Stephen C. Moratti

The efficacy of a novel chitosan gel on hemostasis and wound healing after endoscopic sinus surgery.

Background Postoperative bleeding and adhesion formation are the two most common complications after endoscopic sinus surgery (ESS). Continued bleeding risks airway compromise from the inhalation of blood clots and from the aspiration of blood-stained vomitus. Additionally, adhesion formation is the most common reason for patients requiring revision surgery. This study aimed to determine the efficacy of a novel chitosan/dextran (CD) gel on hemostasis and wound healing after ESS. Methods A randomized controlled trial was performed involving 40 patients undergoing ESS for chronic rhinosinusitis. Immediately after surgery a baseline Boezaart Surgical Field Grading Scale was taken. Computer randomization was performed with one side receiving CD gel and the other side receiving no treatment (control). Boezaart bleeding scores were then calculated for each side every 2 minutes. Patients endoscopic features of wound healing were assessed at 2, 6, and 12 weeks after surgery. Results CD gel achieved rapid hemostasis with the mean time to hemostasis at 2 minutes (95% CI, 2–4 minutes) compared with 10 minutes (95% CI, ≥6 minutes) for the control (p < 0.001). There were significantly less adhesions at all time points with CD gel versus control: 2 versus 18 at 2 weeks (p < 0.001), 3 versus 16 at 6 weeks (p < 0.001), and 2 versus 12 at 3 months (p < 0.001). There was no significant difference between CD gel and control with respect to crusting, mucosal edema, infection, or granulation tissue formation. Conclusions CD gel is rapidly hemostatic immediately after ESS and prevents adhesion formation, addressing two of the most common complications of sinus surgery.

Antimicrobial Properties of a Chitosan Dextran-Based Hydrogel for Surgical Use

ABSTRACT A chitosan dextran-based (CD) hydrogel, developed for use in endoscopic sinus surgery, was tested for antimicrobial activity in vitro against a range of pathogenic microorganisms. The microdilution technique was used to determine minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations. In addition, the time-kill efficacy of CD hydrogel was determined for two bacterial species. Scanning and transmission electron microscopy were carried out to elucidate the antimicrobial mechanism of this compound. CD hydrogel was found to be effective against Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, and Clostridium perfringens at its surgical concentration of 50,000 mg/liter. Minimum bactericidal concentrations ranged from 2,000 to 50,000 mg/liter. Dextran aldehyde (DA) was found to be the antimicrobial component of the CD hydrogel with MBC ranging from 2,000 to 32,000 mg/liter. S. aureus appeared to be killed at a slightly faster rate than E. coli. Candida albicans and Pseudomonas aeruginosa were more resistant to CD hydrogel and DA. Scanning and transmission electron microscopy of E. coli and S. aureus incubated with CD hydrogel and DA alone revealed morphological damage, disrupted cell walls, and loss of cytosolic contents, compatible with the proposed mode of action involving binding to cell wall proteins and disruption of peptide bonds. Motility and chemotaxis tests showed E. coli to be inhibited when incubated with DA. The antibacterial activity of CD hydrogel may make it a useful postsurgical aid at other body sites, especially where there is a risk of Gram-positive infections.

Sensitivity of silver(I) complexes of a pyrimidine-hydrazone ligand to solvent, counteranion, and metal-to-ligand ratio changes.

Metal complexation studies were performed with AgSO(3)CF(3) and AgBF(4) and the ditopic pyrimidine-hydrazone ligand 6-(hydroxymethyl)pyridine-2-carboxaldehyde (2-methylpyrimidine-4,6-diyl)bis(1-methylhydrazone) (1) in both CH(3)CN and CH(3)NO(2) in a variety of metal-to-ligand ratios. The resulting complexes were studied in solution by NMR spectroscopy and in the solid state by X-ray crystallography. Reacting either AgSO(3)CF(3) or AgBF(4) with 1 in either CH(3)CN or CH(3)NO(2) in a 1:1 metal-to-ligand ratio produced a double helicate in solution. This double helicate could be converted into a linear complex by increasing the metal-to-ligand ratio; however, the degree of conversion depended on the solvent and counteranion used. Attempts to crystallize the linear AgSO(3)CF(3) complex resulted in crystals with the dimeric structure [Ag(2)1(CH(3)CN)(2)](2)(SO(3)CF(3))(4) (2), while attempts to crystallize the AgSO(3)CF(3) double helicate from CH(3)CN resulted in crystals of another dimeric complex, [Ag(2)1(SO(3)CF(3))(CH(3)CN)(2)](2)(SO(3)CF(3))(2)·H(2)O (3). The AgSO(3)CF(3) double helicate was successfully crystallized from a mixture of CH(3)CN and CH(3)NO(2) and had the structure [Ag(2)1(2)](SO(3)CF(3))(2)·3CH(3)NO(2) (4). The linear AgBF(4) complex could not be isolated from the double helicate in solution; however, crystals grown from a solution containing both the AgBF(4) double helicate and linear complexes in CH(3)CN had the structure [Ag(2)1(CH(3)CN)(2)](BF(4))(2) (5). The AgBF(4) double helicate could only be crystallized from CH(3)NO(2) and had the structure [Ag(2)1(2)](BF(4))(2)·2CH(3)NO(2) (6).

