Silk-based stabilization of biomacromolecules

Li, Adrian B.; Kluge, Jonathan A.; Guziewicz, Nicholas; Omenetto, Fiorenzo G.; Kaplan, David L.

doi:10.1016/j.jconrel.2015.09.037

Cited by 127 publications

(121 citation statements)

References 175 publications

(208 reference statements)

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“…Air-dried silks provide a protective barrier that physically immobilized blood components with access to minimal residual moisture, in turn conferring conformational stability (34). We directly demonstrated that the physical entrapment provided by the silk matrix was effective in mitigating thermally induced degradation and we can infer there are additional benefits such as preventing exposure to enzymatic and UV stresses (26).…”

Section: Discussionmentioning

confidence: 72%

Silk-based blood stabilization for diagnostics

Kluge

Kahn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Advanced personalized medical diagnostics depend on the availability of high-quality biological samples. These are typically biofluids, such as blood, saliva, or urine; and their collection and storage is critical to obtain reliable results. Without proper temperature regulation, protein biomarkers in particular can degrade rapidly in blood samples, an effect that ultimately compromises the quality and reliability of laboratory tests. Here, we present the use of silk fibroin as a solid matrix to encapsulate blood analytes, protecting them from thermally induced damage that could be encountered during nonrefrigerated transportation or freeze-thaw cycles. Blood samples are recovered by simple dissolution of the silk matrix in water. This process is demonstrated to be compatible with a number of immunoassays and provides enhanced sample preservation in comparison with traditional air-drying paper approaches. Additional processing can remediate interactions with conformational structures of the silk protein to further enhance blood stabilization and recovery. This approach can provide expanded utility for remote collection of blood and other biospecimens empowering new modalities of temperature-independent remote diagnostics.lood contains a variety of proteins, enzymes, lipids, metabolites, and peptides, which can be interrogated as biomarkers for health screening, monitoring, and diagnostics. The integrity of these blood components and thus the quality of information attained from their analysis is determined by the storage conditions from sampling until analysis, or the so-called pre-analytical phase (1, 2). This phase often includes time-consuming processing steps and the requirement for a continuous cold storage. Without temperature regulation, blood-derived biospecimens degrade quickly, accounting for up to 67% of all laboratory testing errors (2, 3). Further, when blood-derived materials are frozen, decreases in thermodynamic free energy and unfavorable ice crystal-protein interactions (4) can occur during subsequent thawing (5, 6), which can further compromise analyte integrity as a gold-standard methodology.As an alternative route, blood and blood derivatives can be dried via newer approaches such as isothermal vitrification (7), lyophilization (8), or on silica chips (9). Isothermal vitrification and lyophilization are inherently resource-intensive techniques and thus not suitable for field use. Silica chips are designed for enrichment of selected fractions of the low-molecular-weight serum proteome, but are not broadly protective at elevated temperature (10). An inexpensive alternative used since the 1960s are dried blood spots (DBS) (11), a paper card system which captures blood components among cellulose fibers as the water phase evaporates. These drying measures decrease sample weight by >90%, thus decreasing transport burden, and in theory can enhance long-term sample stability by decreasing water-dependent analyte degradation caused by hydrolysis and enzyme activity (12). Unfortunately, DBS stored in ...

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Section: Discussionmentioning

confidence: 72%

Silk-based blood stabilization for diagnostics

Kluge

Kahn

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Silk sponge of pore size of 400–500 μm was prepared as previously described [31]. Tubular silk sponge (2 mm inner diameter, 4 mm outer diameter, 4 mm height) were cut from the sponge with dermal punches.…”

Section: Methodsmentioning

confidence: 99%

“…Silk is an unique candidate to address these issue due to its excellent mechanical properties, biocompatibility, tunable degradability [29, 30], as well as the ability of silk to stabilize various of bioactive compounds [31]. We recently demonstrated the feasibility of silk protein as a molding and machinable biomaterial system for the preparation of devices for craniofacial repairs, based on the use of an organic solvent-based process (1,1,1,3,3,3 hexafluro-2-propanol (HFIP)) [29].…”

Section: Introductionmentioning

confidence: 99%

Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing

Hotz

Ling

et al. 2016

Biomaterials

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Silk fibers spun by silkworms and spiders exhibit exceptional mechanical properties with a unique combination of strength, extensibility and toughness. In contrast, the mechanical properties of regenerated silk materials can be tuned through control of the fabrication process. Here we introduce a biomimetic, all-aqueous process, to obtain bulk regenerated silk-based materials for the fabrication of functionalized orthopedic devices. The silk materials generated in the process replicate the nano-scale structure of natural silk fibers and possess excellent mechanical properties. The biomimetic materials demonstrated excellent machinability, providing a path towards the fabrication of a new family of resorbable orthopedic devices where organic solvents are avoided, thus allowing functionalization with bioactive molecules to promote bone remodeling and integration.

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“…Silk fibroin (SF) has emerged as an outstanding material for biomolecule stabilization and delivery [26][27][28][29][30] . SF is biocompatible and biodegradable, eliciting minimal inflammatory response 31,32 , and has been used in medical applications including sutures and surgical mesh scaffolds 33 .…”

Section: Introductionmentioning

confidence: 99%

Stabilization and Sustained Release of HIV Inhibitors by Encapsulation in Silk Fibroin Disks

Zhang

Herrera

Coburn

et al. 2017

ACS Biomater. Sci. Eng.

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Topical microbicides have the potential to provide effective protection against sexual transmission of HIV. Challenges in developing microbicides include their application in resource-poor settings with high temperatures and a lack of refrigeration, and low user adherence to a rigorous daily regimen. Several protein-based HIV inhibitors show great promise as microbicides, being highly specific and not expected to lead to resistance that would affect the efficacy of current antiretroviral treatments. We show that four potent protein HIV inhibitors, 5P12-RANTES, 5P12-RANTES-L-C37, Grft, and Grft-L-C37 can be formulated into silk fibroin (SF) disks and remain functional for 14 months at 25, 37, and 50 °C. These HIV inhibitor-encapsulated SF disks show excellent inhibition properties in PBMC and in human colorectal and cervical tissue explants, and do not induce inflammatory cytokine secretion. Further, the SF provides a mechanically robust matrix with versatile material formats for this type of application. Finally, a formulation was developed to allow sustained release of functional Grft for 4 weeks at levels sufficient to inhibit HIV transmission. This work establishes the suitability of HIV inhibitor-encapsulated SF disks as topical HIV microbicides that can be further developed to allow easy insertion for extended protection.

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Silk-based stabilization of biomacromolecules

Cited by 127 publications

References 175 publications

Silk-based blood stabilization for diagnostics

Silk-based blood stabilization for diagnostics

Regenerated silk materials for functionalized silk orthopedic devices by mimicking natural processing

Stabilization and Sustained Release of HIV Inhibitors by Encapsulation in Silk Fibroin Disks

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