Birth of skin tissue engineering

Skin tissue engineering rat racing:  A coincidence?

The year 1975 seems to be a special year for skin tissue engineering, even before the term “tissue engineering” was officially adopted more than a decade later by the Washington National Science Foundation bioengineering panel meeting in 1987 [5] and later its definition elucidated further by Langer and Vacanti [6] in 1993. The beginnings of skin tissue engineering can be attributed to the pioneering work of two groups in the United States forty years ago. First, Rheinwald and Green reported the successful serial cultivation of human epidermal keratinocytes in vitro [7] in 1975 and later made possible the expansion of these cells into multiple epithelia suitable for grafting [8] from a small skin biopsy. In today’s term, the work is termed “tissue engineering of the skin epidermis”. Concurrently, Yannas, Burke and colleagues reported their maiden work on the in vitro and in vivo characterization of collagen degradation rate [9] in 1975 which we believe pave the way for the design of artificial biological dermal substitute [10], resulting in the “tissue engineering of the skin dermis”.

Another coincidence?

Interestingly, six years later in 1981, both groups independently reported the clinical use of their respective tissue-engineered substitutes for the treatment of severe and extensive burns, albeit in different approaches. O’Connor et al. reported the world’s first grafting of extensive burns with sheets of cultured epithelium (expanded from autologous epidermal cells) on two adult patients with success at the Peter Bent Brigham Hospital [11, 12]. These autologous cultured sheets (Fig. 2) termed cultured epidermal autografts (CEA) were also subsequently demonstrated to provide permanent coverage of extensive full thickness burns in another two paediatric patients [13].

Meanwhile, Burke et al. (a few months after O’Connor et al.’s report) reported the successful use of a physiologically acceptable artificial dermis in the treatment of extensive burn injuries with full thickness component on ten patients [14]. This was followed by a randomized clinical trial for major burns led by Heimbach et al. [15] on the use of this artificial dermis, now known as Integra^TM Dermal Regeneration Template. This successful multi-centre study involving eleven centres and many other studies [16, 17] might have inevitably given this dermal substitute a “gold standard” status for full thickness burns treatment [18].

While ground breaking, the work of the above two groups are still far from reaching the ultimate goal of replacing skin autografts for permanent coverage of deep dermal or full thickness wounds in extensive burns.