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International Journal of Bioprinting                                         3D printed edible bird’s nests



































            Figure 1. Producing replacements for EBN with the tissue-engineering methodology has both environmental and economic impacts. (A) The huge de-
            mand for harvesting wild EBN in Southeast Asia damages the swiftlets’ home and the local ecological system. (B) Illustration of natural EBN’s formation,
            containing both nutritional components secreted from the birds’ epithelial cells and hazard substances like microbes and heavy metals. (C) Scheme of re-
            producing EBN formation with biomaterials, with a feeding layer (upper) of 3D-printed matrix culturing epithelial cells to produce functional ingredients
            to be enriched in a receiving layer (lower) composed of food-grade materials. The receiving layer, representing the TeeBN, contains the essential nutritional
            factors of natural EBN while avoiding heavy metal and microbial contaminations normally occurring in the latter.

            supported by traditional Chinese medicine guarantee a USD   dimensional (3D) biomaterials scaffolds to develop
            6.5 billion market in China alone and a rising international   functional tissue, with notable clinical breakthroughs in
            market prices up to USD 6,600 per kilogram [2-5] . However,   the cartilage, bone, and skin, among other tissue types .
                                                                                                           [10]
            the rapidly increasing demand for EBN has triggered   In fact, it is often overlooked that the natural production
            serious ecological and social issues. The annual export   of EBN by swiftlets is also a physiological function of live
            volume from major producing countries in Southeast Asia   tissue. The bird’s saliva gland cells secrete saliva, which
            exceeds 3,000  tons (Figure  1A). Excessive harvesting and   solidifies to form the bowl nests adhering to the cave
            unsustainable farming irreversibly damage the environment,   wall for the birds’ habitation until being harvested for
            rendering 4 million birds homeless and endangering certain   human consumption (Figure 1B) . The nests contain
                                                                                           [1]
            swallow species [6,7] . Also, natural EBNs on the market are   abundant proteins and carbohydrates (>50% and >30%
            often detected with toxic heavy metal salts and microbial   dry  weight,  respectively) produced by  salivary  epithelial
            contamination . Some products rich in nitrous acids and   cells, which are believed to be the main nutritional
                       [8]
            hence appearing red are portrayed and overpriced as the   ingredients that underpin the healthcare effects of EBN .
                                                                                                           [11]
            rarest “blood bird’s nests,” with no scientific evidence except   Utilizing the TE methodology to recapitulate the process
            for potential adverse effects from sodium nitrite (NaNO )  of EBN production in vitro might open a new avenue for
                                                         2
            [8,9] . Although government authorities and non-government   engineering environmentally friendly EBN.
            organizations have tried establishing artificial caves and large-  The key to realizing this goal is to ensure the engineered
            scale breeding, these attempts are regionally limited and loosely   EBN contains the essential nutritional ingredients of
            regulated. Producing EBN in an environmentally friendly and   natural  EBN  in  two  main  categories—(i)  the  structural
            sustainable manner has emerged as a pressing challenge for   macromolecules (e.g., glycans), which can be mimicked
            both environmental protection and food security .  with existing food-grade materials, and (ii) the small-
                                                 [6]
               Tissue engineering (TE)—a medical technology to   molecule metabolites and growth factors secreted by the
            regenerate the human body—may provide an unexpected   salivary gland, e.g., epithelial growth factor (EGF), sialic
            answer to this challenge. TE promises to repair diseased   acid, and  N-acetylneuraminic acid, which are hard to
            tissue by  in vitro culturing mammalian cells in three-  mimic and should ideally be released by living epithelial


            Volume 9 Issue 5 (2023)                         2                           https://doi.org/10.18063/ijb.691
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