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Chest tubes account for a large proportion of postoperative pain after cardiothoracic operations. The objective of this study was to develop a novel, cost-effective, easy-to-use, lidocaine-eluting coating to reduce pain associated with postoperative chest tubes. A lidocaine-eluting hydrogel was developed by dispersing lidocaine-loaded nanoparticles in an aqueous solution containing gelatin (5%). Glutaraldehyde (1%) was added to crosslink the gelatin into a hydrogel. The hydrogel was dehydrated, resulting in a thin, stable polymer. Sterile lidocaine hydrogel-coated silicone discs and control discs were prepared and surgically implanted in the subcutaneous space of C57B6 mice. Using von Frey filaments, mice underwent preoperative baseline pain testing, followed by pain testing on post-procedure day 1 and 3. On post-procedure day 1, mice implanted with control discs demonstrated no change in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 2.4-fold (P = 0.36) and 4.7-fold (P = 0.01) increase in pain tolerance, respectively. On post-procedure day 3, mice implanted with control discs demonstrated a 0.7-fold decrease in pain tolerance compared to baseline, while mice implanted with 20 mg and 80 mg lidocaine-loaded discs demonstrated a 1.8-fold (P = 0.88) and 8.4-fold (P = 0.02) increase in pain tolerance, respectively. Our results demonstrate successful development of a lidocaine-eluting chest tube with hydrogel coating, leading to improved pain tolerance in vivo. The concept of a drug-eluting drain coating has significant importance due to its potential universal application in a variety of drain types and insertion locations.

Background Myelomeningocele (MMC) is an open neural tube defect of the spinal column. Our laboratory previously introduced a reverse thermal gel (RTG) as the first in situ forming patch for in utero MMC application. To overcome the challenges of anchoring the RTG in the wet amniotic environment to improve MMC coverage, we modified the RTG to mimic the underwater adhesive properties of mussels. We have separated this study into three separate hypotheses-based components: 1 Based on mussel inspired chemistry, modification of the RTG with dopamine will increase the underwater adhesive properties to improve RTG anchoring ability in a wet environment. Methods: The dopamine-modified RTG (DRTG) was synthesized using carbonyldiimidazole chemistry and characterized with proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy. Rheology and underwater adhesive tests measured mechanical properties. Results: DRTG synthesis was confirmed with proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, and ultraviolet-visible spectroscopy. Rheology demonstrated increased elasticity. Underwater adhesion testing revealed DRTG has similar wet adhesive strength to Tisseel fibrin sealant. 2 The DRTG will support in vitro skin cell growth and will be safe for injection in a mouse animal model. Methods: Biocompatibility testing included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, DRTG-fibroblast and keratinocyte cultures, and subcutaneous injections to quantify macrophages stained with immunohistochemistry. Results: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and DRTG cell cultures revealed no cytotoxicity and demonstrated the growth of fibroblasts and keratinocytes. Subcutaneous injections cause a macrophage response that decreases after 4 wk. 3 In utero injection of novel DRTG into a mouse MMC model will be effective with improved patch coverage of the MMC defect. Methods: MMC coverage by DRTG was assessed using in utero mouse injections in the Grainy head-like 3 (Grhl3) mouse model. Results: In utero Grhl3 mouse injections demonstrate statistically significant (P = 0.012) improved MMC coverage of DRTG compared with previous RTG coverage with no significant macrophage response. Conclusions The DRTG demonstrates increased elasticity, cellular scaffolding properties, and improved MMC coverage in the Grhl3 mouse model. Future studies will be translated to the preclinical ovine model to evaluate this novel gel.

Background Myelomeningocele (MMC) results in lifelong neurologic and functional deficits. Currently, prenatal repair of MMC closes the defect, resulting in a 50% reduction in postnatal ventriculoperitoneal shunting. However, this invasive fetal surgery is associated with significant morbidities to mother and baby. We have pioneered a novel reverse thermal gel (RTG) to cover MMC defects in a minimally invasive manner. Here, we test in-vitro RTG long-term stability in amniotic fluid and in vivo application in the Grainy head-like 3 (Grhl3) mouse MMC model. Materials and methods RTG stability in amniotic fluid (in-vitro) was monitored for 6 mo and measured using gel permeation chromatography and solution–gel transition temperature (lower critical solution temperature). E16.5 Grhl3 mouse fetuses were injected with the RTG or saline and harvested on E19.5. Tissue was assessed for RTG coverage of the gross defect and inflammatory response by immunohistochemistry for macrophages. Results Polymer backbone molecular weight and lower critical solution temperature remain stable in amniotic fluid after 6 mo. Needle injection over the MMC of Grhl3 fetuses successfully forms a stable gel that covers the entire defect. On harvest, some animals demonstrate >50% RTG coverage. RTG injection is not associated with inflammation. Conclusions Our results demonstrate that the RTG is a promising candidate for a minimally invasive approach to patch MMC. We are now poised to test our RTG patch in the large preclinical ovine model used to evaluate prenatal repair of MMC.

Starch-converting enzymes, α-amylase and glucoamylase, were immobilized on surface-modified carriers using a co-immobilized as well as a single system. Hydrophilic silica gel and DEAE-cellulose entrapped in alginate beads were selected as the most effective carriers. The hydrophilic and the hydrophobic characteristics of carriers were made by polyethylimine-coating and silanization, respectively, and confirmed by contact angle measurements. All co-enzymes immobilized on hydrophilic carriers exhibited the highest activities in each modulation. The lower K m values (0.102 mg/ml for hydrophilic silica gel and 0.099 mg/ml for DEAE-cellulose entrapped in beads) than that of native enzyme (0.199 mg/ml) represented the higher affinity of immobilized enzymes to substrates. When performing the hydrolysis of starch, the shifts of optimum temperature from 50 to 60 °C (or activation energy) and pH from 5.0 to 5.5 after immobilization were due to covalent bond formation and polyionic characteristics of carriers, respectively. The co-enzymes immobilized on hydrophilic silica gel and DEAE-cellulose entrapped in alginate beads exhibited 92.3 and 88.9% of the remaining activity even after 10 times of reuse.

Biocatalytic synthesis of β-methylglucoside methacrylate/acrylate by the esterification of β-methylglucoside with vinyl methacrylate/acrylate was carried out using an immobilized lipase from Candida antarctica (Novozym 435) in organic solvents. Among five model solvents including t-butanol, t-amyl alcohol, acetone, acetonitrile and 1,4-dioxane, t-butanol was found to be an optimal solvent. The amount of 5% (w/v) Novozym 435 resulted in the highest conversion after 48 h, and 1:3 molar ratio of β-methylglucoside to vinyl methacrylate showed 100% final conversion after 24 h. The optimal initial concentration of β-methylglucoside and temperature determined from the initial rate and final conversion were observed at 60 g/l and 50 °C, respectively. The productivity of sugar esters could be enhanced by the heterogeneous reaction mixture and the addition of β-methylglucoside after one cycle of reaction in homogeneous reaction. Based on the over 95% of cell viability by MTT assay, produced sugar esters were found to be highly biocompatible. Structural analysis of products was performed by FT-IR and 13 C NMR.