Bio-Inspired Design of Skin Replacement Therapies
Division of Plastic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
9.1 Introduction
As the largest organ of the body, the skin provides critical barrier and protective functions. At a basic level, the skin can be described as a bilayer material with a top layer termed the epidermis: an ectodermal derivative that produces a barrier to fluid flux and bacterial invasion. The main cell population is made up of keratinocytes that divide near the dermis, proliferate, and undergo apoptosis with necrotic cells forming a robust barrier known as the stratum corneum. The epidermis is avascular, but has a rich network of nerve endings. It contains melanocytes, which provide color, and Langerhans cells, which provide immune function.
The lower, thicker layer of the skin is the dermal layer, composed primarily of collagen, glycosaminoglycans, and elastin. It is rich in fibroblasts and has both a superficial and deep plexus of blood vessels that are connected by perforating vessels. The dermis is strong, flexible, and provides substantial protection from external trauma. Between the epidermis and the dermis is the basement membrane, which provides a convoluted structure with inverting cones of epidermis invaginating into the dermis. In addition, skin adnexal glands, including hair follicles and sebaceous glands that are epidermal derivatives, also invaginate into the epidermis. Epidermal cells that line these structures have the capacity to divide, proliferate, and reconstitute the epidermis.
Due to burns, frostbite, trauma, malignancy, infection, and congenital defects, humans can present with various degrees of skin loss that can be problematic. For small injuries, there is a well-developed system of wound healing that works through a sequential series of events including hemostasis, inflammation, proliferation, and remodeling. For deeper injuries that reach the dermis, the healing response results in wound contraction and the formation of scar tissue. In cases in which wounds heal under tension and/or patients have a genetic predisposition, healing can produce heavy scars, which can result in hypertrophic scars or keloids.
9.2 Bio-Inspiration of Skin Replacement Therapy
9.2.1 Observations
9.2.1.1 The Epidermis Has the Capacity to Regenerate
Superficial burns, dermabrasion, cosmetic chemical peels, and laser therapy can damage nearly the entire epidermis. The regeneration that occurs often leaves a better cosmetic result than prior to injury. The capacity for stem cells at the base of the epidermis and along the hair follicles is substantial.
9.2.1.2 Only the Superficial Dermis Has the Capacity to Regenerate
Dunkin [1] performed an important study in which an incision of variable depth was made in the forearms of human volunteers. In instances when the incision was less than 0.56 mm, or one-third of the thickness of the dermis, no visible scar was present 3 months after injury. It is well known among surgeons that those patients with superficial burns that can heal within 21 days generally do not form a substantial scar. In contrast, those that heal beyond 21 days have a high likelihood of developing heavy scarring.
9.2.1.3 The Mammalian Response to Deep Dermal Injury Is Wound Contraction and Scarring
Unlike amphibians, which have the capacity to regenerate entire limbs, mammals respond to injury through the twin processes of scarring and wound contraction. There may have been an evolutionary advantage in developing mechanisms for faster wound closure to avoid complications of infection.
9.2.1.4 Structural Dermal Elements Can Block Wound Contraction
Skin grafts are known to block wound contraction [2] with grafts that have a higher percentage of dermal elements, resulting in less wound contraction. This effect is likely due to the innate structure of dermal macromolecules, such as collagen. Erhlich compared wound healing of experimental frostbite injuries, which do not denature macromolecules, with those of burns, which do denature macromolecules, and found that the burns healed through wound contraction, whereas the frostbite injuries healed with very little contraction, preserving the dermal elements [3].
9.2.1.5 Skin Elements Have the Capacity to Self-Organize
Through a variety of manipulations, the skin has a remarkable ability to reorganize with epidermal elements tending to migrate towards the wound surface.
9.3 Biomimetic Solutions
There are many interesting aspects of skin anatomy, immunology, and physiology that have inspired several products that are clinically used today. In this chapter, the author suggests aspects of skin structure and biology that may have inspired the inventors of each of the three technologies that have since led to the design of specific products on the market today. There are many other skin substitute technologies that are either available clinically or in some stage of preclinical development throughout the world. These three examples introduce the concepts of bio-inspired skin by illustrating how the investigators prioritized skin function in their design.
9.3.1 Epidermal Replacement: Epicell® (Genzyme Tissue Repair)
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