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 b...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 thymosinβ4 protein-derived metabolites to pioneer novel applications for peptide metabolites in biomaterials.This study found that the novel peptide metabolite acetyl-thymosinβ4(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.展开更多
Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices.Inspired by the role of galectin-1(Gal-1)in selective functions on...Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices.Inspired by the role of galectin-1(Gal-1)in selective functions on multiple cells and immunomodulatory processes,we prepared a biologically target-specific surface coated with the lipid bilayer containing Gal-1(Gal-1-SLB)and investigate the proof of the biological effects.First,lipoamido-dPEG-acid was deposited on a gold-coated substrate to form a self-assembled monolayer and then conjugated dioleoylphosphatidylethanolamine(DOPE)onto that to produce a lower leaflet of the supported lipid bilayer(SLB)before fusing membrane-derived vesicles extracted from B16-F10 cells.The Gal-1-SLB showed the expected anti-fouling activity by revealing the resistance to protein adsorption and bacterial adhesion.In vitro studies showed that the Gal-1-SLB can promote endothelial function and inhibit smooth muscle cell proliferation.Moreover,Gal-1-SLB presents potential function for endothelial cell migration and angiogenic activities.In vitro macrophage culture studies showed that the Gal-1-SLB attenuated the LPS-induced inflammation and the production of macrophage-secreted inflammatory cytokines.Finally,the implanted Gal-1-SLB reduced the infiltration of immune cells at the tissue-implant interface and increased markers for M2 polarization and blood vessel formation in vivo.This straightforward surface coating with Gal-1 can be a useful strategy for modulating the vascular and immune cells around a blood-contacting device.展开更多
基金supported by the National Research Foundation(NRF)grant funded by the Korean government(NRF-2021K1A3A1A74095929,NRF-2021R1A2C2092375)a Korea Research Council(NRF-2022M3H4A1A0407327112)+1 种基金the intramural grant from the Korea Institute of Science and Technology(Grand Challenge,2Z07012 and Open Research Program,2E33311)Korea National University of Science and Technology grant 2021YS16.
文摘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 thymosinβ4 protein-derived metabolites to pioneer novel applications for peptide metabolites in biomaterials.This study found that the novel peptide metabolite acetyl-thymosinβ4(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.
基金supported by grants the Nano Material Technology Development Program(NRF-2021M3H4A1A04092879)through the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICTthe Materials and Parts Technology Development Program(20023353)Advanced Technology Center(ATC+,20017939)funded by the Ministry of Trade,Industry&Energy(MOTIE,Korea).
文摘Modulating inflammatory cells in an implantation site leads to severe complications and still unsolved challenges for blood-contacting medical devices.Inspired by the role of galectin-1(Gal-1)in selective functions on multiple cells and immunomodulatory processes,we prepared a biologically target-specific surface coated with the lipid bilayer containing Gal-1(Gal-1-SLB)and investigate the proof of the biological effects.First,lipoamido-dPEG-acid was deposited on a gold-coated substrate to form a self-assembled monolayer and then conjugated dioleoylphosphatidylethanolamine(DOPE)onto that to produce a lower leaflet of the supported lipid bilayer(SLB)before fusing membrane-derived vesicles extracted from B16-F10 cells.The Gal-1-SLB showed the expected anti-fouling activity by revealing the resistance to protein adsorption and bacterial adhesion.In vitro studies showed that the Gal-1-SLB can promote endothelial function and inhibit smooth muscle cell proliferation.Moreover,Gal-1-SLB presents potential function for endothelial cell migration and angiogenic activities.In vitro macrophage culture studies showed that the Gal-1-SLB attenuated the LPS-induced inflammation and the production of macrophage-secreted inflammatory cytokines.Finally,the implanted Gal-1-SLB reduced the infiltration of immune cells at the tissue-implant interface and increased markers for M2 polarization and blood vessel formation in vivo.This straightforward surface coating with Gal-1 can be a useful strategy for modulating the vascular and immune cells around a blood-contacting device.
