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 |
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container_title | Journal of biomedical materials research. Part A |
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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. J Biomed Mater Res, 2010</description><identifier>ISSN: 1549-3296</identifier><identifier>ISSN: 1552-4965</identifier><identifier>EISSN: 1552-4965</identifier><identifier>DOI: 10.1002/jbm.a.32580</identifier><identifier>PMID: 19701911</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>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</subject><ispartof>Journal of biomedical materials research. 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Part A</title><addtitle>J. Biomed. Mater. Res</addtitle><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</description><subject>Amino Acid Sequence</subject><subject>Amino Acids - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomedical materials</subject><subject>Biomimetic Materials - pharmacology</subject><subject>Bone Regeneration - drug effects</subject><subject>Bones</subject><subject>Cross-Linking Reagents - pharmacology</subject><subject>Crosslinking</subject><subject>Degradation</subject><subject>Elastic Modulus - drug effects</subject><subject>Fibrinolysin - metabolism</subject><subject>hydrogel</subject><subject>Hydrogels</subject><subject>Hydrogels - pharmacology</subject><subject>Lysine</subject><subject>Medical sciences</subject><subject>Molecular Sequence Data</subject><subject>PEG</subject><subject>peptide</subject><subject>Peptides</subject><subject>Peptides - chemistry</subject><subject>Peptides - pharmacology</subject><subject>plasmin</subject><subject>Polyethylene Glycols - pharmacology</subject><subject>proteolytic degradation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgical implants</subject><subject>Technology. Biomaterials. Equipments</subject><subject>Wound Healing - drug effects</subject><issn>1549-3296</issn><issn>1552-4965</issn><issn>1552-4965</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0Utv1DAQAOAIgeiLE3fkCwIJZeux40eObWm3oNICAiHBwXLsCXWbF3GWsv8eb3cpt1Y-eGR9MyPPZNlzoDOglO1fVe3MzjgTmj7KtkEIlhelFI9XcVHmnJVyK9uJ8SphSQV7mm1BqSiUANvZj8PQt6HFKTjy8XhOLpd-7H9iE4kb-xib0F2jJzdhuiRt6EJrGzI0NqY4j9jFMIXfSKYx5DY99cS64MmAwxQ8xr3sSW2biM8292729eT4y9FpfnYxf3d0cJY7wRnNK0s9s2hrYE75ynkruGDa1xVTqsAKalWkA-BLVNqLwpeucnVNLa3AV5rvZq_WdYex_7XAOJk2RIdNYzvsF9FozdPPCw0PS1kKpQvOHpSKc1kIDTTJ1_dKkAo4SE5lom_W9Ha2I9ZmGNNIx6UBala7NGmXxprbXSb9YlN4UbXo_9vN8hJ4uQE2OtvUo-1ciHeOpfFRylcO1u4mNLi8r6d5f_jhX_N8nRPihH_ucux4baTiSphv53PzVnw-ZcV3bT7xv3IrxiM</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Jo, Yun Suk</creator><creator>Rizzi, Simone C.</creator><creator>Ehrbar, Martin</creator><creator>Weber, Franz E.</creator><creator>Hubbell, Jeffrey A.</creator><creator>Lutolf, Matthias P.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>F28</scope><scope>FR3</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>7QO</scope><scope>P64</scope></search><sort><creationdate>20100601</creationdate><title>Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides</title><author>Jo, Yun Suk ; Rizzi, Simone C. ; Ehrbar, Martin ; Weber, Franz E. ; Hubbell, Jeffrey A. ; Lutolf, Matthias P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5320-ba0d2aeaf12c7dbcda53528dfb2774eb1f7474711d9e78d54d9cbcff0a0b1db83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Amino Acid Sequence</topic><topic>Amino Acids - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomedical materials</topic><topic>Biomimetic Materials - pharmacology</topic><topic>Bone Regeneration - drug effects</topic><topic>Bones</topic><topic>Cross-Linking Reagents - pharmacology</topic><topic>Crosslinking</topic><topic>Degradation</topic><topic>Elastic Modulus - drug effects</topic><topic>Fibrinolysin - metabolism</topic><topic>hydrogel</topic><topic>Hydrogels</topic><topic>Hydrogels - pharmacology</topic><topic>Lysine</topic><topic>Medical sciences</topic><topic>Molecular Sequence Data</topic><topic>PEG</topic><topic>peptide</topic><topic>Peptides</topic><topic>Peptides - chemistry</topic><topic>Peptides - pharmacology</topic><topic>plasmin</topic><topic>Polyethylene Glycols - pharmacology</topic><topic>proteolytic degradation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Surgery (general aspects). 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jo, Yun Suk</au><au>Rizzi, Simone C.</au><au>Ehrbar, Martin</au><au>Weber, Franz E.</au><au>Hubbell, Jeffrey A.</au><au>Lutolf, Matthias P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biomimetic PEG hydrogels crosslinked with minimal plasmin-sensitive tri-amino acid peptides</atitle><jtitle>Journal of biomedical materials research. Part A</jtitle><addtitle>J. Biomed. Mater. Res</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>93A</volume><issue>3</issue><spage>870</spage><epage>877</epage><pages>870-877</pages><issn>1549-3296</issn><issn>1552-4965</issn><eissn>1552-4965</eissn><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. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19701911</pmid><doi>10.1002/jbm.a.32580</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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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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