Application of Deacetylated Poly-N-Acetyl Glucosamine Nanoparticles for the Delivery of miR-126 for the Treatment of Cecal Ligation and Puncture-Induced Sepsis.

Sepsis is an acute inflammatory syndrome in response to infection. In some cases, excessive inflammation from sepsis results in endothelial dysfunction and subsequent increased vascular permeability leading to organ failure. We previously showed that treatment with endothelial progenitor cells, which highly express microRNA-126 (miR-126), improved survival in mice subjected to cecal ligation and puncture (CLP) sepsis.

pGlcNAc Nanofiber Treatment of Cutaneous Wounds Stimulate Increased Tensile Strength and Reduced Scarring via Activation of Akt1.

Treatment of cutaneous wounds with poly-N-acetyl-glucosamine containing nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increased wound closure, antibacterial activities and innate immune responses. We have shown that Akt1 plays a central role in the regulation of these activities. Here, we show that pGlcNAc treatment of cutaneous wounds results in a smaller scar that has increased tensile strength and elasticity.

Poly-N-acetyl glucosamine nanofibers for negative-pressure wound therapies.

The wound healing promoting effect of negative wound pressure therapies (NPWT) takes place at the wound interface. The use of bioactive substances at this site represents a major research area for the development of future NPWT therapies. To assess wound healing kinetics in pressure ulcers treated by NPWT with or without the use of a thin interface membrane consisting of poly-N-acetyl glucosamine nanofibers (sNAG) a prospective randomized clinical trial was performed.

Immunomodulatory effects of IL-12 released from poly-N-acetyl glucosamine gel matrix during schistosomiasis infection.

We have reported recently that Interleukin-12 (IL-12) released from poly-N-acetyl glucosamine gel matrix (F2 gel/IL-12) is more effective than free IL-12 to enhance vaccination of mice with Schistosoma soluble worm antigen preparation. The aim of this study is to evaluate the effect of F2 gel/IL-12 on the inflammatory responses in mice undergoing schistosomiasis infection in absence of vaccination. To achieve this, mice undergoing Schistosoma mansoni infection or cured from this infection, after treatment with praziquantil (PZQ), were treated with subcutaneous injection of IL-12 for 3 consecutive days or once with F2 gel loaded with IL-12 (F2 gel/IL-12).

Evaluation of a novel poly N-acetyl glucosamine (pGlcNAc) hydrogel for treatment of the degenerating intervertebral disc.

Aims: The early stages of degenerative disc disease (DDD) primarily affect the disc nucleus pulposus (NP). Tissue-engineered strategies may enhance intervertebral disc (IVD) functionality. The aim of this study was to develop and evaluate a novel deacetylated poly-N-acetyl glucosamine (pGlcNAc) hydrogel characterizing its biochemical effect on human IVD cells as well as material biomechanical properties.

Integrin-dependent Akt1 activation regulates PGC-1 expression and fatty acid oxidation.

Background: Poly-N-acetyl glucosamine nanofibers derived from a marine diatom have been used to increase cutaneous wound healing. These nanofibers exert their activity by specifically activating integrins, which makes them a useful tool for dissecting integrin-mediated pathways. We have shown that short-fiber poly-N-acetyl glucosamine nanofiber (sNAG) treatment of endothelial cells results in increased cell motility and metabolic rate in the absence of increased cell proliferation.

Poly-N-acetyl glucosamine fibers activate bone regeneration in a rabbit femur injury model.

Background: The purpose of this study was to evaluate the ability of a membrane material, consisting only of short poly-N-acetyl glucosamine (sNAG) nanofibers, to regenerate bone tissue after implantation into circular holes in the rabbit femur.

Methods: Three circular holes were created in the femurs of five male New Zealand white rabbits. The holes were ∼ 2.

mRDH bandage for surgery and trauma: data summary and comparative review.

Background: Bleeding often poses significant life-threatening situations to surgeons. After trauma, a one-third of civilian casualties and one-half of combat casualties die as a result of exsanguination. Recent advances have provided promising new hemostatic dressings that are applied directly to severely bleeding wounds in the pre-hospital period.

Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1.

Background: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also important for wound healing and anti-microbial activities. Therefore, we tested whether sNAG nanofibers induce defensin expression resulting in bacterial clearance.

Poly-N-acetyl glucosamine gel matrix as a non-viral delivery vector for DNA-based vaccination.

Intramuscular administration of plasmid DNA vaccines is one of the main delivery approaches that can generate antigen specific T cell responses. However, major limitations of the intramuscular delivery strategy are the low level of myocyte transfection, resulting in a minimal level of protein expression; the inability to directly target antigen presenting cells, in particular dendritic cells, which are critical for establishment of efficacious antigen-specific immune responses. Although several viral vectors have been designed to improve plasmid DNA delivery, they have limitations, including the generation of neutralizing antibodies in addition to lacking the simplicity and versatility required for universal clinical application.

Using poly-N-acetyl glucosamine gel matrix to deliver IL-12 with anti-schistosomasis vaccination.

Background: Interleukin (IL)-12 is a potential adjuvant in a variety of diseases including schistosomiasis. The clinical use of IL-12, however, is limited by the toxicity associated with its systemic administration. We have developed a novel delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of sustaining the release of proteins (e.

Poly-N-acetyl glucosamine nanofibers: a new bioactive material to enhance diabetic wound healing by cell migration and angiogenesis.

Introduction: In several fields of surgery, the treatment of complicated tissue defects is an unsolved clinical problem. In particular, the use of tissue scaffolds has been limited by poor revascularization and integration. In this study, we developed a polymer, poly-N-acetyl-glucosamine (sNAG), with bioactive properties that may be useful to overcome these limitations.

