Bioengineering of the Skin: A Tool for Skin Repair and Regeneration

Introduction:

Skin, the largest organ of the human body, performs various functions, from acting as a barrier against irritants to thermal regulation and moisture retention. In addition, they can repair and regenerate, which makes wound healing possible. With all these additive points in it, the field of bioengineering has focussed on developing skin substitutes for use in the medical field.

What Is the Basic Anatomy of the Skin?

The skin consists of three layers: epidermis, dermis, and hypodermis. The epidermis is the superficial layer that consists of keratinocytes, melanocytes, Merkel cells, and Langerhans cells. The dermis consists of fibroblasts, collagen fibers, glands, blood vessels, and nerves. Finally, the deepest layer of hypodermis consists of adipose tissue.

Why Is Bioengineering of the Skin Required?

Though the skin can repair and regenerate, tissue-engineered skin is crucial if an individual is defective. In case of wounds like a diabetic ulcer, burn abrasion, puncture, avulsion, pressure ulcer, or contusion, the skin substitutes formed by bioengineering can bring back a skin-like structure, however, with a lack of other appendages. Therefore, using skin substitutes for individuals with problems in wound healing is beneficial. The factors that affect wound healing are,

• Age.

• Health condition of the individual.

• Body fluid content.

• Nutritional status.

• Infections.

• Medications.

• Stress.

• Temperature.

What Were the Conventional Treatments Used to Restore the Skin?

Minor wounds do not require any treatment, and they recover by regeneration. However, large, deep, and infected wounds require skin grafts to restore the skin. The basic wound dressing materials are classified into,

• Autograft.

• Allografts.

• Xenografts.

• Artificial materials.

• Therapeutic agents.

What Is a Bio-Engineered Skin?

A bio-engineered skin is an artificially produced tissue grown from the individual’s cells or other sources, which consists of epidermal and dermal layers of cells embedded in an acellular matrix. Most commercially available bio-engineered skin is derived from neonatal skin. Neonatal skin is preferred because of the high metabolic activity of the cells and the high content of epidermal keratinocytes.

How Does It Work?

Bio-engineered skin temporarily takes over the skin's functions until the wound heals by regenerating skin cells. They provide a moisturized and supportive environment for regenerating new skin cells and wound healing.

What Percentage of Bioengineered Skin Treatments Are Successful?

The success rate of bioengineered skin treatment varies depending on factors such as the specific type of treatment, the condition of the patient, and the technology used. Generally, these treatments have shown effective outcomes, with a success rate of often exceeding 70 percent. For instance, in cases of burn injuries bioengineered skin grafts have demonstrated efficacy in promoting wound healing and reducing complications. Success is measured by the integration of bioengineered skin into the patient's tissue and the restoration of normal skin function.

What Are the Features of a Skin Substitute?

• Rapidly acting and adheres well to the wound surface.

• Impermeable to bacteria.

• Allows water vapor transmission like natural skin.

• Allows proliferation of new skin tissues.

• Low cost.

• Biodegradable.

• Good shelf life.

• No local or systemic toxicity.

How Are Bioengineered Skin Substitutes Classified?

• Human Skin Allografts: These are bio-engineered from human tissues with intact cells being removed or treated to avoid rejection.

• Allogeneic Matrices: These are tissues obtained from neonatal foreskin that are metabolically active and provide support to the tissues and treat soft tissue loss.

• Composite Matrices: These are derived from human fibroblast and keratinocytes supported by a collagen mesh. The active components in the cells regulate the wound-healing process.

• Acellular Matrices: These are derived from other than human skin and contain collagen, membranes, and cellular elements replicating the human skin. It accelerates wound healing by allowing the migration of dermal and epidermal cells to the wound area.

What Are the Commercially Available Skin Substitutes?

• Placental Membranes: These contain epithelial cells, fibroblast, and mesenchymal stem cells that promote wound healing. The mesenchymal stem cells in the placental membrane have several functions, such as promoting the natural skin cells for wound healing, releasing vascular endothelial growth factors to reduce scarring, and promoting the repair and regeneration of the skin by producing pro-generative cytokines.

• Cultured Epithelial Sheets: These consist of keratinocytes derived from the same individual or a donor. They are commonly used for breast reconstruction surgery and burn wounds. However, they lack functionally competent dermal components, so their use is limited to avoid the risk of infections and impaired function and aesthetics.

• Dermal Templates: These templates are prepared by harvesting the fibroblasts from the neonatal foreskin and culturing them in a polyglactin scaffold. These fibroblasts proliferate to secrete collagen, matrix proteins, and growth factors that stimulate the dermal layer. They are suitable for diabetic foot ulcers and deep necrotic cutaneous ulcers.

• Epidermal Templates: Apligraf is an epidermal template that consists of bovine type 1 collagen with human keratinocytes and fibroblasts. They are used for wounds extending up to the dermis and diabetic foot ulcers. There is no clinical evidence of rejection or cellular and humoral response to these epidermal templates.

• Composite Graft: These grafts contain dermis and epidermis in them and thus replicate the natural skin. They can be used for acute and chronic wounds. Or Cel is a Food and Drug Administration(FDA) approved substitute used in the case of epidermolysis bullosa, and it is safe through some clinical studies. It is a good treatment option for promoting wound healing and reducing wound scarring.

What Are the Uses of a Bioengineered Skin Substitute?

The bio-engineered skin substitutes can be used in cases such as,

• Severe burns.

• Stasis ulcer.

• Diabetic foot ulcer.

• Pressure ulcer.

• Vasculitic ulcer.

• Breast reconstruction surgery.

• Epidermolysis bullosa.

• Systemic sclerosis.

• A surgical wound caused by the excision of cancer.

Who Is Not Indicated for Bio-Engineered Skin?

Bio-engineered skin cannot be used for all individuals and is contraindicated in individuals with,

• Known allergy and hypersensitivity.

• Infected wounds.

• Ulcers with sinus tracts.

• Ulcers with signs of clinical infection.

Conclusion:

Though many bio-engineered skin substitutes are available, no ideal substitute could replicate the repairing and regenerating function of natural skin. And the limited amount of clinic studies limits their applications in patients. However, the researchers still focus on various ways to recapitulate the skin properties in the substitutes and provide better results.