Silk fibroin as a vehicle for drug delivery applications.

Silk fibroin (SF), a naturally occurring protein polymer, has several unique properties making it a favorable matrix for the incorporation and delivery of a range of therapeutic agents. SF is biocompatible, slowly biodegradable, and endowed with excellent mechanical properties and processability. Novel manufacturing techniques including mild all-aqueous processes have expanded its range of application even to sensitive protein and nucleic acid therapeutics.

The use of sulfonated silk fibroin derivatives to control binding, delivery and potency of FGF-2 in tissue regeneration.

The development of biomaterials that mimic the physiological binding of growth factors to the extracellular matrix (ECM) is an appealing strategy for advanced growth factor delivery systems. In vivo, fibroblast growth factor 2 (FGF-2) binds to the sulfated glycosaminoglycan heparan sulfate, which is a major component of the ECM. Therefore, we tested whether silk fibroin (SF) decorated with a sulfonated moiety could mimic the natural ECM environment and lead to advanced delivery of this heparin-binding growth factor.

Development of silk fibroin-based beads for immobilized cell fermentations.

Silk fibroin was evaluated as a new matrix for immobilized cell fermentation. Silk fibroin was extracted from Bombyx mori cocoon, purified, concentrated in polyethylene glycol solution and diluted to 3 wt% with distilled water. This fibroin solution was used to encapsulate sensitive cells of the probiotic strain, Bifidobacterium longum ATCC 15707.

Microporous silk fibroin scaffolds embedding PLGA microparticles for controlled growth factor delivery in tissue engineering.

The development of prototype scaffolds for either direct implantation or tissue engineering purposes and featuring spatiotemporal control of growth factor release is highly desirable. Silk fibroin (SF) scaffolds with interconnective pores, carrying embedded microparticles that were loaded with insulin-like growth factor I (IGF-I), were prepared by a porogen leaching protocol. Treatments with methanol or water vapor induced water insolubility of SF based on an increase in beta-sheet content as analyzed by FTIR.

Growth factor gradients via microsphere delivery in biopolymer scaffolds for osteochondral tissue engineering.

Temporally and spatially controlled delivery of growth factors in polymeric scaffolds is crucial for engineering composite tissue structures, such as osteochondral constructs. In the present study, microsphere-mediated growth factor delivery in polymer scaffolds and its impact on osteochondral differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) was evaluated. Two growth factors, bone morphogenetic protein 2 (rhBMP-2) and insulin-like growth factor I (rhIGF-I), were incorporated as a single concentration gradient or reverse gradient combining two factors in the scaffolds.

Silk fibroin spheres as a platform for controlled drug delivery.

The goal of this proof-of-concept study was the fabrication of drug-loaded silk fibroin (SF) spheres under very mild processing conditions. The spheres were fabricated using the laminar jet break-up of an aqueous SF solution, which was induced by a nozzle vibrating at controlled frequency and amplitude. SF particles were spherical in shape as determined by SEM with diameters in the range of 101 microm to 440 microm, depending on the diameter of the nozzle and the treatment to induce water insolubility of SF.

Silk coatings on PLGA and alginate microspheres for protein delivery.

Bombyx mori silk fibroin self-assembles on surfaces to form ultrathin nanoscale coatings based on our prior studies using layer-by-layer deposition techniques driven by hydrophobic interactions between silk fibroin protein molecules. In the present study, poly(lactic-co-glycolic acid) (PLGA) and alginate microspheres were used as substrates and coated with silk fibroin. The coatings were visualized by confocal laser scanning microscopy using fluorescein-labeled silk fibroin.

Silk microspheres for encapsulation and controlled release.

A method was developed to prepare silk fibroin microspheres using lipid vesicles as templates to efficiently load protein drugs in active form for controlled release. The lipid was subsequently removed by methanol or sodium chloride treatments, resulting in silk microspheres consisting of beta-sheet structure and about 2 mum in diameter. NaCl treated microspheres had smoother surfaces compared to the methanol treatments based on SEM analysis, and both types of microspheres had a mixture of multilamellar and unilamellar structures.

Insulin-like growth factor I-releasing alginate-tricalciumphosphate composites for bone regeneration.

Purpose: Development and characterization of an in situ-forming, osteoconductive, and growth factor-releasing bone implant.

Methods: Injectable in situ-forming scaffolds were prepared from a 2% (m/v) alginate solution, tricalciumphosphate (TCP) granules, and poly(lactide-co-glycolide) microspheres (MS), loaded with the osteoinductive growth factor insulin-like growth factor I (IGF-I). Scaffolds were prepared by mixing the components followed by hydrogel formation through calcium carbonate-induced physical cross-linking of the alginate at slightly acidic pH.