Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides

Semi‐synthetic, proteolytically degradable polymer hydrogels have proven effective as scaffolds to augment bone and skin regeneration in animals. However, high costs due to expensive peptide building blocks pose a significant hurdle towards broad clinical usage of these materials. Here we demonstrat...

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Veröffentlicht in:Journal of biomedical materials research. Part A 2010-06, Vol.93A (3), p.870-877
Hauptverfasser: Jo, Yun Suk, Rizzi, Simone C., Ehrbar, Martin, Weber, Franz E., Hubbell, Jeffrey A., Lutolf, Matthias P.
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container_issue 3
container_start_page 870
container_title Journal of biomedical materials research. Part A
container_volume 93A
creator Jo, Yun Suk
Rizzi, Simone C.
Ehrbar, Martin
Weber, Franz E.
Hubbell, Jeffrey A.
Lutolf, Matthias P.
description Semi‐synthetic, proteolytically degradable polymer hydrogels have proven effective as scaffolds to augment bone and skin regeneration in animals. However, high costs due to expensive peptide building blocks pose a significant hurdle towards broad clinical usage of these materials. Here we demonstrate that tri‐amino acid peptides bearing lysine (or arginine), flanked by two cysteine residues for crosslinking, are adequate as minimal plasmin‐sensitive peptides in poly(ethylene glycol)‐based hydrogels formed via Michael‐type addition. Substitution of lysine (or arginine) with serine rendered the matrices insensitive to the action of plasmin. This was demonstrated in vitro by performing gel degradation experiments in the presence of plasmin (0.1 U/mL), and in the in vivo situation of regeneration of critical‐sized bone defects. When placed as implants into rat calvaria, gels formed from the minimal plasmin substrates showed clear signs of cell infiltration and gel remodeling that coincided with extensive bone formation. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
doi_str_mv 10.1002/jbm.a.32580
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However, high costs due to expensive peptide building blocks pose a significant hurdle towards broad clinical usage of these materials. Here we demonstrate that tri‐amino acid peptides bearing lysine (or arginine), flanked by two cysteine residues for crosslinking, are adequate as minimal plasmin‐sensitive peptides in poly(ethylene glycol)‐based hydrogels formed via Michael‐type addition. Substitution of lysine (or arginine) with serine rendered the matrices insensitive to the action of plasmin. This was demonstrated in vitro by performing gel degradation experiments in the presence of plasmin (0.1 U/mL), and in the in vivo situation of regeneration of critical‐sized bone defects. When placed as implants into rat calvaria, gels formed from the minimal plasmin substrates showed clear signs of cell infiltration and gel remodeling that coincided with extensive bone formation. © 2009 Wiley Periodicals, Inc. 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subjects Amino Acid Sequence
Amino Acids - metabolism
Animals
Biological and medical sciences
Biomedical materials
Biomimetic Materials - pharmacology
Bone Regeneration - drug effects
Bones
Cross-Linking Reagents - pharmacology
Crosslinking
Degradation
Elastic Modulus - drug effects
Fibrinolysin - metabolism
hydrogel
Hydrogels
Hydrogels - pharmacology
Lysine
Medical sciences
Molecular Sequence Data
PEG
peptide
Peptides
Peptides - chemistry
Peptides - pharmacology
plasmin
Polyethylene Glycols - pharmacology
proteolytic degradation
Rats
Rats, Sprague-Dawley
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgical implants
Technology. Biomaterials. Equipments
Wound Healing - drug effects
title Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides
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