Hyperbranched Poly Ethylene Glycol Research Articles

Convert bamboo into high-performance, long-time durability, and fire-retardant with hyperbranched polyethylene glycol and boron

Despite renewable bamboo globally available and has been applied in industry, the bamboo modification still absents for achieving long-term anti-mildew, stability and desirable toughness, owing to its inherent hierarchical porous structures, that cannot fully insert and retain ideal drugs/polymers. Hence, a hyperbranched polymer (HPB) with polyether as backbone and phenylboronic acid as binding groups via epoxy ring-opening reactions with amino was designed, and subsequently in situ synthesized in the multi-scaled cellular structures in bamboo. It was demonstrated that the hyperbranched polyether chains filled and swollen the hierarchical bamboo cell walls, which could efficiently replace the inner hydroscopic water in bamboo and greatly improved the bamboo stability, resulted in the wet swelling and dry shrinkage rates reduced by 20.3 % and 14.8 %, respectively. Both the side groups of phenylboronic acid and epoxy on HPB outer layers could generate covalent bonding with bamboo cell walls, which twisted the easy-losing facts of boron and gained a 60.6 % retention rate, surpassed most reported modified bamboo literatures and conferred bamboo with good fire resistance and long-time anti-mildew performance. Importantly, with the cavitation effect of HPB to help stress transmission, the modified bamboo had not expensed bamboo strength, instead of reaching satisfied bending strength and toughness at 154.1 MPa of flexure strength and 10.8 % of bending strain, respectively. That expand the industrial application of bamboo.

A novel hyperbranched polyurethane solid electrolyte for room temperature ultra-long cycling lithium-ion batteries

Low room temperature ionic conductivity of solid polymer electrolytes (SPE) greatly constraints its application in the solid lithium-ion batteries. Hyperbranched polymer with unique topological structure as matrix of SPE is expected to solve this issue due to its low crystallinity and rich functional groups which helps dissociation of lithium salt. Herein, a hyperbranched polyurethane (HPU) solid electrolyte is prepared by the reaction of hyperbranched polyethylene glycol and isophoradione diisocyanate in the presence of lithium salt and ionic liquid for the first time. The obtained HPU1.5-IL1.5 electrolyte possesses a high room temperature ionic conductivity of 0.4 mS cm−1 and a wide electrochemical window of 4.95 V (vs Li/Li+). It is worth noting that the prepared HPU1.5-IL1.5 electrolyte can be adapted to multiple electrodes. Specifically, the assembled LFP half-cell can achieve long cycling up to 1000 cycles at 0.5 C with 83 % capacity retention at room temperature. Notably, the NCM811|HPU1.5-IL1.5|Li cells and LTO|HPU1.5-IL1.5|Li cells can deliver the initial discharge capacity of 148 mAh g−1 at 0.1 C for 160 cycles and the initial discharge capacity of 150 mAh g−1 at 0.2 C for 440 cycles at room temperature, respectively. Meanwhile, the safety of the pouch cell has been confirmed under some extreme conditions.

Hyaluronic Acid-Based Reactive Oxygen Species-Responsive Multifunctional Injectable Hydrogel Platform Accelerating Diabetic Wound Healing.

Diabetic wounds are more likely to develop into complex and severe chronic wounds. The objective of this study is to develop and assess a reactive oxygen species (ROS)-responsive multifunctional injectable hydrogel for the purpose of diabetic wound healing. A multifunctional hydrogel (HA@Cur@Ag) is successfully synthesized with dual antioxidant, antibacterial, and anti-inflammatory properties by crosslinking thiol hyaluronic acid (SH-HA) and disulfide-bonded hyperbranched polyethylene glycol (HB-PBHE) through Michael addition; while, incorporating curcumin liposomes and silver nanoparticles (AgNPs). The HA@Cur@Ag hydrogel exhibits favorable biocompatibility, degradability, and injectivity. The outcomes of in vitro and in vivo experiments demonstrate that the hydrogel can effectively be loaded with and release curcumin liposomes, as well as silver ions, thereby facilitating diabetic wound healing through multiple mechanisms, including ROS scavenging, bactericidal activity, anti-inflammatory effects, and the promotion of angiogenesis. Transcriptome sequencing reveals that the HA@Cur@Ag hydrogel effectively suppresses the activation of the tumour necrosis factor (TNF)/nuclear factor κB (NF-κB) pathway to ameliorate oxidative stress and inflammation in diabetic wounds. These findings suggest that this ROS-responsive multifunctional injectable hydrogel, which possesses the ability to precisely coordinate and integrate intricate biological and molecular processes involved in wound healing, exhibits notable potential for expediting diabetic wound healing.

