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Results for “Wound Healing”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2008

Using Light to Treat Mucositis and Help Wounds Heal

A continuing program of research and development is focusing on the use of controlled illumination by light-emitting diodes (LEDs) to treat mucositis and to accelerate healing of wounds. The basic idea is to illuminate the affected area of a patient with light of an intensity, duration, and wavelength (or combination of wavelengths) chosen to produce a therapeutic effect while generating only a minimal amount of heat. This method of treatment was originally intended for treating the mucositis that is a common complication of chemotherapy and radiation therapy for cancer. It is now also under consideration as a means to accelerate the healing of wounds and possibly also to treat exposure to chemical and radioactive warfare agents. Radiation therapy and many chemotherapeutic drugs often damage the mucosal linings of the mouth and gastrointestinal tract, leading to mouth ulcers (oral mucositis), nausea, and diarrhea. Hyperbaric-oxygen therapy is currently the standard of care for ischemic, hypoxic, infected, and otherwise slowlyhealing problem wounds, including those of oral mucositis. Hyperbaric-oxygen therapy increases such cellular activities as collagen production and angiogenesis, leading to an increased rate of healing. Biostimulation by use of laser light has also been found to be effective in treating mucositis. For hyperbaricoxygen treatment, a patient must remain inside a hyperbaric chamber for an extended time. Laser treatment is limited by laser-wavelength capabilities and by narrowness of laser beams, and usually entails the generation of significant amounts of heat.

Ignatius, Robert W.↗
DOE OSTI2021

Age-associated expression of p21and p53 during human wound healing

In mice, cellular senescence and senescence-associated secretory phenotype (SASP) positively contribute to cutaneous wound healing. In this proof-of-concept study, we investigated the expressions of p16, p21, and other senescence-associated biomarkers during human wound healing in 24 healthy subjects using a double-biopsy experimental design. The first punch biopsy created the wound and established the baseline. The second biopsy, concentric to the first and taken several days after wounding, was used to probe for expression of biomarkers by immunohistochemistry and RNA FISH. To assess the effects of age, we recruited 12 sex-matched younger (30.2 ± 1.3 years) and 12 sex-matched older (75.6 ± 1.8 years) subjects. We found that p21 and p53, but not p16, were induced during healing in younger, but not older subjects. A role for Notch signaling in p21 expression was inferred from the inducible activation of HES1. Further, other SASP biomarkers such as dipeptidyl peptidase-4 (DPP4) were significantly induced upon wounding in both younger and older groups, whereas matrix metallopeptidase 9 (MMP9) was induced only in the younger group. Senescence-associated β-galactosidase (SA-β-gal) was not detectable before or after wounding. This pilot study suggests the possibility that human cutaneous wound healing is characterized by differential expression of p21 and p53 between younger and older subjects.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Characterization of a Human Platelet Lysate-Loaded Keratin Hydrogel for Wound Healing Applications In Vitro

One of the promising approaches to facilitate healing and regenerative capacity includes the application of growth-factor-loaded biomaterials. Human platelet lysate (hPL) derived from platelet-rich plasma through a freeze-thaw process has been used as a growth factor rich therapeutic in many regenerative applications. To provide sustained local delivery of the hPL-derived growth factors such as epidermal growth factor (EGF), the hPL can be loaded into biomaterials that do not degrade rapidly in vivo. Keratin (KSO), a strong filamentous protein found in human hair, when formulated as a hydrogel, is shown to sustain the release of drugs and promote wound healing. In the current study, we created a KSO biomaterial that spontaneously forms a hydrogel when rehydrated with hPL that is capable of controlled and sustained release of pro-regenerative molecules. Our study demonstrates that the release of hPL is controlled by changing the KSO hydrogel and hPL-loading concentrations, with hPL loading concentrations having a greater effect in changing release profiles. In addition, the 15% KSO concentration proved to form a stable hydrogel, and supported cell proliferation over 3 days without cytotoxic effects in vitro. The hPL-loaded keratin hydrogels show promise in potential applications for wound healing with the sustained release of pro-regenerative growth factors with easy tailoring of hydrogel properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Survival, healing, and swim performance of juvenile migratory sea lamprey ( Petromyzon marinus ) implanted with a new acoustic microtransmitter designed for small eel-like fishes

