Biomimetic peptide conjugates as emerging strategies for controlled release from protein-based materials

Abstract

Biopolymers, such as collagens, elastin, silk fibroin, spider silk, fibrin, keratin, and resilin have gained significant interest for their potential biomedical applications due to their biocompatibility, biodegradability, and mechanical properties. This review focuses on the design and integration of biomimetic peptides into these biopolymer platforms to control the release of bioactive molecules, thereby enhancing their functionality for drug delivery, tissue engineering, and regenerative medicine. Elastin-like polypeptides (ELPs) and silk fibroin repeats, for example, demonstrate how engineered peptides can mimic natural protein domains to modulate material properties and drug release profiles. Recombinant spider silk proteins, fibrin-binding peptides, collagen-mimetic peptides, and keratin-derived structures similarly illustrate the ability to engineer precise interactions and to design controlled release systems. Additionally, the use of resilin-like peptides showcases the potential for creating highly elastic and resilient biomaterials. This review highlights current achievements and future perspectives in the field, emphasizing the potential of biomimetic peptides to transform biopolymer-based biomedical applications.

Keywords: Peptide; bioconjugation; biomimetic; collagen; elastin; fibrin; keratin; resilin; silk fibroin; spider silk.

Graphical abstract

Figure 1.

Schematic representation of biomimetic peptides discussed in this review. (Figure created using BioRender.com).

Figure 2.

Example plasmid for production of biomimetic peptide conjugates in bacteria. RBS: ribosome-binding site; MBP: maltose-binding protein; TEV: tobacco etch virus protease site; ori: origin of replication; ROP: repressor of primer.

Figure 3.

Collagen structure and its interactions with collagen-mimetic peptides (CMPs). (A) The hierarchical structure of collagen. (B) A collagen scaffold containing a bioactive protein tagged with a CMP. The CMP interacts with the scaffold’s collagen. (Figure created using BioRender.com).

Figure 4.

Elastin structure and elastin-like peptide-based protein carriers. (A) Elastin contains alternating hydrophobic and hydrophilic domains that tend to adopt β-turns and α-helices, respectively. Lysine residues can be crosslinked by lysyl oxidase to form elastin fibers. (B) The ELP structure mimics elastin repeats and undergoes reversible self-assembly to form micelles for the controlled release of a protein. (Figure created using BioRender.com).

Figure 5.

Silk fibroin structure and its interactions with silk fibroin-mimetic peptides (SFMPs) within a scaffold. (A) The structure of silk fibroin, featuring crystalline anti-parallel β-sheets and amorphous linkers. The sequence of SF repeating units typically used for biomimetic design is shown. (B) The interactions of SFMP-tagged bioactive molecules with the crystalline domains of SF are key to sustaining the release of these molecules. (Figure created using BioRender.com).

Figure 6.

Schematic representation of recombinant spider silk and its functional applications. (A) The structure of eADF4 (C16) and spidroins. (B) Interactions of eADF4 (C16)-tagged bioactive molecules within a spider silk-based hydrogel, highlighting its potential for biomedical applications. (Figure created with BioRender.com).

Figure 7.

From fibrinogen to fibrin to film: Structural and biochemical transitions. (A) The structure of fibrinogen, composed of two sets of three polypeptide chains (Aα, Bβ, and γ) with fibrinopeptide cleavage sites located at N-termini. These cleavage sites are essential for the activation of fibrin formation. (B) Fibrin formation mediated by factor XIII crosslinking, which stabilizes the fibrin network and facilitates its conversion into a stable film. (Figure created with BioRender.com).

Figure 8.

Schematic representation of keratin structures and their biomaterial applications. (A) The coiled-coil structure of α-keratin and its fabrication into various biomaterial forms, highlighting its mechanical properties and versatility. (B) The pleated β-sheet structure of β-keratin, emphasizing its role in providing rigidity and structural stability. (Figure created with BioRender.com).

Figure 9.

Schematic representation of the structure of resilin from Drosophila melanogaster. (Figure created using BioRender.com).