In Vivo & In Vitro Research Models
Rabbit Ear Model for Wound Healing Study
We developed the rabbit ear model, which has been accepted as clinically relevant in preclinical studies for the FDA, and has the advantage of easy quantification of epithelialization and granulation tissue formation. In addition to the ability to create large numbers of wounds, a unique advantage of the rabbit ear model, is the ability to evaluate the role of therapeutic treatment in acute and chronic wounds.
Mouse Splinted Excisional Wound Model
Open wounds in rodents heal quickly. This is accomplished almost entirely by wound contraction that is in marked contrast to human skin wounds which heal to a significant degree by generation of new tissue (granulation tissue and re-epithelialization). In the mouse splinted excisional wound model, a circular silicone splint is attached to the skin just beyond the wound periphery. The splint serves to prevent healing by skin contraction and to ensure that healing occurs by granulation tissue deposition and epithelialization.
Rabbit Ear Hypertrophic Scar Model
The rabbit ear hypertrophic scar model has a number of parameters which behave in similar fashion to human hypertrophic scars: visual appearance, histological appearance, response to therapeutics, and factors which influence scarring. In addition to the ability to create large numbers of wounds and relatively short time points for evaluation of hypertrophic scar (28-35 days).
In Vivo Bioreactor
Severe burns can cause life-threatening infections and loss of homeostatic function. Commercially available skin substitutes have major functional and aesthetic limitations. Current efforts in tissue engineering have been unsuccessful in part due to the inability to engineer a vascular network ex-vivo. In order to address this limitation we have developed a modular in-vivo bioreactor capable of generating vascularized new tissue. The modular components of the bioreactor allow the delivery of growth factors, nutrients, and therapeutics to guide tissue growth. Our device provides a regulated environment suitable for bioengineered tissue growth.
Rabbit Wound Biofilm Model
Bacterial biofilms represent a critical component of nonhealing wounds, utilizing several different mechanisms to inhibit innate inflammatory pathways and resist traditional therapeutics. An understanding of biofilm pathophysiology is essential to the development of appropriate wound care principles and novel, anti-biofilm therapies. We have established and validated a rabbit in vivo wound biofilm model which is an accurate and consistent simulation of biofilm-infected human chronic wounds.
Mouse Wound Biofilm Model
Bacteria are present in a large number of chronic wounds. Bacteria in chronic wounds form biofilms, which are sessile aggregates of bacteria embedded in extracellular structures. Biofilms are notoriously difficult to eliminate and organization into biofilms confers a number of advantages to pathogenic invaders, including antibiotic resistance, quorum sensing, and modulation of host immunity. Biofilms are now known to adversely affect host tissues in a number of ways, including impairment of wound healing. We have established and validated a mouse in vivo wound biofilm model.
Ischemic Rabbit Ear Model
Local tissue hypoxia constitutes a major pathophysiologic factor in human chronic wounds. We developed and refined an ischemic variant of the rabbit ear model in which to study the effects of hypoxia on wound healing. Surgical ligation of the caudal and central arteries, leaving the rostral artery as the sole inflow source, produces sustained, measurable ischemia with a significant effect on wound healing.
Ischemia-Reperfusion (IR) Model
IR injury has been increasingly recognized as a major factor in the pathogenesis of chronic skin wounds. We developed a novel rabbit ear model for the induction of subclinical, cyclic IR injury in cutaneous tissue that will serve as a valuable tool for the testing of new therapeutics.
Rabbit Ear Burn Model
Hypertrophic scarring is common following burn injury and remains a source of significant morbidity both in physical and psychosocial domains. Individuals can experience cosmetic disfigurement, pain, itching, and tightening or shortening of the skin and/or underlying muscles. As the current therapies provide limited benefit, prevention of such scarring is key. We established a reproducible model of hypertrophic scar following burn injury in the rabbit in order to facilitate study targets for prevention of hypertrophic scar in the burn population.
Pig Skin Flap Model
We developed a pig skin flap model with reliable distal necrosis and a marginally perfused tissue with local ischemia. Four skin flaps with 4x14 cm were created on each side of the animal’s back; the base (4 cm width) of the flaps lying about 4 cm from the dorsal midline and direction of the flap being ventrally in the direction of the body somite. The flaps were incised ventrally and along both sides, carrying the incision through the panniculus carnosus. The flaps were raised completely by incision and sutured back into position with running 3-0 nylon suture. Flaps were covered with gauze and wrapped with 2-layer bandage, protected with jacket.
Mouse Dermatitis Model
Dermatitis leads to significant discomforting and aesthetically displeasing skin changes including erythema, drying, scaling, and excoriation of the skin. However, the cause of dermatitis is not known and present treatments have limited ability to alleviate symptoms without cure. We developed a mouse dermatitis model and evaluated the effect of various therapeutic agents in the treatment of dermatitis.
Human Ex Vivo Skin Culture (HESC)
We developed an optimized partial-thickness of HESC model to maintain human skin characteristics in vitro. Rather than the full-skin ex vivo culture model, HESC model includes epidermis and only a very thin layer of dermis. Our HESC model retains important elements of in vivo skin and has significant advantages for the wound healing studies in vitro.
Three-Dimensional Skin Culture
The 3D culture model mimics the natural human skin environment for the cell growth of keratinocytes and dermal fibroblasts. Human epidermal keratinocytes were co-cultured with dermal fibroblasts in the presence of decellularized human dermis. Both histological and biochemical analyses show that the properties of skin found in vivo were maintained in our 3D culture model.
Mature Adipocyte Culture
Difficulty of using conventional cell culture methods for mature adipocytes, due to their buoyancy, has limited their functional study in vitro. We established a novel in vitro culture method for the mature adipocytes by enclosing them in a hydrogel in this report. Hydrogel-enclosed adipocytes displayed viability in in vitro culture and were capable of expressing foreign genes for at least a month. Mature adipocytes can be cultured in vitro within a matrix, and that they are functionally active cells that respond to environmental changes.