Background: Little is known about the transformer stage of the parasitic lampreys, a brief but critical period that encompasses juvenile out-migration from rivers to lakes or oceans to begin parasitic feeding. Information about this life stage could have significant conservation implications for both imperiled and invasive lampreys. We investigated tag retention, survival, wound healing, and swim performance of newly transformed sea lamprey (Petromyzon marinus) implanted with a new micro-acoustic transmitter, the eel–lamprey acoustic transmitter (ELAT), in a controlled laboratory environment. Results: The 61-day survival of our tagged subjects was 71%, within the range reported in similar studies of juvenile lampreys. However, survival was significantly lower in the tagged animals (vs control), with no effect statistically attributable to measures of animal length, mass, condition, or population of origin (Great Lakes vs. Atlantic drainage). Mortality in tagged fish was concentrated in the first four days post-surgery, suggesting injury from the surgical process. An unusually long recovery time from anesthesia may have contributed to the increased mortality. In a simple burst swim assay, tagged animals swam significantly slower (– 22.5%) than untagged animals, but were not significantly different in endurance swim tests. A composite wound healing score at day four was a significant predictor of maximum burst swim speed at day 20, and wound condition was related to animal mass, but not length, at the time of tagging. Conclusions: Impairments to survival and swim performance of juvenile sea lamprey implanted with the ELAT transmitter were within currently reported ranges for telemetry studies with small, difficult to observe fishes. Our results could be improved with more refined anesthesia and surgical techniques. The ability to track migratory movements of imperiled and pest populations of parasitic lampreys will improve our ability to estimate vital rates that underlie recruitment to the adult population (growth, survival) and to investigate the environmental factors that regulate the timing and rates of movement, in wild populations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Methyl jasmonate effects on sugarbeet root responses to postharvest dehydration

Background: Sugarbeet (Beta vulgaris L.) roots are stored under conditions that cause roots to dehydrate, which increases postharvest losses. Although exogenous jasmonate applications can reduce drought stress in intact plants, their ability to alleviate the effects of dehydration in postharvest sugarbeet roots or other stored plant products is unknown. Research was conducted to determine whether jasmonate treatment could mitigate physiological responses to dehydration in postharvest sugarbeet roots. Methods: Freshly harvested sugarbeet roots were treated with 10 µM methyl jasmonate (MeJA) or water and stored under dehydrating and non-dehydrating storage conditions. Changes in fresh weight, respiration rate, wound healing, leaf regrowth, and proline metabolism of treated roots were investigated throughout eight weeks in storage. Results: Dehydrating storage conditions increased root weight loss, respiration rate, and proline accumulation and prevented leaf regrowth from the root crown. Under dehydrating conditions, MeJA treatment reduced root respiration rate, but only in severely dehydrated roots. MeJA treatment also hastened wound-healing, but only in the late stages of barrier formation. MeJA treatment did not impact root weight loss or proline accumulation under dehydrating conditions or leaf regrowth under non-dehydrating conditions. Both dehydration and MeJA treatment affected expression of genes involved in proline metabolism. In dehydrated roots, proline dehydrogenase expression declined 340-fold, suggesting that dehydration-induced proline accumulation was governed by reducing proline degradation. MeJA treatment altered proline biosynthetic and catabolic gene expression, with greatest effect in nondehydrated roots. Overall, MeJA treatment alleviated physiological manifestations of dehydration stress in stored roots, although the beneficial effects were small. Postharvest jasmonate applications, therefore, are unlikely to significantly reduce dehydrationrelated storage losses in sugarbeet roots.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

A dehydrated, aseptically-processed human amnion/chorion allograft accelerates healing in a delayed murine excisional wound model

