Poly Ethylene Glycol Acrylate Research Articles

Macroporous PEG-Alginate Hybrid Double-Network Cryogels with Tunable Degradation Rates Prepared via Radical-Free Cross-Linking for Cartilage Tissue Engineering.

Trauma or repeated damage to joints can result in focal cartilage defects, significantly elevating the risk of osteoarthritis. Damaged cartilage has an inherently limited self-healing capacity and remains an urgent unmet clinical need. Consequently, there is growing interest in biodegradable hydrogels as potential scaffolds for the repair or reconstruction of cartilage defects. Here, we developed a biodegradable and macroporous hybrid double-network (DN) cryogel by combining two independently cross-linked networks of multiarm polyethylene glycol (PEG) acrylate and alginate.Hybrid DN cryogels are formed using highly biocompatible click reactions for the PEG network and ionic bonding for the alginate network. By judicious selection of various structurally similar cross-linkers to form the PEG network, we can generate hybrid DN cryogels with customizable degradation kinetics. The resulting PEG-alginate hybrid DN cryogels have an interconnected macroporous structure, high mechanical strength, and rapid swelling kinetics. The interconnected macropores in the cryogels support efficient mesenchymal stem cell infiltration at a high density. Finally, we demonstrate that PEG-alginate hybrid DN cryogels allow sustained release of chondrogenic growth factors and support chondrogenic differentiation of mouse mesenchymal stem cells. This study provides a novel method to generate macroporous hybrid DN cryogels with customizable degradation rates and a potential scaffold for cartilage tissue engineering.

Electrospun composite-coated endotracheal tubes with controlled siRNA and drug delivery to lubricate and minimize upper airway injury

Endotracheal Tubes (ETTs) maintain and secure a patent airway; however, prolonged intubation often results in unintended injury to the mucosal epithelium and inflammatory sequelae which complicate recovery. ETT design and materials used have yet to adapt to address intubation associated complications. In this study, a composite coating of electrospun polycaprolactone (PCL) fibers embedded in a four-arm polyethylene glycol acrylate matrix (4APEGA) is developed to transform the ETT from a mechanical device to a dual-purpose device capable of delivering multiple therapeutics while preserving coating integrity. Further, the composite coating system (PCL-4APEGA) is capable of sustained delivery of dexamethasone from the PCL phase and small interfering RNA (siRNA) containing polyplexes from the 4APEGA phase. The siRNA is released rapidly and targets smad3 for immediate reduction in pro-fibrotic transforming growth factor-beta 1 (TGFϐ1) signaling in the upper airway mucosa as well as suppressing long-term sequelae in inflammation from prolonged intubation. A bioreactor was used to study mucosal adhesion to the composite PCL-4APEGA coated ETTs and investigate continued mucus secretory function in ex vivo epithelial samples. The addition of the 4APEGA coating and siRNA delivery to the dexamethasone delivery was then evaluated in a swine model of intubation injury and observed to restore mechanical function of the vocal folds and maintain epithelial thickness when observed over 14 days of intubation. This study demonstrated that increase in surface lubrication paired with surface stiffness reduction significantly decreased fibrotic behavior while reducing epithelial adhesion and abrasion.

Revealing the effect of double bond-modified Li6.75La3Zr1.75Ta0.25O12 on the Li-ion conduction of composite solid electrolytes

Lithium metal batteries with polyethylene oxide (PEO) electrolytes have shown great potential to be one of the next-generation energy candidates. As the branch family of PEO electrolytes, poly(ethylene glycol) acrylates (PEGAs) attract more attention owing to their better electrochemical properties than that of PEO electrolytes. Introducing double bond-modified Li6.75La3Zr1.75Ta0.25O12 fillers (KH@LLZTO) has been a popular method to improve the electrochemical properties of PEGAs electrolytes due to the homogeneous dispersion of LLZTO. However, in this work, an inverse phenomenon is discovered. The electrochemical properties of PEGAs electrolytes get worse when introducing KH@LLZTO. By exploring the Li+ transport mechanism, the reason for the inverse phenomenon is revealed. More importantly, the design principle of PEGAs electrolytes with fast ionic conductor fillers is presented. Double bond-modified LLZTO can decrease the electrochemical properties of PEGAs electrolytes instead when there are low-molecular weight monomers that can participate in the PEGAs polymer network and interact with Li+, while the double bond-modified LLZTO can improve the electrochemical properties of PEGAs electrolytes when there are not aforementioned low-molecular weight monomers. This work provides a new understanding for componential design and optimization of PEGAs electrolytes with fast ionic conductors, hoping to promote the practical application of PEGAs electrolytes.

