Reverse-engineered Silk Hydrogels for Cell and Drug Delivery

Seib, F. Philipp

doi:10.4155/tde-2018-0016

Cited by 38 publications

(40 citation statements)

References 96 publications

(162 reference statements)

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“…1 Silk has several important and exploitable characteristics, including (i) excellent mechanical properties, (ii) a long-term track record of its safe use in humans, (iii) broad biocompatibility and biodegradability, (iv) mild aqueous processing conditions, and (v) the ability to stabilize and protect therapeutic payloads (e.g., proteins and small molecular drugs). 3,4 In addition, a reversed engineered silk solution can be processed into numerous material formats, including hydrogels, scaffolds, lms, microspheres, and nanoparticles (reviewed in 5,6 ). For these reasons, silk nanoparticles are emerging as interesting carriers for drug delivery and are now oen proposed for solid tumor drug targeting.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic-assisted silk nanoparticle tuning

et al. 2019

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Silk is now making inroads into advanced pharmaceutical and biomedical applications. Both bottom-up and top-down approaches can be applied to silk and the resulting aqueous silk solution can be processed into a range of material formats, including nanoparticles. Here, we demonstrate the potential of microfluidics for the continuous production of silk nanoparticles with tuned particle characteristics. Our microfluidic-based design ensured efficient mixing of different solvent phases at the nanoliter scale, in addition to controlling the solvent ratio and flow rates. The total flow rate and aqueous : solvent ratios were important parameters affecting yield (1 mL min À1 > 12 mL min À1 ). The ratios also affected size and stability; a solvent : aqueous total flow ratio of 5 : 1 efficiently generated spherical nanoparticles 110 and 215 nm in size that were stable in water and had a high beta-sheet content. These 110 and 215 nm silk nanoparticles were not cytotoxic (IC50 > 100 mg mL À1 ) but showed size-dependent cellular trafficking. Overall, microfluidicassisted silk nanoparticle manufacture is a promising platform that allows control of the silk nanoparticle properties by manipulation of the processing variables.

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Section: Introductionmentioning

confidence: 99%

Microfluidic-assisted silk nanoparticle tuning

et al. 2019

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“…The biocompatibility and biodegradation of the regenerated silk fibroin has been evaluated both in vitro and in vivo often with superior performance than fully synthetic or other biopolymer materials (reviewed in ( 1 , 60 , 61 )). Silk is not of mammalian origin (like other clinically used biomaterials e.g.…”

Section: Introductionmentioning

confidence: 99%

“…The ability of silk fibroin to self-assemble into hydrogels in an aqueous solution, coupled with its biocompatibility, makes it an attractive polymer for ocular drug delivery of macromolecules, such as antibodies and other therapeutic proteins (reviewed in ( 60 )). One example is the incorporation of bevacizumab, an antibody that inhibits the protein vascular endothelial growth factor for the treatment of wet age-related macular degeneration, into a silk hydrogel.…”

Section: Introductionmentioning

confidence: 99%

“…The authors then conducted an in vitro assessment of the photocrosslinking process using heavy water D 2 O, sodium azide and superoxide dismutase and determined that the silk gelation was driven principally by dityrosine formation radicalised by the excited riboflavin. The formation of dityrosine complexes from the tyrosine amino acid residues covalently bound the silk molecules together to form the elastic hydrogel ( 21 ) (as opposed to physically cross-linked silk hydrogels, which are brittle ( 60 )).…”

Section: Introductionmentioning

confidence: 99%

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A Review of the Emerging Role of Silk for the Treatment of the Eye

2018

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Silk is a remarkable biopolymer with a long history of medical use. Silk fabrications have a robust track record for load-bearing applications, including surgical threads and meshes, which are clinically approved for use in humans. The progression of top-down and bottom-up engineering approaches using silk as the basis of a drug delivery or cell-loaded matrix helped to re-ignite interest in this ancient material. This review comprehensively summarises the current applications of silk for tissue engineering and drug delivery, with specific reference to the eye. Additionally, the review also covers emerging trends for the use of silk as a biologically active biopolymer for the treatment of eye disorders. The review concludes with future capabilities of silk to contribute to advanced, electronically-enhanced ocular drug delivery concepts.

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“…Silk fibroin has been extensively studied as a drug delivery system for its unique and highly versatile structure and its strong clinical track record. Silk hydrogels have unlimited applications and have several advantages, such as high biocompatibility, tunable biodegradation and low immunogenicity [ 11 , 12 ]. Silk fibroin solution has been used to produce hydrogels as injectable systems for load-bearing of cartilage tissue [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels

et al. 2020

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Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty–GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty–GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2–5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty–GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty–GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.

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Reverse-engineered Silk Hydrogels for Cell and Drug Delivery

Cited by 38 publications

References 96 publications

Microfluidic-assisted silk nanoparticle tuning

Microfluidic-assisted silk nanoparticle tuning

A Review of the Emerging Role of Silk for the Treatment of the Eye

Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels

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