate Cd in the organelles was greatly improved upon Cu exposure. We also found that genes involving metal transport and cell wall remodeling were distinctly regulated to mediate Cd accumulation in HE S. alfredii. These findings indicate that Cu-dependent decrease of root cell-wall-bound Cd, and stimulation of efflux/influx of organelle Cd transport in root and leaf cells plays a role in the dramatic Cd hyperaccumulation expressed in naturally survived HE S. alfredii.

Static Magnetic Fields Promote Generation of Muscle Lineage Cells from Pluripotent Stem Cells and Myoblasts.

Static magnetic fields (SMFs) exhibit numerous biological effects and regulate the proliferation and differentiation of several adult stem cells. However, the role of SMFs in the self-renewal maintenance and developmental potential of pluripotent embryonic stem cells (ESCs) remains largely uninvestigated. Here, we show that SMFs promote the expression of the core pluripotent markers Sox2 and SSEA-1. Furthermore, SMFs facilitate the differentiation of ESCs into cardiomyocytes and skeletal muscle cells. Consistently, transcriptome analysis reveals that muscle lineage differentiation and skeletal system specification of ESCs are remarkably strengthened by SMF stimuli. Additionally, when treated with SMFs, C2C12 myoblasts exhibit an increased proliferation rate, improved expression of skeletal muscle markers and elevated myogenic differentiation capacity compared with control cells. Together, our data show that SMFs effectively promote muscle cell generation from pluripotent stem cells and myoblasts. The noninvasive and convenient physical stimuli can be used to increase the production of muscle cells in regenerative medicine and the manufacture of cultured meat in cellular agriculture.

Snap29 Is Dispensable for Self-Renewal Maintenance but Required for Proper Differentiation of Mouse Embryonic Stem Cells.

Pluripotent embryonic stem cells (ESCs) can self-renew indefinitely and are able to differentiate into all three embryonic germ layers. Synaptosomal-associated protein 29 (Snap29) is implicated in numerous intracellular membrane trafficking pathways, including autophagy, which is involved in the maintenance of ESC pluripotency. However, the function of Snap29 in the self-renewal and differentiation of ESCs remains elusive. Here, we show that Snap29 depletion via CRISPR/Cas does not impair the self-renewal and expression of pluripotency-associated factors in mouse ESCs. However, Snap29 deficiency enhances the differentiation of ESCs into cardiomyocytes, as indicated by heart-like beating cells. Furthermore, transcriptome analysis reveals that Snap29 depletion significantly decreased the expression of numerous genes required for germ layer differentiation. Interestingly, Snap29 deficiency does not cause autophagy blockage in ESCs, which might be rescued by the SNAP family member Snap47. Our data show that Snap29 is dispensable for self-renewal maintenance, but required for the proper differentiation of mouse ESCs.

Harnessing polymer-derived drug delivery systems for combating inflammatory bowel disease.

The inflammatory bowel disease (IBD) is incurable, chronic, recrudescent disorders in the inflamed intestines. Current clinic treatments are challenged by systemic exposure-induced severe side effects, inefficiency after long-term treatment, and increased risks of infection and malignancy due to immunosuppression. Fortunately, naturally bioactive small molecules, reactive oxygen species scavengers (or antioxidants), and gut microbiota modulators have emerged as promising candidates for the IBD treatment. Polymeric systems have been engineered as a delivery vehicle to improve the bioavailability and efficacy of these therapeutic agents through targeting the mucosa and enhancing intestinal adhesion and retention, and reduce their systemic toxicity. Herein we survey polymer-derived drug delivery systems for combating the IBD. Advanced delivery technologies, therapeutic intervention strategies, and the principles for the construction of hierarchical, mucosa-targeting, and bioresponsive systems are elaborated, providing insights into design and development of from-bench-to-bedside drug delivery polymeric systems for the IBD treatment.

A reactive oxygen species-replenishing coordination polymer nanomedicine disrupts redox homeostasis and induces concurrent apoptosis-ferroptosis for combinational cancer therapy.

Reactive oxygen species (ROS) are important signal molecules and imbalanced ROS level could lead to cell death. Elevated ROS levels in tumor tissues offer an opportunity to design ROS-responsive drug delivery systems (DDSs) or ROS-based cancer therapies such as chemodynamic therapy. However, their anticancer efficacies are hampered by the ROS-consuming nature of these DDSs as well as the high concentration of reductive agents like glutathione (GSH). Here we developed a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde (CA)-based ROS-replenishing organic ligand (TCA). TCA can ROS-responsively release CA to supplement intracellular ROS and deplete GSH by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitated efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies revealed that ROS-replenishing PCFD exhibited much better anticancer effect than ROS-consuming control nanoparticle PAFD. The ingenious ROS-replenishing strategy could be expanded to construct versatile ROS-responsive DDSs and ROS-based nanomedicines with potentiated anticancer activity. STATEMENT OF SIGNIFICANCE: We develop a doxorubicin (DOX)-incorporated iron coordination polymer nanoparticle (PCFD) for efficient chemo-chemodynamic cancer therapy by using a cinnamaldehyde-based reactive oxygen species (ROS)-replenishing organic ligand. This functional ligand can ROS-responsively release cinnamaldehyde to supplement intracellular H2O2 and deplete glutathione (GSH) by a thiol-Michael addition reaction, which together with DOX-triggered ROS upregulation and Fe3+-enabled GSH depletion facilitates efficient DOX release and enhanced Fenton reaction, thereby inducing redox dyshomeostasis and cancer cell death in a concurrent apoptosis-ferroptosis way. Both in vitro and in vivo studies reveal that ROS-replenishing PCFD exhibit much better anticancer effect than ROS consuming counterpart. This study provides a facile and straightforward strategy to design ROS amplifying nanoplatforms for cancer treatment.

