Highly Angiogenic Peptide Nanofibers

Abstract

Major limitations of current tissue regeneration approaches using artificial scaffolds are fibrous encapsulation, lack of host cellular infiltration, unwanted immune responses, surface degradation preceding biointegration, and artificial degradation byproducts. Specifically, for scaffolds larger than 200 500 μm, implants must be accompanied by host angiogenesis in order to provide adequate nutrient/waste exchange in the newly forming tissue. In the current work, we design a peptide-based self-assembling nanofibrous hydrogel containing cell-mediated degradation and proangiogenic moieties that specifically address these challenges. This hydrogel can be easily delivered by syringe, is rapidly infiltrated by cells of hematopoietic and mesenchymal origin, and rapidly forms an extremely robust mature vascular network. scaffolds show no signs of fibrous encapsulation and after 3 weeks are resorbed into the native tissue. These supramolecular assemblies may prove a vital paradigm for tissue regeneration and specifically for ischemic tissue disease.

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

“…Having established these key chemical and biomechanical facets, future studies in sophisticated in vivo cancer models can now be envisioned. These syringe-deliverable constructs may help a variety of strategies that allow localized drug delivery, 34 complemented by functional peptide signaling, 33 that ultimately offer another tool for targeted therapeutics.…”

Harnessing supramolecular peptide nanotechnology in biomedical applications

“…Another multidomain peptide, ie, KK(SL) 7 KK, has also been tested along with the following three other analogs: 1) K(SL) 2 SLRG(SL) 3 K that possesses an enzyme cleavage site, 2) K(SL) 2 SLRG(SL) 3 KGRGDS that possesses both an enzyme cleavage site and a cell adhesion motif, and 3) K(SL) 2 SLRG(SL) 3 KGKLTWQELYQLKY KGI that possesses both an enzyme cleavage site and the VEGF mimic. 66 The cleavage enzyme site was incorporated as a way for the body to gradually break down the hydrogel so that new tissue can take the place of the hydrogel. Unsurprisingly, multidomain peptide decorated with the VEGF mimic promoted angiogenesis to the greatest extent.…”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Further work has aimed to enhance the angiogenic capacity of self-assembling peptides. Kumar et al, for instance, developed a peptide sequence that incorporates a VEGF-165 mimicking peptide that enhanced angiogenesis in vivo without the need for delivery of exogenous GFs (Kumar et al, 2015). A drawback for many of these studies is that material injection must occur directly into the myocardium via an open chest procedure as the material gels instantly once exposed to native pH and osmolarity.…”