Novel Nanofibrous Peptide Scaffolds for Tissue Regeneration

Abstract

A huge discrepancy between the number of patients on the waiting list for organ transplants and the actual available donors has led to search for alternative approaches to substitute compromised or missing tissues and organs. Tissue engineering is a promising alternative to organ transplantation with the aim to fabricate functional organs through the use of biological or biocompatible scaffolds. Nanogels made from self-assembling ultrashort peptides are promising biomaterials for a variety of biomedical applications. Our group at KAUST is interested in the development of novel synthetic peptide-based biomaterials that combine the advantages of both natural and synthetic hydrogels for various applications. In this study, we have investigated two compounds of a novel class of rationally designed ultrashort peptides, Ac-IVFK-NH2 (Ac-Ile-Val-Phe-Lys-NH2) and Ac-IVZK-NH2 (Ac-Ile-Val-Cha-Lys-NH2). These compounds have an innate tendency to self-assemble into nanofibrous hydrogels which can be used as 3D scaffolds, for example for the fabrication of 3D skin grafts for wound healing. We have evaluated the efficacy of the peptide scaffolds in treating full-thickness wounds in minipigs. Additionally, we assessed the ability of these scaffolds in supporting skeletal muscle tissue proliferation and differentiation. We found that our innovative nanogels supported a substantial increase in human dermal fibroblast and myoblast growth and cells viability, and supported myoblast differentiation. Also, microscopic observation of the direct contact of keratinocytes and fibroblasts revealed enhancement in keratinocytes proliferation. In addition, we demonstrated the ability of human umbilical vein endothelial cells to form tube like structure within peptide nanogels using immunofluorescence staining. Moreover, we successfully produced artificial 3D vascularized skin substitutes using these peptide scaffolds. We selected these peptide nanogels and were able to produce in situ silver nanoparticles within the nanogels, solely through UV irradiation, with no reducing agent present. We then assessed the efficacy of the silver nanoparticle-containing peptide nanogels on minipigs with full-thickness excision wounds. The application of the peptide nanogels on full thickness minipig wounds demonstrated that the scaffolds were biocompatible and did not trigger wound inflammation, and thus safe for topical application. The effect of nanogels, both with and without the addition of the silver nanoparticles, revealed that the scaffold itself has a high potential to act as an antibacterial agent. Interestingly, the effect of the peptide nanogels on wound closure was comparable to that of standard care hydrogels. Furthermore, we have demonstrated that both peptides can act as printable bioinks which opens up the possibility of 3D bioprinting of different cell types in the future. We believe that the described results represent an advancement in the context of engineering skin and skeletal muscle tissue, thereby providing the opportunity to rebuild missing, failing, or damaged parts.