A Mg2+/polydopamine composite hydrogel for the acceleration of infected wound healing.

Bacterial infection is a vital factor to delay the wound healing process. The antibiotics abuse leads to drug resistance of some pathogenic bacteria. Non-antibiotic-dependent multifunctional biomaterials with accelerated wound healing performance are urgently desired. Herein, we reported a composite antibacterial hydrogel PDA-PAM/Mg2+ that shows excellent self-healing and tissue adhesive property, and photothermal antibacterial functions for accelerating wound healing. The gel was composed of polyacrylamide (PAM), polydopamine (PDA), and magnesium (Mg2+) and prepared via a two-step procedure: an alkali-induced dopamine pre-polymerization and followed radical polymerization process. The composite gel shows excellent tissue adhesiveness and Mg2+-synergized photothermal antibacterial activity, inducing a survival rate of 5.29% for S. aureus and 7.06% for E. coli after near infrared light irradiation. The composite hydrogel further demonstrated efficient bacteria inhibition, enhanced wound healing and collagen deposition in a full-thickness skin defect rat model. Together, the PDA-PAM/Mg2+ hydrogel presents an excellent wound dressing with excellent tissue adhesion, wound healing, and antibacterial functions.

A double-layer dura mater based on poly(caprolactone-co-lactide) film and polyurethane sponge: preparation, characterization, and biodegradation study.

Synthetic, biodegradable polymers hold great potential in dura mater substitution. In this study, a dura mater-mimetic double-layer film@sponge composite was developed. The composite contains a poly(caprolactone-co-lactide) (PCLA) film and polyurethane (PU) sponge, which simulates the hard and soft layers of dura mater, respectively. PCLA films were prepared by a solution-casting method and showed excellent mechanical properties and tolerance to water. PU sponge was hydrophilic and had a high water-absorption rate (about 500%). The double-layer composite (film@sponge) integrated the good mechanical properties of the films and the good water absorption of the sponge. The excellent biocompatibility and biodegradability of the PCLA film@PU sponge composites were verified by in vitro degradation and cytotoxicity study and the in vivo implantation in the back of rats. Importantly, the film@sponge composite had a suitable degradation rate and good biocompatibility, holding potential in the field of dural repair.

Thermosensitive polymer hydrogel as a physical shield on colonic mucosa for colitis treatment.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis (UC), is a chronic disease characterized by diffuse mucosal inflammation limited to the colon. Topical drug delivery systems that could be facilely performed and efficiently retained at colon sites are attractive for clinical IBD treatment. Herein, we report the exploration of an injectable thermosensitive copolymer hydrogel as a topical formulation for IBD treatment and demonstrate its feasibility in UC treatment by shielding ulcer sites from the external environment and being a drug reservoir for sustained release. Poly(aliphatic ester)-based triblock copolymer, poly(dl-lactic acid)-poly(ethylene glycol)-poly(dl-lactic acid) (PDLLA-PEG-PDLLA), adopts the solution state at room temperature yet a gel state at body temperature when the polymer concentration is more than 11%. The gel acts not only as a physical mucosal barrier for protecting ulcer sites from microorganisms like bacteria but also as a mesalazine depot for enhanced drug retention in the colon for localized, sustained drug release. In vivo UC treatment reveals that blank gel as a mucosal protector shows nearly the same treatment effect to mesalazine SR granules. Mesalazine-loaded gel significantly suppresses inflammation and has the best outcomes of indices such as colonic length, mucosal injury index, pathological tissue, and inflammatory factor. The injectable thermosensitive polymer hydrogel represents a novel, robust platform for the efficient treatment of IBD by acting as a physical shield to block out the pro-inflammatory factors as well as a drug depot for enhanced drug retention and controlled delivery.

ABC Triblock Copolymers Antibacterial Materials Consisting of Fluoropolymer and Polyethylene Glycol Antifouling Block and Quaternary Ammonium Salt Sterilization Block.