Improving Liposome Delivery with Macroporous Granular Hydrogels Synthesized through Freezing‐Facilitated Secondary Crosslinking of Macromonomers

AbstractThe integration of liposomes into hydrogels through direct soaking presents advantages such as facile formulation, enhanced drug stability, and controlled release kinetics. However, the feasibility of this approach is impeded by the difficulty of developing matching porous structures within hydrogels and achieving appropriate affinity with liposomes. To address these challenges, an alternative method is proposed for synthesizing macroporous hydrogels using thiolated hyaluronic acid and hyperbranched polyethylene glycol macromonomers in combination with a freezing‐induced secondary crosslinking process. This approach allows the locking of macropores formed by ice crystals during freezing and enables easy modification of the hydrogels with cholesterol groups to promote liposome association. Furthermore, these macroporous hydrogels can be crushed into granular hydrogels, which offer numerous benefits such as high loading capacity, injectability, self‐healing properties, and convenience in storage, dosing, and administration. Therefore, a liposome‐in‐hydrogel system can be formulated without any gelation or pre‐treatment, providing valuable insights for the further development of liposome‐based formulations for medical and cosmetic applications.

In situ Forming Hyperbranched PEG-Thiolated Hyaluronic Acid Hydrogels With Honey-Mimetic Antibacterial Properties.

The rapidly increasing resistance of bacteria to currently approved antibiotic drugs makes surgical interventions and the treatment of bacterial infections increasingly difficult. In recent years, complementary strategies to classical antibiotic therapy have, therefore, gained importance. One of these strategies is the use of medicinal honey in the treatment of bacterially colonized wounds. One of the several bactericidal effects of honey is based on the in situ generation of hydrogen peroxide through the activity of the enzyme glucose oxidase. The strategy underlying this work is to mimic this antibacterial redox effect of honey in an injectable, biocompatible, and rapidly forming hydrogel. The hydrogel was obtained by thiol–ene click reaction between hyperbranched polyethylene glycol diacrylate (HB PEGDA), synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization, and thiolated hyaluronic acid (HA-SH). After mixing 500 µL HB PEGDA (10%, w/w) and 500 µL HA-SH (1%, w/w) solutions, hydrogels formed in ∼60 s (HB PEGDA/HA-SH 10.0–1.0), as assessed by the tube inverting test. The HB PEGDA/HA-SH 10.0–1.0 hydrogel (200 µL) was resistant to in vitro dissolution in water for at least 64 days, absorbing up to 130 wt% of water. Varying glucose oxidase (GO) amounts (0–500 U/L) and constant glucose content (2.5 wt%) were loaded into HB PEGDA and HA-SH solutions, respectively, before hydrogel formation. Then, the release of H2O2 was evaluated through a colorimetric pertitanic acid assay. The GO content of 250 U/L was selected, allowing the formation of 10.8 ± 1.4 mmol H2O2/L hydrogel in 24 h, under static conditions. The cytocompatibility of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with different GO activities (≤ 500 U/L) at a constant glucose amount (2.5 wt%) was investigated by in vitro assays at 24 h with L929 and HaCaT cell lines, according to DIN EN ISO 10993-5. The tests showed cytocompatibility for GO enzyme activity up to 250 U/L for both cell lines. The antibacterial activity of HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with increasing amounts of GO was demonstrated against various gram-positive bacteria (S. aureus and S. epidermidis), antibiotic-resistant gram-positive bacteria (MRSA and MRSE), gram-negative bacteria (P. aeruginosa, E. coli, and A. baumanii), and antibiotic-resistant gram-negative strains (P. aeruginosa and E. coli) using agar diffusion tests. For all gram-positive bacterial strains, increasing efficacy was measured with increasing GO activity. For the two P. aeruginosa strains, efficacy was shown only from an enzyme activity of 125 U/L and for E. coli and A. baumanii, efficacy was shown only from 250 U/L enzyme activity. HB PEGDA/HA-SH 10.0–1.0 hydrogels loaded with ≤250 U/L GO and 2.5 wt% glucose are promising formulations due to their fast-forming properties, cytocompatibility, and ability to produce antibacterial H2O2, warranting future investigations for bacterial infection treatment, such as wound care.

Spatial modulation of biomolecules immobilization by fabrication of hierarchically structured PEG-derived brush micropatterns: An versatile cellular microarray platform

