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In cases of deep skin defects, spontaneous tissue regeneration and excessive collagen deposition lead to hyperplastic scars. Conventional remedial action after scar formation is limited with a high recurrence rate. In this study, we designed a new artificial skin bilayer using silk fibroin nanofibers films (SNF) as the epidermis, and silk fibroin (SF) / hyaluronic acid (HA) scaffold as the dermal layer. The regenerated SF film was used as a binder to form a functional SNF-SF-HA bilayer scaffold. The bilayer scaffold showed high porosity, hydrophilicity, and strength, and retained its shape over 30 days in PBS. In vitro , human umbilical vein endothelial cells were seeded into the bilayer scaffold and showed superior cell viability. In vivo analyses using the rabbit ear hypertrophic scar (HS) model indicated that the bilayer scaffold not only supported the reconstruction of new tissue, but also inhibited scar formation. The scaffold possibly achieved scar inhabitation by reducing wound contraction, weakening inflammatory reactions, and regulating collagen deposition and type conversion, which was partly observed through the downregulation of type I collagen, transforming growth factor-β, and α-smooth muscle actin. This study describes a new strategy to expand the application of silk-based biomaterials for the treatment of hyperplastic skin scars. • Silk-based bilayer scaffold accurately mimicking tissue structure and composition was fabricated. • This bilayer scaffold enhances cell growth and wound healing significantly. • The multifunctional bilayer scaffold could significantly inhibit the scarring during skin regeneration. [ABSTRACT FROM AUTHOR]

Proteins and polysaccharides are primary components in mammal soft tissue. In this study, we established a rapid hydrogel to imitate the nature extracellular matrix via silk fibroin (SF) and hyaluronic acid (HA) blend hydrogel. SF/HA hydrogel was prepared effectively, and its formation time was shorted. With the increase of HA content, the water absorption, porosity and breaking strengths of the hydrogel increased, while hydrophilic of the hydrogel was enhanced extremely determined by contact angle decreasing. Especially, the SF/HA hydrogel with a ratio of 5:5 presented the highest water absorption and mechanical properties. The molecule conformation of the composite hydrogel was mainly amorphous structure and contained the small number of β-sheets which gradually decreases with the increase of HA content. In drug release test, accumulative release ratio of the composite gel was about 80% at day 40. And the mass loss of the hydrogel reached approximately 78% in vitro degradation. In vivo, the SF/HA hydrogels presented good histocompatibility and promoted vascular-like tissue regeneration when were implanted subcutaneously of Sprague Dawley rats. This study provides a new approach to fabricate silk-based biomaterials for soft tissue regeneration. [ABSTRACT FROM AUTHOR]

Scarless skin regeneration for full-thickness wounds remains a challenge in skin tissue engineering. The surprising scar-free repair function of fetal skin has inspired that the ideal wound dressing can be designed by recapitulating the biophysical and biochemical properties. However, there is no more powerful effective scaffold put into practice due to their mismatched structures and inappropriate components. Here, a novel bioactive scaffold was detailly designed by mimicking extracellular matrix from its chemical components and biophysical nanostructures. Through introduction of hyaluronic acid (HA) and natural silk fibroin nanofibers (SNFs), the silk fibroin (SF)-based scaffolds with higher porosity (~92.5 %), water-uptake ratio (~96 %) and swelling ratio (~90 %) were facilely prepared by lyophilization. In vitro , human umbilical vein endothelial cells (HUVECs) were seeded in the scaffold with nanostructures. The results showed better cytocompatibility of the scaffolds to support cell spread, proliferation and differentiation. In vivo , effect of the scaffolds on full-thickness skin defects of the nude mouse demonstrated that the SNFs incorporated scaffolds could not only accelerated wound healing (up to 98.2 ± 0.5 % within 4 weeks) but also can regulate collagen arrangement by nanofibers as a template to inhibit the scar forming. This study provides a useful strategy for exploring bioactive SF-based scaffolds by natural SNFs decoration for novel wound dressing and artificial skin. Schematic illustration showing the SF-HA-SNFs scaffold was fabricated into wound dressing or artificial skin to promote cell proliferation and adhesion in vitro , and enhance repair efficacy for skin tissue in vivo , which indicated a promising alternative for wound healing. [Display omitted] • Design bioactive scaffold with natural silk nanofibers (SNFs) decorated firstly. • The scaffold provided a beneficial microenvironment to improve cell growth through chemical and physical cues. • Improved repair efficacy for skin tissue defects in nude mouse was confirmed. • The bioactive scaffold has great potential for scarless reconstruction during skin repair. [ABSTRACT FROM AUTHOR]

