Gregory S Schultz

University of Florida, Gainesville, Florida, United States

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Publications (269)778.5 Total impact

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    ABSTRACT: Significance: Broad-spectrum metalloproteinase (MMP) reduction along with inherent aspects of an extracellular matrix (ECM) dressing can bring about improved wound healing outcomes and shorter treatment duration. Initial reports of clinical effectiveness of a new ovine-based collagen extracellular matrix (CECM) dressing demonstrate benefits in chronic wound healing. Recent Advances: CECM dressings are processed differently than oxidized regenerated cellulose/collagen dressings. CECM dressings consist primarily of collagens I and III arranged as native fibers that retain the three-dimensional architecture present in tissue ECM. As such, ovine-based ECM dressings represent a new generation of collagen dressings capable of impacting a broad spectrum of MMP excess known to be present in chronic wounds. Critical Issues: While MMPs are essential in normal healing, elevated presence of MMPs has been linked to wound failure. Collagen has been shown to reduce levels of MMPs, acting as a sacrificial substrate for excessive proteases in a chronic wound. Preserving collagen dressings in a more native state enhances bioactivity in terms of the ability to affect the chronic wound environment. Clinical observation and assessment may not be sufficient to identify a wound with elevated protease activity that can break down ECM, affect wound fibroblasts, and impair growth factor response. Future Directions: Collagen dressings that target broad-spectrum excessive MMP levels and can be applied early in the course of care may positively impact healing rates in difficult wounds. Next-generation collagen dressings offer broader MMP reduction capacity while providing a provisional dermal matrix or ECM.
    No preview · Article · Feb 2016
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    Full-text · Article · Jan 2016 · American Journal of Respiratory and Critical Care Medicine
  • Sonal S Tuli · Mark B Sherwood · Gregory S Schultz
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    ABSTRACT: Regulation of wound healing following GFS is a complex process and involves multiple growth factors, cytokines, and proteases, and the TGF-β and CTGF systems appear to play major roles in promoting scarring and contraction that result in bleb failure. An ideal outcome of GFS is a diffuse, but healthy, bleb that filters aqueous humor without leaking. Achieving this goal is challenging, as the currently available interventions utilize broadly acting anti-metabolites that can cause early complications, such as toxicity, and delayed complications, such as bleb leaks and scleral melts. The ideal modulator of GFS would, therefore, not only be cell-specific, but also, preferably, gene-specific to selectively alter the healing of the sub-Tenon's fibroblasts without off-target or delayed effects on the surrounding tissues and the fibroblasts themselves. Understanding the molecular regulation of healing following GFS in conjunctival/Tenon's capsule tissues facilitates the design of therapies that utilize drugs which selectively interfere with genes and proteins that promote scar formation and contraction without undesirable side effects.
    No preview · Chapter · Dec 2015
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    ABSTRACT: For proper wound healing, control of bacteria or bacterial infections is of major importance. While caring for a wound, dressing material plays a key role as bacteria can live in the bandage and keep re-infecting the wound. They do this by forming biofilms in the bandage, which slough off planktonic bacteria and overwhelm the host defense. It is thus necessary to develop a wound dressing that will inhibit bacterial growth. This study examines the effectiveness of a polyurethane foam wound dressing bound with polydiallyl-dimethylammonium chloride (pDADMAC) to inhibit the growth of bacteria in a wound on the back of a mouse. This technology does not allow pDADMAC to leach away from the dressing into the wound, thereby preventing cytotoxic effects. Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii were chosen for the study to infect the wounds. S. aureus and P. aeruginosa are important pathogens in wound infections, while A. baumannii was selected because of its ability to acquire or upregulate antibiotic drug resistance determinants. In addition, two different isolates of methicillin-resistant S. aureus (MRSA) were tested. All the bacteria were measured in the wound dressing and in the wound tissue under the dressing. Using colony-forming unit (CFU) assays, over six logs of inhibition (100%) were found for all the bacterial strains using pDADMAC-treated wound dressing when compared with control-untreated dressing. The CFU assay results obtained with the tissues were significant as there were 4–5 logs of reduction (100%) of the test organism in the tissue of the pDADMAC-covered wound versus that of the control dressing-covered wound. As the pDADMAC cannot leave the dressing (like other antimicrobials), this would imply that the dressing acts as a reservoir for free bacteria from a biofilm and plays a significant role in the development of a wound infection.
    No preview · Article · Dec 2015 · International Wound Journal
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    ABSTRACT: To determine if sequential treatment with Bevacizumab (Avastin), a monoclonal, VEGF antibody that blocks angiogenesis; Saratin, a 12 kD polypeptide with anti-inflammatory and anti-thrombotic properties; and Ilomastat, a matrix metalloproteinase (MMP) inhibitor, prolongs bleb life following glaucoma filtration surgery (GFS) in a rabbit model. Thirty-two New Zealand White rabbits (eight rabbits per group) underwent GFS in the left eye. Group 1 received a perioperative injection of both Saratin and Bevacizumab, and later, subconjuctival injections of Ilomastat on days 8 and 15. Group 2 received only Saratin perioperatively, and also received Ilomastat injections on days 8 and 15. Group 3, the negative control, received a single perioperative injection of Balanced Saline Solution (BSS) along with post-operative BSS injections on days 8 and 15. Group 4, the positive control, received topical treatment with Mitomycin-C (MMC) at the time of surgery with no further treatment. Blebs were evaluated by an observer masked to treatment every third day. Histology was obtained on two eyes in each group on post-op day twelve as well as all eyes following bleb failure. Eyes in group 1 had a mean bleb survival time of 29 ± 2.7 days, whereas those in group 2 that received the experimental treatment without Bevacizumab had a mean survival time of 25.5 ± 2.7 days. An ANOVA test showed that the Saratin/Ilomastat/Bevacizumab group demonstrated a significant prolongation of bleb survival compared to the BSS control-mean survival time of 19.7 ±2.7 days-(p = 0.0252) and was not significantly different from the MMC positive control group (p = 0.4238)-mean survival time of 32.5 ± 3.3. From tissue histology at day 12, the four different groups showed marked differences in the cellularity and capsule fibrosis. The MMC eyes showed minimal cellularity, were avascular and had minimal fibrous tissue. BSS group showed high cellularity, moderate to high fibrosis, and thicker and more defined capsules than either of the treatment groups and the positive control. Both the Saratin/Ilomastat/Bevacizumab and Saratin/Ilomastat only eyes showed moderate cellularity with minimal fibrosis, with less cellularity and fibrosis present in the triple treatment group. Sequential therapy with multiple agents, including Bevacizumab, prolonged bleb function following GFS in the rabbit model and were significantly better than the negative BSS control. The experimental group did not show the same surface tissue histological thinning and side effects associated with MMC treatment.
    Preview · Article · Sep 2015 · PLoS ONE
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    Full-text · Poster · Jul 2015
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    C. Yang · C. Gendics · Q. Yang · D. Gibson · G. Schultz · J. Lantis

