Histamine receptor agonism differentially induces immune and reparative healing responses in biomaterial-facilitated tissue repair.

Tissue repair is a highly regulated process involving immune, stromal, vascular, and parenchymal cell responses. Mediators of cellular responses at different phases of the healing process stimulate transitions through the continuum of repair. Histamine is an early mediator of healing, which, in skin, is released by resident cells (e.

Skin repair and infection control in diabetic, obese mice using bioactive laser-activated sealants.

Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice.

In situ light-activated materials for skin wound healing and repair: A narrative review.

Dermal wounds are a major global health burden made worse by common comorbidities such as diabetes and infection. Appropriate wound closure relies on a highly coordinated series of cellular events, ultimately bridging tissue gaps and regenerating normal physiological structures. Wound dressings are an important component of wound care management, providing a barrier against external insults while preserving the active reparative processes underway within the wound bed.

Inflammasome modulation with P2X7 inhibitor A438079-loaded dressings for diabetic wound healing.

The inflammasome is a multiprotein complex critical for the innate immune response to injury. Inflammasome activation initiates healthy wound healing, but comorbidities with poor healing, including diabetes, exhibit pathologic, sustained activation with delayed resolution that prevents healing progression. In prior work, we reported the allosteric P2X7 antagonist A438079 inhibits extracellular ATP-evoked NLRP3 signaling by preventing ion flux, mitochondrial reactive oxygen species generation, NLRP3 assembly, mature IL-1β release, and pyroptosis.

Bioactive nanomaterials kickstart early repair processes and potentiate temporally modulated healing of healthy and diabetic wounds.

Slow-healing and chronic wounds represent a major global economic and medical burden, and there is significant unmet need for novel therapies which act to both accelerate wound closure and enhance biomechanical recovery of the skin. Here, we report a new approach in which bioactives that augment early stages of wound healing can kickstart and engender effective wound closure in healthy and diabetic, obese animals, and set the stage for subsequent tissue repair processes. We demonstrate that a nanomaterial dressing made of silk fibroin and gold nanorods (GNR) stimulates a pro-neutrophilic, innate immune, and controlled inflammatory wound transcriptomic response.

Gold nanobipyramids-based laser-activated sealants for effective skin sealing and repair.

Anisotropic gold nanostructures have gained increased attention for biomedical applications because of their remarkable optical properties. An emerging type of gold nanostructure-gold nanobipyramids (AuNBP)-has been shown to exhibit superior absorption properties compared to conventionally used gold nanoparticles, which makes them attractive for photothermal applications. We generated a high-shape-purity dispersion of AuNBP using a seed-mediated method and embedded them as photothermal conversion agents in a silk fibroin matrix to investigate their efficacy in photothermal sealing of incisional wounds in immunocompetent mice.

Alpha-ketoglutaric acid based polymeric particles for cutaneous wound healing.

Metabolites are not only involved in energy pathways but can also act as signaling molecules. Herein, we demonstrate that polyesters of alpha-ketoglutararte (paKG) can be generated by reacting aKG with aliphatic diols of different lengths, which release aKG in a sustained manner. paKG polymer-based microparticles generated via emulsion-evaporation technique lead to faster keratinocyte wound closures in a scratch assay test.

Temporal evaluation of efficacy and quality of tissue repair upon laser-activated sealing.

Injuries caused by surgical incisions or traumatic lacerations compromise the structural and functional integrity of skin. Immediate approximation and robust repair of skin are critical to minimize occurrences of dehiscence and infection that can lead to impaired healing and further complication. Light-activated skin sealing has emerged as an alternative to sutures, staples, and superficial adhesives, which do not integrate with tissues and are prone to scarring and infection.

Evaluation of drug carrier hepatotoxicity using primary cell culture models.

This study aims to establish a primary rat hepatocyte culture model to evaluate dose-dependent hepatotoxic effects of drug carriers (lipopolymer nanoparticles; LPNs) temporal. Primary rat hepatocyte cell cultures were used to determine half-maximal Inhibition Concentrations (IC) of the drug-carrier library. Drug-carrier library, at concentrations <50 μg/mL, is benign to primary rat hepatocytes as determined using albumin and urea secretions.

Versatile Detection and Monitoring of Ionizing Radiation Treatment Using Radiation-Responsive Gel Nanosensors.

Modern radiation therapy workflow involves complex processes intended to maximize the radiation dose delivered to tumors while simultaneously minimizing excess radiation to normal tissues. Safe and accurate delivery of radiation doses is critical to the successful execution of these treatment plans and effective treatment outcomes. Given extensive differences in existing dosimeters, the choice of devices and technologies for detecting biologically relevant doses of radiation has to be made judiciously, taking into account anatomical considerations and modality of treatment (invasive, e.

Radiation-Responsive Amino Acid Nanosensor Gel (RANG) for Radiotherapy Monitoring and Trauma Care.

Accurate detection of doses is critical for the development of effective countermeasures and patient stratification strategies in cases of accidental exposure to ionizing radiation. Existing detection devices are limited by high fabrication costs, long processing times, need for sophisticated detection systems, and/or loss of readout signal over time, particularly in complex environments. Here, we describe fundamental studies on amino acid-facilitated templating of gold nanoparticles following exposure to ionizing radiation as a new colorimetric approach for radiation detection.

Antimicrobial laser-activated sealants for combating surgical site infections.

Surgical-site infections (SSIs) occur in 2-5% of patients undergoing surgery in the US alone, impacting 300 000-500 000 lives each year, and presenting up to 11 times greater risk of death compared to patients without SSIs. The most common cause of SSI is Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) is the most common pathogen in community hospitals.

