Stephen Davis Lab : Research

Research

I am research professor who has over 30 years’ experience using various wound healing and infection models in swine. I have had the privilege to work with William H. Eaglstein, MD, and Patricia M. Mertz who pioneered the first animal porcine model in the mid 1970s. Using these models we have expanded current knowledge of moist wound healing, evaluated the in-vivo effects of numerous agents on bacterial proliferation and bacterial biofilms as well as help to determine mechanisms and efficacy of various products/technologies that are on the market today e.g. DuoDerm dressing, Kerlix A.M.D., Liquid Bandage, Iodoflex and Procellera. These models have also been used to study the effect of early debridement, burn cooling and scar prevention/treatment.

William Eaglstein, MD
William Eaglstein, MD

Patricia M. Mertz
Patricia M. Mertz

In addition to working with well over 100 different companies in the development of new therapies, my laboratory has been has been funded research by DARPA (topical oxygen emulsion/plasma energy), Canadian Defense (antimicrobial gels), US Army (platelet rich plasma, chitosan matrices, stem cells/scars), and the Office of Naval Research (antimicrobial peptides), as well as for numerous NIH and NSF grants.

Some of my interests include: occlusive therapy, electrical stimulation, low energy light therapy and bacterial biofilm formation.

Wound Healing

Although in vitro evaluations can help find study potential mechanisms of action as well as assist determine optimal doses to be used, in vivo studies that take into account the effects of wound fluid, growth factors, proteases, etc. are required. Over the years we have shown that various types of occlusive dressings, e.g. hydrocolloids, can epithelialize deep partial thickness wounds faster than other kind of dressings. We have also shown that treatments that may be effective at stimulating one type of injury may not be effective on another injury. For example, we have seen that hydrocolloid and polyurethane dressings are effective on acute deep partial thickness but do not stimulate healing of second degree burns.

Dressigns DPTWH vs. Burns

Another focus of our laboratory has been to study prevention and treatment of scars. Working closely with the University of Miami’s Stem Cell Institute and Ryder trauma center, we have developed a third degree burn scar model in which we are trying to modulate existing scars. Using clinical, histological and molecular assessments we determine whether various treatment modalities are effective. Products that stimulate healing and reduce infection are sorely needed. Since agents that can reduce infection may also impede the healing process, it is imperative that well controlled studies are conducted.

In vivo porcine models used

• Third-degree burn – study of scar formation and treatment
• Second-degree burn – study of healing and infection
• Deep partial thickness – study of healing and infection
• Full thickness – study of healing and infection
• Ischemic wound model – study the effects ischemia on wound healing
• Laser model – study of agents that effect healing after laser injury

Wound Infection

Many colonized wounds harbor bacterial loads that can eventually lead to infections that not only can result in significant delays in healing but also increase rates of morbidity and mortality. We have carried out numerous studies to examine the effectiveness of various antimicrobial agents and/dressing on wound pathogenic bacteria in vivo. We have developed a wound infection model of bacterial biofilms. Biofilms are the preferred state for many organisms and consist of organisms that have formed a glycocalyx matrix. These microorganisms in biofilms cause diverse and persistent infections which are resistant to antimicrobial therapy. By causing the microorganisms to form a wound biofilm in vivo real time treatment data can be acquired.

Using the above wound healing models we can inoculate wounds with various types of microorganisms that are common in wound infection, e.g. Pseudomonas aeruginosa, Methicillin-Resistant Staphylococcus aureus (MRSA), Methicillin-Sensitive Staphylococcus aureus (MSSA), Acinetobacter baumannii, and Candida albicans. After treatment, we recover the microorganisms with either a scrub or biopsy technique,(making sure to neutralize any antimicrobial used) perform serial dilutions and use a Spiral Plater System to quantitate bacterial counts. Selective media is used depending on the microorganism examined.

Lab images

We have found a significant difference in bacterial reduction when wounds were treated with a topical antibiotic after 20 minutes of inoculation (planktonic bacteria) or 48 hours (biofilm associated bacteria). We have seen that once a biofilm forms, it takes several more days of treatment to demonstrate significant reducing in bacterial loads. We have also shown that some of the silver dressings are not able to reduce the bacterial load of wounds (planktonic or bioflm).

Some of the advantages of using occlusive dressings are that they can maintain a moist environment which allows easier epithelial migration as well as providing an environment for the viability of growth factors to stimulate healing. One of the concerns of using dressings is the fear of infection. However we have shown that some dressings, even various gauze materials, can reduce and/or prevent the entrance of bacteria. An example of this is work we performed with a polyhexamethylene biguanide (PHMB) gauze. We showed wounds covered with the antimicrobial gauze significantly reduced the ability of a motile organism (Pseudomonas aeruginosa: PA) to gain entrance into wounds. The ability of dressings or agents to reduce the likelihood of infection is extremely important when choosing particular products to treat wounds.

We also study the how polymicrobial infections can have an effect on virulence factors produced by the microorganims as well as their effects on the host. Recently we reported that wounds with mixed-species reduce epithelialization through suppression of KGF1 and change in cytokine expression (assessed by rtPCR) can be observed depending on the bacteria present.

In vitro models:

• Minimal inhibitory concentration
• Ex vivo model
• Modified Kirby Bauer (test to determine the antimicrobial activity of active compounds)
• In vitro antifungal assay

In vivo models used:

• Same type of wound described in wound healing section above.