    Full-text · Poster · Jul 2015
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    C. Yang · S. Goss · S. Alcantara · Q. Yang · G. Schultz · J. Lantis

    Full-text · Article · Jul 2015 · Wound Repair and Regeneration

  • No preview · Article · Apr 2015 · American Journal Of Pathology
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    Full-text · Poster · Mar 2015
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    ABSTRACT: The purpose of this study was to assess the potential differences in antibacterial activity and fluid flow rates Of 2 commonly used silver dressings: an alginate-only dressing and an alginate dressing with a nonadherent contact layer. Materials and Methods. The dressings' antibacterial activities were tested against 2 major bacterial pathogens for skin wounds Staphylococcus aureus and Pseudomonas aeruginosa using 2 in vitro models of skin wounds. The fluid flow rate through the 2 dressings was also measured and compared. Results. While materially similar, the choice to include a nonadherent layer leads to reduced antibacterial performance and a reduced rate of fluid flow into and through the dressing. Conclusion. The use of the silver antimicrobial alginate dressing with a nonadherent layer provides a welcome feature in that it does not adhere to surfaces; however, the results demonstrate lower rate Of fluid removal when compared to a silver antimicrobial alginate without the nonadherent layer.
    Full-text · Article · Jan 2015 · Wounds UK
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    ABSTRACT: Chronic wounds, including diabetic foot ulcers, pressure ulcers and venous leg ulcers, impact the lives of millions of people worldwide. These types of wounds represent a significant physical, social and financial burden to both patients and health care systems. Wound care has made great progress in recent years as a result of the critical research performed in academic, clinical and industrial settings. However, there has been relatively little translation of basic research discoveries into novel and effective treatments. One underlying reason for this paucity may be inconsistency in the methods of wound analysis and sample collection, resulting in the inability of researchers to accurately characterise the healing process and compare results from different studies. This review examines the various types of analytical methods being used in wound research today with emphasis on sampling techniques, processing and storage, and the findings call forth the wound care research community to standardise its approach to wound analysis in order to yield more robust and comparable data sets.
    Full-text · Article · Jan 2015 · International Wound Journal
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    ABSTRACT: Purpose. Utilization of self complementary adeno-associated virus(scAAV) to rapidly deliver and express a ribozyme (Rz) targeting profibrotic connective tissue growth factor (CTGF) in the cornea to reduce corneal haze formation. Methods: Secreted alkaline phosphatase (sAP) reporter system was used to analyze the ability of scAAV-CTGF-Active-Rz to target CTGF mRNA in cell culture. Next, scAAV expressing green fluorescent protein (scAAV-GFP) was delivered to rabbit corneas following excimer laser ablation to assess expression patterns in corneas. Corneas were removed at 0, 1, 2, 3, 4, 7, 30 and 180 days after scAAV-GFP application and expression was visualized by direct fluorescence. Finally, rat corneas were ablated and treated with scAAV-CTGF-Active-Rz or PBS control. Re-epitheliaization rate was determined and haze was graded by masked observers for 14 days. After 14 days, corneas were removed and CTGF protein was quantified using ELISA. Results: In HEK293 cells, CTGF mRNA was reduced by 9, 24, and 30% at 24, 48 and 72 hours, respectively, after transfection compared to control plasmid. In ablated rabbit corneas, GFP fluorescence was first detected at 24 hours and peaked at day 7 which was 22 times greater than day 0. The transgene was expressed in all cell types of the cornea; epithelium, keratocytes and endothelium. Finally, scAAV-CTGF-Active-Rz resulted in significant knockdown of 19% of CTGF protein on day 14. No significant difference in re-epitheliaization rates or haze grading scores of treated and untreated rat corneas were found. Conclusion: The scAAV vectors had the ability to rapidly transduce and express the scAAV-CTGF-Active-Rz and create a small, but significant reduction of the CTGF protein. This level of reduction did not significantly reduce the clinically observed haze in a rat model of corneal injury.
    No preview · Chapter · Jan 2015
