Self‐Assembly of Thermoresponsive Recombinant Silk‐Elastinlike Nanogels

Abstract

strength to SELPs, while elastin units provide lower critical solution temperature (LCST)-based elastomeric activity. [2,3] The LCST behavior induces a disorder-to-order transition that renders SELPs a viable option for macroscale applications such as temperature-induced liquid-to-solid transarterial chemoembolics, [4,5] in situ gelling enemas, [6] localized hydrogel drug and adenovirus release matrices, [7,8] 3D tissue engineering scaffolds, [9] and crosslinked protein films. [10] The ratio and sequence of silk and elastin motifs allows for a high degree of control over gelation properties and material strength. [11] Furthermore, responsive peptide sequences can be inserted into the poly mer backbone to achieve biodegradation and controlled release. [12] While SELP hydrogels have been extensively investigated for controlled delivery of bioactive agents, very limited research involving the design and development of SELP nanoparticles has been accomplished. Recent work reports the use of self-assembly techniques to achieve micelle formation with SELPs with drug-loading capabilities, [13,14] controlling size via silk-to-elastin ratio. [15] When SELPs with His tags were used to coat nickel-functionalized plasmonic gold nanoparticles, hexamer number proved highly influential on overall particle size. [16] These SELP-coated nanoparticles exhibited reversible, thermally induced aggregation, allowing for a thermal on-off switch between individual and collective plasmon resonances. Self-assembly of SELPs has also been accomplished for nanofiber formation, using both surfaceinduced and nanomechanical stimuli. [17,18] It was shown that the formation frequency of sphere-like aggregates over nanofibers increased with increasing solvent ionic strength. [17] Optimization of silk and elastin block lengths resulted in a core-sheath nanofiber structure (silk in the core, elastin in the sheath). [19] While self-assembly and design techniques have allowed for the creation of micelle-like, coated nanoparticle, and nanofiber structures, cases of self-assembled, physically crosslinked SELP nanogels have yet to be reported. Nanogels are nanoscale polymer networks bound together via crosslinks between individual polymer chains and differ substantially from other nanoparticle structures, such as micelles (Figure 1a). Crosslinks can be formed via covalent or physical bonds and provide overall structural stability. [20] In drug delivery, nanogel systems have been shown to achieve high drug loading efficiency (up to 30 wt%), often outcompeting Silk-Elastinlike Protein NanogelsRecombinant silk-elastinlike protein polymers (SELPs) combine the biocompatibility and thermoresponsiveness of human tropoelastin with the strength of silk. Direct control over structure of these monodisperse polymers allows for precise correlation of structure with function. This work describes the fabrication of the first SELP nanogels and evaluation of their physicochemical properties and thermoresponsiveness. Self-assembly of dilute concentrations of SELPs results...

Structure–Property Relationships of Elastin-like Polypeptides: A Review of Experimental and Computational Studies

“…Silk-elastin-like polypeptides (SELPs) combine the stiffness and tensile strength of the crystalline domain of silk (usually using the GAGAGS motif) with the elasticity and water solubility of ELPs. SELPs display the LCST behavior characteristic of ELPs and have been used to synthesize nanoparticles, fibers, , free-standing or injectable hydrogels, , or films (Figure b,c) for applications including tissue scaffolds, drug and gene carriers, − or as transfer devices for organoids …”

Genetically Fusing Order‐Promoting and Thermoresponsive Building Blocks to Design Hybrid Biomaterials

“…[168] All SELPs underwent thermally triggered self-assembly and increased capacity for encapsulation of a hydrophobic fluorescent molecule (8-anilino-1-naphthalenesulfonic acid ammonium salt, 1,8-ANS) in the assembled state (Figure 6 d-g). [168] SEM micrographs highlighted that all SELP variants can self-assemble into stable protein-based nanogels beyond a critical concentration (Figure 6 h-k). The structural integrity, governed by physical crosslinking in silk regions, allows the elastin domains to modulate nanogel size in response to temperature fluctuations.…”

Trends in the design and use of elastin-like recombinamers as biomaterials

“…Furthermore, it is also noteworthy the increasing number of works describing the combination of ELRs with other polymers or structural proteins, giving blends or biohybrids that recapitulate the properties of all the components. The first, and probably the most exploited blend, came from the recombinant fusion of ELRs with silk-like domains to give silk-elastin-like recombinamers (SELRs) that are able to form fibers and hydrogels, among other structures, whose stability relies on the β-sheet cross-linking between silk-like motifs [8,71,[121][122][123]. Collagen-like peptides have also been explored as partners of ELRs in a recombinant way [124], even achieving nanoplatelets [125].…”