Local application of lactoferrin promotes bone regeneration in a rat critical‐sized calvarial defect model as demonstrated by micro‐CT and histological analysis

Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Spra...

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Veröffentlicht in:Journal of tissue engineering and regenerative medicine 2018-01, Vol.12 (1), p.e620-e626
Hauptverfasser: Gao, Ryan, Watson, Maureen, Callon, Karen E., Tuari, Donna, Dray, Michael, Naot, Dorit, Amirapu, Satya, Munro, Jacob T., Cornish, Jillian, Musson, David S.
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container_title Journal of tissue engineering and regenerative medicine
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creator Gao, Ryan
Watson, Maureen
Callon, Karen E.
Tuari, Donna
Dray, Michael
Naot, Dorit
Amirapu, Satya
Munro, Jacob T.
Cornish, Jillian
Musson, David S.
description Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Sprague–Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post‐operatively, and the calvaria were excised and evaluated with micro‐CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin‐treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  
doi_str_mv 10.1002/term.2348
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The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Sprague–Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post‐operatively, and the calvaria were excised and evaluated with micro‐CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin‐treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  &lt;  0.05); and 12.2  ±  1.3%, 13.6  ±  1.5%, 21.9  ±  1.2% and 29.3  ±  0.8%, respectively, at 12 weeks (P  &lt;  0.05). Histological analysis revealed that the newly formed bone within the calvarial defects of all groups was a mixture of woven and lamellar bone, with more bone in the group treated with lactoferrin at both timepoints. Our study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical‐sized calvarial defect model. The profound effect of lactoferrin on bone regeneration has therapeutic potential to improve the poor clinical outcomes associated with bony non‐union. LF In Vivo JTERM Authors Contributions. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley &amp; Sons, Ltd.</description><identifier>ISSN: 1932-6254</identifier><identifier>EISSN: 1932-7005</identifier><identifier>DOI: 10.1002/term.2348</identifier><identifier>PMID: 27860377</identifier><language>eng</language><publisher>England: Hindawi Limited</publisher><subject>Animals ; Bone growth ; bone healing ; bone regeneration ; Bone Regeneration - drug effects ; Calvaria ; calvarial defect ; Cattle ; Collagen ; Computed tomography ; Concentration (composition) ; Defects ; Disease Models, Animal ; Gels ; Glycoproteins ; Histology ; Lactoferrin ; Lactoferrin - pharmacology ; Lamellar bone ; Male ; Nonunion ; Organ Size - drug effects ; Parietal bone ; Rats ; Rats, Sprague-Dawley ; Regeneration (physiology) ; Regenerative medicine ; Rodents ; Skin ; Skull - diagnostic imaging ; Skull - drug effects ; Skull - pathology ; Skull - physiopathology ; Tissue engineering ; X-Ray Microtomography</subject><ispartof>Journal of tissue engineering and regenerative medicine, 2018-01, Vol.12 (1), p.e620-e626</ispartof><rights>Copyright © 2016 The Authors Published by John Wiley &amp; Sons, Ltd.</rights><rights>Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley &amp; Sons, Ltd.</rights><rights>Copyright © 2018 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4758-7a17c4fbb08bd335567501852b98adc97fe5dd7ae4db81bffe1f6c64d00777a83</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fterm.2348$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fterm.2348$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27860377$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gao, Ryan</creatorcontrib><creatorcontrib>Watson, Maureen</creatorcontrib><creatorcontrib>Callon, Karen E.</creatorcontrib><creatorcontrib>Tuari, Donna</creatorcontrib><creatorcontrib>Dray, Michael</creatorcontrib><creatorcontrib>Naot, Dorit</creatorcontrib><creatorcontrib>Amirapu, Satya</creatorcontrib><creatorcontrib>Munro, Jacob T.</creatorcontrib><creatorcontrib>Cornish, Jillian</creatorcontrib><creatorcontrib>Musson, David S.</creatorcontrib><title>Local application of lactoferrin promotes bone regeneration in a rat critical‐sized calvarial defect model as demonstrated by micro‐CT and histological analysis</title><title>Journal of tissue engineering and regenerative medicine</title><addtitle>J Tissue Eng Regen Med</addtitle><description>Lactoferrin is a multifunctional glycoprotein with therapeutic potential for bone tissue engineering. The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Sprague–Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post‐operatively, and the calvaria were excised and evaluated with micro‐CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin‐treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  &lt;  0.05); and 12.2  ±  1.3%, 13.6  ±  1.5%, 21.9  ±  1.2% and 29.3  ±  0.8%, respectively, at 12 weeks (P  &lt;  0.05). Histological analysis revealed that the newly formed bone within the calvarial defects of all groups was a mixture of woven and lamellar bone, with more bone in the group treated with lactoferrin at both timepoints. Our study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical‐sized calvarial defect model. The profound effect of lactoferrin on bone regeneration has therapeutic potential to improve the poor clinical outcomes associated with bony non‐union. LF In Vivo JTERM Authors Contributions. