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Xingxiang Ji,1,* Yanyan Li,2,* Jingsheng Wang,3,* Gang Wang,3,* Bin Ma,4 Jingfei Shi,5 Chao Cui,6,7 Ruiming Wang1 1State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong, 250353, People’s Republic of China; 2Key Laboratory of Maternal & Fetal Medicine of National Health Commission of China, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250014, People’s Republic of China; 3Department of Cardiovascular Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, 271000, People’s Republic of China; 4Department of Cardiovascular Medicine, Taian City Taishan District People’s Hospital, Taian, Shandong, 271000, People’s Republic of China; 5Department of Clinical and Basic Medicine, Shandong First Medical University, Jinan, Shandong, 250000, People’s Republic of China; 6Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, 253000, People’s Republic of China; 7Department of Pharmacy, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, 271000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Cui, Scientific Research Department, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, Shandong, 253000, People’s Republic of China, Email hbkjcuichao@126.com Ruiming Wang, State Key Laboratory of Biobased Material and Green Papermaking, Qilu University of Technology, Shandong Academy of Sciences, Jinan, Shandong, 250353, People’s Republic of China, Email ruiming3k@163.comAbstract: Silk protein, as a natural polymer material with unique structures and properties, exhibits tremendous potential in the biomedical field. Given the limited production and restricted properties of natural silk proteins, molecular biotechnology has been extensively applied in silk protein genetic engineering to produce novel silk proteins with specific properties. This review outlines the roles of major model organisms, such as silkworms and spiders, in silk protein production, and provides a detailed introduction to the applications of gene editing technologies (eg, CRISPR-Cas9), transgenic expression technologies, and synthetic biology techniques in silk protein genetic engineering. By analyzing the genetic factors influencing silk protein expression, this review further elaborates on the innovative applications of silk proteins in drug delivery systems, tissue engineering and regenerative medicine (eg, skin, bone, cartilage, and vascular repair), as well as antibacterial immune strategies. Notably, modified silk proteins expressed by transgenic silkworms demonstrate significant advantages in enhancing drug bioavailability and promoting cell proliferation and differentiation. In conclusion, silk protein gene engineering, through continuous innovations in molecular biotechnology, has provided an effective pathway for the production of high-performance silk protein materials. The extensive applications of these modified silk proteins in the biomedical field have not only expanded the functionality of silk proteins but also offered new approaches to address medical challenges. In the future, the development of silk protein gene engineering will further rely on interdisciplinary integration to promote in-depth research and the expansion of industrial applications of silk proteins.Keywords: silk protein, genetic engineering, molecular biotechnology, performance optimization, biomedical applications, tissue engineering, regenerative medicine

Physical unclonable functions (PUFs) are emerging as a cutting-edge technology for enhancing information security by providing robust security authentication and non-reproducible cryptographic keys. Incorporating renewable and biocompatible materials into PUFs ensures safety for handling, compatibility with biological systems, and reduced environmental impact. However, existing PUF platforms struggle to balance high encoding capacity, diversified encryption signatures, and versatile functionalities with sustainability and biocompatibility. Here, all-biomaterial-based unclonable anti-counterfeiting labels featuring multi-mode encoding, multi-level cryptographic keys, and multiple authentication operations are developed by imprinting biomimetic-grown calcites on versatile silk protein films. In this label, the inherent non-clonability comes from the randomized characteristics of calcites, mediated by silk protein during crystal growth. The successful embedding of photoluminescent molecules into calcite lattices, assisted by silk protein, allows the resulting platform to utilize fluorescence patterns alongside birefringence for high-capacity encoding. This design facilitates easy and rapid authentication through Hamming distance and convolutional neural networks using standard cameras and portable microscopes. Moreover, angle-dependent polarization patterns enable multi-level key generation, while multi-spectral fluorescence signals offer multi-channel keys. The developed anti-counterfeiting labels combine biodegradability, green manufacture, easy authentication, high-level complexity, low cost, robustness, patternability, and versatility, offering a practical and high-security solution to combat counterfeiting across various applications., (© 2024 Wiley‐VCH GmbH.)