Objective The goal of this prospective clinical study was to assess the effectiveness of a novel bioresorbable polymeric matrix impregnated with ionic and metallic silver as a primary wound contact dressing in healing stagnant or deteriorating chronic wounds. Materials and methods Thirty-two patients with a total of 35 chronic wounds undergoing treatment at the Wound Healing and Hyperbaric Center at Mission Hospital were recruited under a protocol approved by the institutional review board. The wounds included venous stasis ulcers, diabetic foot ulcers, postoperative surgical wounds, burn wounds, and chronic, nonpressure lower extremity ulcers. At baseline, all wounds were nonhealing (ie, stagnant or deteriorating) for a median of 39 weeks (range, 3-137 weeks) and suspected of persistent microbial colonization that had not responded to traditional antimicrobial products and/or antibiotics. The aforementioned matrix was applied to wounds once every 3 days and covered with a secondary dressing. Previously prescribed protocols of care, such as debridement or compression wraps, were continued, but prior antimicrobial dressings or antibiotics were replaced with the matrix. Wound assessments at 3 weeks and 12 weeks post intervention are reported. Results Three patients were excluded due to patients lost to follow-up after initial application. At 3 weeks, 72% of wounds (22/32) had significantly improved healing with an average wound area reduction of 66%. By 12 weeks, 91% of wounds (29/32) either healed completely (ie, fully reepithelialized) or improved significantly with an average wound area reduction of 73%. The matrix was well tolerated; no patient reported discomfort with the application of the matrix. Conclusions The micrometer-thick bioresorbable matrix presents a new form factor to wound management, conforming intimately to the underlying wound bed to exert localized and sustained antimicrobial action of noncytotoxic levels of silver. The application of the matrix on the wound surface in protocols of care was safe and well tolerated, and it facilitated improvements in healing of a majority of the stagnant or deteriorating complex chronic wounds.
Waterman Manning, Sarah MD, MPA; Humphrey, David A. MD; Shillinglaw, WIlliam R. DO, FACS; Schurr, Michael J. MD, FACS; Crawford, Eric C. BS; Agarwal, Ankit PhD; Pranami, Gaurav C. PhD Author Information
Silver is a widely used antimicrobial agent, yet, when impregnated in macroscopic dressings, it stains wounds, can lead to tissue toxicity, and can inhibit healing. Recently, polymeric nanofilms containing silver nanoparticles were reported to exhibit antimicrobial activity at loadings and release rates of silver that are 100× lower than conventional dressings. Here, fabrication of composite microfilm constructs that provide a facile way to transfer the silver‐loaded polymeric nanofilms onto wounds in vivo is reported. The construct is fabricated from a silver nanoparticle‐loaded polymeric nanofilm that is laminated with a micrometer‐thick‐soluble film of polyvinylalcohol (PVA). When placed on a moist wound, the PVA dissolves, leaving the silver‐loaded nanofilm immobilized on the wound‐bed. In vitro, the immobilized nanofilms release <1 μg cm−2 d‐1 of silver over 30 d from skin dermis and they kill 5 log10 CFUs of Staphylococcus aureus in 24 h. In mice, wounds inoculated with 105 CFU S. aureus presented up to 3 log10 less bacterial burden when treated with silver/nanofilms for 3 d, as compared to unmodified wounds. In uncontaminated wounds, silver/nanofilms allow normal and complete wound closure by re‐epithelialization. Dissolvable microfilm constructs may overcome key limitations associated with current uses of silver in wound healing.