Natural silk nanofibers (SNFs) have been attracted more attentions in flexible functional devices and biomaterials. However, its mass production and complex fabrication process remains challenging. In this study, we successfully developed a new physical-chemical strategy to fabricate natural SNFs with high yield (~87%). The natural SNFs performed an excellent dispersion in aqueous solution with uniform diameter (approximately 280 nm) and 10–30 μm length. The high-flexible natural SNFs/single-wall carbon nanotube (CNTs) composite films were prepared to evaluate their potential in electronic devices. The composite films exhibited remarkable dimensional stability, chemical durability, and Young's modulus (498.7 ± 64.4 MPa). Furtherly, the composite films also presented excellent electrical heating properties and potential utilities in electronics. These natural SNFs/CNTs composite films with high-mechanical and electrical features offer new starting materials for bioelectronics devices applications, such as conductive wire, electronical heater, and capacitor. Natural silk nanofibers/carbon nanotubes composite films with high electroconductivity and flexibility are prepared based on facile deconstruction of the silk fibroin fibers. Image 1 • It is the first time to prepare natural silk nanofibers with high yield (~87%). • The silk nanofibers are fabricated by an environment-friendly approach avoiding use of toxic agents. • The SNFs-CNTs composites exhibit good mechanical property, electrical conductivity and energy storage stability. • The SNFs-CNTs composites have versatile utilities in electronic devices. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) printing is regarded as a critical technological-evolution in material engineering, especially for customized biomedicine. However, a big challenge that hinders the 3D printing technique applied in biomedical field is applicable bioink. Silk fibroin (SF) is used as a biomaterial for decades due to its remarkable high machinability and good biocompatibility and biodegradability, which provides a possible alternate of bioink for 3D printing. In this review, we summarize the requirements, characteristics and processabilities of SF bioink, in particular, focusing on the printing possibilities and capabilities of bioink. Further, the current achievements of cell-loading SF based bioinks were comprehensively viewed from their physical properties, chemical components, and bioactivities as well. Finally, the emerging issues and prospects of SF based bioink for 3D printing are given. This review provides a reference for the programmable and multiple processes and the further improvement of silk-based biomaterials fabrication by 3D printing. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) hydrogels are explored for diverse applications, ranging from cosmetic thickeners to support matrices for drug delivery and regenerative medicine. However, their utilities remain inherent challenges in inadequate mechanical properties and sophisticated process. Hyaluronic acid (HA) is a natural polysaccharide with outstanding physiological activities and superior water retaining capacity. In this study, HA was used as a skeleton of interpenetrating network to fabricate SF/HA hydrogel with high-flexibility and micro or nanofibers networks. The flexibility and water-absorbing quality of SF/HA hydrogels are improved dramatically due to super hydrophilicity of HA addition. By the synergistic effect of HA and solvent exchange, SF molecular conformation is induced efficiently to form β-sheet structures and assembling directly by physical crosslinking, which are determined by structure analysis. Moreover, the condense structure of the SF/HA hydrogel is mainly silk II, which contributes to their high thermal stability. The HA also plays a dominating role in formation of the micro or nanofibers networks on the wall of the SF/HA hydrogels, confirming by elements analysis. Investigation on fibroblast vitality and morphology showed that these SF/HA hydrogels can support cell adhesion, differentiation, and proliferation in vitro and present a better biocompatibility in comparison to pure SF hydrogel. Thus, it is believed that this work provides a facile way to fabricate protein-polysaccharide biomaterials and tissue engineering scaffolds. In this work, we report a new approach to assemble directly high-flexibility and biocompatible silk fibroin (SF)/hyaluronic acid (HA) hydrogel without chemical crosslinking. HA macromolecular chains and β-sheet content enriched contribute to the SF molecules conformational transitions and remarkable mechanical property in terms of physical crosslinking efficiently. Fibroblasts growth, morphology and viability on the hydrogels indicate good alternatives for tissue engineering. Image 1 • Composite hydrogels of silk fibroin and hyaluronic acid were fabricated by novel solvent exchange technique. • Hyaluronic acid acted as a skeleton of interpenetrating network to induce robust silk-based hydrogel formation without chemical agents. • Silk fibroin/hyaluronic acid hydrogels with nano or submicron fibers and good biocompatibility made them as expected candidates for soft tissue repair in future. [ABSTRACT FROM AUTHOR]