1. Ayman Grada, MD, Joshua Mervis BS, Vincent Falanga, MD, FACP
Research Techniques Made Simple Animal Models of Wound Healing in Disease
Ayman Grada, MD, Joshua Mervis BS, Vincent Falanga, MD, FACP

2. What is an Animal Model?
An animal model is a living, non-human organism used to study human biological processes under controlled conditions, for the purpose of better understanding, and to enable predictions about these processes, without the added risk of harming an actual human being during the process.

3. Purpose of Animal Models in Wound Healing
Better understanding of the healing process
Development of biological therapeutics pertinent to wound healing
Test the efficacy and safety of a particular therapy in a living model prior to its use in humans

4. Proliferation Migration
Acute Wound
Chronic Wound
Time
Coagulation
Coagulation
Day 1
Inflammation
Remodeling
Time
Inflammation
Proliferation
Migration
Days 3-5
Proliferation Migration
Weeks
Months
Remodeling

5. Choice of Animal Species in Wound Models
Mouse
Rat
Rabbit
Pig
Guinea pig
Greyhound
Zebrafish
Cost
Size
Ease of handling
Physical space
Degree of similarity to human skin
Genetic tractability
Experimental objectives
Expertise

6. Animal Models of Acute Healing
Excisional wounds
Partial-thickness model
Full-thickness model
Incisional wounds
Burn wounds

7. Animal Models of Impaired Healing
Diabetes-associated wounds
Drug induced models
Genetic models
Pressure wound
Rat magnet ischemia-reperfusion model
Fuzzy rat model
Ischemic wounds
Rabbit ear model
Pig flap ischemic model
Skin banding model
Infected-biofilm wounds
Pig wound infection
Rabbit ear, wound biofilm model

8. Ischemic rabbit ear model
Clinically relevant to ischemic ulcers
Suturing of blood vessels generates an ischemic zone within which wounds can be made
Benefits: accessible/suitable for pharmacological testing
Drawbacks: does not fully replicate human hypoxic wounds and not genetically tractable

9. Diabetic mouse wound model
Clinically relevant to diabetic ulcers
Diabetic mice are chemically or genetically induced
Benefits: enable testing of pharmacological agents/multiple wounds per animal
Drawbacks: mouse diabetes does not fully reflect human diabetic complications. variability between different diabetic models
Diabetic ulcer

10. Excision wound splinting model in mouse
Clinically relevant to acute and chronic wounds
Splinting ring tightly placed on the skin around the excisional wound
Benefits: splinting minimizes contraction
Drawbacks: anatomical differences between rodent and human skin; splinting materials may detach and move into the wound site

11. Rat magnet ischemic-reperfusion
Clinically relevant to pressure ulcers
A steel plate is inserted beneath the dorsal skin
A magnet is applied over a number of cycles to generate chronic skin wound
Benefits: can vary in degree of blood perfusion to skin and thus grade of ulcer
Drawbacks: anatomical differences between rodent and human skin

12. Pig wound infection Clinically relevant to infected ulcers
Wounds are seeded with bacteria that produce a biofilm
Benefits: skin anatomically and physiologically similar to humans
Drawbacks: expensive and not genetically tractable

13. Pig flap ischemia Clinically relevant to ischemic ulcers
Surgical incisions severs blood flow to specific regions of skin, creating hypoxic zones
Benefits: skin anatomically and physiologically similar to humans
Drawbacks: expensive and not genetically tractable

14. Mouse tail full-thickness wound model
Clinically relevant to delayed wound healing
Rectangular full-thickness excision on the dorsum of the tail
Benefits: delayed healing (up to 21 days), minimal contraction, and can be used in wild-type animal
Drawbacks: anatomical differences between rodent and human skin

15. Limitations of Animal Wound Models
Anatomical and physiological differences among and within animal species, including humans
No one model can recapitulate the heterogeneity and complexity of chronic wounds in humans
Lack of standardization in design, procedure, and evaluation