Spatial Constraints of Rectangular Hydrogel Microgrooves Regulate the Morphology and Arrangement of Human Umbilical Vein Endothelial Cells

To construct microscale rectangular hydrogel grooves and to investigate the morphology and alignment of human umbilical vein endothelial cells (HUVECs) under spatial constraints. Vascular endothelial cell morphology and alignment are important factors in vascular development and the maintenance of homeostasis. A 4-arm polyethylene glycol-acrylate (PEG-acrylate) hydrogel was used to fabricate rectangular microgrooves of the widths of 60 μm, 100 μm, and 140 μm. The sizes and the fibronectin (FN) adhesion of these hydrogel microgrooves were measured. HUVECs were seeded onto the FN-coated microgrooves, while the flat surface without micropatterns was used as the control. After 48 hours of incubation, the morphology and orientation of the cells were examined. The cytoskeleton was labelled with phalloidine and the orientation of the cytoskeleton in the hydrogel microgrooves was observed by laser confocal microscopy. The hydrogel microgrooves constructed exhibited uniform and well-defined morphology, a complete structure, and clear edges, with the width deviation being less than 3.5%. The depth differences between the hydrogel microgrooves of different widths were small and the FN adhesion is uniform, providing a micro-patterned growth interface for cells. In the control group, the cells were arranged haphazardly in random orientations and the cell orientation angle was (46.9±1.8)°. In contrast, the cell orientation angle in the hydrogel microgrooves was significantly reduced (P<0.001). However, the cell orientation angles increased with the increase in hydrogel microgroove width. For the 60 μm, 100 μm, and 140 μm hydrogel microgrooves, the cell orientation angles were (16.4±2.8)°, (24.5±3.2)°, and (30.3±3.5)°, respectively. Compared to that of the control group (35.7%), the number of cells with orientation angles <30° increased significantly in the hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cells with orientation angles <30° gradually decreased (79.9%, 62.3%, 54.7%, respectively), while the number of cells with orientation angles between 60°-90° increased (P<0.001). The cell bodies in the microgrooves were smaller and more rounded in shape. The cells were aligned along the direction of the microgrooves and corresponding changes occurred in the arrangement of the cell cytoskeleton. In the control group, cytoskeletal filaments were aligned in random directions, presenting an orientation angle of (45.5±3.7)°. Cytoskeletal filaments were distributed evenly within various orientation angles. However, in the 60 μm, 100 μm, and 140 μm hydrogel microgrooves, the orientation angles of the cytoskeletal filaments were significantly decreased, measuring (14.4±3.1)°, (24.7±3.5)°, and (31.9±3.3)°, respectively. The number of cytoskeletal filaments with orientation angles <30° significantly increased in hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cytoskeletal filaments with orientation angles <30° gradually decreased, while the number of cytoskeletal filaments with orientation angles between 60°-90° gradually increased (P<0.001). Hydrogel microgrooves can regulate the morphology and orientation of HUVECs and mimic to a certain extent the in vivo microenvironment of vascular endothelial cells, providing an experimental model that bears better resemblance to human physiology for the study of the unique physiological functions of vascular endothelial cells. Nonetheless, the molecular mechanism of spatial constraints on the morphology and the assembly of vascular endothelial cell needs to be further investigated.

Enzyme-Polymer Conjugates with Photocleavable Linkers for Control Over Protein Activity.

