Recombinant human collagen I/carboxymethyl chitosan hydrogel loaded with long-term released hUCMSCs derived exosomes promotes skin wound repair.

BACKGROUND: Stem cell exosomes are beneficial in accelerating wound repair. However, the therapeutic function is limited due to its rapid clearance in vivo. To improve the functionality of exosomes in cutaneous wound healing, a novel hydrogel was designed and fabricated by recombinant human collagen I and carboxymethyl chitosan loaded with exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs), named as the rhCol I/CMC-Exos hydrogel. METHODS: Exosomes were extracted from hUCMSCs and were characterizated by TEM (Transmission Electron Microscopy), and biomarker detection. The rhCol I hydrogel, rhCol I/carboxymethyl chitosan (rhCol I/CMC) hydrogel and the rhCol I/CMC-Exos hydrogel composites were cross-linked by genipin. These materials were assessed and compared for their physical characteristics, including cross-sectional morphology, porosity, pore distribution, and hydrophilicity. Cell biocompatibility on biomaterials was investigated using scanning electron microscopy and CFDA staining, as well as assessed in vivo through histological examination of major organs in mice. Effects of the hydrogel composite on wound healing were further evaluated by using the full-thickness skin defect mice model. RESULTS: Successful extraction of hUCMSCs-derived exosomes was confirmed by TEM，Western Blotting and flow cytometry. The synthesized rhCol I/CMC-Exos hydrogel composite exhibited cytocompatibility and promoted cell growth in vitro. The rhCol I/CMC-Exos hydrogel showed sustained release of exosomes. In the mice full skin-defects model, the rhCol I/CMC-Exos-treated group showed superior wound healing efficiency, with 15 % faster wound closure compared to controls. Histological examinations revealed thicker dermis formation and more balanced collagen deposition in wounds treated with rhCol I/CMC-Exos hydrogel. Mechanistically, the application of rhCol I/CMC-Exos hydrogel increased fibroblasts proliferation, alleviated inflammation responses as well as promoted angiogenesis, thereby was beneficial in promoting skin wound healing and regeneration. CONCLUSION: Our study, for the first time, introduced recombinant human Collagen I in fabricating a novel hydrogel loaded with hUCMSCs-derived exosomes, which effectively promoted skin wound closure and regeneration, demonstrating a great potential in severe skin wound healing treatment.

Epoxy Resin-Encapsulated Polymer Microparticles for Room-Temperature Cold Sprayable Coatings.

We designed and synthesized epoxy-encapsulated microparticles with core-shell structures via suspension polymerization to enable high-efficiency, room-temperature cold spray processing. The soft core of the microparticles was comprised of a thermoset resin, diglycidyl ether of bisphenol A (DGEBA), which was optionally blended with the thermoplastic, poly(butyl acrylate); the protective shell was formed using polyurea. The composition, morphology, and thermal behavior of the microparticles were investigated. An inverse relationship between deposition efficiency and particle size was demonstrated by varying the surfactant concentration that was used during particle synthesis. We also determined that the microparticles that had pure resin as the core had the lowest viscosity, exhibited a decrease in the critical impact velocity required for adhesion, had the best flowability, and yielded a dramatic increase in deposition efficiency (56%). We have demonstrated that our in-house synthesized particles can form homogeneous, smooth, and fully coalesced coatings using room-temperature cold spray.

High-Performance, UV-Curable Crosslinked Films via Grafting of Hydroxyethyl Methacrylate Methylene Malonate.

Thermoset coatings have been used extensively to protect and enhance the appearance of substrates for industrial maintenance and architectural applications. Here, we demonstrate that anionic polymerization can be used to first graft hydroxyethyl methacrylate methylene malonate (HEMA-MM) onto a latex particle at ambient conditions, while subsequent ultraviolet (UV) exposure enabled their crosslinking into robust coatings. At room temperature, in the presence of air and water, the polymerization of HEMA-MM was initiated by anionic carboxyl groups present on the MAA latex particles and subsequently grafted onto the surface of particles. The pendent hydroxyethyl methacrylate (HEMA) group enabled UV-curing via free radical polymerization and the formation of a crosslinked network. Systematic investigations were conducted to study the formation and performance of the crosslinked coatings as a function of HEMA-MM incorporation. The incorporation of 10 wt% HEMA-MM into MAA latex yielded crosslinked coatings with decreased swelling, a heightened glass transition temperature (by ~20 °C) and a 2.9-fold improvement in the Young's moduli compared to controls (without HEMA-MM). Here, we demonstrate a facile method that provides a one-step grafting-functionalization approach using functional methylene malonates to produce UV-curable and high-performance coatings at room temperature and under atmospheric environments.

