Recombinant keratin: Comprehensive review of synthesis, hierarchical assembly, properties, and applications

Keratin has gained attention for its remarkable mechanical properties, thermal stability, and beneficial biological properties, such as promoting hemostasis and wound healing. Traditionally, keratin has been extracted from natural sources, including human hair, wool, and feathers, and processed into biomaterials, including films, hydrogels, and nanoparticles, primarily for biomedical applications. However, extraction methods often result in heterogeneous keratin mixtures with residual impurities and structural degradation due to harsh purification conditions, complicating efforts to understand how specific keratins and their hierarchical assemblies contribute to desired material properties. Recombinant keratin technology addresses these challenges by enabling the synthesis of individual keratin types with high purity and batch-to-batch consistency. These advancements facilitate studies on how individual and combined keratins at various assembly stagesfrom molecular components and heterodimers to intermediate filaments (IFs) and IF networksimpact material properties. Moreover, this technology allows for precise genetic modifications, potentially leading to engineered keratin variants with tailored characteristics for targeted applications. Despite these advantages, translating recombinant keratin into practical applications requires overcoming key manufacturing challenges, such as optimizing large-scale production and improving purification efficiency. This review presents the current state of recombinant keratin research by highlighting its advancements and exploring current biomaterial applications. While its applications remain limited compared to extracted keratin at this early stage, its potential offers future opportunities for extending its use in advanced material design and beyond biomedical fields. STATEMENT OF SIGNIFICANCE: Keratin and keratinized structures provide essential protection to tissues against mechanical stress and environmental damage, serving as foundational elements across diverse biological systems. This review discusses advancements in recombinant keratin technology, enabling high-purity, reproducible synthesis with controlled composition modifications that effectively overcome the limitations of traditional extraction methods. The innovations deepen our understanding of hierarchical assembly in keratin structures across various length scales, along with their reinforcing mechanisms and mechanical and biofunctional properties. These insights lay the groundwork for biomaterials tailored to regenerative medicine, wound healing, and other biomedical applications. By focusing on the unique capabilities of recombinant keratin, this review offers a valuable resource for future advancements in high-performance biomaterials across biomedical and biotechnological fields.