Microarray technology holds enormous promise in the development of various fields ranging from tissue engineering, regenerative medicine to high-throughput screening. Here, based on the digital micromirror device (DMD)-based spatiotemporal regulation of surface-initiated photoinduced atom transfer radical polymerization (Photo-ATRP) process, a flexible and versatile methodology was developed to fabricate a hierarchical microarray structure constituted with a homogeneous hyperbranched polyethylene glycol (PEG)-derived brush layer as anti-fouling background and an extension layer of square-grid poly(2-(2-azido-2-methyl-1-oxopropoxy) ethyl methacrylate) (PAMEMA) brushes micropatterns on the silicon substrate. The terminal azido groups on the side chains of PAMEMA brushes provide abundant reactive sites to realize the covalent immobilization of target biomolecules, including RGD peptide, fibronectin, BSA and streptavidin. The TOF-SIMS and fluorescence characterizations demonstrated the feasibility and efficiency of spatially modulating the density of surface-bound biomolecules through regulating the 3D architecture parameters of the PAMEMA brush micropatterns and consequentially the azido chemical functionality. Moreover, culture experiments of human bone-derived marrow stromal cells (BMSCs) and mouse L929 cells were conducted on the obtained hierarchical microarray structure in a high-throughput manner. The presented hierarchical microarray structure holds excellent potential as a high-throughput screening platform, allowing for the parallel assessment of cell-surface interactions.

Post-synthesis modification of polyethersulfone membrane by grafting hyperbranched polyethylene glycol for oily wastewater treatment

The main goal of this study is to modify the polyethersulfone membrane by the grafting hyperbranched polyethylene glycol (HB-PEG) via a two-step grafting method: (1) membrane surface activation with a photo-initiator under UV irradiation and (2) grafting HB-PEG onto the surface-activated membrane. The separation efficiency and fouling tendency of the modified membranes were evaluated for the treatment of a synthetic oily wastewater. A mechanism was proposed for the grafting reaction, and Lambert–Beer law was employed to determine the effect of benzophenone (BP) concentration as a photo-initiator on the grafting reaction. It was found that the rate of the grafting reaction has a maximum at the BP concentration of 0.33 mol/L. The FTIR and SEM analyses confirmed that the HB-PEG was successfully grafted on the surface of activated PES membranes. Moreover, the grafting HB-PEG onto the surface of the PES membranes alerted the surface hydrophilicity and led to the improvement of the anti-fouling property and oil–water permeation flux of all modified membranes without any remarkable changes in the oil rejection, as 48% and 52% enhancement in the pure water flux and oil–water flux were observed, respectively, compared to the neat PES membrane. Finally, the chemical stability of the modified membrane was investigated and the recovery of the fouled membrane after basic and acidic cleaning was 58% and 94%, respectively.

Surface modification of a PES membrane by corona air plasma-assisted grafting of HB-PEG for separation of oil-in-water emulsions.

The main goal of this study is to modify a polyethersulfone (PES) membrane by grafting with hyperbranched polyethylene glycol (HB-PEG) using corona air plasma to intensify the anti-fouling properties of the prepared membrane. The separation efficiency and fouling tendency of the modified membranes were evaluated for the treatment of a synthetic oily wastewater. A mechanism was proposed for the HB-PEG grafting on the surface of the corona treated PES membranes and all steps of the grafting were described in detail. The effects of corona treatment operating conditions on the morphology, surface properties, separation performance and anti-fouling efficiency of the modified PES membranes were investigated. Also, the HB-PEG grafted PES membranes were characterized by FTIR, AFM and contact angle analysis. Finally, the HB-PEG grafting on the surface of the PES membranes altered the surface hydrophilicity and led to the improvement of the anti-fouling property and oil–water permeation flux of all modified membranes without any remarkable changes in oil rejection.

Support vector machine-based modeling of grafting hyperbranched polyethylene glycol on polyethersulfone ultrafiltration membrane for separation of oil–water emulsion

In present study, a new method based on the support vector machine (SVM) approach was employed to calculate the oil–water permeation flux and grafting yield of maleic anhydride and hyperbranched polyethylene glycol (PEG) on the polyethersulfone (PES) membrane surface. A set of 7 input/output experimental data was applied for training and testing the results of the model. The results of the developed SVM model showed good compliance with the experimental data, as the value of correlation index for the developed model is 0.96, 0.95 and 0.98 for the maleic anhydride and hyperbranched PEG grafting and oil–water permeation flux, respectively. The model was also validated against the kinetic reaction of benzophenone formation on the PES membrane which derives from combination of benzophenone formation reactions and the Lambert–Beer law. Also, to validate the SVM results, the oil–water permeation flux and antifouling characteristics of the modified and neat membranes were investigated, and based on the results, the SVM can be considered as a strong modeling approach in membrane process technologies.

Effects of Transplanted Islets Nano-Encapsulated with Hyperbranched Polyethylene Glycol and Heparin on Microenvironment Reconstruction and Glucose Control.