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    ABSTRACT: Bacterial infection of acute and chronic wounds impedes wound healing significantly. Part of this impediment is the ability of bacterial pathogens to grow in wound dressings. In this study, we examined the effectiveness of a polyurethane foam wound dressings coated with poly diallyl-dimethylammonium chloride (pDADMAC-PU) to inhibit the growth and biofilm development by three main wound pathogens: Staphylococcus aureus, Pseudomonas aeruginosa and Acinetobacter baumannii, within the wound dressing. pDADMAC-PU inhibited the growth of all three pathogens. Time-kill curves were conducted both with and without serum to determine the killing kinetic of pDADMAC-PU. pDADMAC-PU killed S. aureus, A. baumannii, and P. aeruginosa. The effect of pDADMAC-PU on biofilm development was analyzed quantitatively and qualitatively. Quantitative analysis, (CFU) assay, revealed that pDADMAC-PU dressing produced more than 8 log reduction in biofilm formation by each pathogen. Visualization of the biofilms by either confocal laser scanning microscopy or scanning electron microscopy confirmed these findings. In addition, it was found that the pDADMAC-PU treated foam totally inhibited migration of bacteria through the foam for all three bacterial strains. These results suggest that pDADMAC-PU is an effective wound dressing that inhibits the growth of wound pathogens both within the wound and in the wound dressing. This article is protected by copyright. All rights reserved.
    Full-text · Article · Dec 2014 · Wound Repair and Regeneration
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    ABSTRACT: This study sought to determine whether silver-containing dressings and medical-grade honey gel interfere with one another in measurable ways. Dressings applied together in clinical use were tested using in vitro and ex vivo methods to determine whether the combined modalities maintain their individual properties. In order to determine if the presence of silver dressings interfere with honey's osmotic strength, which is a key physical property of medical honey, changes in honey's 2 primary sugars were measured, as well as changes in its overall osmotic strength. Finally, the antibacterial barrier activity of the dressings were tested individually and in honey/silver pairs in 2 in vitro models with 2 clinical strains of bacteria. The data demonstrate that honey with silver dressings resulted in an increased osmolarity, since both the concentration of the 2 primary sugars in honey as well as its overall osmolarity increased. The data also demonstrate that the in vitro antibacterial barrier activity seen with silver-containing dressings does not decrease with the addition of medical honey and in some instances increased. Altogether, these data suggest that these 2 classes of dressings do not interfere with each other. Clinical evidence is still required to fully validate these findings.
    Full-text · Article · Nov 2014 · Wounds UK
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    ABSTRACT: Unlabelled: Connective tissue growth factor (CTGF) is a matricellular protein that mediates cell-matrix interaction through various subtypes of integrin receptors. This study investigated the role of CTGF and integrin αvβ6 in hepatic progenitor/oval cell activation, which often occurs in the form of ductular reactions (DRs) when hepatocyte proliferation is inhibited during severe liver injury. CTGF and integrin αvβ6 proteins were highly expressed in DRs of human cirrhotic livers and cholangiocarcinoma. Confocal microscopy analysis of livers from Ctgf promoter-driven green fluorescent protein reporter mice suggested that oval cells and cholangiocytes were the main sources of CTGF and integrin αvβ6 during liver injury induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). Deletion of exon 4 of the Ctgf gene using tamoxifen-inducible Cre-loxP system down-regulated integrin αvβ6 in DDC-damaged livers of knockout mice. Ctgf deficiency or inhibition of integrin αvβ6, by administrating the neutralizing antibody, 6.3G9 (10 mg/kg body weight), caused low levels of epithelial cell adhesion molecule and cytokeratin 19 gene messenger RNAs. Also, there were smaller oval cell areas, fewer proliferating ductular epithelial cells, and lower cholestasis serum markers within 2 weeks after DDC treatment. Associated fibrosis was attenuated, as indicated by reduced expression of fibrosis-related genes, smaller areas of alpha-smooth muscle actin staining, and low collagen production based on hydroxyproline content and Sirius Red staining. Finally, integrin αvβ6 could bind to CTGF mediating oval cell adhesion to CTGF and fibronection substrata and promoting transforming growth factor (TGF)-β1 activation in vitro. Conclusions: CTGF and integrin αvβ6 regulate oval cell activation and fibrosis, probably through interacting with their common matrix and signal partners, fibronectin and TGF-β1. CTGF and integrin αvβ6 are potential therapeutic targets to control DRs and fibrosis in related liver disease.
    No preview · Article · Sep 2014 · Hepatology

