Silk Fibroin as an Efficient Biomaterial for Drug Delivery, Gene Therapy, and Wound Healing

Abstract

Silk fibroin (SF), an organic material obtained from the cocoons of a silkworm Bombyx mori, is used in several applications and has a proven track record in biomedicine owing to its superior compatibility with the human body, superb mechanical characteristics, and its controllable propensity to decay. Due to its robust biocompatibility, less immunogenic, non-toxic, non-carcinogenic, and biodegradable properties, it has been widely used in biological and biomedical fields, including wound healing. The key strategies for building diverse SF-based drug delivery systems are discussed in this review, as well as the most recent ways for developing functionalized SF for controlled or redirected medicines, gene therapy, and wound healing. Understanding the features of SF and the various ways to manipulate its physicochemical and mechanical properties enables the development of more effective drug delivery devices. Drugs are encapsulated in SF-based drug delivery systems to extend their shelf life and control their release, allowing them to travel further across the bloodstream and thus extend their range of operation. Furthermore, due to their tunable properties, SF-based drug delivery systems open up new possibilities for drug delivery, gene therapy, and wound healing.

Keywords: biomaterials; biopolymers; drug delivery applications; gene therapy; silk fibroin; wound healing.

Figure 5

Burn wound tissues stained with hematoxylin and eosin (C: surgical gauze, S: SF nanomatrix, and M: Medifoam^®, scale: 100 µm). Reprinted with permission from reference [157].

Figure 6

Photos of burn wound tissues stained with H&E at 7, 14, and 21 days. (A) Hospital gauze (14 days), (B) SF nanomatrix (7 days), and (C) Medifoam^® (7 days). (Scale: 50 µm, NT: necrosis tissue, nt: natural tissue, circle: Keratinocytes). Reprinted with permission from reference [157].

Figure 7

At 7 days, PCNA expression was observed in the tissue covering the infected region. Medical gauze (A), SF nanomatrix (B), and Medifoam^® (C) (scale: 50 µm). Reprinted with permission from reference [157].

Figure 8

(A) Burn wound area on rat skin right after the creation. (B) Residual wound area change with healing time (28 days). (C) Gross findings of wound area treated with different wound dressing materials (C: medical gauze, S: SF nanomatrix, and M: Medifoam^®) (scale: 50 µm). Reprinted with permission from reference [157].

Figure 1

For pharmaceutical and biomedical implementations, a versatile range of functional arrangements and chemical treatment for manufacturing a variety of silk fibroin (SF) formats are available. Image reproduced from reference [39] which was published under a CC BY license.

Figure 2

Processing of SF.

Figure 3

SF microcapsules of plasmid DNA are packaged. (A) A diagram depicting the initialization of pDNA before and after it has been loaded. Preloading: pDNA was adsorbed onto bPEI25 functionalized PS particles; SF was mounted on the pDNA-coated particles using LbL; the SF was stabilised, and the core was removed. PS particles were coated with bPEI25 after loading; SF was assembled LbL onto bPEI25-coated PS particles; the center was removed after pDNA was adsorbed onto the bPEI25eSF casing after another bPEI25 coating. (B) Photos obtained with a fluorescence microscope of 4 mm SF microcapsules that had been pre- or post-loaded with pDNA. FITC (green) was used to mark SF, and Cy5 was used to label pDNA (red). 10 mm scale bar. Reprinted with permission from reference [97].

Figure 4

The results of various loading methods and measures of pDNA loaded SF micro capsules on release activity and cell capsule interactions are depicted in this diagram. (A) Preloading: pDNAebPEI complexes are released from SF capsules through diffusion. After charging, desorption from its membrane of SF capsules releases complexes. (B) For the same total amount of pDNA, varying sizes of gene carriers have various transmission densities on the cell surface, affecting cell viability and transfection. Reprinted with permission from reference [97].