The development of versatile methods that provide spatial and temporal control over the presentation of physical and biochemical cues on wound beds can lead to new therapeutic approaches that expedite wound healing by favorably influencing cellular behaviors. Toward that goal, we report that native chemical functional groups presented by wound beds can be utilized for direct covalent attachment of polymeric microbeads. Specifically, we demonstrated the covalent attachment of maleimide-functionalized and catechol-functionalized microbeads, made of either polystyrene (non-degradable) or poly(lactic-co-glycolic acid) ((PLGA), degradable), to sulfhydryl and amine groups present on porcine dermis used here as an ex vivo model wound bed. A pronounced increase (10-70 fold) in the density and persistence of the covalently reactive microbeads was observed relative to microbeads that adsorb via non-covalent interactions. Complementary characterization of the surface chemistry of the ex vivo wound beds using Raman microspectroscopy provides support for our conclusion that the increased adherence of the maleimide-functionalized beads results from their covalent bond formation with sulfhydryl groups on the wound bed. The attachment of maleimide-functionalized microbeads to wounds created in live wild-type and diabetic mice led to observations of differential immobilization of microbeads on them and were consistent with anticipated differences in the presentation of sulfhydryl groups on the two different wound types. Finally, the incorporation of maleimide-functionalized microbeads in wounds created in wild-type mice did not impair the rate of wound closure relative to an untreated wound. Overall, the results presented in this paper enable a general and facile approach to the engineering of wound beds in which microbeads are covalently immobilized to wound beds. Such immobilized microbeads could be used in future studies to release bioactive factors (e.g., antimicrobial agents or growth factors) and/or introduce topographical cues that promote cell behaviors underlying healing and wound closure. Published by Elsevier Ltd.
Silver is a commonly used topical antimicrobial. However, technologies to immobilize silver at the wound surface are lacking, while currently available silver-containing wound dressings release excess silver that can be cytotoxic and impair wound healing. We have shown that precise concentrations of silver at lower levels can be immobilized into a wound bed using a polyelectrolyte multilayer attachment technology. These silver nanoparticle-impregnated polyelectrolyte multilayers are noncytotoxic yet bactericidal in vitro, but their effect on wound healing in vivo was previously unknown. The purpose of this study was to determine the effect on wound healing of integrating silver nanoparticle/polyelectrolyte multilayers into the wound bed. A full-thickness, splinted, excisional murine wound healing model was employed in both phenotypically normal mice and spontaneously diabetic mice (healing impaired model). Gross image measurements showed an initial small lag in healing in the silver-treated wounds in diabetic mice, but no difference in time to complete wound closure in either normal or diabetic mice. Histological analysis showed modest differences between silver-treated and control groups on day 9, but no difference between groups at the time of wound closure. We conclude that silver nanoparticle/polyelectrolyte multilayers can be safely integrated into the wound beds of both normal and diabetic mice without delaying wound closure, and with transient histological effects. The results of this study suggest the feasibility of this technology for use as a platform to affect nanoscale wound engineering approaches to microbial prophylaxis or to augment wound healing.
This paper advances the design of stimuli-responsive materials based on colloidal particles dispersed in liquid crystals (LCs). Specifically, thin films of colloid-in-liquid crystal (CLC) gels undergo easily visualized ordering transitions in response to reversible and irreversible (enzymatic) biomolecular interactions occurring at the aqueous interfaces of the gels. In particular, LC ordering transitions can propagate across the entire thickness of the gels. However, confinement of the LC to small domains with lateral sizes of ∼10 μm does change the nature of the anchoring transitions, as compared to films of pure LC, due to the effects of confinement on the elastic energy stored in the LC. The effects of confinement are also observed to cause the response of individual domains of the LC within the CLC gel to vary significantly from one to another, indicating that manipulation of LC domain size and shape can provide the basis of a general and facile method to tune the response of these LC-based physical gels to interfacial phenomena. Overall, the results presented in this paper establish that CLC gels offer a promising approach to the preparation of self-supporting, LC-based stimuli-responsive materials.
The response of a thin film of a gel comprised of liquid crystal (LC) and colloids that is immersed in water is reported on page 2785 by S. K. Pal, N. L. Abbott, and co-workers. The time-lapse polarized light micrographs are shown in the image in a clockwise direction.
