Drug-Triggered and Cross-Linked Self-Assembling Nanofibrous Hydrogels

Abstract

Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G′ and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype.

Treatment of hind limb ischemia using angiogenic peptide nanofibers

“…Similar to this study, and previously published work, the ability for MDP to rapidly infiltrate cells creates a niche for the rapid (within 7 days) development of mature SMC lined microvessels. Second, the propensity for multidomain peptides to stimulate a biocompatible host-response that is characterized by rapid cellular infiltration, lack of fibrous encapsulation and deposition of host tissue ECM [17–19]. This further bolsters the ability for host-implant communication and potentiation of continued angiogenic signaling.…”

Ag-loaded thermo-sensitive composite microgels for enhanced catalytic reduction of methylene blue

“…The beauty of these materials is its smart behavior; that is, we can tune the properties of metal nanoparticles by changing the properties of polymer network with external stimuli before or during the process of reduction, e.g., temperature [22][23][24], pH [25][26][27], ionic strength [28,29]. In current years, many investigators have a great interest in the field of stimulus-responsive composite systems composed of continuous organic and dispersed inorganic phase [30] for different applications, e.g., drug delivery [31][32][33], sensors [34,35], electrical [36], catalysis [37][38][39].…”

Controlled Angiogenesis in Peptide Nanofiber Composite Hydrogels

“…28,29 The MDP in this study, termed SLac, has a sequence of KSLSLSLRGSLSLSLKGRGDS. 18,20,21 It contains a cell adhesion fibronectin-derived (RGD) moiety promoting infiltration.…”