Due to their various applications in human healthcare and industrial fields, engineering surfaces with antiadhesion and antibacteria properties is still a challenging task. In this work, the fluoropolymer with low surface energy and poly(poly(ethylene glycol) methyl ether methacrylate) (PEGMA) with electrostatic repulsion and interfacial hydration was chosen as a common antiadhesion block and quaternary ammonium salt with bactericide properties as a sterilization block. The triblock copolymers of poly(2-(dimethylamino)ethyl methacrylate)-b-poly(poly(oligo ethylene glycol) methyl ether methacrylate)-b-poly(dodecafluoroheptyl methacrylate) (PDMAEMA-b-PEGMA-b-PDFHMA) were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization method. Then, the synthesized triblock copolymers were quaternized to obtain the antibacterial materials (QPDMAEMA-b-PEGMA-b-PDFHMA). It has been found that the QPDMAEMA-b-PEGMA-b-PDFHMA triblock copolymer coating has excellent antiadhesion and antibacterial properties against S. aureus and E. coli. The synergistic effects of fluoropolymer and PEGMA can enhance the antifouling properties of the coating. At the same time, it has a good antifouling effect on platelets and red blood cells. In addition, the triblock copolymer coating has long-term stability in high ionic strength solution of PBS in dynamic conditions. These kind of materials with antifouling and antibacterial properties may have potential applications on the surface of various public utilities and medical equipment.

pH-sensitive polymeric micelles assembled by stereocomplexation between PLLA-b-PLys and PDLA-b-mPEG for drug delivery.

pH-responsive stereocomplexed micelles based on poly(l-lactic acid)-b-polylysine/poly(d-lactic acid)-b-methoxy poly(ethylene glycol) (PLLA-b-PLys/PDLA-b-mPEG) were fabricated by stereocomplexation between enantiomeric PLA segments. The morphology, critical micelle concentration, formation of stereocomplexation and pH sensitivity of the stereocomplexed micelles were investigated by TEM, DLS, fluorescence spectra, DSC, XRD, and the acid-base titration method. Interestingly, it was observed that compared to PLLA-b-PLys micelles, the stereocomplexed micelles showed lower critical micelle concentration. Anticancer drug doxorubicin (DOX) was encapsulated in the stereocomplexed micelles and then they were incubated with Hela cells to study the in vitro anti-tumor effect. The results showed that the DOX-loaded stereocomplexed micelles exhibited a slower drug release behavior and a weaker efficacy of intracellular proliferation inhibition than PLLA-b-PLys micelles. Stereocomplexation would provide a favorable platform to construct stable micelles for cancer therapy.

Cinnamaldehyde-Based Poly(ester-thioacetal) To Generate Reactive Oxygen Species for Fabricating Reactive Oxygen Species-Responsive Nanoparticles.

Due to the high oxidative stress of the tumor microenvironment, more and more researchers have been devoted to reactive oxygen species (ROS)-responsive nanodrug delivery systems for anticancer therapy. Herein, a ROS-responsive moiety, thioacetal, was synthesized, and cinnamaldehyde (CA) was introduced in the polymer chain to trigger the generation of ROS to expect the enhancement of the ROS-responsive effect. The poly(ester-thioacetal) mPEG2k - b-(NTA-HD)12 polymer, its self-assembled micelles, and the ROS-responsive behavior were characterized by 1H NMR and DLS. The anticancer drug doxorubicin (DOX) was adopted to prepare DOX-loaded poly(ester-thioacetal) micelles. The intracellular ROS detection indicated that the mPEG2k - b-(NTA-HD)12 polymer could degrade via the high concentration of ROS in cancer cells, and the released CA stimulated mitochondria to regenerate additional ROS. The flow cytometry results indicated that the ROS-responsive polymeric micelles showed faster cellular uptake compared to the control mPEG2k - b-PCL5k micelles. The ROS responsive DOX/mPEG2k - b-(NTA-HD)12 micelles exhibited much better anticancer efficiency on both 4T1 and HeLa cancer cells than DOX/mPEG2k - b-PCL5k micelles.

Mesoporous iron-carboxylate metal-organic frameworks synthesized by the double-template method as a nanocarrier platform for intratumoral drug delivery.

Metal-organic frameworks as a powerful platform for drug delivery have attracted significant attention in recent years. In this study, mesoporous iron-metal-organic framework nanoparticles (mesoMOFs) were synthesized via the double-template method. Cetyltrimethylammonium bromide (CTAB) and citric acid (CA) were chosen as the double-template agent. The mesoMOFs were characterized by EDX, elemental analysis, TG, BET, SEM, TEM, and DLS. The anticancer drug doxorubicin hydrochloride (DOX) was encapsulated in the mesoMOFs, and the DOX loading content was up to 55 wt%. The mesoMOFs are non-toxic to both 4T1 breast cancer cells and 3T3 fibroblasts. The DOX-loaded mesoMOFs exhibit a better anti-tumor effect than free doxorubicin in vitro. The in vivo anticancer activities of the DOX-loaded mesoMOFs were investigated in 4T1 breast cancer-bearing mice. The intratumoral injection of DOX-loaded mesoMOFs revealed that the mesoMOFs could significantly reduce the systemic toxicity of DOX, sustainably release DOX, and maintain an effective DOX concentration for chemotherapy. The DOX-loaded mesoMOFs exhibit excellent therapeutic efficacy and low side effects in local chemotherapy.