Anionic Polymerization of Methylene Malonate for High-Performance Coatings.

Here, we demonstrate the anionic polymerization and the high reactivity of the novel monomer diethyl methylene malonate (DEMM). At room temperature and under atmospheric conditions, water and anionic functional groups (i.e., carboxyl, boronic, and phenol) quickly initiate DEMM. The polymerization of DEMM in water and the final molecular weight of the polymer were both demonstrated to be pH-dependent. Systematically, investigations were conducted to study the conversion rate of DEMM with various functional groups, and the polymerization was verified to occur with anionic groups using a carboxylate-initiated DEMM system. For coating applications, we also investigated a multifunctional derivative monomer called (DEMM)6 that is an oligomeric polyester of DEMM esterified with butanediol that contains on average six repeat units of reactive DEMM (commercially known as Forza B3000 XP). The incorporation of 15 wt % (DEMM)6 into latex containing methacrylate acid as a functional monomer yielded cross-linked coatings with a gel content of 76.25 wt % that had a 289% improvement in rub-resistance performance compared to controls (without (DEMM)6). This study provides a facile methodology to synthesize cross-linked latex coatings at room temperature.

Bacteria-Resistant, Transparent, Free-Standing Films Prepared from Complex Coacervates.

We report the fabrication, properties, and bacteria-resistance of polyelectrolyte complex (PEC) coatings and free-standing films. Poly(4-styrenesulfonic acid), poly(diallyldimethyl-ammonium chloride), and salt were spin-coated into PEC films. After thermal annealing in a humid environment, highly transparent, mechanically strong, and chemically robust films were formed. Notably, we demonstrate that PEC coatings significantly reduce the attachment of Escherichia coli K12 without killing the micro-organisms. We suggest that forming bacteria-resistant surface coatings from commercially available polymers holds the potential for use across a wide range of applications including high-touch surfaces in medical settings.

Biosynthesis of a Flavonol from a Flavanone by Establishing a One-pot Bienzymatic Cascade.

Flavonols are a major subclass of flavonoids with a variety of biological and pharmacological activities. Here, we provide a method for the in vitro enzymatic synthesis of a flavonol. In this method, Atf3h and Atfls1, two key genes in the biosynthetic pathway of the flavonols, are cloned and overexpressed in Escherichia coli. The recombinant enzymes are purified via an affinity column and then a bienzymatic cascade is established in a specific synthetic buffer. Two flavonols are synthesized in this system as examples and determined by TLC and HPLC/LC/MS analyses. The method displays obvious advantages in the derivation of flavonols over other approaches. It is time- and labor-saving and highly cost-effective. The reaction is easy to be accurately controlled and thus scaled up for mass production. The target product can be purified easily due to the simple components in the system. However, this system is usually restricted to the production of a flavonol from a flavanone.

Enhanced Recovery After Surgery to Change Process Measures and Reduce Opioid Use After Cesarean Delivery: A Quality Improvement Initiative.