Reversible conjugation of polymers to proteins is important for a variety of applications, for example to control protein activity. Light is often employed as an external trigger to allow for spatio and temporal control over release of a payload. In this report, we demonstrate preparation of photocleavable poly(polyethylene glycol) acrylate)-lysozyme (pPEGA-Lys) conjugates via ortho-nitrobenzyl linkages. The conjugates were made by both grafting-to and grafting-from in order to compare and contrast the two synthetic approaches. First, a lysine-reactive ortho-nitrobenzyl atom transfer radical polymerization (ATRP) initiator was synthesized. For the grafting-to strategy, the initiator was employed in the ATRP of PEGA, and the subsequent polymer was conjugated to the lysine residues of lysozyme. For the grafting-from strategy, lysozyme was modified first with the photocleavable initiator, and the purified macroinitiator was then subjected to polymerization conditions to synthesize the protein-polymer conjugate. The polymer was cleaved from the protein via UV light, and activity before and after polymer removal was evaluated, showing 83% recovery. This work provides evidence that reversing conjugation is successful for activity modulation for ortho-nitrobenzyl linked protein-polymer conjugates.

Enhancing hydrogel toughness by uniform cross-linking using modified polyhedral oligomeric silsesquioxane

The use of macro cross-linkers is one of the most effective approaches for developing tough hydrogels. However, the presence of uneven cross-linking and the resulting hydrogel inhomogeneity restrict further improvement. Here, we achieve uniform cross-linking by employing polyhedral oligomeric silsesquioxane (POSS)-grafted acrylated polyethylene glycol (PEG) as a cross-linker to enhance the toughness of hydrogels. The nano-sized hard silica core of POSS facilitates energy dissipation, and its dissolved form ensures uniform cross-linking through molecular-level dispersion. The peripheral acrylate groups introduce multiple interacting points, and the physical entanglements of long-chain PEG contribute to enhanced toughness. Incorporating acrylated POSS-PEG into polyacrylamide hydrogel yields enhanced properties such as toughness of up to 6531 kJ m−3 and break elongation up to 9455%, where the length of PEG chains grafted onto POSS is demonstrated to play a crucial role in facilitating energy dissipation and achieving high toughness.

Varying the Stiffness and Diffusivity of Rod‐Shaped Microgels Independently through Their Molecular Building Blocks

AbstractMicrogels are water‐swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method—all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications. In this report, we systematically vary the architecture and molar mass of polyethylene glycol‐acrylate (PEG‐Ac) precursors, as well as their concentration and combination, to gain insight in the different parameters that affect the internal structure of rod‐shaped microgels. We characterize the mechanical properties and diffusivity, as well as the conversion of acrylate groups during photopolymerization, in both bulk hydrogels and microgels produced from the PEG‐Ac precursors. Furthermore, we investigate cell‐microgel interaction, and we observe improved cell spreading on microgels with more accessible RGD peptide and with a stiffness in a range of 20 kPa to 50 kPa lead to better cell growth.

Varying the Stiffness and Diffusivity of Rod-Shaped Microgels Independently through Their Molecular Building Blocks.

Microgels are water-swollen, crosslinked polymers that are widely used as colloidal building blocks in scaffold materials for tissue engineering and regenerative medicine. Microgels can be controlled in their stiffness, degree of swelling, and mesh size depending on their polymer architecture, crosslink density, and fabrication method-all of which influence their function and interaction with the environment. Currently, there is a lack of understanding of how the polymer composition influences the internal structure of soft microgels and how this morphology affects specific biomedical applications. In this report, we systematically vary the architecture and molar mass of polyethylene glycol-acrylate (PEG-Ac) precursors, as well as their concentration and combination, to gain insight in the different parameters that affect the internal structure of rod-shaped microgels. We characterize the mechanical properties and diffusivity, as well as the conversion of acrylate groups during photopolymerization, in both bulk hydrogels and microgels produced from the PEG-Ac precursors. Furthermore, we investigate cell-microgel interaction, and we observe improved cell spreading on microgels with more accessible RGD peptide and with a stiffness in a range of 20 kPa to 50 kPa lead to better cell growth.