Biologic wound dressings contain animal-derived components and are susceptible to high infection rates. To address this issue, we report an approach that permits incorporation of non-toxic levels of the small molecule antiseptic 'chlorhexidine' into biologic dressings. The approach relies on the fabrication of polyelectrolyte multilayer (PEMs) films containing poly(allylaminehydrochloride) (PAH), poly(-acrylicacid) (PAA), and chlorhexidine acetate (CX) on elastomeric poly(dimethylsiloxane) (PDMS) sheets. The PEMs (20-100 nm thick) are subsequently stamped onto the wound-contact surface of a synthetic biologic dressing, Biobrane, which contains collagen peptides. Chlorhexidine loading in the PEMs was tailored by tuning the number of (CX/PM) bilayers deposited, providing burst release of up to 0.98 +/- 0.06 mu g/cm(2) of CX over 24 h, followed by zero-order release of 0.35 +/- 0.04 mu g/cm(2)/day for another week. Although the CX concentrations released were below the reported in vitro cytotoxicity limit (5 mu g/mL over 24 h) for human dermal fibroblasts, they killed 4 logo counts of pathogenic bacteria Staphylococcus aureus in solution. The CX/PEMs could be stamped onto Biobrane with high efficiency to provide CX release kinetics and in vitro antibacterial activity similar to that on PDMS stamps. In a full-thickness 'splinted' dermal wound-model in normal wild-type mice, the CX-functionalized Biobrane showed no decrease in either its adherence to the wound-bed or wound closure rate over 14 days. The murine wounds topically inoculated with similar to 105 CFU/cm(2) of S. aureus and treated with CX-functionalized Biobrane demonstrated a 3 log(10) decrease in the wound's bacterial burden within 3 days, compared to persistent bacterial colonization found in wounds treated with unmodified Biobrane (n = 10 mice, p < 0.005). Overall, this study presents a promising approach to prevent bacterial colonization in wounds under biologic dressings. (C) 2012 Elsevier Ltd. All rights reserved.
This paper is a review of principles and aims of partnering to improve quality and efficiency within the manufacturing industry. Partnering is used to carry out this research so that we can ascertain the features and issues that contribute to trust within the partnering arrangements. There are many other procurement routes available in manufacturing industries which are having different qualities in them but we want to see whether partnering is more appropriate route as compared to other forms of procurement. To support our research, opinions of clients and contractors were gathered and an analysis was done according to their feedbacks. The collection of data and analysis provided primarily information proving the aim and objectives were identified in methodology. The main outcome of this methodology was how important trust is and whether trust can be achieved through partnering procurement. Also the advantages and the disadvantages of partnering were evaluated from the results. This research found from the analysis of data that partnering has a good and positive impact on trust which other procurement routes find difficult to prove. Long term relationship through partnering did not satisfy all the clients. Other procurement routes can offer the client a better quality options when it comes to risk allocation and price certainty. After all the study and research it was been proved that trust can be achieved through Partnering.
A software framework for secure and efficient communication between two nodes using the Windows Operating system is proposed. The proposed system aims to overcome the drawbacks of virtual private network, by reducing the number of buffer copies and the protocol overhead. It involves only a single copy of the data and a single context switch thus creating a tunnel between the two end points. It uses the patent mutual identity algorithm to secure the two end points of a tunnel. It uses a 128 bit advanced encryption standard algorithm for encryption/decryption. This framework resides on the NDIS (Network Driver Interface Specification). It performs a set of modifications on each network packet which is about to hit the wire. The system eliminates the drawback of VPN system by increasing the throughput and reducing the processing overhead.
The design of polyelectrolyte multilayers (PEMs) that can be prefabricated on an elastomeric stamp and mechanically transferred onto biomedically‐relevant soft materials, including medical‐grade silicone elastomers (E’∼450–1500 kPa; E’‐elastic modulus) and the dermis of cadaver skin (E’∼200–600 kPa), is reported. Whereas initial attempts to stamp PEMs formed from poly(allylamine hydrochloride) and poly(acrylic acid) resulted in minimal transfer onto soft materials, we report that integration of micrometer‐sized beads into the PEMs (thicknesses of 6–160 nm) led to their quantitative transfer within 30 seconds of contact at a pressure of ∼196 kPa. To demonstrate the utility of this approach, PEMs were impregnated with a range of loadings of silver‐nanoparticles and stamped onto the dermis of human cadaver skin (a wound‐simulant) that was subsequently incubated with bacterial cultures. Skin dermis stamped with PEMs that released 0.25 ± 0.01 μg cm−2 of silver ions caused a 6 log10 reduction in colony forming units of Staphylococcus epidermidis and Pseudomonas aeruginosa within 12 h. Significantly, this level of silver release is below that which is cytotoxic to NIH 3T3 mouse fibroblast cells. Overall, this study describes a general and facile approach for the functionalization of biomaterial surfaces without subjecting them to potentially deleterious processing conditions.