OBJECTIVE: To evaluate implementation of an enhanced recovery after surgery (ERAS) program for patients undergoing elective cesarean delivery by comparing opioid exposure, multimodal analgesia use, and other process and outcome measures before and after implementation. METHODS: An ERAS program was implemented among patients undergoing elective cesarean delivery in a large integrated health care delivery system. We conducted a pre-post study of ERAS implementation to compare changes in process and outcome measures during the 12 months before and 12 months after implementation. RESULTS: The study included 4,689 patients who underwent an elective cesarean delivery in the 12 months before (pilot sites: March 1, 2015-February 29, 2016, all other sites: October 1, 2015-September 30, 2016), and 4,624 patients in the 12 months after (pilot sites: April 1, 2016-March 31, 2017, all other sites: November 1, 2016-October 31, 2017) ERAS program implementation. After ERAS implementation mean inpatient opioid exposure (average daily morphine equivalents) decreased from 10.7 equivalents (95% CI 10.2-11.3) to 5.4 equivalents (95% CI 4.8-5.9) controlling for age, race-ethnicity, prepregnancy body mass index, patient reported pain score, and medical center. The use of multimodal analgesia (ie, acetaminophen and neuraxial anesthesia) increased from 9.7% to 88.8%, the adjusted risk ratio (RR) for meeting multimodal analgesic goals was 9.13 (RR comparing post-ERAS with pre-ERAS; 95% CI 8.35-10.0) and the proportion of time patients reported acceptable pain scores increased from 82.1% to 86.4% (P<.001). Outpatient opioids dispensed at hospital discharge decreased from 85.9% to 82.2% post-ERAS (P<.001) and the average number of dispensed pills decreased from 38 to 26 (P<.001). The hours to first postsurgical ambulation decreased by 2.7 hours (95% CI -3.1 to -2.4) and the hours to first postsurgical solid intake decreased by 11.1 hours (95% CI -11.5 to -10.7). There were no significant changes in hospital length of stay, surgical site infections, hospital readmissions, or breastfeeding rates. CONCLUSIONS: Implementation of an ERAS program in patients undergoing elective cesarean delivery was associated with a reduction in opioid inpatient and outpatient exposure and with changes in surgical process measures of care without worsened surgical outcomes.

Polymer Particles with a Low Glass Transition Temperature Containing Thermoset Resin Enable Powder Coatings at Room Temperature.

Epoxy-based powder coatings are an attractive alternative to solvent-borne coatings. Here, in-house synthesized low glass transition temperature (Tg) particles containing epoxy resin and polymethyl methacrylate formed coatings at room temperature upon impact with a surface. Suspension polymerization was used to prepare particles as a function of diglycidyl ether of bisphenol A (DGEBA) and methyl methacrylate ratios. Higher incorporation of DGEBA decreased the Tg to below ~20°C and eliminated the need to heat the particles and/or aluminum substrates to form coatings. Using an electrostatic powder coating apparatus, a ~70% particle deposition efficiency was achieved on aluminum substrates heated to 200°C. Whereas, at room temperature, high-speed single particle impact experiments proved that particle bonding occurred at a critical velocity of 438 m/s, comparable to commercial cold spray technologies. The in-house synthesized particles used in this study hold potential in traditional and emerging additive manufacturing applications.

The Kaiser Permanente Northern California Enhanced Recovery After Surgery Program: Design, Development, and Implementation.

Complications are common after surgery, highlighting the need for innovations that reduce postsurgical morbidity and mortality. In this report, we describe the design, development, and implementation of an Enhanced Recovery After Surgery program in the Kaiser Permanente Northern California integrated health care delivery system. This program was implemented and disseminated in 2014, targeting patients who underwent elective colorectal resection and those who underwent emergent hip fracture repair across 20 Medical Centers. The program leveraged multidisciplinary and broad-based leadership, high-quality data and analytic infrastructure, patient-centered education, and regional-local mentorship alignment. This program has already had an impact on more than 17,000 patients in Northern California. It is now in its fourth phase of planning and implementation, expanding Enhanced Recovery pathways to all surgical patients across Kaiser Permanente Northern California.

Enhanced Recovery After Surgery Program Implementation in 2 Surgical Populations in an Integrated Health Care Delivery System.

