Fibroin-Hybrid Systems: Current Advances in Biomedical Applications

Abstract

Fibroin, a protein extracted from silk, offers advantageous properties such as non-immunogenicity, biocompatibility, and ease of surface modification, which have been widely utilized for a variety of biomedical applications. However, in vivo studies have revealed critical challenges, including rapid enzymatic degradation and limited stability. To widen the scope of this natural biomacromolecule, the grafting of polymers onto the protein surface has been advanced as a platform to enhance protein stability and develop smart conjugates. This review article brings into focus applications of fibroin-hybrid systems prepared using chemical modification of the protein with polymers and inorganic compounds. A selection of recent preclinical evaluations of these hybrids is included to highlight the significance of this approach.

Keywords: biomedical applications; chemical modification; hybrid system; silk fibroin; surface-grafting polymerization.

Figure 1

Publications search analysis based on the Scopus^® database records using the keywords: fibroin nanoparticles (A) and fibroin hybrid (B).

Figure 2

Schematic representation of fibroin-based hybrid systems with emphasis on two main categories: polymer- and inorganic-hybrid systems. Key applications include tissue engineering, drug delivery, and gene therapy, with challenges such as enzymatic degradation and limited stability.

Figure 3

General procedure for fibroin isolation. The raw silk cocoons are boiled in a solution of sodium carbonate to remove sericin (S₁), and the silk fibers are dissolved in a highly concentrated solution, such as lithium bromide or Ajisawa’s reagent, to break down the fibers into a fibroin solution (S₂). The fibroin solution is dialyzed against distilled water to remove the solvent and any other small molecules (S₃), resulting in a purified fibroin solution, and at the end of the process, the solution is centrifuged (S₄) to remove any remaining impurities.

Figure 4

Scheme for the synthesis of fibroin-polyaniline (PAni) hybrid. Reproduced and adapted with permission from [82].

Figure 5

Cell viability (%) of NIH/3T3 fibroblast cells after exposure to various concentrations of Fib-g-PAni (1:05 and 1:1 mass ratios), Fib-NH₂, and polyaniline (PAni). The results demonstrate dose-dependent cytotoxicity, with Fib-g-PAni showing higher cell viability compared to pure PAni at similar concentrations, indicating improved biocompatibility due to the incorporation of fibroin. Reproduced and adapted with permission from [82].

Figure 6

Preclinical evaluation of different therapeutic systems applied to control three main phenotypic psoriatic activities (erythema, thickness, and scaling) in an imiquimod-induced psoriatic mouse model. Different treatment and control groups were constituted as follows: Group 1 (Normal untreated mice); Group 2 (IMQ-induced psoriatic mice); Group 3 (Blank NPs-gel treatment); Group 4 (CUR-gel treatment); Group 5 (CUR-NPs-gel treatment); Group 6 (Clobetasol treatment as the positive control group). (A) Representative images of skin conditions: Normal skin, IMQ-induced psoriatic skin, and skin after treatment with various formulations. (B) PASI scoring of psoriatic skin over 10 days of treatment: (a) Erythema scores comparing control, normal, CUR-gel, CUR-NPs-gel, and clobetasol treatments; (b) Thickness scores for the same treatment groups; (c) Scaling scores across treatment groups. Data are expressed as Mean ± SD (n = 12) Reproduced with permission [89].

Figure 7

Scheme for the synthesis of the hybrid system. (A) Phosmer M reacts with silk fibroin, with tyrosine serving as the preferential reaction site; (B) grafting of a Phosmer M molecule onto the tyrosine side chain of silk fibroin; (C) and (D) subsequent polymerization. Reproduced and adapted with permission from supplementary material in [85].

Figure 8

Octreotide concentration profile in rat plasma after intramuscular injection. (a) elevated dose group (8 mg/kg), (b) reduced dose group (2 mg/kg), (c) blank octreotide group at reduced dose. Reproduced with permission [99].

Figure 9

Assessment of wound healing: (A) Illustrative images of the wound area versus various gel groups and (B) calculated remaining wound area for different groups on days 0, 7, and 14, respectively (n = 4) (* p < 0.05; ** p < 0.01; *** p < 0.001). Reproduced with permission [107].