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley &amp; Sons, Ltd.</description><subject>Animals</subject><subject>Bone growth</subject><subject>bone healing</subject><subject>bone regeneration</subject><subject>Bone Regeneration - drug effects</subject><subject>Calvaria</subject><subject>calvarial defect</subject><subject>Cattle</subject><subject>Collagen</subject><subject>Computed tomography</subject><subject>Concentration (composition)</subject><subject>Defects</subject><subject>Disease Models, Animal</subject><subject>Gels</subject><subject>Glycoproteins</subject><subject>Histology</subject><subject>Lactoferrin</subject><subject>Lactoferrin - pharmacology</subject><subject>Lamellar bone</subject><subject>Male</subject><subject>Nonunion</subject><subject>Organ Size - drug effects</subject><subject>Parietal bone</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Regeneration (physiology)</subject><subject>Regenerative medicine</subject><subject>Rodents</subject><subject>Skin</subject><subject>Skull - diagnostic imaging</subject><subject>Skull - drug effects</subject><subject>Skull - pathology</subject><subject>Skull - physiopathology</subject><subject>Tissue engineering</subject><subject>X-Ray Microtomography</subject><issn>1932-6254</issn><issn>1932-7005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNpdkk1uFDEQhVsIREJgwQWQJTZsJrH7z-4NEholgDQICQ1ryz_VE0duu7E9QcOKI-QQnIyTUMMMEbDys-ur52e5quo5o-eM0vqiQJrO66YVD6pTNjT1glPaPTzqvu7ak-pJzjd42PVd87g6qbnoacP5afVjFY3yRM2zd0YVFwOJI_HKlDhCSi6QOcUpFshExwAkwQYCpAOJVUVQE5NcwXb_8_tddt_AEtS3Kjl0tjCCKWSKFvCajPsphlywCzG9I5MzKWLfck1UsOTa5RJ93LjfqYLyu-zy0-rRqHyGZ8f1rPp8dblevlusPr59v3yzWpiWd2LBFeOmHbWmQtumwcfyjjLR1XoQypqBj9BZyxW0VgumxxHY2Ju-tZRyzpVozqrXB995qyewBgLm9HJOblJpJ6Ny8t9KcNdyE29lJxjjvEeDV0eDFL9sIRc5uWzAexUgbrNkomWC0qGvEX35H3oTtwkfjNQwsJrXGB-pF38nuo_y5wMRuDgAX52H3X2dUbmfDLmfDLmfDLm-_PRhL5pfdlGyhA</recordid><startdate>201801</startdate><enddate>201801</enddate><creator>Gao, Ryan</creator><creator>Watson, Maureen</creator><creator>Callon, Karen E.</creator><creator>Tuari, Donna</creator><creator>Dray, Michael</creator><creator>Naot, Dorit</creator><creator>Amirapu, Satya</creator><creator>Munro, Jacob T.</creator><creator>Cornish, Jillian</creator><creator>Musson, David S.</creator><general>Hindawi Limited</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>M7Z</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201801</creationdate><title>Local application of lactoferrin promotes bone regeneration in a rat critical‐sized calvarial defect model as demonstrated by micro‐CT and histological analysis</title><author>Gao, Ryan ; 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The aim of this study was to assess the efficacy of local application of lactoferrin on bone regeneration. Five‐millimetre critical‐sized defects were created over the right parietal bone in 64 Sprague–Dawley rats. The rats were randomized into four groups: group 1 (n  =  20) had empty defects; group 2 (n  =  20) had defects grafted with collagen gels (3 mg/ml); group 3 (n  =  20) had defects grafted with collagen gels impregnated with bovine lactoferrin (10 μg/gel); and group 4 (n  =  4) had sham surgeries (skin and periosteal incisions only). The rats were sacrificed at 4 or 12 weeks post‐operatively, and the calvaria were excised and evaluated with micro‐CT (Skyscan 1172) followed by histology. The bone volume fraction (BV/TV) was higher in lactoferrin‐treated animals at both timepoints, with groups 1, 2, 3 and 4 measuring 10.5  ±  1.1%, 8.6  ±  1.4%, 16.5  ±  0.6% and 24.27  ±  2.6%, respectively, at 4 weeks (P  &lt;  0.05); and 12.2  ±  1.3%, 13.6  ±  1.5%, 21.9  ±  1.2% and 29.3  ±  0.8%, respectively, at 12 weeks (P  &lt;  0.05). Histological analysis revealed that the newly formed bone within the calvarial defects of all groups was a mixture of woven and lamellar bone, with more bone in the group treated with lactoferrin at both timepoints. Our study demonstrated that local application of lactoferrin significantly increased bone regeneration in a rat critical‐sized calvarial defect model. The profound effect of lactoferrin on bone regeneration has therapeutic potential to improve the poor clinical outcomes associated with bony non‐union. LF In Vivo JTERM Authors Contributions. Copyright © 2016 The Authors Journal of Tissue Engineering and Regenerative Medicine Published by John Wiley &amp; Sons, Ltd.</abstract><cop>England</cop><pub>Hindawi Limited</pub><pmid>27860377</pmid><doi>10.1002/term.2348</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; Wiley Online Library Journals Frontfile Complete
subjects Animals
Bone growth
bone healing
bone regeneration
Bone Regeneration - drug effects
Calvaria
calvarial defect
Cattle
Collagen
Computed tomography
Concentration (composition)
Defects
Disease Models, Animal
Gels
Glycoproteins
Histology
Lactoferrin
Lactoferrin - pharmacology
Lamellar bone
Male
Nonunion
Organ Size - drug effects
Parietal bone
Rats
Rats, Sprague-Dawley
Regeneration (physiology)
Regenerative medicine
Rodents
Skin
Skull - diagnostic imaging
Skull - drug effects
Skull - pathology
Skull - physiopathology
Tissue engineering
X-Ray Microtomography
title Local application of lactoferrin promotes bone regeneration in a rat critical‐sized calvarial defect model as demonstrated by micro‐CT and histological analysis
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