Tissue Engineering of the Skin

1. Tissue Engineering of the Skin Connor Walsh

2. The Skin • The skin is the largest organ in the human body. • It consists of about ten percent of our body mass. • The skin is composed of three distinct layers: the epidermis, the dermis, and the subcutaneous fat, sometimes called the hypodermis.

3. Layers of the Skin

4. Layers of the Skin • The epidermis is the outermost skin layer and consists of keratinocytes, rapidly dividing stem cells, that help generate epidermal cells. • The second layer, the dermis, consists of collagen fibers in a gel like state and also fibroblasts. It helps binds the epidermis so it conforms to the shape of the body. • The deepest skin layer, the subcutaneous layer, consists mainly of fatty tissue.

5. Keratinocytes and Fibroblasts Keratinocytes Fibroblasts

6. Function of the Skin • A main function of the external skin layer is to provide a tough barrier covering the entire body. • It provides defense from radiation, disease, gases, chemicals, and many other destructive forces. • However, if the skin is damaged it can lead to difficult complications.

7. Burns • A common problem we see with skin damage are burns. • Approximately 2,000,000 burns per year in the United States require medical attention. • Of these, about 70,000 require hospitalization, and 20,000 need referral to a specialized burn center. • About 10,000 patients die each year of infections subsequent to sustaining serious burns • These burns can lead to embarrassing scarring and pain for the remainder of the victim’s life.

8. Burn Classification

9. Skin Grafting • In the past, a burn victims only option for repair was a method known as a skin graph. • This requires doctors to surgically cut a piece of unburned skin from your body and place it on the burned area. • This can cause bleeding, infection, nerve damage, and in some cases, a repeat graph is required.

10. Current Skin Engineering • Tissue-engineered skin exists as cells grown in vitro and subsequently seeded onto a scaffold or some porous material which is then placed in vivo at the site of injury. • Three categories of skin substitutes: • Epidermal Substitutes • Dermal Substitutes • Dermo-epidermal Substitutes

11. Process of Skin Engineering • Patient has a skin biopsy • The skin is then peeled and separated into the epidermis and dermis. • Keratinocytes and Fibroblasts are then isolated from one another. • Transferred into a culture on top of a scaffold. • The final skin is finished after about 3 to 4 weeks.

12. Process

13. IntegraTM • Most well known design of skin engineering. • Consists of two layers: • Bottom layer of collagen fibers that create the basis of a scaffold for the dermal cells • Top layer of a protective film that can be removed once the dermal layer has been established. • Does not provide any assistance to epidermal cell rejuvenation.

14. Epidermal and Dermal Substitutes • Epidermal substitutes contain only keratinocytes grown in vitro and can be applied or sprayed onto the wound site. • Dermal substitutes try to restore dermal growth with minimum scarring. Example: IntegraTM • It is applied to the wound site and the skin regenerates and grows naturally. • Both processes take around 3 to 4 weeks to complete.

15. Dermo-epidermal Substitutes • Dermo-epidermal substitutes have been difficult to create. • The technique involves taking keratinocytes and fibroblasts from the burned patients epidermis and dermis and adding them to a collagen substrate. • Both the dermis and epidermis are regenerated through one piece of skin.

16. Limitations • The average wait time ranges anywhere from 3 to 12 weeks after the biopsy is taken. • The cost of the treatment and the amount of time it takes makes the process cost-inefficient. • Currently there are few dermo-epidermal substitutes which require patients with an injured dermis to require both epidermis and dermis substitutes. • Skin grafting remains the most popular treatment for skin replacement.

17. Towards the Future • Skin engineering still has much room to evolve. • More dermo-epidermal substitutes will be created that will speed the process and the wait time for the patient. • An increase of “off the shelf” dermal and epidermal substitutes will allow patients quick and easy access to repairing their burns or wounds. • A skin that includes sweat glands and hair follicles to help mimic real skin is also being created. • In the future, engineered skin will replace skin graphs as the predominant method for treating skin defects.

18. References • The Skin. Robert F. Rushmer, Konrad J. K. Buettner, John M. Short and George F. Odland.Science. New Series, Vol. 154, No. 3747 (Oct. 21, 1966), pp. 343-348; Published by: American Association for the Advancement of Science • Brenner, Robert A. Medical Care Guide: Burn Statistics. Law Offices of Robert A. Brenner. 2010 <http://www.burnsurvivor.com/burn_statistics.html> • Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. Anthony D Metcalfe and Mark W.J Ferguson. J R Soc Interface. 2007 June 22; 4(14): 413–437. • Groeber, Florian. Skin tissue engineering - In vivo and in vitro applications. Advanced drug delivery reviews 15 Jan 2011: null. Elsevier. 02 Mar 2011. • Burns, Volume 36, Issue 4, June 2010, Pages 450-460Sophie Böttcher-Haberzeth, Thomas Biedermann, Ernst Reichmann • Biomaterials, Volume 28, Issue 34, December 2007, Pages 5100-5113Anthony D. Metcalfe, Mark W.J. Ferguson • Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration Anthony D Metcalfe and Mark W.J Ferguson J R Soc Interface. 2007 June 22; 4(14): 413–437