Hyperbranched PEG-based multi-NHS polymer and bioconjugation with BSA

Star-shaped poly(ethylene glycol)-N-hydroxysuccinimide (star- PEG-NHS) has shown great promise in a variety of biomedical applications owing to its non-toxicity, innate non-immunogenic properties and versatile, multifunctional end groups. However, its complex and sophisticated synthetic methods, as well as high costs, have significantly impeded its wide application. Here, we report the design and synthesis of a hyperbranched PEG-based polymer with multiple NHS functional groups (>12). The hyper- branched PEG-based multi-NHS polymer can react easily with a protein (bovine serum albumin, BSA) to form a PEG-protein hydro- gel that displays great potential for biomedical applications

Complex polymer architectures through free-radical polymerization of multivinyl monomers

The construction of complex polymer architectures with well-defined topology, composition and functionality has been extensively explored as the molecular basis for the development of modern polymer materials. The unique reaction kinetics of free-radical polymerization leads to the concurrent formation of crosslinks between polymer chains and rings within an individual chain and, thus, free-radical (co)polymerization of multivinyl monomers provides a facile method to manipulate chain topology and functionality. Regulating the relative contribution of these intermolecular and intramolecular chain-propagation reactions is the key to the construction of architecturally complex polymers. This can be achieved through the design of new monomers or by spatially or kinetically controlling crosslinking reactions. These mechanisms enable the synthesis of various polymer architectures, including linear, cyclized, branched and star polymer chains, as well as crosslinked networks. In this Review, we highlight some of the contemporary experimental strategies to prepare complex polymer architectures using radical polymerization of multivinyl monomers. We also examine the recent development of characterization techniques for sub-chain connections in such complex macromolecules. Finally, we discuss how these crosslinking reactions have been engineered to generate advanced polymer materials for use in a variety of biomedical applications

Ureteral inflammatory edema grading clinical application

PurposeTo evaluate the relationship between endoscopic ureteral inflammatory edema (UIE) and ureteral lumen, formulate a preliminary grading method for the severity of UIE, and analyze the impact of different grades of UIE on endoscopic ureteral calculi surgery and prognosis.Materials and methodsWe retrospectively analyzed 185 patients who underwent ureteroscopic lithotripsy (URSL) for upper urinary tract stones between January 2021 and November 2021. The UIE grade and lumen conditions were assessed by endoscopic observation. The effect of UIE grade on URSL and on patient prognosis were analyzed by multiple linear regression and binary logistic regression.ResultsA total of 185 patients were included in the study. UIE grade showed a significant correlation with age, hydronephrosis grading (HG), ureteroscope placement time (UPT), surgery time (ST), hemoglobin disparity value (HDV), and postoperative ureteral stenosis (PUS) (P < 0.05). Logistics regression analysis showed a gradual increase in intraoperative UPT and ST with increase in UIE grade. The severity of UIE showed a negative correlation with improvement of postoperative hydronephrosis (IPH) and the appearance of PUS. HDV was significantly increased in patients with UIE grade 3.ConclusionsUIE grading can be used as an adjunctive clinical guide for endoscopic treatment of upper urinary tract stones. The postoperative management measures proposed in this study can help inform treatment strategy for ureteral stones

3D Bioprinting of stimuli-responsive polymers synthesised from DE-ATRP into soft tissue replicas

Synthetic polymers possess more reproducible physical and chemical properties than their naturally occurring counterparts. They have also emerged as an important alternative for fabricating tissue substitutes because they can be molecularly tailored to have vast array of molecular weights, block structures, active functional groups, and mechanical properties. To this date however, there has been very few successful and fully functional synthetic tissue and organ substitutes and with the rapidly spreading 3D printing technology beginning to reshape the tissue engineering and regenerative field, the need for an effective, safe, and bio printable biomaterial is becoming more and more urgent. Here, we have developed a synthetic polymer from controlled living radical polymerization that can be printed into well-defined structures. The polymer showed low cytotoxicity before and after printing. Additionally, the incorporation of gelatine-methacrylate coated PLGA microparticles within the hydrogel provided cell adhesion surfaces for cell proliferation. The results point to possible application of the microparticle seeded, synthetic hydrogel as a direct printable tissue or organ substitute

Improvement of Electron Field Emission in Patterned Carbon Nanotubes by High Temperature Hydrogen Plasma Treatment

In this paper, we report a significant improvement of electron field emission property in patterned carbon nanotubes films by using a high temperature (650 °C) hydrogen plasma treatment. This treatment was found to greatly increase the emission current, emission uniformity and stability. The mechanism study showed that these enhanced properties are attributed to the lowering of the potential barrier and the creation of geometrical features through the removal of amorphous carbon, catalyst particles and the saturation of dangling bonds after such a hydrogen plasma treatment

A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing

The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system were fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. The new HP-PEGs were synthesized via in situ reversible addition fragmentation chain transfer (RAFT) polymerization using an FDA approved anti-alcoholic drug - Disulfiram (DS) as the RAFT agent precursor. HP-PEGs can form injectable hydrogels with HA-SH rapidly via thiol-ene click reaction under physiological conditions. The hydrogels exhibited stable mechanical properties, non-swelling and anti-fouling properties. Hydrogels encapsulating adipose-derived stem cells (ADSCs) have demonstrated promising regenerative capabilities such as the maintenance of ADSCs’ stemness and secretion abilities. The ADSCs embedded hydrogels were tested on the treatment of diabetic wound in a diabetic murine animal model, showing enhanced wound healing.Statement of significanceDiabetic wounds, which are a sever type of diabetes, have become one of the most serious clinical problem. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholi drug - Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment

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

Versatile Hyperbranched Poly(β-Hydrazide Ester) Macromers as Injectable Antioxidative Hydrogels

Synthetic reactive oxygen species (ROS)-responsive biomaterials have emerged as a useful platform for regulating critical aspects of ROS-induced pathologies and can improve such hostile microenvironments. Here, we report a series of new hyperbranched poly­(β-hydrazide ester) macromers (HB-PBHEs) with disulfide moieties synthesized via an “A2 + B4” Michael addition approach. The three-dimensional structure of HB-PBHEs with multiacrylate end groups endows the macromers with rapid gelation capabilities to form (1) injectable hydrogels via cross-linking with thiolated hyaluronic acid and (2) robust UV-cross-linked hydrogels. The disulfide-containing macromers and hydrogels exhibit H2O2-responsive degradation compared with the counterparts synthesized by a dihydrazide monomer without disulfide moieties. The cell viability under a high ROS environment can be well-maintained under the protection of the disulfide containing hydrogels

Enhanced Gene Transfection Efficacy and Safety Through Granular Hydrogel Mediated Gene Delivery Process

Although gene therapy has made great achievements in both laboratory research and clinical translation, there are still challenges such as limited control of drug pharmacokinetics, acute toxicity, poor tissue retention, insufficient efficacy, and inconsistent clinical translation. Herein, a gene therapy gel is formulated by directly redispersing polyplex nanoparticles into granular hydrogels without any gelation pre-treatment, which provides great convenience for storage, dosing and administration. In vitro studies have shown that use of granular hydrogels can regulate the gene drug release, reduce dose dependent toxicity and help improve transfection efficacy. Moreover, the developed gene therapy gel is easy to operate and can be directly used in vitro to evaluate its synergistic efficacy with various gene delivery systems. As such, it represents a major advance over many conventional excipient-based formulations, and new regulatory strategies for gene therapy may be inspired by it