A Comprehensive Review on Silk Fibroin as a Persuasive Biomaterial for Bone Tissue Engineering

Abstract

Bone tissue engineering (BTE) utilizes a special mix of scaffolds, cells, and bioactive factors to regulate the microenvironment of bone regeneration and form a three-dimensional bone simulation structure to regenerate bone tissue. Silk fibroin (SF) is perhaps the most encouraging material for BTE given its tunable mechanical properties, controllable biodegradability, and excellent biocompatibility. Numerous studies have confirmed the significance of SF for stimulating bone formation. In this review, we start by introducing the structure and characteristics of SF. After that, the immunological mechanism of SF for osteogenesis is summarized, and various forms of SF biomaterials and the latest development prospects of SF in BTE are emphatically introduced. Biomaterials based on SF have great potential in bone tissue engineering, and this review will serve as a resource for future design and research.

Keywords: biomaterials; bone tissue engineering; silk fibroin.

Figure 1

Structure diagram of silk fibroin (SF). The hydrophobic heavy (H-) chain and hydrophilic light (L-) chain are linked by disulfide bonds. Reproduced with permission from [47]. Copyright © 2018 American Chemical Society.

Figure 2

A schematical representation of obtaining regenerated silk fibroin (RSF) solution. Silk cocoons are cut into small pieces, which are purified from sericin by boiling them in degumming agents. The bulk of SF was obtained by drying overnight. RSF was formed by dissolving the bulk of SF in LiBr and then dialyzing.

Figure 3

Monocyte responsiveness to silk-based biomaterials with different physic-chemical characteristics: cytokine gene expression. (A) Gene expression of IL-1β. (B) Gene expression of IL-6. Reproduced with permission from [83]. Copyright © 2013 Published by Elsevier Ltd.

Figure 4

Multiple typical forms of SF as a functional biomaterial for bone tissue engineering (BTE): (A) Film; (B) Nanoparticle; (C) Hydrogel; (D) Sponge; (E) Nanofiber; (F) 3D-printed scaffold.

Figure 5

The capacity of SF/HAP/GPM scaffolds for osteogenesis. (A) The ALP activities of MC3T3-E1 cells on SF-based scaffolds for 7, 14, or 21 days. (B) The expression levels of ATF4, p-Akt, Akt, p-ERK1/2, ERK1/2, RUNX2, and OCN in MC3T3-E1 cells cultured on SF, SF/HAP, and SF/HAP/GPM scaffolds for 14 days. (C,D) The expression levels of RUNX2 and OCN on SF, SF/HAP, and SF/HAP/GPM scaffolds were measured by qRT-PCR. (E) Reconstructed micro-CT images of calvarial deficiencies following implantation of SF, SF/HAP, and SF/HAP/GPM scaffolds for 4, 8, 12 and 16 weeks. (F,G) Histological sections of control, SF, SF/HAP, and SF/HAP/GPM scaffolds were stained with H&E and Masson’s trichrome after 4 and 12 weeks of implantation. * p < 0.05 and ** p < 0.01. Reproduced with permission from [146]. Copyright © 2019 Ivyspring International Publisher.