Prying or pushing? The dispersion mechanism of amphiphilic molecules on graphene in aqueous solution: A molecular dynamics simulation

Amphiphilic molecule aqueous solutions are widely used in the dispersion of graphene. Previous experimental studies have focused on selecting amphiphilic molecules with high dispersion yield and stability through a large number of “trial and error” methods, without delving into their dispersion mechanism. In this study, the graphene dispersing processes in aqueous solutions of three amphiphilic dispersants with different structures, flavin mononucleotide sodium, polyvinyl pyrrolidone and the oligomer of poly(pyrenemethyl acrylate)-b-poly[(polyethylene glycol) acrylate], were investigated by molecular dynamics simulation. By characterizing the influence of three dispersants on the intercalation effect of water molecules, their distribution relative to graphene, and their influence on the equilibrium conformation of graphene, the simulation conclusion was drawn that the arrangement of hydrophilic and hydrophobic structures of amphiphilic molecules is the decisive factor in their mechanism of dispersing graphene. Two different dispersion mechanisms have been concluded and the relationship between them and the structure of amphiphilic molecules was elaborated. This article also explored the driving forces of two mechanisms and the influence of graphene lateral area on the dispersion effectiveness. This investigation provided theoretical clues to design the amphiphilic molecules with suitable structure and select appropriate mechanical operations to achieve higher dispersion yield.

Evaluation of Poly(N-Ethyl Pyrrolidine Methacrylamide) (EPA) and Derivatives as Polymeric Vehicles for miRNA Delivery to Neural Cells.

MicroRNAs (miRNAs) are endogenous, short RNA oligonucleotides that regulate the expression of hundreds of proteins to control cells' function in physiological and pathological conditions. miRNA therapeutics are highly specific, reducing the toxicity associated with off-target effects, and require low doses to achieve therapeutic effects. Despite their potential, applying miRNA-based therapies is limited by difficulties in delivery due to their poor stability, fast clearance, poor efficiency, and off-target effects. To overcome these challenges, polymeric vehicles have attracted a lot of attention due to their ease of production with low costs, large payload, safety profiles, and minimal induction of the immune response. Poly(N-ethyl pyrrolidine methacrylamide) (EPA) copolymers have shown optimal DNA transfection efficiencies in fibroblasts. The present study aims to evaluate the potential of EPA polymers as miRNA carriers for neural cell lines and primary neuron cultures when they are copolymerized with different compounds. To achieve this aim, we synthesized and characterized different copolymers and evaluated their miRNA condensation ability, size, charge, cytotoxicity, cell binding and internalization ability, and endosomal escape capacity. Finally, we evaluated their miRNA transfection capability and efficacy in Neuro-2a cells and rat primary hippocampal neurons. The results indicate that EPA and its copolymers, incorporating β-cyclodextrins with or without polyethylene glycol acrylate derivatives, can be promising vehicles for miRNA administration to neural cells when all experiments on Neuro-2a cells and primary hippocampal neurons are considered together.

Alternative Chemistries for Free Radical-Initiated Targeting and Immobilization.

Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism. To build on these promising results, we evaluated PEG dialkenes and dithiols as alternative polymer chemistries for targeting. The reactivity, toxicity, crosslinking kinetics, and immobilization potential of PEG dialkenes and dithiols were characterized. Both the alkene and thiol chemistries crosslinked in the presence of ROS, generating high molecular weight polymer networks that immobilized fluorescent payloads in tissue mimics. Thiols were especially reactive and even reacted with acrylates in the absence of free radicals, and this motivated us to explore a two-phase targeting approach. Delivering thiolated payloads in a second phase, after the initial polymer net formation, allowed greater control over the payload dosing and timing. Two-phase delivery combined with a library of radical-sensitive chemistries can enhance the versatility and flexibility of this free radical-initiated platform delivery system.