The microenvironment of pancreatic islets gets disrupted during enzyme digestion and causes islets to remain in a vulnerable state, leading to poor outcome in the initial days of transplantation. To avoid immune invasion while allowing the reconstruction of the microenvironment of the transplanted site, we propose immunoisolation polymers, which can nanoencapsulate islets quickly without cytotoxicity. Here, nonhuman primate (NHP) islets were nanoencapsulated with hyperbranched polyethylene glycol (hb-PEG) and heparin by layer-by-layer technology and transplanted into the kidney subcapsular space of diabetic C57BL/6 mice. An immunosuppressive drug protocol was applied to increase the survival time until the animals were sacrificed. The recipients of NHP islets exhibited high nonfasting blood glucose level (BGL) for 2-3 weeks, which was normalized afterward. Immunohistochemical (IHC) analysis revealed an immature vascular basement membrane and cell surface integrins directly associated with poor initial insulin production. The transplanted grafts regained their own microenvironment within a month without any outside stimuli. No lymphocyte infiltration was observed in the grafts at any time. Humoral and cell-mediated immune responses were prominently diminished by the hb-PEG/Heparin nanoencapsulated islets. Immunoisolation accompanied by an immunosuppressive drug protocol protects islets by helping them avoid immunogenesis while at the same time allowing them to reconstruct their microenvironment.

Combination strategy of multi-layered surface camouflage using hyperbranched polyethylene glycol and immunosuppressive drugs for the prevention of immune reactions against transplanted porcine islets

This study suggests a novel method of stabilizing fragile porcine islets to prevent the dissociation after isolation and reducing immune cell invasion in a combination therapy of ‘surface camouflaging’ and immunosuppressive drugs (FK506, Rapamycin, MR-1, anti-CD19 mAb, and Clodrosome®) to effectively alleviate overall immune reactions against xenotransplanted porcine islets. The surface camouflage of pancreatic islets using biocompatible materials improved stabilization of pancreatic islet and prevented the infiltration of immune cells. Firstly, the surface of porcine islets was camouflaged by SH-6-arm-PEG-lipid and gelatin-catechol (artificial extracellular matrix) in order to stabilize the fragile isolated islets. Secondly, three different PEG layers (6-arm-PEG-SH, 6-arm-PEG-catechol, and linear PEG-SH) were chemically conjugated onto the surface of the stabilized porcine islets. Both artificial extracellular matrix (artificial ECM) and PEGylation effectively covered the surface of porcine islets without increasing the size of the whole islet. In addition, the viability and functionality of the islets were not affected by this multi-layer surface modification. The multi-layer modification significantly reduced the attachment of human serum albumin, fibronectin, and immunoglobulin G in comparison to the control collagen surface. The combination effect of multi-layer PEGylation and cocktailed immunosuppressive drugs on the survival time of the transplanted islets was assessed in a xenogeneic porcine-to-mouse model. The median survival time (MST) of ‘artificial ECM + PEGylation' group was 4-fold increased compared to that of control group. In addition, the MST of ‘artificial ECM + PEGylation + drug' group was 2.16-fold increased, compared to the ‘control + drug’ group. In conclusion, we proposed a novel porcine islet transplantation protocol using surface multi-layer modification and cocktailed immunosuppressive drugs, for stabilization and immunoprotection against xenogeneic immune reactions.

A hyperbranched dopamine-containing PEG-based polymer for the inhibition of α-synuclein fibrillation

Aggregation of α-synuclein is believed to play an important role in Parkinson's disease and in other neurodegenerative maladies. Small molecule inhibitors of this process are among the most promising drug candidates for neurodegenerative diseases. Dendrimers have also been studied for anti-fibrillation applications but they can be difficult and expensive to synthetize. Here we show that RAFT polymerization can be used to produce a hyperbranched polyethylene glycol structure via a one-pot reaction. This polymer included a dopamine moiety, a known inhibitor of α-synuclein fibril formation. Dopamine within the polymer structure was capable of aggregation inhibition, although not to the same degree as free dopamine. This result opens up new avenues for the use of controlled radical polymerizations as a means of preparing hyperbranched polymers for anti-fibrillation activity, but shows that the incorporation of functional groups from known small molecules within polymers may alter their biological activity.

Hyperbranched PEGmethacrylate linear pDMAEMA block copolymer as an efficient non-viral gene delivery vector

A unique hyperbranched polymeric system with a linear poly-2-dimethylaminoethyl methacrylate (pDMAEMA) block and a hyperbranched polyethylene glycol methyl ether methacrylate (PEGMEMA) and ethylene dimethacrylate (EGDMA) block was designed and synthesized via deactivation enhanced atom transfer radical polymerisation (DE-ATRP) for efficient gene delivery. Using this unique structure, with a linear pDMAEMA block, which efficiently binds to plasmid DNA (pDNA) and hyperbranched polyethylene glycol (PEG) based block as a protective shell, we were able to maintain high transfection levels without sacrificing cellular viability even at high doses. The transfection capability and cytotoxicity of the polymers over a range of pDNA concentration were analysed and the results were compared to commercially available transfection vectors such as polyethylene imine (branched PEI, 25kDa), partially degraded poly(amido amine)dendrimer (dPAMAM; commercial name: SuperFect®) in fibroblasts and adipose tissue derived stem cells (ADSCs).