Improving functional re-endothelialization of acellular liver scaffold using REDV cell-binding domain

Abstract

There is a critical need for novel organ replacement therapies as the grafts for transplantation fall short of demand. Recent advances in tissue engineering, through the use of decellularized scaffolds, have opened the possibility that engineered grafts could be used as substitutes for donor livers. However, successful implantation has been challenged by the inability to create a functional vasculature. Our research study reports a new strategy to increase efficiency of endothelialization by increasing the affinity of the vascular matrix for endothelial cells. We functionalized decellularized liver scaffold using elastin-like peptides grafted with REDV cell binding domain. We showed that REDV-ELP conjugation improve endothelial cell attachment and proliferation within the scaffold, demonstrating the feasibility of re-endothelializing a whole liver vasculature using our technique.

Combinatorial functionalization with bisurea‐peptides and antifouling bisurea additives of a supramolecular elastomeric biomaterial

“…Nonetheless, inconsistent results have been reported for the efficacy of REDV functionalization. Some studies report improved adhesion of endothelial cells but do not compare to RGD or other peptides for functionalization, or adhesion of other mammalian cell types., or show unexpected failed refunctionalization for other cell‐types with RGD . Other studies also unexpectedly show reduced endothelial cell adhesion on REDV functionalized surfaces compared to RGD …”

“…Besides peptides such as RGD, which induce cell adhesion in general, peptide sequences have been discovered for which specific cell types have an increased affinity over other cell types, due to increased expression of the binding motif on these cells . The REDV peptide, for which endothelial cell‐specificity has been reported, attributed to binding to integrin α4β1, has been extensively applied to enhance endothelialization of biomaterials . In another approach, a peptide derived from stromal cell derived factor‐1α (SDF1α), a chemoattractant of lymphocytes, monocytes, and progenitors cells, has been applied for improved in situ cellularization…”

Using GRGDSPC peptides to improve re‐endothelialization of decellularized pancreatic scaffolds

“…However, it was reported that spontaneous endothelialization failed to take place in humans following implantation of small‐diameter vascular grafts made of synthetic polymers even after long‐term implantation. In order to improve both biocompatibility and EC adhesion, many peptide sequences, such as RGD and REDV, have been grafted onto artificial vascular grafts. While peptides have been used for vascular tissue engineering for a decade, they have not been extensively studied in whole organ bioengineering.…”

“…The decellularization process for the production of an acellular organ scaffold has been under development for many years, and the results have been quite remarkable . However, the recellularization process has proven to be very challenging, and the major obstacle to successful organ bioengineering is re‐endothelialization . Improving the re‐endothelialization efficiency would be a dramatic breakthrough for the regeneration of transplantable organs.…”

Strategies in cell‐free tissue‐engineered vascular grafts

“…et al constructed a vascular graft based on electrospun PCL matrix, on which organoseleniumimmobilized polyethyleneimine (SePEI) for in situ nitric oxide (NO) generation and hyaluronic acid (HA) grafted with poly (ethylene glycol) (PEG) modified Tyr-Ile-Gly-Ser-Arg (YIGSR) for antifouling and ECs adhesion were deposited through electrostatic layer-by-layer assembly. Since α 4 β 1 integrin mainly expressed on ECs and EPCs, REDV possesses the capability of specifically enhancing ECs/EPCs adhesion(Devalliere, Chen, Dooley, Yarmush, & Uygun, 2018;Wei et al, 2011).Tetsuji Yamaoka et al modified REDV peptides on their decellularized graft, which was the first TEVG study using a long-bypass graft in an animal model. The outmost layer of YIGSR peptides exhibited the facilitation of more rapid and organized ECs adhesion compared to PCLand non-modified grafts(Tang et al, 2018).…”