Face detection is one of the challenging problems in image processing. A novel face detection system is presented in this paper and we propose a new approach using Takagi-Sugeno (T-S) fuzzy model and Hue Saturation and Value (HSV) color model. The algorithm uses fuzzy classifier in conjunction with HSV color model to quickly locate faces in the image. The fuzzy classifier basically examines small windows of an image to detect presence of faces in that window and the HSV color model detects the skin in the image. The algorithm is characterized by its simplicity and inexpensive computational requirements. The method shows that our system has comparable performance in terms of detection rates and false positive rates.
Liquid-crystalline materials are a promising class of stimuli-responsive materials that have been demonstrated to undergo surface-induced orientational ordering transitions that can be highly sensitive and specific to chemical species. However, past studies demonstrating surface-induced transitions in liquid crystals (LCs) have employed thin films of low-molecular-weight LCs that are difficult to stabilize (due to dewetting of the LC on a surface). Here, it is reported that it is possible to prepare liquid-crystalline gels using a mixture of polystyrene microspheres and nematic LCs that undergo changes in orientational order, and thus optical appearance, in response to exposure to specific chemical compounds. These colloid-in-liquid-crystal (CLC) gels are mechanically stable and can be molded on chemically functionalized surfaces into thin films containing micrometer-sized LC-rich domains that span the two interfaces of the gels. In contrast to other reports of LC gels, where the presence of a polymeric or self-assembled small-molecule gelator network within a nematic LC frustrates ordering transitions from propagating through the gels over distances, it is demonstrated that thin films of CLC gels, when supported on chemically functionalized surfaces, do undergo easily visualized ordering transitions upon exposure to organophosphonate compounds. Because these optically responsive CLC gels are mechanically robust and can be molded, this class of composite LC material may be broadly useful for the design of chemically responsive LC devices.
Silver is widely used as a biocidal agent in ointments and wound dressings. However, it has also been associated with tissue toxicity and impaired healing. In vitro characterization has also revealed that typical loadings of silver employed in ointments and dressings (∼100 μg/cm2) lead to cytotoxicity. In this paper, we report the results of an initial study that sought to determine if localization of carefully controlled loadings of silver nanoparticles within molecularly thin films immobilized on surfaces can lead to antimicrobial activity without inducing cytotoxicity. Polymeric thin films of poly(allylamine hydrochloride) (PAH) and poly(acrylic acid) (PAA) were prepared by layer-by-layer deposition and loaded with ∼0.4 μg/cm2 to ∼23.6 μg/cm2 of silver nanoparticles. Bacterial killing efficiencies of the silver-loaded films were investigated against Staphylococcus epidermidis, a gram-positive bacterium, and it was determined that as little as ∼0.4 μg/cm2 of silver in the polymeric films caused a reduction of 6 log10 CFU/mL (99.9999%) bacteria in suspensions incubated in contact with the films (water-borne assays). Significantly, whereas the antibacterial films containing high loadings of silver were found to be toxic to a murine fibroblast cell line (NIH-3T3), the polymeric films containing ∼0.4 μg/cm2 of silver were not toxic and allowed attachment, and growth of the mammalian cells. Thus, the results of this study go beyond prior reports by identifying silver-impregnated, polymeric thin films that are compatible with in vitro mammalian cell culture yet exhibit antibacterial activity. These results support the hypothesis that localization of carefully controlled loadings of silver nanoparticles within molecularly thin polymeric films can lead to antimicrobial activity without cytotoxicity. More broadly, this strategy of modifying surfaces with minimal loadings of bioactive molecules indicates the basis of approaches that may permit management of microbial burden in wound beds without impairment of wound healing.