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Materials Science in Additive Manufacturing Fibrous silk in biomedicine

and heart valves). In addition, they have been extensively Although approximately 20 review articles have been
2-4
used in drug delivery, gene therapy, and related fields. published on the fabrication, structures, properties, and
5,6
With the rapid development of molecular biology, cell applications of SF-based biomaterials, it is important to
biology, clinical medicine, and other disciplines, as well note that SF is merely a fibrous protein sharing the primary
as cross-disciplinary adventures, biomedical materials sequence structure with FS. Natural FS exhibits a far more
20
are playing an increasingly vital role in shaping the future intricate and ordered assembly of SF chains. In contrast,
directions of medical research. the number of research articles specifically focused on FS
As a historically significant and iconic material in remains relatively small. Given the in-depth knowledge
the textile industry, silk fibers produced by silkworms now available regarding FS’s comprehensive material
have garnered significant attention throughout human properties and the growing breadth of its biomedical
history owing to their unparalleled luster and exceptional applications, a timely review of recent advances in FS
mechanical attributes. In this review, we deliberately refer research is warranted.
7,8
to silk in its fiber form as fibrous silk (FS) to distinguish This review focuses on FS-based materials for
it from the constituent silk fibroin (SF) proteins found in biomedical applications, covering research progress
other forms. The production of FS begins with the in vivo over the past two decades (2004 – 2024). First, the
biosynthesis of fibrous SF proteins by specialized epithelial structure and morphology of FS are described, including
cells within the silkworm gland, followed by transport natural FS, derived FS, and assembled FS. Next, critical
through a long duct for structural condensation before properties relevant to biomedical applications –
final spinning. At the molecular level, FS is characterized including mechanical performance, biocompatibility,
9
by highly ordered β-pleated structures (β-sheets), biodegradation, and antimicrobial characteristics – are
primarily arising from hydrophobic domains composed of discussed. Subsequently, the applications of FS-based
GAGAGS segments (where G = glycine, A = alanine, and materials across various biomedical fields are examined,
S = serine) in its primary sequence. The interconnected underscoring the advantages of FS. Finally, future
10
crystalline regions, alongside a non-crystalline continuous prospects, current limitations, and possible directions for
phase containing less-ordered diffused chains, collectively optimizing FS-based materials for biomedical applications
contribute to the remarkable mechanical performance of are tentatively proposed.
silk fibers. 11
2. The source, composition, and structure
Concerning the biological properties, FS exhibits
non-immunogenicity, controllable biodegradability, non- of FS
toxic degradation products, compatibility with a wide Natural silk fibers are fibrous materials commonly
variety of tissues, and renewability. 12,13 As understanding produced by certain species of arthropods and insects,
of the intricate structure and remarkable properties of including the domestic silkworm, spider, scorpion, mite,
FS has deepened, research focus has rapidly shifted from and bee. These species share a specialized set of organs
traditional textile applications to the realm of biomedical adapted for silk production. 21-23 Silk protein fibers are
materials, encompassing nearly all aspects of medicine. 14-18 either spun continuously (i.e., by silkworms) or produced
In recent years, additive manufacturing (AM) upon demand (i.e., by spiders) during their life cycle. The
and 3D printing have emerged as powerful tools for intricate process of silk formation, occurring through
fabricating FS-based biomedical materials with highly the posterior, middle, and anterior parts of the silk gland
complex and customized architectures. AM techniques, duct, is regulated by variations in pH as well as potassium
24-26
including selective laser sintering, stereolithography, and and calcium ion concentrations. These conditions are
extrusion-based printing, enable precise control over the critical for controlling the transport and conformational
microstructure, porosity, and mechanical properties of transition of SF.
FS-based scaffolds. These technologies have significantly Although spiders can produce significant quantities of
expanded the application of FS in tissue engineering silk – reaching up to 137 m at a time – their cannibalistic
and regenerative medicine by facilitating the creation of behavior limits large-scale silk harvesting and,
patient-specific implants and functionalized biomaterials consequently, the practical application of spider silk. 27,28
with enhanced bioactivity and tailored degradation rates. In contrast, silkworms are dedicated to silk producers,
19
The integration of AM and 3D printing with FS-based generating silk lengths ranging from 600 m to 1,500 m,
materials holds great promise for advancing personalized relative to their body weight, to construct robust woven
medicine and improving the efficacy of tissue repair and cocoons. Since the domestication of silkworms, silk fibers
regeneration. have been widely used in the textile industry, prized for

Volume 4 Issue 2 (2025) 2 doi: 10.36922/MSAM025130020