A Degradable and Biocompatible Supercapacitor Implant Based on Functional Sericin Hydrogel Electrode

AbstractImplantable power sources face great challenges in balancing multiple factors including high performance, biocompatibility, mechanical properties for soft tissue fit, and biodegradability. Toward this goal, a simple and feasible method is proposed to prepare implantable a hydrogel‐based supercapacitor (SC). Specially, a multinetwork conductive electrode is in situ formed by aminated‐reduced‐graphene‐oxide‐and‐methacrylic‐anhydride‐comodified sericin (SrMA/A‐rGO) sequentially cross‐linking with four‐arm polyethylene glycol succinimide carbonate and polyethylene glycol acrylate. The conductive multinetwork endows the SrMA/A‐rGO‐based SC implant an equivalent series resistance of 21 Ω cm−2, a volumetric energy density of 26.0 µW cm−2, and a high specific capacitance retention (over 76.4%) after long‐term charging/discharging. Two SCs connected in tandem are able to light up a light‐emitting diode for both in vitro and in vivo studies. Moreover, they can work as a direct output power source to electrically stimulate a stopped heart to start beating again. Additionally, the SC exhibits superior biocompatibility and biodegradability in vivo, and holds the value of specific capacitance above 30% 2 weeks after implantation. Thus, this work demonstrates the SrMA/A‐rGO‐based SC's potential to serve as a power storage unit for medical implants (such as a temporary pacemaker).

Preparation and analysis of pure and surface modified nanohydroxyapatite derived from eggshells and its in-vitro studies for bone graft applications

The need and significance for quality bone graft substitute increases due to the worldwide increment in the health problems such as osteoporosis, accidental loss and teeth decay etc. Nowadays, nanohydroxyapatite and its polymeric composites are effectively used as bone grafts and dentin. In this work, nanohydroxyapatite (nHAp) and surface-modified nanohydroxyapatite were synthesized through the precipitation method using bio-wastes (eggshells) as a Calcium precursor. The polymers Polyethylene glycol (PEG) and polyvinyl acrylate (PVA) were used as surface modifiers to control the particle size. The prepared samples were analyzed through X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Thermogravimetric Differential Thermal Analysis (TG-DTA), Scanning Electron Microscopy (SEM), High-Resolution Transmission Electron Microscopy (HR-TEM) and X-ray Photoelectronic Spectroscopy (XPS). Also, the samples were subjected to simulated body fluid analysis, antimicrobial and hemolytic assay to analyze the apatite forming ability and hemolytic nature. The XRD, SEM and HR-TEM results show the crystallite and particle sizes are about 41 nm, 57 nm and 66.6 nm (rod-shaped) respectively. While the EDAX spectra show the presence of Calcium, Phosphate, Oxygen and Sodium in the prepared sample. However, the FT-IR spectra confirm the presence of OH, PO43−, and CO32− functional groups in the sample. The thermogram depicts the stability of nHAp/PVA composite is better than nHAp without polymer. This study reports that reprocessing of eggshells to nHAp and its composites paves the way to recover the ecosphere and the obtained value-added product, which may use in making a promising material for bone implants, dental fillers and coatings at low cost.

L-asparaginase immobilization in supramolecular nanogels of PEG-grafted poly HPMA and bis(α-cyclodextrin) to enhance pharmacokinetics and lower enzyme antigenicity

L-asparaginase (ASNase) enzyme has limited therapeutic use due to its poor pharmacokinetics and immunogenicity. To overcome these obstacles, we immobilized ASNase in biocompatible poly hydroxypropyl methacrylamide (P(HPMA))-based nanogels simply formed through the host-guest inclusion complex of ASNase-conjugated random copolymer of HPMA and polyethylene glycol (PEG) acrylate (P(HPMA-MPEGA)) and α-cyclodextrin dimer (bisCD) using cystamine as a linker. The effects of bisCD and polymer concentrations on particle size, gelation time, and recovery of enzyme activity were investigated. The ASNase-conjugated bisCD nanogels were discrete, homogeneous, and spherical with a mean projected diameter of 148 ± 41 nm. ASNase immobilized in the bisCD nanogels caused cytotoxicity on HL-60 cell line with IC50 of 3 IU/ml. In-vivo rat study revealed that the immobilized ASNase reduced the enzyme antigenicity and resulted in 8.1 folds longer circulation half-life than the native enzyme. Conclusively, immobilization of ASNase in P(HPMA-MPEGA) and bisCD supramolecular nanogels could enhance the therapeutic value of ASNase in cancer chemotherapy.