Active-template synthesis of "click" (2)rotaxane ligands: self-assembly of mechanically interlocked metallo-supramolecular dimers, macrocycles and oligomers†

Due to potential applications in the biological and material sciences there is considerable interest in the development of mechanically interlocked ligands (MILs). The mild functional-group tolerant copper(I)-catalysed azide–alkyne cycloaddition active-metal-template (CuAAC-AMT) method has been exploited to generate mono- and bi-functionalised [2]rotaxanes by interlocking an exo-alcohol functionalised macrocycle and functionalised triphenylmethyl stoppers. These [2]rotaxanes were post-synthetically conjugated to either one or two 2,2′,6′,2′′-terpyridine (terpy) coordinating units to generate mechanically interlocked “super” ligands. Addition of Fe(II) ions to the mono-terpy ligand leads to the formation of a metallo-bis-([2]rotaxane). At high dilution the bi-terpy [2]rotaxane ligand forms a [2]rotaxane metallo-macrocycle, in the presence of Fe(II) ions. Conversely, at high concentration self-assembly of the bi-terpy [2]rotaxane ligand with Fe(II) ions results in the generation of a metallo-supramolecular poly-[2]rotaxane oligomer. The [2]rotaxane ligands and corresponding Fe(II) complexes have been characterised with 1H and 13C NMR and UV-vis spectroscopies, high resolution electrospray ionisation mass spectrometry (HR-ESMS), and elemental analyses. Additionally, 1H DOSY NMR spectroscopy and GPC analysis were used to provide evidence for the constitution of the self-assembled metallo-supramolecular mechanically-interlocked architectures.

Hydrogels for biomedical applications

Hydrogels are swollen, crosslinked networks that have great potential for use in biomedicine. Their softness, biocompatibility and ability for rapid diffusion of molecules make them useful for drug delivery, cell culture, wound healing and sensing applications. The chemical functionality of the gels can be easily modified to provide signalling and growth factors for cell proliferation. To allow the ingress of large cells, either porosity of the substrate can be controlled, or the gel can be made biodegradable. One ultimate goal is the growth of entire organs in the laboratory for eventual transplantation. Gels can be used as drug-delivery vehicles, either as implantable depots, or as microgels in blood-based delivery systems. One expanding area is the use of gels as surgical aides to prevent bleeding, infection and post-operative complications.

The efficacy of a novel chitosan gel on hemostasis after endoscopic sinus surgery in a sheep model of chronic rhinosinusitis.

Background Postoperative bleeding remains a major problem after endoscopic sinus surgery (ESS). Patients who continue to bleed after ESS are at risk of airway compromise from inhalation of blood clots or from aspiration of blood-stained vomitus. The aim of this study was to determine the in vivo efficacy of a novel gel on hemostasis after ESS in a sheep model of chronic rhinosinusitis. Methods Twenty-one sheep infested with Oestrus ovus underwent ESS with standardized mucosal injuries created at the anterior ethmoid region using a microdebrider. Immediately after injury a baseline bleeding time was taken using the Boezaart Surgical Field Grading Scale. Computer randomization was performed to either receive chitosan/dextran (CD) gel or no treatment (control). Boezaart bleeding scores were calculated for each side every 2 minutes. Each postoperative day videoendoscopy was performed to document crusting/CD gel dissolution. Results The CD gel side was significantly more hemostatic at 2, 4, and 6 minutes after injury. Average time to hemostasis was significantly better for the intervention side versus control side, 4.09 (±1.61) versus 6.57 (±2.20), respectively (p = 0.049). Complete hemostasis occurred by 6 minutes for all CD gel sides; however, control side bleeding was noted on three sides at 8 minutes and on one side at 10 minutes. There was no significant difference in crusts scores at days 1, 3, 7, and 14. Conclusion In the sheep model of ESS, CD gel significantly improved hemostasis compared with the control at 2, 4, and 6 minutes after mucosal injury.

