Silk Fibroin Cryogel Building Adaptive Organohydrogels with Switching Mechanics and Viscoelasticity

Abstract

In contrast to synthetic gels, their biological counterparts such as cells and tissues have synergistic biphasic components containing both hydrophilic and lyophilic phases, providing them some special abilities including adaptive biomechanics and freezing tolerance. Hydrogels containing both hydrophilic and lyophilic phases, referred to as organohydrogels (OHGs), are capable of mimicking the biological systems, and they might have great potential in various applications. Here, we present a facile strategy to obtain adaptive OHGs with tunable and programmable mechanics and viscoelasticity. We utilize a hydrophilic cryogel scaffold as the continuous phase of OHGs, while the pores of the scaffold act as the reaction loci for the formation of organogel microinclusions. Thus, we first prepared mechanically robust cryogels based on silk fibroin (SF) via cryogelation reactions at −18 °C. The cryogels with 94% porosity containing interconnected μm-sized pores were then immersed in an ethanolic solution of acrylic acid (AAc), n-octadecyl acrylate (C18A), N,N′-methylenebis­(acrylamide), and a free-radical initiator. Polymerization reactions conducted within the pores of the cryogels lead to mechanically strong adaptive OHGs consisting of a SF scaffold containing semi-crystalline poly­(AAc-co-C18A) organogel microinclusions. The mechanical strength of OHGs is much higher than that of their components due to the significant energy dissipation in the OHG networks. Depending on the amount of the crystallizable C18A monomer units, the melting temperature T m and the degree of crystallinity of OHGs could be varied between 49 and 54 °C and 1.3 and13%, respectively. The crystallinity created in OHGs provided them switchable mechanics and viscoelasticity in response to a temperature change between below and above T m. All OHGs exhibited shape-memory function with a shape-recovery ratio of more than 92%. The strategy developed here to obtain high-strength smart OHGs is suitable for a wide variety of combinations of hydrophilic scaffolds and organogels.

Designing Silk-Based Cryogels for Biomedical Applications

“…In addition to the traditional β-sheet formation of SF, chemical and/or surface modifications of SF prior to cryogelation have also been investigated recently. Yetiskin et al [ 48 ] used methacrylated SF (met-SF), instead of pure SF for the cryogel preparation to improve the stretchability and toughness of the cryogels. In their study, glycidyl methacrylate is used for the methacrylation of SF in an aqueous LiBr solution [ 49 ].…”

“…Compared to pure scaffolds, the composites have a rough surface, enlarged pore size, and a six-fold increase in compression modulus. Unlike the composite studies described above, Yetiskin et al [ 48 ] have combined the concepts of a DN strategy and composite material by polymerizing acrylic acid and octadecyl acrylate in the pores of SF cryogel. They produced a cryogel with met-SF in the presence of BDDE at −18 °C.…”

“…Therefore, currently, some biomedical applications might be out of reach for silk-based cryogels. Similarly, injectable silk-based cryogels need to be improved in terms of their potential stimuli responsiveness using triggers such as oxygen [ 97 ], pH [ 98 ], and temperature [ 48 ] that could propel applications in immunotherapy and cancer treatments. In addition, the use of oxygen-releasing silk cryogels could aid in wound healing applications when combined with improvements in cell adhesion and antimicrobial activity by the use of various silk nanocomposites [ 16 ].…”

Silk Fibroin-Based Shape-Memory Organohydrogels with Semicrystalline Microinclusions

“…Similarly, antifreezing, conductive, self-healing OHGs were prepared by physical cross-linking of aqueous poly­(vinyl alcohol) solutions containing an antifreezing binary solvent system . Recently, cryogelation technology was used by Yetiskin et al to create OHGs with switching mechanics and viscoelasticity . They utilized a mechanically robust hydrophilic cryogel scaffold based on silk fibroin (SF) as the continuous phase of OHG, while the macropores of the scaffold acted as the reaction loci for the formation of organogel microinclusions.…”

“… 19 Recently, cryogelation technology was used by Yetiskin et al to create OHGs with switching mechanics and viscoelasticity. 20 They utilized a mechanically robust hydrophilic cryogel scaffold based on silk fibroin (SF) as the continuous phase of OHG, while the macropores of the scaffold acted as the reaction loci for the formation of organogel microinclusions. Another strategy is to prepare emulsion-based OHGs by dispersing hydrophobic monomer droplets and/or alkanes in a continuous aqueous phase containing hydrophilic monomers and an emulsion stabilizer such as surfactants, followed by polymerization.…”