Enhanced L-asparaginase stability through immobilization in supramolecular nanogels of PEG-grafted poly HPMA with bis(α-cyclodextrin)

This paper presents the fabrication of a biocompatible supramolecular nanogel containing immobilized L-asparaginase (ASNase), an anti-leukemic therapeutic agent, to improve the enzyme’s physicochemical stability. The ASNase-conjugated random copolymer of N-(2-Hydroxypropyl)methacrylamide (HPMA) and polyethylene glycol (PEG) acrylate was simply combined with inter-molecularly crosslinked α-cyclodextrin (bisCD) in physiologic condition to prepare inclusion complex nanogels. The introduction of bisCD led to the formation of discrete, homogenous, and spherical nanogels with a mean projected diameter of 148 nm for the best formulation of ASNase bioconjugate in terms of polymer succination ratio and polymer:protein ratio. The Michaelis-Menten constant (Km) for immobilized ASNase was 1.6-fold lower than the free form, indicating a higher affinity for the asparagine substrate. The ASNase immobilization significantly extended the pH stability range. In addition, when compared to the free enzyme, ASNase-bisCD nanogel exhibited superior stability against elevated temperature, freeze-thaw cycles, and proteolysis. Overall, the immobilization of ASNase in bisCD nanogels yields a novel stabilized preparation with promising biomedical applications.

Hydrogel Dressing Containing Basic Fibroblast Growth Factor Accelerating Chronic Wound Healing in Aged Mouse Model.

Due to the decreasing self-repairing ability, elder people are easier to form chronic wounds and suffer from slow and difficult wound healing. It is desirable to develop a novel wound dressing that can accelerate chronic wound healing in elderly subjects to decrease the pain of patients and save medical resources. In this work, Heparin and basic fibroblast growth factor(bFGF) were dissolved in the mixing solution of 4-arm acrylated polyethylene glycol and dithiothreitol to form hydrogel dressing in vitro at room temperature without any catalysts, which is convenient and easy to handle in clinic application. In vitro re-lease test shows the bFGF could be continuously released for at least 7 days, whereas the dressing surface integrity maintained for 3 days degradation in PBS solution. Three groups of treatments including bFGF-Gel, bFGF-Sol and control without any treatment were applied on the full-thickness wound on the 22 months old mice back. The wound closure rate and histological and immunohistochemical staining all illustrated that bFGF-Gel displayed a better wound healing effect than the other two groups. Thus, as-prepared hydrogel dressing seems supe-rior to current clinical treatment and more effective in elderly subjects, which shows promising potential to be applied in the clinic.

3D biomaterial P scaffolds carrying umbilical cord mesenchymal stem cells improve biointegration of keratoprosthesis

Biointegration of a keratoprosthesis (KPro) is critical for the device stability and long-term retention. Biointegration of the KPro device and host tissue takes place between the surrounding corneal graft and the central optic (made by poly (methyl methacrylate)). Our previous clinical results showed that auricular cartilage reinforcement is able to enhance the KPro biointegration. However, the auricular cartilage is non-renewable and difficult to acquire. In this study, we developed a novel type of biomaterial using a three-dimensional porous polyethylene glycol acrylate scaffold (3D biological P-scaffold) carrier with chondrocytes differentiated from induced human umbilical cord mesenchymal stem cells (hUC-MSCs) and tested in rabbit corneas. The results showed hUC-MSCs bear stem cell properties and coule be induced into chondrocytes, P-scaffold is beneficial to the growth and differentiation of hUC-MSCs both in vivo and in vitro. Besides, after implanting the P-scaffold into the corneal stroma, no serious immune rejection response, such as corneal ulcer or perforation were seen, suggested a good biocompatibility of P-scaffold with the corneal tissue. Moreover, after implanting P-scaffold in together with the differentiated chondrocytes into the rabbit corneal stroma, they significantly increased corneal thickness and strengthened the host cornea, and chondrocytes could stably persist inside the cornea. In summary, the 3D biological P-scaffold carrying differentiated hUC-MSCs could be the preferable material for KPro reinforcement.

