Udo Greiser's research while affiliated with National Park Service and other places

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 HASH (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 HASH solutions, respectively, before hydrogel formation. Then, the release of H 2 O 2 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 H 2 O 2 /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

Chondroitin sulfate (CS), as a popular material for cartilage tissue engineering scaffolds, has been extensively studied and reported for its safety and excellent biocompatibility. However, the rapid degradation of pure CS scaffolds has brought a challenge to regenerate neo-tissue similar to natural articular cartilage effectively. Meanwhile, the poly(ethene glycol) (PEG) -based biopolymer is frequently applied as a structural constituent material because of its remarkable mechanical properties, long-lasting in vivo stability, and hypo-immunity. Here, we report that the combination of CS and hyperbranched multifunctional PEG copolymer (HB-PEG) could synergistically promote cartilage repair. The thiol functionalised CS (CS-SH)/HB-PEG hydrogel scaffolds were fabricated via thiol-ene reaction, which exhibits rapid gelation, excellent mechanical properties and prolonged degradation properties. We found that rat adipose-derived mesenchymal stem cells presented great cell viability and improved chondrogenesis in CS-SH/HB-PEG hydrogels. Moreover, the injectable hydrogel scaffolds reduced stem cell inflammatory response, consistent with the well-documented anti-inflammatory activities of CS.

Current therapies for most neurodegenerative disorders are only symptomatic in nature and do not change the course of the disease. Gene therapy plays an important role in disease modifying therapeutic strategies. Herein, we have designed and optimized a series of highly branched poly(β-amino ester)s (HPAEs) containing biodegradable disulfide units in the HPAE backbone (HPAESS) and guanidine moieties (HPAESG) at the extremities. The optimized polymers are used to deliver minicircle DNA to multipotent adipose derived stem cells (ADSCs) and astrocytes, and high transfection efficiency is achieved (77% in human ADSCs and 52% in primary astrocytes) whilst preserving over 90% cell viability. Furthermore, the top-performing candidate mediates high levels of nerve growth factor (NGF) secretion from astrocytes, causing neurite outgrowth from a model neuron cell line. This synergistic gene delivery system provides a viable method for highly efficient non-viral transfection of ADSCs and astrocytes.

Abstract Book: Drug-Free Antibacterial Technology for Medical Applications - First Cambridge International Conference - December 14th, 2018 - Cambridge, UK

It is well known that free radical (co)polymerization of multivinyl monomers (MVMs) leads to insoluble gels even at a low monomer conversion, and the gelation point can be predicted by Flory–Stockmayer theory (F–S theory) based on two assumptions: (1) equal reactivity of all vinyl groups and (2) the absence of intramolecular cyclization. This theory has been experimentally studied and verified with conventional free radical (co)polymerization (FRP) of several MVMs (e.g., divinylbenzene, DVB). However, it is still debatable whether this theory is applicable for the polymerization of MVMs using reversible deactivation radical polymerization (RDRP) approaches, such as atom transfer radical polymerization (ATRP). Herein, Monte Carlo simulations using two statistical models—with cyclization (w.c.) and without cyclization (wo.c., corresponding to F–S theory)—and dynamic lattice liquid (DLL) models were conducted to study ATRP of divinyl monomers. The simulated gel points using w.c. and wo.c. models were compared with those obtained from ATRP experiments, from calculation using F–S theory, and from simulations using DLL models. The molecular weights, dispersity, and extent of intermolecular/intramolecular cross-linking were calculated as a function of double bond and cross-linker conversion. The results demonstrated that the gel points obtained from both w.c. and wo.c. models were lower than the values from DLL models and experiments. This indicates that F–S theory cannot be used to accurately predict the polymerization of divinyl monomers via ATRP. Our study shows that the limitation of F–S theory in predicting ATRP reaction of divinyl monomers is not only due to neglecting intramolecular cyclization but also due to spatial restrictions which can cause the reactivity and accessibility of vinyl groups becoming nonequivalent in ATRP of divinyl monomers.

Microbial colonization on biomaterials is the main cause of failure of a successful implantation. In fact, local infections can eventually evolve in severe sepsis that might finally end up in a multi-organ failure and death of the patient. Besides, infection has become one of the toughest problems in the medical world, as microorganisms become more resistant to known drugs. Scientific research has been focussing on exploring new strategies to combat this life-threatening problem. In this review, information was collected about currently used polymeric biomaterials in the medical field and the main bacterial infections associated with their implantation. Furthermore, drug-free strategies to overcome this complication are explored, and the existing methodology required for assessment of the antibacterial activity is also described.

Statement of significance: Diabetic 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.

Back Cover: By a combination of Cu(0)- and Cu(II)-mediated homopolymerization of multivinyl monomers (MVMs) and thiol-ene click chemistry, amphiphilic multifunctional star polymers with high arm numbers are prepared by using single-chain cyclized/knotted nanoparticle (SCKPs) as the core. Further details can be found in article number 1700473 by Dezhong Zhou,* Guangfu Yin,* and co-workers.