CHAPTER 11: Ultrashort Tetrameric Peptide Nanogels Support Tissue Graft Formation, Wound Healing and 3D Bioprinting

Tissue engineering is a promising alternative to organ transplantation, where the number of waiting patients is not supported by the number of available donors. Tissue engineering aims to fabricate functional tissue using biocompatible scaffolds. Nanogels made from self-assembling ultrashort peptides are promising scaffold biomaterials. We focus on two compounds of a novel class of rationally designed tetrameric peptides for biomedical applications that have the advantage of being natural but synthetic hydrogels. These compounds have an innate tendency to self-assemble into nanofibrous hydrogels, which can be used for the fabrication of three-dimensional (3D) skin grafts, treating full-thickness wounds in minipigs and skeletal muscle tissue proliferation and differentiation. We were able to produce in situ silver nanoparticles within the peptide nanogels, solely through ultraviolet irradiation, with no reducing agent present. Applying the peptide nanogels on full-thickness minipig wounds demonstrated that the scaffolds were biocompatible, with no notable wound inflammation, and comparable to standard care solutions. Interestingly, the peptide scaffolds revealed a high potential to act as antibacterial agents. Microscopic observation demonstrated the ability of human umbilical vein endothelial cells to form tube-like structures within peptide nanogels. Moreover, we successfully produced artificial 3D vascularized skin substitutes using these peptide scaffolds. Additionally, we could demonstrate that both tetrameric peptides support 3D bioprinting, indicating their possible use as future bioinks. We believe that the results described represent an advancement in the context of engineering skin and skeletal muscle tissue, thereby providing the opportunity to rebuild missing, failing, or damaged parts.