Reloadable Silk-Hydrogel Hybrid Scaffolds for Sustained and Targeted Delivery of Molecules.

Abstract

Tunable repeated drug administration is often inevitable in a number of pathological cases. Reloadable 3D matrices for sustained drug delivery are predicted as a prospective avenue to realize this objective. This study was directed toward sonication-induced fabrication of novel reloadable Bombyx mori silk fibroin (SF) (4, 6, and 8 wt %) hydrogel, injected within 3D porous (8 wt %) scaffolds. The focus was to develop a dual-barrier reloadable depot system for sustained molecular cargo release. Both the varying SF concentration (4, 6, and 8 wt %) and the sonication time (30, 45, and 60 s) dictated the extent of cross-linking, β-sheet content, and porosity (1-10 μm) influencing the release behavior of model molecules. Release studies of model molecules (trypan blue, TB, 961 Da and bovine serum albumin, BSA, 66 kDa) for 28 days attested that the variations in their molecular weight, the matrix cross-linking density, and the scaffold-hydrogel interactions dictated the release behavior. The Ritger and Peppas equation was further fitted into the release behavior of model molecules from various SF matrices. The hybrid constructs exhibited high compressive strength along with in vitro compatibility using primary porcine chondrocytes and tunable enzymatic degradation as assessed for 28 days. The aptness of the constructs was evinced as a reloadable model molecule (BSA and fluorescein isothiocyanate-inulin, 3.9 kDa) depot system through UV-visible and fluorescence spectroscopic analyses. The novel affordable platform developed using silk scaffold-hydrogel hybrid constructs could serve as a sustained and reloadable drug depot system for administration of multiple and repeated drugs.