Control of Self-Assembly through the Influence of Terminal Hydroxymethyl Groups on the Metal Coordination of Pyrimidine−Hydrazone Cu(II) Complexes

The synthesis and characterization of 6-hydroxymethylpyridine-2-carboxaldehyde (2-methyl-pyrimidine-4,6-diyl)bis(1-methylhydrazone) (1) is reported. Ligand 1 was designed as a ditopic pyrimidine-hydrazone molecular strand with hydroxymethyl groups attached to the terminal pyridine rings. Coordination of 1 with Cu(ClO(4))(2) x 6 H(2)O or Cu(SO(3)CF(3))(2) x 4 H(2)O in a 1:2 molar ratio resulted in the dinuclear Cu(II) complexes [Cu(2)1(CH(3)CN)(4)](ClO(4))(4) x CH(3)CN (4) and [Cu(2)1(SO(3)CF(3))(2)(CH(3)CN)(2)](SO(3)CF(3))(2) x CH(3)CN (5). X-ray crystallography and (1)H NMR NOESY experiments showed that 1 adopted a horseshoe shape with both pyrimidine-hydrazone (pym-hyz) bonds in a transoid conformation, while 4 and 5 were linear in shape, with both pym-hyz bonds in a cisoid conformation. Coordination of 1 with Cu(ClO(4))(2) x 6 H(2)O or Cu(SO(3)CF(3))(2) x 4 H(2)O in a 1:1 molar ratio resulted in three different bent complexes, [Cu(1H)(ClO(4))(2)](ClO(4)) (6), [Cu(1H)(CH(3)CN)](ClO(4))(3) x 0.5 H(2)O (7), and [Cu1(SO(3)CF(3))](2)(SO(3)CF(3))(2) x CH(3)CN (8), where the pym-hyz bond of the occupied coordination site adopted a cisoid conformation, while the pym-hyz bond of the unoccupied site retained a transoid conformation. Both 6 and 7 showed protonation of the pyridine nitrogen donor in the empty coordination site; complex 8, however, was not protonated. A variety of Cu(II) coordination geometries were seen in structures 4 to 8, including distorted octahedral, trigonal bipyramidal, and square pyramidal geometries. Coordination of the hydroxymethyl arm in the mononuclear Cu(II) complexes 6, 7, and 8 appeared to inhibit the formation of a [2 x 2] grid by blocking further access to the Cu(II) coordination sphere. In addition, the terminal hydroxymethyl groups contributed to the supramolecular structures of the complexes through coordination to the Cu(II) ions and hydrogen bonding.

A blinded randomized controlled trial evaluating the efficacy of chitosan gel on ostial stenosis following endoscopic sinus surgery

Stenosis of sinus ostia following endoscopic sinus surgery (ESS) is the most common reason for revision surgery. Chitosan‐dextran (CD) gel has been shown to be an effective hemostatic agent; however, its effects on ostial stenosis are unknown. This study aims to quantify the effect of CD gel on circumferential scarring following ESS.

Soft-Etch Mesoporous Hole-Conducting Block Copolymer Templates

We present a mesoporous hole-conducting polymer film resulting from spontaneous block copolymer self-assembly based on a simple spin-coating protocol. A diblock copolymer consisting of a triphenylamine side group polymer and a poly(d,l-lactide) block (PSTPA-b-PLA) is shown to microphase separate to form ordered 13 nm cylindrical PLA microdomains embedded in the semiconducting PSTPA matrix. Partially ordered and film-spanning PLA domains could be identified in films immediately after spin coating from toluene solutions on conducting substrates. Selective mild etching of the minority PLA domains (in weak aqueous base) leads to a mesoporous hole-conducting polymer matrix. The pore structure is replicated electrochemically in platinum, demonstrating the viability of this approach to producing nano-organized heterojunction structures in thin films.

Conformational changes in regioregular polythiophenes due to crosslinking

Regioregular polythiophene copolymers 10a-d containing hexyl and 11-hydroxyundecyl side chains have been synthesised, by nickel-catalysed cross-coupling of well-defined Grignard intermediates. The hydroxy groups were protected during the polymerisation as tetrahydropyranyl ethers, and subsequently transformed into azide groups. These azide-functionalised copolymers 11a-d were heated under vacuum, leading to azide decomposition, nitrene formation and crosslinking. The resultant polymer films showed decreased solubility (or insolubility) and a shift in the absorption spectrum to shorter wavelengths dependent on the azide content of the polymer. This colour change is rationalised in terms of the conformational change in the polythiophene backbone, associated with thermochromism, which has been partially fixed by the crosslinking at high temperature. This is supported by the modified thermochromism and photoluminescence behaviour of the crosslinked polymer films.