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Review
. 2019 Nov 24;11(12):1933.
doi: 10.3390/polym11121933.

Silk Fibroin-Based Biomaterials for Biomedical Applications: A Review

Thang Phan Nguyen  1   2 , Quang Vinh Nguyen  3 , Van-Huy Nguyen  4 , Thu-Ha Le  5 , Vu Quynh Nga Huynh  6 , Dai-Viet N Vo  7 , Quang Thang Trinh  8 , Soo Young Kim  9 , Quyet Van Le  3
Affiliations
Review

Silk Fibroin-Based Biomaterials for Biomedical Applications: A Review

Thang Phan Nguyen et al. Polymers (Basel). .

Abstract

Since it was first discovered, thousands of years ago, silkworm silk has been known to be an abundant biopolymer with a vast range of attractive properties. The utilization of silk fibroin (SF), the main protein of silkworm silk, has not been limited to the textile industry but has been further extended to various high-tech application areas, including biomaterials for drug delivery systems and tissue engineering. The outstanding mechanical properties of SF, including its facile processability, superior biocompatibility, controllable biodegradation, and versatile functionalization have allowed its use for innovative applications. In this review, we describe the structure, composition, general properties, and structure-properties relationship of SF. In addition, the methods used for the fabrication and modification of various materials are briefly addressed. Lastly, recent applications of SF-based materials for small molecule drug delivery, biological drug delivery, gene therapy, wound healing, and bone regeneration are reviewed and our perspectives on future development of these favorable materials are also shared.

Keywords: biologics delivery; bone regeneration; drug delivery; silk fibroin; wound healing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the origin and structures of silk fibroin. (A) Popular silk sources include Nephila clavipes (1.) and Araneus diadematus (2.) spiders, Antheraea pernyi (3.) and Samia cynthia ricini (4.) wild silkworms, and Bombyx Mori (5.) domestic silkworms. (B) Among them, B. mori silkworm is the most dominant source for silk fibers production. (C) Main proteins of silkworm silk fibers are fibroin and sericin (reproduced with permission [15]). (D) Hydrogen bonds between primary amino acid sequence of fibroin contribute to the generation of β-sheet crystallites (reproduced with permission [16]). (E) Fibroin is assembled from nanofibril units which crystal network consists of β-sheet crystallites dispersed within an amorphous matrix (reproduced with permission [17]).
Figure 2
Figure 2
Key advantageous properties of silk fibroin for biomedical applications include: (A) robust mechanical strength with high tensile strength, modulus, stiffness, and extensibility (reproduced with permission [11]); (B) enzymatic biodegradation with controllable rate (reproduced with permission [26]); (C) payloads stabilization capability due to hydrophobic interactions with β-sheet crystallite domains (reproduced with permission [27]); and (D) biocompatibility proved by normal growth of ECV304 cells with no adverse influence after culturing with silk fibroin (SF) films (reproduced with permission [28]).
Figure 3
Figure 3
Overview of SF-based materials fabrication and modification. (A) Aqueous solution of silk fibroin can be obtained from silk cocoons through degumming, rehydration, and dialysis steps (reproduced with permission [47]). (B) Basic structures of SF-based materials include film (1.), hydrogel (2.), micro/nanoparticles (3.), fibers (4.), and scaffold (5.) (reproduced with permission [50,51]). (C) Functional SF-based materials can be designed via multi-level modification techniques, for example, self-assembly of SF nanofibrils network mediated by bovine serum albumin-gold (BSA-Au) nanocluster complex (reproduced with permission [52]). (D) Top-down liquid exfoliation methods or bottom-up self-assembly approach can be used to generate SF nanofibrils (reproduced with permission [53,54]). (E) Advanced manufacturing techniques can be applied to fabricate complex SF-based structures such as microneedles (reproduced with permission [55]).
Figure 4
Figure 4
With favorable characteristics and properties, SF-based materials have been widely applied for important biomedical applications including small molecule drug delivery, biological drug delivery, gene therapy, wound healing, and bone regeneration. (A) For example, doxorubicin-loaded shear-thinning hydrogel can be prepared by SF aqueous solution (reproduced with permission [109]). (B) An entrapped monoclonal antibody can be released after water penetrating into the lyophilized SF network (reproduced with permission [110]). (C) Chemically crosslinked hydrogel from silk-elastin like protein is applied for gene therapy (reproduced with permission [111]). (D) Positive in vivo wound healing efficacy can be achieved using SF films (reproduced with permission [112]). (E) Scaffolds from SF and hydroxyapatite (HA) with/without drug are used for bone regeneration (reproduced with permission [113]).
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