Silk Biomaterials: From Biofabrication to Future Precision Regenerative Applications

Silk proteins have emerged as a versatile class of natural biomacromolecules for regenerative medicine, owing to their exceptional biocompatibility, tunable biodegradation, robust mechanical properties, and remarkable processing versatility. The most widely studied silk protein is silk fibroin from the silkworm Bombyx mori, while this broader family also includes fibroins from other silkworm species, spidroins that constitute spider silk, and recombinant or engineered silk proteins produced in heterologous hosts, each offering distinct sequence, structural, and functional characteristics that can be exploited for biomedical engineering applications. By controlling their hierarchical molecular assembly and β-sheet crystallinity, silk proteins can be processed into a diverse functional formats, including hydrogels, fibers, porous scaffolds, nanoparticles, films, and printable bioinks, providing a highly adaptable platform for tissue engineering and regenerative medicine.

Recent advances in biofabrication have transformed the design and manufacture of silk-based biomaterials. 3D/4D bioprinting, in situ bioprinting, and light-based printing including digital light processing and stereolithography, enable the fabrication of geometrically complex constructs from digitally defined designs, while electrospinning and microfluidic manufacturing provide additional control over fibrous architecture, particle formation, molecular assembly, and microscale organization. Together, these methods enable constructs with programmable internal structure, tissue-specific mechanical properties, spatially controlled biological cues, and patient-specific geometries derived from medical imaging.

At the same time, the field is undergoing a fundamental paradigm shift. Rather than serving solely as structural scaffolds, silk proteins are increasingly being engineered as functional and intelligent biomaterial platforms capable of actively regulating cell behavior, modulating immune responses, delivering therapeutics, and orchestrating tissue regeneration. Emerging strategies including bioactive peptide conjugation, growth factor immobilization, extracellular vesicle integration, stimuli-responsive systems, nanomedicine, and multifunctional composite design are expanding the biological functionality of silk far beyond passive tissue support.

Despite these remarkable advances, significant challenges remain in translating silk biofabrication from laboratory innovation to clinical practice. Critical issues include scalable, reproducible, and sustainable production of silk proteins, including recombinant fibroins and spidroins, standardized bioink development, quality control, regulatory compliance, and rigorous validation of long-term therapeutic efficacy.

This Research Topic aims to showcase the latest advances in functional silk biofabrication, bringing together interdisciplinary research spanning materials science, biofabrication, nanotechnology, cell biology, and translational medicine. We particularly encourage contributions that establish clear relationships between molecular design, fabrication strategies, biological function, and regenerative outcomes, while highlighting emerging concepts that will shape the next generation of precision regenerative biomaterials.

We welcome manuscripts covering, but not limited to, the following topics:

o Advanced Silk Biofabrication: Native and recombinant/engineered silk bioinks for 3D/4D and in situ bioprinting; electrospinning, microfluidic, digital, and hybrid fabrication; hierarchical, patient-specific scaffolds.

o Functional and Intelligent Silk Biomaterials: Bioactive, stimuli-responsive, immunomodulatory, and antimicrobial silk systems; multifunctional composites and hybrid biomaterials.

o Silk Nanomedicine: Silk nanoparticles and nanostructures for drug, protein, nucleic acid, and gene delivery; targeted and stimuli-responsive nanotherapeutics; theragnostic and precision-medicine platforms.

o Structure–Function Engineering: β-sheet crystallinity, hierarchical assembly, degradation, and mechanics across fibroin and spidroin systems; hydrogels (including SilMA), scaffolds, fibers, films; and structure–property–function relationships.

o Tissue-Specific Biofabrication: Bone, cartilage, tendon /ligament, and intervertebral disc; skin and wound healing; neural, vascular, cardiac, and soft tissue; organoids and organ-on-chip systems.

o Cell–Material Interactions: Stem cell engineering and mechanobiology; immune regulation; vascularization and ECM remodeling; bioreactor-assisted maturation.

o Translation and Future Directions: Scalable manufacturing and process standardization; sustainable silk production and recombinant/engineered silk proteins; quality control, regulatory pathways and clinical translation; AI-assisted design and digital manufacturing.