Synthesis and Biological Evaluation of New 1,2,3-Triazole Derivatives of the Chrysin Flavonoid as Anticancer Agents.

Background And Objective: Chrysin and its derivatives proved to possess potential anti-tumour activity.

Materials And Methods: A new series of chrysin analogs containing 1,2,3-triazoles with different substituent groups (5a-5l) was designed, synthesized, and evaluated as potential anticancer agents. The synthesized compounds were characterized using FT-IR, 1H NMR 13C NMR spectroscopy and mass spectrometry.

A library of aminoglycoside-derived lipopolymer nanoparticles for delivery of small molecules and nucleic acids.

Simultaneous delivery of small molecules and nucleic acids using a single vehicle can lead to novel combination treatments and multifunctional carriers for a variety of diseases. In this study, we report a novel library of aminoglycoside-derived lipopolymers nanoparticles (LPNs) for the simultaneous delivery of different molecular cargoes including nucleic acids and small-molecules. The LPN library was screened for transgene expression efficacy following delivery of plasmid DNA, and lead LPNs that showed high transgene expression efficacies were characterized using hydrodynamic size, zeta potential, 1H NMR and FT-IR spectroscopy, and transmission electron microscopy.

Copper-Eluting Fibers for Enhanced Tissue Sealing and Repair.

Copper ions play an important role in several physiological processes, including angiogenesis, growth factor induction and extracellular matrix remodeling, that modulate wound healing and tissue repair. In this work, copper-loaded alginate fibers were generated and used as surgical sutures for repair of incisional wounds in live mice. Approximately 95% of initially loaded copper ions were released from the sutures within the first 24 h following an initial burst release.

PolyRad - Protection Against Free Radical Damage.

The effects of elevated levels of radiation contribute to the instability of pharmaceutical formulations in space compared to those on earth. Existing technologies are ineffective at maintaining the therapeutic efficacies of drugs in space. Thus, there is an urgent need to develop novel space-hardy formulations for preserving the stability and efficacy of drug formulations.

Metabolite releasing polymers control dendritic cell function by modulating their energy metabolism.

Metabolites control immune cell functions, and delivery of these metabolites in a sustained manner may be able to modulate function of the immune cells. In this study, alpha-ketoglutarate (aKG) and diol based polymeric-microparticles (termed paKG MPs) were synthesized to provide sustained release of aKG and promote an immunosuppressive cellular phenotype. Notably, after association with dendritic cells (DCs), paKG MPs modulated the intracellular metabolic-profile/pathways, and decreased glycolysis and mitochondrial respiration in vitro.

Plasmonic gel nanocomposites for detection of high energy electrons.

Radiation therapy is a common treatment modality employed in the treatment of cancer. High energy photons are the primary source of radiation but when administered, they leave an exit dose resulting in radiation damage to the adjacent healthy tissues. To overcome this, high energy electrons are employed in cases of skin cancer to minimize radiation induced toxicity.

Flow-induced Shear Stress Confers Resistance to Carboplatin in an Adherent Three-Dimensional Model for Ovarian Cancer: A Role for EGFR-Targeted Photoimmunotherapy Informed by Physical Stress.

A key reason for the persistently grim statistics associated with metastatic ovarian cancer is resistance to conventional agents, including platinum-based chemotherapies. A major source of treatment failure is the high degree of genetic and molecular heterogeneity, which results from significant underlying genomic instability, as well as stromal and physical cues in the microenvironment. Ovarian cancer commonly disseminates via transcoelomic routes to distant sites, which is associated with the frequent production of malignant ascites, as well as the poorest prognosis.

Determination of topographical radiation dose profiles using gel nanosensors.

Despite the emergence of sophisticated technologies in treatment planning and administration, routine determination of delivered radiation doses remains a challenge due to limitations associated with conventional dosimeters. Here, we describe a gel-based nanosensor for the colorimetric detection and quantification of topographical radiation dose profiles in radiotherapy. Exposure to ionizing radiation results in the conversion of gold ions in the gel to gold nanoparticles, which render a visual change in color in the gel due to their plasmonic properties.

Delivery of TRAIL-expressing plasmid DNA to cancer cells in vitro and in vivo using aminoglycoside-derived polymers.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand that can preferentially induce apoptosis in cancer cells over normal cells. The transmembrane form of TRAIL has been shown to elicit much stronger activity than its soluble counterpart but delivery is a potential challenge. Here, we investigated the potential of aminoglycoside-derived polymers to enhance delivery of a plasmid (pEF-TRAIL) that expresses the transmembrane form of TRAIL in order to determine the effect on cell death in vitro and tumor growth in vivo.

A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling.

Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases and inflammation, in a mouse excisional wound model.

Protein-facilitated gold nanoparticle formation as indicators of ionizing radiation.

The use of X-ray radiation in radiotherapy is a common treatment for many cancers. Despite several scientific advances, determination of radiation delivered to the patient remains a challenge due to the inherent limitations of existing dosimeters including fabrication and operation. Here, we describe a colorimetric nanosensor that exhibits unique changes in color as a function of therapeutically relevant radiation dose (3-15 Gy).

Light-Activated Tissue-Integrating Sutures as Surgical Nanodevices.

Sutures are typically the primary means of soft tissue repair in surgery and trauma. Despite their widespread use, sutures do not result in immediate sealing of approximated tissues, which can result in bacterial infection and leakage. Nonabsorbable sutures and staples can be traumatic to tissue, and the trauma can be exacerbated by their subsequent removal.