Micro-structured, spontaneously eroding hydrogels accelerate endothelialization through presentation of conjugated growth factors.
Growth factors represent highly potent and highly efficacious means of communication to cells. At the same time, these proteins are fragile and relatively small sized--rendering their immobilization and controlled release from biomaterials challenging. In this work, we establish a method to incorporate growth factors into the physical hydrogels based on poly(vinyl alcohol), PVA. The latter have a long and successful history of biomedical applications and approval for diverse use in human patients, but are also characterized with scant opportunities for bioconjugation and functionalization. Herein, we develop the conjugation of growth factors to the micro-structured, spontaneously eroding physical hydrogels based on PVA. Protein conjugation was elaborated using model substrates, albumin and lysozyme, which aided to reveal specificity of chemical reactions and benign, non-harmful nature of the established protocols. Surface-adhered format of hydrogel analyses allowed to quantify bioconjugation reactions and enzymatic activity of the immobilized proteins and to visualize the hydrogels with immobilized cargo. In cell culture, immobilized growth factors were effective in communicating to adhering cells and specifically enhanced proliferation rates of the cells containing the corresponding receptors. At the same time, proliferation of the cells devoid of these receptors was un-altered.
Department of Chemistry, Aarhus University, Aarhus, Denmark.
Bettina E B
BE
Jensen
Department of Chemistry, Aarhus University, Aarhus, Denmark.
Katrine
K
Edlund
Department of Chemistry, Aarhus University, Aarhus, Denmark; iNANO Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark. Electronic address: zelikin@chem.au.dk.
Alexander N
AN
Zelikin
D000818:Animals; D002417:Cattle; D004727:Endothelium / Q000187:drug effects / Q000502:physiology*; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects; D011142:Polyvinyl Alcohol / Q000737:chemistry
D020100:Hydrogels; D036341:Intercellular Signaling Peptides and Proteins; D011142:Polyvinyl Alcohol; D009113:Muramidase; D016650:Fluorescein-5-isothiocyanate
Bioconjugation; Biomaterials; Growth factors; Hydrogels