Importance: Novel approaches to perioperative surgical care focus on optimizing nutrition, mobility, and pain management to minimize adverse events after surgical procedures. Objective: To evaluate the outcomes of an enhanced recovery after surgery (ERAS) program among 2 target populations: patients undergoing elective colorectal resection and patients undergoing emergency hip fracture repair. Design, Setting, and Participants: A pre-post difference-in-differences study before and after ERAS implementation in the target populations compared with contemporaneous surgical comparator groups (patients undergoing elective gastrointestinal surgery and emergency orthopedic surgery). Implementation began in February and March 2014 and concluded by the end of 2014 at 20 medical centers within the Kaiser Permanente Northern California integrated health care delivery system. Exposures: A multifaceted ERAS program designed with a particular focus on perioperative pain management, mobility, nutrition, and patient engagement. Main Outcomes and Measures: The primary outcome was hospital length of stay. Secondary outcomes included hospital mortality, home discharge, 30-day readmission rates, and complication rates. Results: The study included a total of 3768 patients undergoing elective colorectal resection (mean [SD] age, 62.7 [14.1] years; 1812 [48.1%] male) and 5002 patients undergoing emergency hip fracture repair (mean [SD] age, 79.5 [11.8] years; 1586 [31.7%] male). Comparator surgical patients included 5556 patients undergoing elective gastrointestinal surgery and 1523 patients undergoing emergency orthopedic surgery. Most process metrics had significantly greater changes in the ERAS target populations after implementation compared with comparator surgical populations, including those for ambulation, nutrition, and opioid use. Hospital length of stay and postoperative complication rates were also significantly lower among ERAS target populations after implementation. The rate ratios for postoperative complications were 0.68 (95% CI, 0.46-0.99; P = .04) for patients undergoing colorectal resection and 0.67 (95% CI, 0.45-0.99, P = .05) for patients with hip fracture. Among patients undergoing colorectal resection, ERAS implementation was associated with decreased rates of hospital mortality (0.17; 95% CI, 0.03-0.86; P = .03), whereas among patients with hip fracture, implementation was associated with increased rates of home discharge (1.24; 95% CI, 1.06-1.44; P = .007). Conclusions and Relevance: Multicenter implementation of an ERAS program among patients undergoing elective colorectal resection and patients undergoing emergency hip fracture repair successfully altered processes of care and was associated with significant absolute and relative decreases in hospital length of stay and postoperative complication rates. Rapid, large-scale implementation of a multidisciplinary ERAS program is feasible and effective in improving surgical outcomes.

Enhanced and Differential Capture of Circulating Tumor Cells from Lung Cancer Patients by Microfluidic Assays Using Aptamer Cocktail.

Collecting circulating tumor cells (CTCs) shed from solid tumor through a minimally invasive approach provides an opportunity to solve a long-standing oncology problem, the real-time monitoring of tumor state and analysis of tumor heterogeneity. However, efficient capture and detection of CTCs with diverse phenotypes is still challenging. In this work, a microfluidic assay is developed using the rationally-designed aptamer cocktails with synergistic effect. Enhanced and differential capture of CTCs for nonsmall cell lung cancer (NSCLC) patients is achieved. It is also demonstrated that the overall consideration of CTC counts obtained by multiple aptamer combinations can provide more comprehensive information in treatment monitoring.

Electromembrane extraction of salivary polyamines followed by capillary zone electrophoresis with capacitively coupled contactless conductivity detection.

Electromembrane extraction (EME) as a novel sample preparation technique was firstly applied for the purification and enrichment of four polyamines mainly present in saliva samples. These four target analytes, putrescine, cadaverine, spermidine, and spermine, were directly determined by CZE with capacitively coupled contactless conductivity detection (CZE-C(4)D) after EME procedure. Several factors affecting extraction efficiency, electrophoretic separation, and detection were investigated. Under the optimum conditions, four polyamines were baseline separated within 22 min, exhibiting a linear calibration over three orders of magnitude (r>0.999); the highest enrichment factor could reach 106-fold (for spermidine), and the LODs were in the range of 1.4-7.0 ng mL(-1). The proposed EME/CZE-C(4)D method has been successfully applied to analyze human saliva samples with recoveries in the range of 78-97%.

Human cortical activity evoked by the assignment of authenticity when viewing works of art.

The expertise of others is a major social influence on our everyday decisions and actions. Many viewers of art, whether expert or naïve, are convinced that the full esthetic appreciation of an artwork depends upon the assurance that the work is genuine rather than fake. Rembrandt portraits provide an interesting image set for testing this idea, as there is a large number of them and recent scholarship has determined that quite a few fakes and copies exist. Use of this image set allowed us to separate the brain's response to images of genuine and fake pictures from the brain's response to external advice about the authenticity of the paintings. Using functional magnetic resonance imaging, viewing of artworks assigned as "copy," rather than "authentic," evoked stronger responses in frontopolar cortex (FPC), and right precuneus, regardless of whether the portrait was actually genuine. Advice about authenticity had no direct effect on the cortical visual areas responsive to the paintings, but there was a significant psycho-physiological interaction between the FPC and the lateral occipital area, which suggests that these visual areas may be modulated by FPC. We propose that the activation of brain networks rather than a single cortical area in this paradigm supports the art scholars' view that esthetic judgments are multi-faceted and multi-dimensional in nature.