title: Design and synthesis of biomimetic hydrogel scaffolds with controlled organization of cyclic RGD peptides.
abstract: We report on the rational design and synthesis of a new type of bioactive poly(ethylene glycol) diacrylate (PEGDA) macromers, cyclic Arg-Gly-Asp (cRGD)-PEGDA, to mimic the cell-adhesive properties of extracellular matrix (ECM), aiming to create biomimetic scaffolds with controlled spatial organization of ligands and enhanced cell binding affinity for tissue engineering. To attach the cRGD peptide in the middle of PEGDA chain, a tailed cRGD peptide, c[RGDfE(SSSKK-NH2)] (1), was synthesized with c(RGDfE) linked to a tail of SSSKK. The tail consists of a spacer with three serine residues and a linker with two lysine residues for conjugating with acryloyl-PEG-NHS (5) to create cRGD-PEGDA (6). cRGD-PEGDA possesses good photopolymerization ability to fabricate hydrogel scaffolds under UV radiation. Surface morphology and composition analysis demonstrates that cRGD-PEGDA hydrogels were well-constructed with porous three-dimensional (3D) structures and uniform distribution of cRGD ligands. Our results show that cRGD-PEGDA hydrogels facilitate endothelial cell (EC) adhesion and spreading on the hydrogel surfaces and exhibit significantly higher EC population in comparison with linear RGD-modified hydrogels at low peptide incorporation. Since ligand presentation in biomimetic scaffolds plays an important role in controlling cell behavior, cRGD-PEGDA has great advantages of controlling hydrogel properties and ligand spatial organization in the resulting scaffolds. Furthermore, cRGD-PEGDA is an attractive candidate for the future development of tissue engineering scaffolds with optimum cell adhesive strength and ligand density.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. junmin.zhu@case.edu
authors.forename: Junmin
authors.initials: J
authors.lastname: Zhu
authors.forename: Chad
authors.initials: C
authors.lastname: Tang
authors.forename: Kandice
authors.initials: K
authors.lastname: Kottke-Marchant
authors.forename: Roger E
authors.initials: RE
authors.lastname: Marchant
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000595:Amino Acid Sequence; D040761:Biomimetic Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008024:Ligands; D010456:Peptides, Cyclic / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D013499:Surface Properties; D023822:Tissue Engineering
chemical_list: D000179:Acrylates; D008024:Ligands; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; C036658:acrylic acid