Protein to biomaterials: Unraveling the antiviral and proangiogenic activities of Ac-Tβ_1-17 peptide, a thymosin β4 metabolite, and its implications in peptide-scaffold preparation

Peptide metabolites are emerging biomolecules with numerous possibilities in biomaterial-based regenerative medicine due to their inherent bioactivities. These small, naturally occurring compounds are intermediates or byproducts of larger proteins and peptides, and they can have profound effects, such as antiviral therapeutics, proangiogenic agents, and regenerative medicinal applications. This study is among the first to focus on using thymosin β4 protein-derived metabolites to pioneer novel applications for peptide metabolites in biomaterials. This study found that the novel peptide metabolite acetyl-thymosin β4 (amino acid 1–17) (Ac-Tβ_1-17) exhibited significant protease inhibition activity against SARS-CoV-2, surpassing its precursor protein. Additionally, Ac-Tβ_1-17 demonstrated beneficial effects, such as cell proliferation, wound healing, and scavenging of reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVEC). Integrating Ac-Tβ_1-17 into a peptide-based scaffold facilitated cell growth and angiogenesis inside the scaffold and through gradual release into the surrounding environment. The Ac-Tβ_1-17 peptide treatment induced significant biochemical responses in HUVEC, increasing Akt, ERK, PI3K, MEK, and Bcl-2 gene expression and proangiogenic proteins. Ac-Tβ_1-17 peptide treatment showed similar results in ex vivo by enhancing mouse fetal metatarsal growth and angiogenesis. These findings highlight the potential of natural protein metabolites to generate biologically active peptides, offering a novel strategy for enhancing biomaterial compatibility. This approach holds promise for developing therapeutic biomaterials using peptide metabolites, presenting exciting prospects for future research and applications.