Click chemistry functionalization of self‐assembling peptide hydrogels

Abstract

Self‐assembling peptide (SAP) hydrogels provide a fibrous microenvironment to cells while also giving users control of biochemical and mechanical cues. Previously, biochemical cues were introduced by physically mixing them with SAPs prior to hydrogel assembly, or by incorporating them into the SAP sequence during peptide synthesis, which limited flexibility and increased costs. To circumvent these limitations, we developed “Click SAPs,” a novel formulation that can be easily functionalized via click chemistry thiol‐ene reaction. Due to its high cytocompatibility, the thiol‐ene click reaction is currently used to crosslink and functionalize other types of polymeric hydrogels. In this study, we developed a click chemistry compatible SAP platform by addition of a modified lysine (lysine‐alloc) to the SAP sequence, enabling effective coupling of thiol‐containing molecules to the SAP hydrogel network. We demonstrate the flexibility of this approach by incorporating a fluorescent dye, a cellular adhesion peptide, and a matrix metalloproteinase‐sensitive biosensor using the thiol‐ene reaction in 3D Click SAPs. Using atomic force microscopy, we demonstrate that Click SAPs retain the ability to self‐assemble into fibers, similar to previous systems. Additionally, a range of physiologically relevant stiffnesses can be achieved by adjusting SAP concentration. Encapsulated cells maintain high viability in Click SAPs and can interact with adhesion peptides and a matrix metalloproteinase biosensor, demonstrating that incorporated molecules retain their biological activity. The Click SAP platform supports easier functionalization with a wider array of bioactive molecules and enables new investigations with temporal and spatial control of the cellular microenvironment.

In situ stimulus-responsive self-assembled nanomaterials for drug delivery and disease treatment

“…Peptide vaccines with Amp can self-assemble into peptide NFs, which have a fibrillar structure that plays a crucial role in regulating cell-matrix interactions affecting cell adhesion, migration, proliferation, and in vivo drug response. 23 Compared to the peptide NP vaccine, the retention time of the peptide NF vaccine in dendritic cells is prolonged, leading to cell maturation, accumulation in lymph nodes, T cells infiltrating into tumor tissue, thus realizing the immune response of the peptide vaccine. 45 NPs are typically neutral or negatively charged under a normal physiological environment, and thus remain stable in the bloodstream and are not taken up by macrophages.…”

“…This reaction makes new cellular microenvironment models have higher spatiotemporal complexity and flexibility than previously feasible. 23 In the last two decades, a plethora of studies on molecular self-assembly have led to a deeper understanding of the basic principles and established the relationship between the structure and function of self-assembled systems. In situ selfassembly based on peptides has been widely discussed, [24][25][26][27] but this method is not limited to peptides, as other nanomaterials such as polymers, 28 small molecule prodrugs, 29 inorganic metals, 30 and nucleic acids 31,32 can also self-assemble.…”

“…This reaction makes new cellular microenvironment models have higher spatiotemporal complexity and flexibility than previously feasible. 23…”

Tissue engineering modalities in skeletal muscles: focus on angiogenesis and immunomodulation properties

“…In a similar study, the encapsulation of C2C12 myoblasts in the hyaluronic acid-based hydrogel with modulus similar to skeletal muscle tissue increased innervation, vascularization, and functional restoration of muscle tissue in the volumetric muscle loss animal model (Fig. 1 ) [ 218 ].…”

“…One-way ANOVA analysis with Tukey test; * p < 0.05. Adapted from [ 218 ]. (2021; Bioactive Materials; https://doi.org/10.1016/j.bioactmat.2020.10.012 ) …”