A genetically engineered silkworm bioreactor enabling efficient recombinant human lactoferrin production for functional silk fiber biomanufacturing

The silkworm, Bombyx mori , is an economically important insect resource in China. With the transformation and upgrading of the sericulture industry, genetically engineered silkworms have emerged as efficient animal bioreactors for producing bioactive proteins and functional compounds. However, the diversity of available transgenic silkworm bioreactor resources remains limited and requires further expansion. Herein, we focused on human lactoferrin (hLF), which exhibits potent antibacterial activity due to its strong iron‐chelating capacity, and established an efficient recombinant hLF (rhLF) expression system in the posterior silk glands (PSGs) of transgenic silkworms using piggyBac technology. The rhLF production reached 45.13 ± 2.46 mg/g cocoon shell weight, with N‐glycosylation modifications consistent with those of native hLF. Functionally, rhLF exhibited robust antibacterial activity, achieving inhibition rates of 31.64% ± 4.66% against Escherichia coli and 74.35% ± 0.87% against Staphylococcus aureus . Additionally, rhLF significantly promoted cell migration and accelerated wound healing, with a migration rate of 17.06% ± 4.05%. The resulting chimeric fibroin fibers containing rhLF demonstrated enhanced antibacterial activity while maintaining cytocompatibility. Collectively, we constructed a novel transgenic silkworm strain enabling high‐yield rhLF production and achieved the biomanufacturing of functional silk fibers. These findings provide a cost‐effective strategy for generating high‐value products within conventional agricultural systems.