Since chronic, non-healing wounds represent an increasing source of economic and temporal burden for patients who suffer from them and healthcare professionals that treat them, therapeutic modalities that promote closure of delayed and non-healing wounds are of utmost importance. Recent clinical results of allografts derived from amnion and chorion placental layers encourage further investigation of the mechanisms underlying clinical efficacy of these products for treatment of wounds. Here, we utilized a diabetic murine splinted excisional wound model to investigate the effects of a dehydrated human amnion/chorion-derived allograft (dHACA) on delayed wound healing, as well as the effects of dehydrated allograft derived solely from amnion tissue of the same donor. We examined wound healing by histological endpoint analysis, and we assessed other parameters relevant to functional wound healing in the wound bed including angiogenesis, macrophage phenotypes, proliferative activity, and gene expression. Herein we demonstrate that application of dHACA to a murine diabetic model of delayed wound progression results in better macroscale wound resolution outcomes, including rate of closure, compared to unaided wound progression, while dehydrated human amnion allograft (dHAA) fails to improve outcomes. Improved gross wound resolution observed with dHACA was accompanied by increased granulation tissue formation, proliferation and vascular ingrowth observed in the wound bed, early macrophage polarization towards anti-inflammatory phenotypes, and downregulation of pro-fibrotic gene expression. Overall, our data suggest that improvements in the rates of delayed wound closure observed from combined amnion/chorion allografts are associated with modulation of critical cellular and tissue processes commonly found to be dysregulated in delayed healing wounds, including proliferation, vascularization, inflammation, and re-epithelialization.

60 APPLIED LIFE SCIENCES↗
NASA NTRS2011

Summer Research Paper

Certain populations such as chemotherapy patients and atomic bomb survivors have been exposed to ionizing radiation and experience tissue damage and cancer initiation and progression. One cancer that can be initiated from radiation is esophageal squamous cell carcinoma (ESCC), an epithelial cancer that has a survival rate as low as 20%. Researchers have found that when protein tyrosine kinase receptors (RPTK) activate oncogenes, they can create epithelial tumors and cause deadly cancers like ESCC. The RPTK family has one group, MET, that has only two receptors, MET and RON, present in the human body. MET s ligand is the hepatocyte growth factor (HGF) and RON's ligand is the macrophage-stimulating protein (MSP-1). Both HGF and MSP-1 have been shown to activate their receptors and are implicated in certain processes. Since radiation damages cells throughout the biological system, researchers are investigating whether or not HGF and MSP-1 protects or kills certain normal and cancerous cells by being part of cell recovery processes. One research group recently reviewed that the HGF-MET pathway has an important role in the embryonic development in the liver, migration of myogenic precursor cells, regulation of epithelial morphogenesis and growth, and regeneration and protection in tissues. In addition, since the RON receptor is more commonly expressed in cells of epithelial origin, and when activated is part of epithelial cell matrix invasion, dissociation, and migration processes, scientists conclude that RON might be one of the factors causing epithelial cancer initiation in the biological system. In order to examine HGF and MSP-1 s effect on cancer initiation and progression we used two immortalized esophageal epithelial cell lines. One is a normal human cell line (EPC2-hTERT), while the other had a p53 mutation at the 175th amino acid position (EPC2-hTERT-p53(sup R175H)). For this investigation, we used 0(control), 2, and 4 Gray doses of gamma (Cs137) radiation and selected various concentrations from 0-100 ng/mL of HGF and MSP-1 in our assays. Since the HGF and MSP-1 pathways have proliferative roles in epithelial cells, we conducted the MTT proliferation assay to see if either drug enhances or inhibits cell proliferation over time. Also, a MTT cytotoxicity assay was necessary to observe whether the drugs are protecting the cells from radiation and if a trend is occurring depending upon the amount of dose added. In addition, a wound healing assay was done since both drugs have been to known to promote cell motility. Since cell damage occurs when radiation is added, apoptosis and micronuclei assays are vital to see if HGF and MSP-1 increase or decrease cell death and damage in normal and pre-cancerous cells and by how much based on the radiation dosage. Overall, we used the MTT, wound healing, apoptosis and micronuclei assays to investigate the effects ofHGF and MSP-1 on irradiated esophageal epithelial cells.