The design and testing of a dual fiber textile matrix for accelerating surface hemostasis.

The standard treatment for severe traumatic injury is frequently compression and application of gauze dressing to the site of hemorrhage. However, while able to rapidly absorb pools of shed blood, gauze fails to provide strong surface (topical) hemostasis. The result can be excess hemorrhage-related morbidity and mortality.

Differential effect of materials for surface hemostasis on red blood cell morphology.

The design of devices for surface (topical) hemostasis has been based on maximizing activation of platelets and accelerating coagulation pathways. The studies reported herein examine another aspect of blood contact with topical hemostasis materials, i.e.

Non-classical processes in surface hemostasis: mechanisms for the poly-N-acetyl glucosamine-induced alteration of red blood cell morphology and surface prothrombogenicity.

It is well established that platelets and the intrinsic plasma coagulation pathway can be activated when blood contacts artificial surfaces. Experiments were performed to assess the effect of hemostatic poly-N-acetyl glucosamine (pGlcNAc) nanofibers on red blood cells. The pGlcNAc nanofibers, isolated from a marine diatom, interact with red blood cells (RBCs) to produce stomatocytes.

Effects of poly-N-acetyl glucosamine (pGlcNAc) patch on wound healing in db/db mouse.

Background: Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-based materials, produced by a marine microalga, have been characterized as effective hemostatic agents. In this study, we hypothesized that a pGlcNAc fiber patch may enhance wound healing in the db/db mouse.

Methods: pGlcNAc patches were applied on 1-cm, full-thickness, skin wounds in the db/db mouse model.

Poly-N-acetyl glucosamine nanofibers regulate endothelial cell movement and angiogenesis: dependency on integrin activation of Ets1.

Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-derived materials effectively achieve hemostasis during surgical procedures. Treatment of cutaneous wounds with pGlcNAc in a diabetic mouse animal model causes marked increases in cell proliferation and angiogenesis. We sought to understand the effect of the pGlcNAc fibers on primary endothelial cells (EC) in culture and found that pGlcNAc induces EC motility.

Hemostatic properties of glucosamine-based materials.

Glucosamine- and N-acetyl glucosamine-containing polymers are being used in an increasing number of biomedical applications, including in products for surface (topical) hemostasis. The studies presented here investigate the relationship between the structure (conformation) and function (activation of hemostasis) of glucosamine-based materials. Several polymer systems were studied, including fibers isolated from a microalgal source containing poly-N-acetyl glucosamine polymers that are organized in a parallel, hydrogen-bonded tertiary structure and can be chemically modified to an antiparallel orientation; and gel formulation derivatives of the microalgal fibers consisting of partially deacetylated (F2 gel) and fully deacetylated (F3 gel) polymers.

Review: novel nonviral delivery approaches for interleukin-12 protein and gene systems: curbing toxicity and enhancing adjuvant activity.

It has become increasingly apparent that the ability to generate an optimal host immune response requires effective cross talk between the innate and adaptive components of the immune system. Pro-inflammatory cytokines, in particular those that can induce a danger signal, often called signal 3, are crucial in this role of initiating and augmenting the presentation of exogenous antigen to T cells by dendritic cells. Interleukin-12 (IL-12) in particular has been defined as a "signal 3" cytokine required for the antigen cross priming.

Synergistic platelet integrin signaling and factor XII activation in poly-N-acetyl glucosamine fiber-mediated hemostasis.

The polymer poly-N-acetylglucosamine (pGlcNAc) containing fiber material is becoming increasingly important as a topical agent for hemostasis at wound sites. The pGlcNAc polymeric fiber provides hemostasis through redundant mechanisms that include platelet activation for fibrin network formation. The research presented here better defines the mechanism for the effect of pGlcNAc containing fibers on platelet-mediated processes.

Arterial embolization using poly-N-acetyl glucosamine gel in a rat kidney model.

Aqueous solutions of poly-N-acetyl glucosamine (p-GlcNAc) exhibit a liquid-gel transition at physiological pH and temperature. This feature inspired the authors to conduct a study to evaluate the macro- and histological changes of rat kidneys after embolization using either p-GlcNAc gel injection into the renal artery or ligation of the renal artery. The procedures were performed in 46 rats through open abdominal surgeries.

Isolation, purification, and characterization of poly-N-acetyl glucosamine use as a hemostatic agent.

Background: A new polymeric material, poly-N-acetyl glucosamine (p-GlcNAc) fiber, has been identified and is effective in achieving hemostasis in surgical procedures and trauma. The p-GlcNAc material is purified from large-scale cultures of a marine microalga.

Methods: Poly-N-acetyl glucosamine materials have been formulated as films, sponges, gels, and microspheres.

Paracrine release of IL-12 stimulates IFN-gamma production and dramatically enhances the antigen-specific T cell response after vaccination with a novel peptide-based cancer vaccine.

Interleukin-12 can act as a potent adjuvant for T cell vaccines, but its clinical use is limited by toxicity. Paracrine administration of IL-12 could significantly enhance the response to such vaccines without the toxicity associated with systemic administration. We have developed a novel vaccine delivery system (designated F2 gel matrix) composed of poly-N-acetyl glucosamine that has the dual properties of a sustained-release delivery system and a potent adjuvant.

The RDH bandage: hemostasis and survival in a lethal aortotomy hemorrhage model.

Background: The Rapid Deployment Hemostat (RDH) Bandage has been designed in collaboration with the Office of Naval Research for the treatment of bleeding because of extremity trauma. It is intended as both a battlefield and civilian severe trauma wound dressing. It consists of a specific formulation of Marine Polymer Technologies' proprietary hemostatic polymer poly-N-acetyl glucosamine, and has received FDA clearance.