Bioengineered Artificial Skin

Tissue engineering is an emerging interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that can maintain, restore or improve tissue function. Tissue engineering involves transforming cells, engineering materials, and suitable biochemical and physicochemical factors to establish and maintain desired tissue. With advances in material science, cellular and molecular biology, researchers are now able to develop functional substitutes of skin and other tissues in the laboratory.

Constructing the Epidermis

The uppermost layer of the skin, or epidermis, acts as a protective barrier against microbes, temperature changes, chemicals, and injury. To reconstruct skin, researchers first focus on developing an epidermal layer. They isolate keratinocytes, which are the main cells of the epidermis, from a small skin biopsy. In the laboratory, the keratinocytes are grown on a scaffolding made of collagen, fibronectin or other biodegradable materials. As the keratinocytes multiply and form new cell layers, they organize themselves and produce new extracellular matrix proteins to resemble natural skin structure. Within 2-3 weeks of culture, fully stratified epidermis resembling the outermost protective skin layer can be constructed in vitro.

Generating the Dermis

Below the epidermis lies the dermis layer which provides strength, elasticity and nutrients to the Bioengineered Artificial Skin. It contains collagen, elastin and fibroblasts. Researchers use different approaches to generate a dermal substitute. Acellular human dermis obtained from donated skin tissue can be used as a scaffold. It maintains the native extracellular matrix components but lacks living cells. Alternatively, fibroblasts are seeded onto naturally derived or synthetic matrices like collagen gels or nanofibrous polymers to create a cellular dermal equivalent. The fibroblasts remodel the matrix by producing new collagen and reconstituting the dermal architecture.

Assembling Skin Substitutes

To assemble a bioengineered skin substitute, the regenerated dermal and epidermal layers are combined. The epidermal sheets containing keratinocytes are placed on top of the dermal matrices containing fibroblasts. Lifting the composite to the air-liquid interface promotes further differentiation and stratification of keratinocytes to form a multi-layered epidermis resembling native skin. In some engineered skin products, additional components such as growth factors, cytokines or skin stem cells may be incorporated to enhance tissue development and healing outcomes. After 2-4 weeks of maturation, a multi-layered skin substitute that mimics the anatomical and functional attributes of native skin is obtained.

Applications in Burn Treatment

Skin substitutes hold promise for the treatment of massive burns which currently pose a significant clinical challenge. Deep burns destroy both dermal and epidermal layers leaving patients vulnerable to fluid loss, infection and lack of barrier function. Conventional therapies involve temporary wound coverage using skin grafts from donor sites which are limited in availability and prone to failure if grafted over infective burn eschars. Bioengineered skin substitutes can serve as permanent wound coverage as well as scaffolds for regeneration of both dermal and epidermal components when grafted over properly prepared wounds. The porous nature of these substitutes allows for cellular infiltration and angiogenesis from wound bed while its intact layered architecture facilitates rapid re-epithelialization.

Several bioengineered skin products have received regulatory approvals and are being utilized to treat burns and other wounds. Some examples include Epicel, a cultured epithelial autograft, and Dermagraft, a biosynthetic skin substitute composed ofnewborn foreskin fibroblasts within a collagen-glycosaminoglycan matrix. Studies show that application of cultured skin substitutes allows for better take of grafts, reduction in wound bed preparation, fewer further procedures, shortened hospital stay and improved quality of life. Their use in massive burns significantly improves survival rates compared to conventional therapies alone. Various large multicentre trials also demonstrate reduced scarring and improved functionality with the use of engineered skin in pediatric populations.

Overcoming Current Bioengineered Artificial Skin

While tissue engineered skin products represent significant advances over availability of donor skin, some key challenges still remain. Scalability of the laboratory processes needs improvement to meet the massive demand for significantly burned patients. Stability of these constructs during transport and storage prior to use also needs optimization. Ensuring standardized product quality across batches manufactured by different operators is another area requiring enhancement. Ability to engineer skin substitutes that can precisely recapitulate the functions of thicker skin in stress bearing regions like palms and soles is still limited. Incorporation of skin stem cells, growth of hair follicles and sweat glands within the substitutes presents additional engineering complexities. Continuous efforts to address these issues will help expand the clinical impact of bioengineered skin in managing a wider variety of acute and chronic wounds.



Advances in the fields of cell biology, biomaterials and tissue engineering have made it possible to bioengineer skin substitutes that mimic the anatomical structure as well as functional properties of native human skin. Several commercially available skin substitutes have demonstrated efficacy in treating massive burns and complex wounds. While current generation products already represent a major advance over donor skin limitations, continuous improvements are being made to address challenges like scalability, stability and functionality. With further refinement, personalized living skin replacements are envisioned that can regenerate severely damaged skin and restore form and function. Bioengineered skin holds great promise to revolutionize the management of burns and other hard-to-heal wounds.

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