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

Yun Suk Jo, Simone C. Rizzi, Martin Ehrbar, Franz E. Weber, Jeffrey A. Hubbell, Matthias P. Lutolf

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)870-877
Number of pages8
JournalJournal of Biomedical Materials Research - Part A
Volume93
Issue number3
DOIs
StatePublished - Jun 1 2010
Externally publishedYes

Fingerprint

Hydrogels
Fibrinolysin
Biomimetics
Peptides
Polyethylene glycols
Amino acids
Bone
Arginine
Gels
Amino Acids
Bearings (structural)
Lysine
Scaffolds (biology)
Infiltration
Crosslinking
Rats
Skin
Animals
Substitution reactions
Serine

Keywords

  • Hydrogel
  • PEG
  • Peptide
  • Plasmin
  • Proteolytic degradation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides. / Jo, Yun Suk; Rizzi, Simone C.; Ehrbar, Martin; Weber, Franz E.; Hubbell, Jeffrey A.; Lutolf, Matthias P.

In: Journal of Biomedical Materials Research - Part A, Vol. 93, No. 3, 01.06.2010, p. 870-877.

Research output: Contribution to journalArticle

Jo, Yun Suk ; Rizzi, Simone C. ; Ehrbar, Martin ; Weber, Franz E. ; Hubbell, Jeffrey A. ; Lutolf, Matthias P. / Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides. In: Journal of Biomedical Materials Research - Part A. 2010 ; Vol. 93, No. 3. pp. 870-877.
@article{df2aeb15b30a4996b18653f72cab6764,
title = "Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides",
abstract = "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.",
keywords = "Hydrogel, PEG, Peptide, Plasmin, Proteolytic degradation",
author = "Jo, {Yun Suk} and Rizzi, {Simone C.} and Martin Ehrbar and Weber, {Franz E.} and Hubbell, {Jeffrey A.} and Lutolf, {Matthias P.}",
year = "2010",
month = "6",
day = "1",
doi = "10.1002/jbm.a.32580",
language = "English",
volume = "93",
pages = "870--877",
journal = "Journal of Biomedical Materials Research - Part A",
issn = "1549-3296",
publisher = "Heterocorporation",
number = "3",

}

TY - JOUR

T1 - Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides

AU - Jo, Yun Suk

AU - Rizzi, Simone C.

AU - Ehrbar, Martin

AU - Weber, Franz E.

AU - Hubbell, Jeffrey A.

AU - Lutolf, Matthias P.

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

KW - Hydrogel

KW - PEG

KW - Peptide

KW - Plasmin

KW - Proteolytic degradation

UR - http://www.scopus.com/inward/record.url?scp=77950684167&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950684167&partnerID=8YFLogxK

U2 - 10.1002/jbm.a.32580

DO - 10.1002/jbm.a.32580

M3 - Article

C2 - 19701911

AN - SCOPUS:77950684167

VL - 93

SP - 870

EP - 877

JO - Journal of Biomedical Materials Research - Part A

JF - Journal of Biomedical Materials Research - Part A

SN - 1549-3296

IS - 3

ER -