Tissue Engineering of the Skin Connor Walsh. The Skin The skin is the largest organ in the human body. It consists of about ten percent of our body mass.

Tissue Engineering of the Skin

Connor Walsh

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.

Layers of the Skin

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.

Keratinocytes and Fibroblasts

Keratinocytes

Fibroblasts

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.

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.

Burn Classification

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.

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

Process of Skin Engineering

1. Patient has a skin biopsy2. The skin is then peeled and

separated into the epidermis and dermis.

3. Keratinocytes and Fibroblasts are then isolated from one another.

4. Transferred into a culture on top of a scaffold.

5. The final skin is finished after about 3 to 4 weeks.

Process

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.

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.

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.

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.

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.

References1. 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

2. Brenner, Robert A. Medical Care Guide: Burn Statistics. Law Offices of Robert A. Brenner. 2010 <http://www.burnsurvivor.com/burn_statistics.html>

4. 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.

5. Groeber, Florian. Skin tissue engineering - In vivo and in vitro applications. Advanced drug delivery reviews 15 Jan 2011: null. Elsevier. 02 Mar 2011.

6. Burns, Volume 36, Issue 4, June 2010, Pages 450-460Sophie Böttcher-Haberzeth, Thomas Biedermann, Ernst Reichmann

7. Biomaterials, Volume 28, Issue 34, December 2007, Pages 5100-5113Anthony D. Metcalfe, Mark W.J. Ferguson

8. 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