Tumor-Targeted Injectable Double-Network Hydrogel for Prevention of Breast Cancer Recurrence and Wound Infection via Synergistic Photothermal and Brachytherapy.

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)‐alginate double‐network nanocomposite hydrogel (GPA) embedded with 125I‐labeled RGDY peptide‐modified gold nanorods (125I‐GNR‐RGDY) is fabricated. The double‐network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature‐induced PEGDA polymerization driven by near‐infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double‐network hydrogel possesses a dense polymer network and tightly fixes 125I‐GNR‐RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self‐repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single‐photon emission computerized tomography imaging owing to isotope labeling of loaded 125I‐GNR‐RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.

Electrospun Fibers Improving Cellular Respiration via Mitochondrial Protection.

Cellular respiration is the prerequisite for cell survival and functions, and mitochondrial function and microcirculation oxygen supply are essential for cellular respiration. However, in diabetic fracture, cellular respiration of bone marrow stem cells (BMSCs) is disrupted because of the dysfunction of mitochondria and microcirculation disorders. Here, the electrospun fibers of GelMA loaded with Hif-1 pathway activator (DFO) are constructed to improve the cellular respiration of BMSCs via protecting mitochondrial function and reconstructing microcirculation. The sequential process of electrospinning and UV crosslinking endowed the electrospun fibers with breathability and the biomechanical properties like the periosteum. In vitro biomolecular experiments showed that by crosslinking grafted polyethylene glycol acrylate liposomes loaded with DFO, the functional electrospun fibers can release DFO locally to activate Hif-1 in BMSCs, which can regulate the balance of Bcl-2/Bax to protect mitochondria and upregulate the expression of VEGF to reconstruct microcirculation. Animal experiments confirmed that the functional electrospun fibers can promote the recovery of diabetic fracture in vivo. These suggested that the functional electrospun fibers can improve cellular respiration for cell survival and functions of BMSCs. This study provides a new treatment strategy for diabetic fracture and other tissue regeneration on basis of cellular respiration improvement.

Effects of crosslinked polycarboxylate superplasticizers with crosslinking agent containing ester and amide groups on the properties of cementitious systems

AbstractHerein, crosslinked polycarboxylate superplasticizers were synthesized using acrylic acid, sodium methylallyl sulfonate and methyl polyethylene glycol acrylate as monomers, and monomers that contain either ester or amide groups as crosslinking agents. The superplasticizers that were synthesized from the ester‐ and amide‐based crosslinking agents were respectively denoted as SP‐E and SP‐N. In addition, a series of performance characterizations were carried out to explore the influence of different functional groups in crosslinking agents on the performance of superplasticizers. Fluidity test results showed that the dispersibility and fluidity retention of cement pastes treated with the SP‐E were better than those of cement pastes treated with SP‐N. Meanwhile, the viscosity of the sample containing SP‐E was lower than that containing SP‐N. In addition, the amount of the two superplasticizers that had become adsorbed onto the surfaces of cement particles also differed, and in this case the adsorption capacity of SP‐E was greater than that of SP‐N. X‐ray diffraction, thermogravimetric analysis, and scanning electron microscopy tests showed that the ester‐group based SP‐E superplasticizers promoted cement hydration to a greater degree than that was achieved with their amide‐bearing SP‐N counterparts. This study would provide valuable insight for the development of crosslinked polycarboxylate superplasticizers.