P-068

A human composite tissue model for studying burn treatments in geriatric patients

PD Dr. Mahtab Nourbakhsh,
Uniklinik RWTH Aachen,
02/2019-01/2021

Burns have been often inflicted on living animals for testing of new treatments for human burn wounds. A new burn model on human surgical wastes is more relevant to human system and testing of wound treatments for the elderly.

Burns still are one of the most common and devastating forms of trauma leading to increased morbidity and mortality especially in elderly individuals. The incidence of burn injury is significantly higher among the elderly population due to decreased physical strength, poor vision and decreased reaction time. Furthermore, aging-related deterioration of immune system, immunosenescence or chronic low-grade inflammation, predisposes geriatric burn patients to infectious complications and impaired tissue regeneration. With the steady growth of elderly population in Western countries, more effective burn treatments for geriatric patients have become of paramount importance.

The majority of human burn injuries affect the cutaneous and subcutaneous adipose tissue, inducing a local inflammatory response that promotes tissue regeneration and wound healing. In addition to lipid-filled adipocytes, the subcutaneous adipose tissue contains a number of different stem and immune cells that contribute to wound repair and structural integrity after burns. These cells include stromal-vascular cells (SVCs), adipose stem cells (ASCs), macrophages and fibrocytes. Adipose tissue macrophages (ATMs) constitute an important fraction of the immunomodulatory cells that have been implicated in tissue homeostasis and in resolving or non-resolving inflammation.

Rodents have been the most frequently employed species for preclinical testing of burn wound treatments and several rodent models of aging are available. However, rodents significantly differ from human systems, and their general acceptance in burn research is continuously declining. Moreover, burn experiments on animals are very cruel, imprecise, expensive, and generally less applicable to human burns. Therefore, the burn research community needs to develop new methods for studying burns and testing treatments that replace animals and are actually relevant to human health.

Our project is committed to improve and develop conservative treatments for burn wounds of geriatric patients. In reconstructive surgical procedures, viable parts of human tissue composed of cutaneous and subcutaneous adipose tissue are removed to reshape a body structure or provide a necessary function. With ethical approval from local authorities and patient consent, we used the human tissue sections to be discarded during surgical procedures, and developed a new procedure for maintaining them in vitro for experimental study of burns.

Fig. 1:   Sectioning of human skin tissue from surgical procedures.

We developed also relevant procedures to isolate and characterize adipose stem cells and different subtype of macrophages from human subcutaneous adipose tissue.

For experimental burn injuries, we employed a modified flat-flame McKenna burner. The use of a McKenna burner in our studies allowed for more precise, stable and repeatable adjustment of the temperature and exposure time. The dimensions of the thermal damage became obvious in comparison to the unburned control or to the unharmed fields in the burned samples.

Fig. 2:   Schematic presentation of the burner together with a water cooled matrix and a temperature measurement system.

Using the human composite tissue model for experimental study of burns, we will pursue three main tasks:

First, the activation potential of subcutaneous macrophages and mesenchymal stem cells will be compared in composite tissue flaps from geriatric patients and younger adults in response to thermal forces.

Second, the effectiveness and efficacy of current conventional burn therapeutics will be reassessed on composite tissue flaps from geriatric patients.

Third, the most effective therapeutics will be combined with nanomaterials to enhance their efficacy in treatment of burn wounds in geriatric patients. The relatively new nanomaterials have often unique physiochemical properties that greatly improve the efficacy of therapeutics due to enhanced permeability and retention effect in tissue.

 

Institution

Department of Geriatric Medicine
Uniklinik RWTH Aachen
Pauwelsstr. 30, D-52074 Aachen

Duration

02/2019 - 01/2021