Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial c...Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues.Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze–drying of collagen suspensions,followed by chemical cross-linking which maintains their stability.However,cross-linking scaffolds renders their biological activity suboptimal for many cell types,including human umbilical vein endothelial cells(HUVECs),by inhibiting cell–collagen interactions.Here,we have improved crucial HUVEC interactions with such cross-linked collagen biomaterials by covalently coupling combinations of triple-helical peptides(THPs).These are ligands for collagen-binding cell-surface receptors(integrins or discoidin domain receptors)or secreted proteins(SPARC and von Willebrand factor).THPs enhanced HUVEC adhesion,spreading and proliferation on 2D collagen films.THPs grafted to 3D-cross-linked collagen scaffolds promoted cell survival over seven days.This study demonstrates that THP-functionalized collagen scaffolds are promising candidates for hosting endothelial cells with potential for the production of vascularized engineered tissues in regenerative medicine applications.展开更多
基金supported in the Department of Biochemistry by grants from British Heart Foundation(SP/15/7/31561,FS/15/20/31335 , RG/15/4/31268)funded by EPSRC fellowship(EP/N019938/1)+2 种基金supported by BHF grants FS/18/46/33663 , RM/17/2/33380funding from the Wellcome Trust and MRC to the Wellcome-Medical Research Council Cambridge Stem Cell InstituteConfocal imaging of scaffolds was performed at the Microscopy Core facility at the Sainsbury Laboratory,Cambridge,UK and was supported by the Gatsby Charitable Foundation.
文摘Porous biomaterials which provide a structural and biological support for cells have immense potential in tissue engineering and cell-based therapies for tissue repair.Collagen biomaterials that can host endothelial cells represent promising tools for the vascularization of engineered tissues.Three-dimensional collagen scaffolds possessing controlled architecture and mechanical stiffness are obtained through freeze–drying of collagen suspensions,followed by chemical cross-linking which maintains their stability.However,cross-linking scaffolds renders their biological activity suboptimal for many cell types,including human umbilical vein endothelial cells(HUVECs),by inhibiting cell–collagen interactions.Here,we have improved crucial HUVEC interactions with such cross-linked collagen biomaterials by covalently coupling combinations of triple-helical peptides(THPs).These are ligands for collagen-binding cell-surface receptors(integrins or discoidin domain receptors)or secreted proteins(SPARC and von Willebrand factor).THPs enhanced HUVEC adhesion,spreading and proliferation on 2D collagen films.THPs grafted to 3D-cross-linked collagen scaffolds promoted cell survival over seven days.This study demonstrates that THP-functionalized collagen scaffolds are promising candidates for hosting endothelial cells with potential for the production of vascularized engineered tissues in regenerative medicine applications.
