Skin defects, ulcers and wounds caused by accidental harm and disease are always inevitable issues for human, therefore it aroused wide concern on the development of artificial skin [1], [2]. Artificial dermal substitutes are essential for physiological wound healing because they guarantee reliable and long-lasting wound closure and serve as an appropriate scaffold for tissue repair [3], [4], [5]. Existing representative collagen-based products, Apligraf® [6], Biobrane [7], Integra [8], and Pelnac [9] have demonstrated promising outcomes in the treatment of diseases such as burns and severe skin defects caused by large-scale scar excision. The matrix material of these products is derived from collagen extracted from animals, which cause a potential risk of infection and allergy [10], [11]. The Food and Drug Administration (FDA) approved StrataGraft®, a new advanced artificial skin substitute manufactured with recombinant collagen cultured keratinocytes and dermal fibroblasts [12]. Although StrataGraft® has not yet been reported to have transmitted infectious diseases or agents, there is a risk of transmission because the animal cells were employed in early stages of product development. In comparison, synthetic polymers (i.e., polyurethane (BioTemporizing Matrix [13]), polyglycolic acid (DermaGraft®) [14], [15]) are degraded by hydrolysis, have fewer microbial binding sites, and are more resistant to microbial contamination. However, these acellular materials may take 2–4 weeks to vascularize sufficiently, which would have a negative influence on cell survival and impair cellular engraftment and wound closure [4].

Yanas and Burke have proposed the design principles for skin substitutes, with the selection of a suitable dermal substitute being of the most importance [16]. Dermal substitute material should promote the infiltration and growth of autologous histiocytes to form new and regular dermoid tissue, thereby reconstructing the dermis [17]. To research and develop properties that match real skin engineering, natural polymer materials (i.e., cellulose [18], chitosan [19], [20], hyaluronic acid [21], [22], collagen [23], [24], silk protein [25], [26]) have drawn much attention because of their good biocompatibility. Elastin is a key component of the extracellular matrix (ECM) and endows biological tissues (lungs, blood vessels, ligaments, or skin) elasticity [27], [28]. Elastic properties, coupled with the ability to interact directly with cell receptors and trigger cell adhesion, make elastin a promising biopolymer in the biomedical field [29], [30], [31], [32], [33]. Silk-elastin-like protein (SELP) is a block copolymer composed of serially repeated silk like protein modules (GAGAGS) and elastin like protein modules (GXGVP) [34], [35], [36], [37]. SELP achieves a combination of the excellent mechanical properties of silk protein and the elastic function of elastin [38], [39]. In addition, it exhibits high suitability [40], good biocompatibility [37] and biodegradability [41], making it an ideal candidate of dermal substitute.

Nathoo et. al suggested that an “ideal skin substitute” must also have the qualities of protecting against fluid loss and providing extensive coverage for wounds [42]. Bacterial cellulose (BC) has high water retention capacity, good permeability, biocompatibility, and excellent mechanical properties, making it ideally suitable as a wound dressing to reduce irritation, alleviate pain and accelerate skin regeneration [43], [44].

Herein, we demonstrated the design and fabrication of a fully bio-based artificial skin substitute based on genetically engineered SELP. We suggested that electrospun SELP nanofiber membrane with loose structure act as a dermal substitute, while nano-fibrous BC serve as epidermal equivalents to protect the underlying dermis due to its favorable penetration and strong water retention ability. The SELP and BC membranes can stick together by tyrosinase-modified SELP (m-SELP) containing DOPA. After the tissue engineered skin is reconstructed, the inner SELP layer will be degraded and absorbed, leaving the outer protective layer of BC either left in place until spontaneous separation or removal through a simple surgical procedure.