  • No preview · Article · Sep 2014 · Wound Repair and Regeneration
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    ABSTRACT: The effects of a triple combination of siRNAs targeting key scarring genes was assessed using an ex vivo organ culture model of excimer ablated rabbit corneas. The central 6 mm diameter region of fresh rabbit globes was ablated to a depth of 155 microns with an excimer laser. Corneas were excised, cultured at the air-liquid interface in defined culture medium supplemented with transforming growth factor beta 1 (TGFB1), and treated with either 1% prednisolone acetate or with 22.5 μM cationic nanoparticles complexed with a triple combination of siRNAs (NP-siRNA) targeting TGFB1, TGFB Receptor (TGFBR2) and connective tissue growth factor (CTGF). Scar formation was measured using image analysis of digital images and levels of smooth muscle actin (SMA) were assessed in ablated region of corneas using qRT-PCR and immunostaining. Ex vivo cultured corneas developed intense haze-like scar in the wounded areas and levels of mRNAs for pro-fibrotic genes were significantly elevated 3 to 8 fold in wounded tissue compared to unablated corneas. Treatment with NP-siRNA or steroid significantly reduced quantitative haze levels by 55% and 68%, respectively, and reduced SMA mRNA and immunohistostaining. This ex vivo corneal culture system reproduced key molecular patterns of corneal scarring and haze formation generated in rabbits. Treatment with NP-siRNAs targeting key scarring genes or an anti-inflammatory steroid reduced corneal haze and SMA mRNA and protein.
    No preview · Article · Jun 2014 · Experimental Eye Research
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    Full-text · Article · Mar 2014
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    ABSTRACT: Purpose: This study aimed to elucidate the role of connective tissue growth factor (CTGF) in healthy eyes and wounded corneas of mice and rabbits. Conditional knockout mice were used to determine the role of CTGF in corneal healing. Methods: CTGF expression was determined using transgenic mice carrying CTGF promoter driven-eGFP, quantitative RT-PCR, and immunofluorescent staining. Mice that carried two floxed CTGF alleles and a Cre/ERT2 transgene under the control of human ubiquitin C (ubc) promoter were used to conditionally delete CTGF gene in a tamoxifen-inducible manner. Phototherapeutic keratectomy (PTK) was used to generate an acute corneal wound and corneal re-epithelialization was assessed by fluorescein staining. Results: Connective tissue growth factor expression was found in multiple ocular tissues with relatively high levels in the corneal endothelium, lens subcapsular epithelium, and in the vasculature of the iris and retina. Wounded corneas responded with an immediate upregulation of CTGF in the epithelium at the wound margin and a sustained CTGF induction during re-epithelialization. At the onset of haze formation, CTGF protein becomes more focused in the basal epithelium. Deletion of the CTGF gene caused a 40% reduction (P < 0.01) in the cornea re-epithelialization rate in knockout mice compared with wild-type mice. Conclusions: Connective tissue growth factor is expressed in the naïve cornea, lens, iris, and retina, and is expressed immediately after epithelial injury. Loss of CTGF impairs efficient re-epithelialization of corneal wounds.
    No preview · Article · Mar 2014 · Investigative ophthalmology & visual science

Publication Stats

11k Citations
778.50 Total Impact Points

Institutions

  • 1989-2015
    • University of Florida
      • • Department of Obstetrics and Gynecology
      • • Department of Ophthalmology
      • • College of Medicine
      Gainesville, Florida, United States
  • 2010
    • Walter Reed National Military Medical Center
      • Department of Surgery
      Washington, D. C., DC, United States
  • 2009
    • Lovelace Respiratory Research Institute
      • Respiratory Immunology and Asthma Program
      Albuquerque, New Mexico, United States
  • 2006
    • Northwestern University
      Evanston, Illinois, United States
  • 2003
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 2002-2003
    • University of Miami
      كورال غيبلز، فلوريدا, Florida, United States
  • 2000-2003
    • Cornell University
      • Department of Clinical Sciences
      Итак, New York, United States
  • 1997
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1995
    • Schepens Eye Research Institute
      Boston, Massachusetts, United States
  • 1993
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
  • 1984-1993
    • University of Louisville
      • • Department of Surgery
      • • Department of Medicine
      Louisville, Kentucky, United States
  • 1992
    • The University of Florida Academic Health Center
      Jacksonville, Florida, United States