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The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity
It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100μm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100μm). More recently researchers have inves...
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Published in: | Acta biomaterialia 2010-08, Vol.6 (8), p.3283-3291 |
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creator | Lan Levengood, Sheeny K. Polak, Samantha J. Poellmann, Michael J. Hoelzle, David J. Maki, Aaron J. Clark, Sherrie G. Wheeler, Matthew B. Wagoner Johnson, Amy J. |
description | It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100μm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100μm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than ∼50μm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores ( |
doi_str_mv | 10.1016/j.actbio.2010.02.026 |
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As a result, most studies have focused on scaffold macroporosity (>100μm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than ∼50μm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores (<10μm), of biphasic calcium phosphate (BCP) scaffolds. The combined effect of BMP-2, a potent osteoinductive growth factor, and multiscale porosity has yet to be investigated. In this study we implanted BCP scaffolds into porcine mandibular defects for 3, 6, 12 and 24weeks and evaluated the effect of BMP-2 on multiscale osteointegration. The results showed that given this in vivo model BMP-2 influences osteointegration at the microscale, but not at the macroscale, but not at the macroscale. Cell density was higher in the rod micropores for scaffolds containing BMP-2 compared with controls at all time points, but BMP-2 was not required for bone formation in micropores. In contrast, there was essentially no difference in the fraction of bone in macropores for scaffolds with BMP-2 compared with controls. Additionally, bone in macropores seemed to have reached steady-state by 3weeks. Multiscale osteointegration results in bone-scaffold composites that are fully osteointegrated, with no ‘dead space’. These composites are likely to contain a continuous cell network as well as the potential for enhanced load transfer and improved mechanical properties.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2010.02.026</identifier><identifier>PMID: 20176148</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Bone and Bones - cytology ; Bone and Bones - diagnostic imaging ; Bone and Bones - drug effects ; Bone ingrowth ; Bone Morphogenetic Protein 2 - pharmacology ; Calcium phosphate ; Calcium Phosphates - pharmacology ; Cell Count ; Gelatin - pharmacology ; Humans ; Microscopy, Electron, Scanning ; Microspheres ; Organ Size - drug effects ; Osseointegration - drug effects ; Osteogenesis - drug effects ; Osteointegration ; Porosity ; Porosity - drug effects ; Robotics ; Scaffold ; Sus scrofa ; Tissue Scaffolds - chemistry ; Tomography, X-Ray Computed</subject><ispartof>Acta biomaterialia, 2010-08, Vol.6 (8), p.3283-3291</ispartof><rights>2010 Acta Materialia Inc.</rights><rights>Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-2474c1b54cb7a6fb8d6fd03af356712a54f58d9b4d917049009e49242d1496cd3</citedby><cites>FETCH-LOGICAL-c393t-2474c1b54cb7a6fb8d6fd03af356712a54f58d9b4d917049009e49242d1496cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20176148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lan Levengood, Sheeny K.</creatorcontrib><creatorcontrib>Polak, Samantha J.</creatorcontrib><creatorcontrib>Poellmann, Michael J.</creatorcontrib><creatorcontrib>Hoelzle, David J.</creatorcontrib><creatorcontrib>Maki, Aaron J.</creatorcontrib><creatorcontrib>Clark, Sherrie G.</creatorcontrib><creatorcontrib>Wheeler, Matthew B.</creatorcontrib><creatorcontrib>Wagoner Johnson, Amy J.</creatorcontrib><title>The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100μm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100μm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than ∼50μm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores (<10μm), of biphasic calcium phosphate (BCP) scaffolds. The combined effect of BMP-2, a potent osteoinductive growth factor, and multiscale porosity has yet to be investigated. In this study we implanted BCP scaffolds into porcine mandibular defects for 3, 6, 12 and 24weeks and evaluated the effect of BMP-2 on multiscale osteointegration. The results showed that given this in vivo model BMP-2 influences osteointegration at the microscale, but not at the macroscale, but not at the macroscale. Cell density was higher in the rod micropores for scaffolds containing BMP-2 compared with controls at all time points, but BMP-2 was not required for bone formation in micropores. In contrast, there was essentially no difference in the fraction of bone in macropores for scaffolds with BMP-2 compared with controls. Additionally, bone in macropores seemed to have reached steady-state by 3weeks. Multiscale osteointegration results in bone-scaffold composites that are fully osteointegrated, with no ‘dead space’. These composites are likely to contain a continuous cell network as well as the potential for enhanced load transfer and improved mechanical properties.