Patel, Zarana↗
DOE OSTI2026

Nematic cell alignment directs calcium waves in an epithelial monolayer

Tissues rely on supracellular signals to coordinate their cells over a long range. Two such tissuescale cues are calcium waves and patterns of cell-cell alignment or nematic order. During wound healing, for example, calcium waves propagate across a tissue to guide directed cell migration and reepithelialization. Defects in long-range cell-cell alignment, or nematic orientation, can act to localize morphogenetic events in a tissue. Although these two cues have been considered in isolation, we demonstrate a relationship in epithelial tissue between long-range calcium signaling and the cell’s nematic order: The speed of a wound-induced calcium wave depends monotonically on the angle between the wave vector and cell axis, with maximal wave speed occurring perpendicular to the tissue’s orientation. Including anisotropic di↵usive coupling between cells in a canonical reactiondi↵usion model recapitulates our measured calcium wave dynamics. Our model demonstrates how orientation defects can desynchronize information propagation across a tissue. A calcium wave front is bent around nematic defects, therefore cells the same distance from a wound can receive the calcium signal at di↵erent times. Our work elucidates how spatial patterns in global cell alignment can control collective communication via calcium signaling during development, wound healing, and disease.

Winterstrain, Annemarie C. [Brandeis University, W↗
NASA NTRS2002

Second International Conference on Near-Field Optical Analysis: Photodynamic Therapy and Photobiology Effects

The International NASA/DARPA Photobiology Conference held at the Johnson Space Center in Houston/TX demonstrated where low level laser therapy (LLLT), respectively low intensity light activated biostimulation (LILAB) and nanotechnological applications employing photobiomodulation techniques will presumably go in the next ten years. The conference was a continuation of the 1st International Conference on Nearfield Optical Analysis organized by Andrei Sommer (ENSOMA Lab, University of Ulm, Germany) in November 2000 at Castle Reisenburg, Germany, which started with a group of ten scientists from eight different countries. The 1st conference was co-sponsored by the American Chemical Society to evaluate the molecular mechanism of accelerated and normal wound healing processes. The 2nd conference was co-sponsored by DARPA, NASA-JSC and the Medical College of Wisconsin. Despite the short time between events, the 2nd conference hosted 40 international experts form universities, research institutes, agencies and the industry. The materials published here are expected to become milestones forming a novel platform in biomedical photobiology. The multidisciplinary group of researchers focused on LLLT/LILAB-applications under extreme conditions expected to have beneficial effects particularly in space, on submarines, and under severe battlefield conditions. The group also focused on novel technologies with possibilities allowing investigating the interaction of light with biological systems, molecular mechanisms of wound healing, bone regeneration, nerve regeneration, pain modulation, as well as biomineralization and biofilm formulation processes induced by nanobacteria.

Bulgher, Debra L.↗
DOE OSTI2021

Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling

Background:: The fibroblast growth factor (FGF) family is comprised of 23 highly regulatedmonomeric proteins that regulate a plethora of developmental and pathophysiological processes,including tissue repair, wound healing, angiogenesis, and embryonic development. Binding ofFGF to fibroblast growth factor receptor (FGFR), a tyrosine kinase receptor, is facilitated by a glycosaminoglycan,heparin. Activated FGFRs phosphorylate the tyrosine kinase residues that mediateinduction of downstream signaling pathways, such as RAS-MAPK, PI3K-AKT, PLCγ, andSTAT. Dysregulation of the FGF/FGFR signaling occurs frequently in cancer due to gene amplification,FGF activating mutations, chromosomal rearrangements, integration, and oncogenic fusions.Aberrant FGFR signaling also affects organogenesis, embryonic development, tissue homeostasis,and has been associated with cell proliferation, angiogenesis, cancer, and other pathophysiologicalchanges. Objective:: This comprehensive review will discuss the biology, chemistry, and functions of FGFs,and its current applications toward wound healing, diabetes, repair and regeneration of tissues, andfatty liver diseases. In addition, specific aberrations in FGFR signaling and drugs that target FGFRand aid in mitigating various disorders, such as cancer, are also discussed in detail. Conclusion:: Inhibitors of FGFR signaling are promising drugs in the treatment of several types ofcancers. The clinical benefits of FGF/FGFR targeting therapies are impeded due to the activationof other RTK signaling mechanisms or due to the mutations that abolish the drug inhibitory activityon FGFR. Thus, the development of drugs with a different mechanism of action for FGF/FGFRtargeting therapies is the recent focus of several preclinical and clinical studies.

Pharmacology & Pharmacy↗