Versatile Mitogenic and Differentiation‐Inducible Layer Formation by Underwater Adhesive Polypeptides

Abstract

Artificial materials have no biological functions, but they are important for medical devices such as artificial organs and matrices for regenerative medicine. In this study, mitogenic and differentiation‐inducible materials are devised via the simple coating of polypeptides, which contain the sequence of epidermal growth factor or insulin‐like growth factor with a key amino acid (3,4‐dihydroxyphenylalanine) of underwater adhesive proteins. The adhesive polypeptides prepared via solid‐phase synthesis form layers on various substrates involving organic and inorganic materials to provide biological surfaces. Through the direct activation of cognate receptors on interactive surfaces, the materials enable increased cell growth and differentiation compared to that achieved by soluble growth factors. This superior growth and differentiation are attributed to the long‐lasting signal transduction (triggered by the bound growth factors), which do not cause receptor internalization and subsequent downregulation.

Photo-reactive polymers for the immobilisation of epidermal growth factors

“…Compared with soluble EGF, immobilised EGF enhanced the cell growth through multivalent stimulation, high local concentrations in the area of interaction between cell and substrate, and by inhibiting the down-regulation of EGF receptors in cells. 15,26,31 The matrix polymers significantly affected the growth enhancement. In the presence of soluble EGF, AB-gelatin was the most effective, followed by B-gelatin.…”

“…Insulin, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were immobilised to increase the mitogenic responses, and bone morphogenic protein (BMP) and insulin-like growth factor-1 (IGF-1) were immobilised to induce cell differentiation. 15,16,24–26 Immobilised GFs and bioactive molecules have been extensively used for a variety of purposes; for example, immobilised transforming growth factor-beta1 has been used in collagen synthesis 27 and the immobilised leukaemia inhibitory factor has been used for maintaining the undifferentiated state of stem cells. 28…”

“…Insulin, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) were immobilised to increase the mitogenic responses, and bone morphogenic protein (BMP) and insulinlike growth factor-1 (IGF-1) were immobilised to induce cell differentiation. 15,16,[24][25][26] Immobilised GFs and bioactive molecules have been extensively used for a variety of purposes; for example, immobilised transforming growth factor-beta1 has been used in collagen synthesis 27 and the immobilised leukaemia inhibitory factor has been used for maintaining the undifferentiated state of stem cells. 28 Among the various promising methods for GF immobilisation and photo-immobilisation, a technique using polymers containing photo-reactive groups, is advantageous in immobilising biomolecules using simple photochemistry and visualisation of GF stimulation through micro-patterning by lithography.…”

An osteoinductive surface by adhesive bone morphogenetic protein-2 prepared using the bioorthogonal approach for tight binding of titanium with bone

“…[29][30][31] Therefore, a peptide containing both DOPA and lysine was incorporated into several polypeptides, which were then used as active forms of monomers for preparing growth factors capable of adhering to inorganic or organic materials. [32][33][34][35][36][37] However, dimer formation is essential for BMP-2 to exhibit its biological activity. 10,11,38 Although various approaches have been tested, the process of preparing biologically active BMP-2 dimers remains challenging.…”

Ternary Synergy of Lys, Dopa, and Phe Results in Strong Cohesion of Peptide Films

“…l -3,4-Dihydroxyphenylalanine (Dopa, Y*), a hydroxylated amino acid of tyrosine, has been identified as a key chemical motif for underwater attachment capacities of marine organisms, including mussels and sandcastle worms. − Numerous Dopa-based underwater adhesives (polymers and proteins) have been produced through chemical synthesis and recombinant protein productions. , Researchers also have developed abundant peptide-based underwater adhesives containing Dopa due to their simple structure, easy production, and excellent biocompatibility. − For example, Zhang et al have designed a series of hydrogels modified with a sandcastle worm-inspired dibutylamine-Dopa-lysine-Dopa tripeptide, which can be used for cell adhesion and wound repair . In recent studies, the synergistic interplay of Dopa and cationic residues (lysine and arginine) in improving underwater adhesion has been highlighted. ,,− Flanking lysine (Lys, K) residues can enhance adhesive forces of Dopa on mica surfaces but disrupt the adhesive interactions between Fe 3+ and Dopa because of the electrostatic repulsion between Fe 3+ and lysine .…”