</description><subject>Animals</subject><subject>Bone and Bones - cytology</subject><subject>Bone and Bones - diagnostic imaging</subject><subject>Bone and Bones - drug effects</subject><subject>Bone ingrowth</subject><subject>Bone Morphogenetic Protein 2 - pharmacology</subject><subject>Calcium phosphate</subject><subject>Calcium Phosphates - pharmacology</subject><subject>Cell Count</subject><subject>Gelatin - pharmacology</subject><subject>Humans</subject><subject>Microscopy, Electron, Scanning</subject><subject>Microspheres</subject><subject>Organ Size - drug effects</subject><subject>Osseointegration - drug effects</subject><subject>Osteogenesis - drug effects</subject><subject>Osteointegration</subject><subject>Porosity</subject><subject>Porosity - drug effects</subject><subject>Robotics</subject><subject>Scaffold</subject><subject>Sus scrofa</subject><subject>Tissue Scaffolds - chemistry</subject><subject>Tomography, X-Ray Computed</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNqFkUtv1TAQhS1ERR_wDxDyjlUutuP4sUGCCihSK1iUteX4wfVVEofYKeqG385cpbBspZE8Gn3njDUHodeU7Cih4t1hZ13tU94xAiPCoMQzdEaVVI3shHoOveSskUTQU3ReyoGQVlGmXqBTkEhBuTpDf273AYcYg6s4R_zx5nvDcJ7wmNySG2wnj0cLbXF2CDiXGnKaavi52JoAA0mf5r0tyWEgXFpHPO9zgVENGEQx5sEX_DvVPR7XoabNaM5gmer9S3QS7VDCq4f3Av34_On28qq5_vbl6-WH68a1uq0N45I72nfc9dKK2CsvoietjW0nJGW247FTXvfcayoJ14TowDXjzFOuhfPtBXq7-c5L_rWGUs0IPwnDYKeQ12I0VUR0kuknSdm2rJOqU0DyjTyepywhmnlJo13uDSXmGJE5mC0ic4zIEAYlQPbmYcHaj8H_F_3LBID3GxDgIHcpLKa4FCYXfFogJuNzenzDX6hwpOM</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Lan Levengood, Sheeny K.</creator><creator>Polak, Samantha J.</creator><creator>Poellmann, Michael J.</creator><creator>Hoelzle, David J.</creator><creator>Maki, Aaron J.</creator><creator>Clark, Sherrie G.</creator><creator>Wheeler, Matthew B.</creator><creator>Wagoner Johnson, Amy J.</creator><general>Elsevier Ltd</general><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>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20100801</creationdate><title>The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity</title><author>Lan Levengood, Sheeny K. ; Polak, Samantha J. ; Poellmann, Michael J. ; Hoelzle, David J. ; Maki, Aaron J. ; Clark, Sherrie G. ; Wheeler, Matthew B. ; Wagoner Johnson, Amy J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-2474c1b54cb7a6fb8d6fd03af356712a54f58d9b4d917049009e49242d1496cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Bone and Bones - cytology</topic><topic>Bone and Bones - diagnostic imaging</topic><topic>Bone and Bones - drug effects</topic><topic>Bone ingrowth</topic><topic>Bone Morphogenetic Protein 2 - pharmacology</topic><topic>Calcium phosphate</topic><topic>Calcium Phosphates - pharmacology</topic><topic>Cell Count</topic><topic>Gelatin - pharmacology</topic><topic>Humans</topic><topic>Microscopy, Electron, Scanning</topic><topic>Microspheres</topic><topic>Organ Size - drug effects</topic><topic>Osseointegration - drug effects</topic><topic>Osteogenesis - drug effects</topic><topic>Osteointegration</topic><topic>Porosity</topic><topic>Porosity - drug effects</topic><topic>Robotics</topic><topic>Scaffold</topic><topic>Sus scrofa</topic><topic>Tissue Scaffolds - chemistry</topic><topic>Tomography, X-Ray Computed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lan Levengood, Sheeny K.</creatorcontrib><creatorcontrib>Polak, Samantha J.</creatorcontrib><creatorcontrib>Poellmann, Michael J.</creatorcontrib><creatorcontrib>Hoelzle, David J.</creatorcontrib><creatorcontrib>Maki, Aaron J.</creatorcontrib><creatorcontrib>Clark, Sherrie G.</creatorcontrib><creatorcontrib>Wheeler, Matthew B.</creatorcontrib><creatorcontrib>Wagoner Johnson, Amy J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lan Levengood, Sheeny K.</au><au>Polak, Samantha J.</au><au>Poellmann, Michael J.</au><au>Hoelzle, David J.</au><au>Maki, Aaron J.</au><au>Clark, Sherrie G.</au><au>Wheeler, Matthew B.</au><au>Wagoner Johnson, Amy J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>6</volume><issue>8</issue><spage>3283</spage><epage>3291</epage><pages>3283-3291</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100μm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100μm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than ∼50μm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores (<10μm), of biphasic calcium phosphate (BCP) scaffolds. The combined effect of BMP-2, a potent osteoinductive growth factor, and multiscale porosity has yet to be investigated. In this study we implanted BCP scaffolds into porcine mandibular defects for 3, 6, 12 and 24weeks and evaluated the effect of BMP-2 on multiscale osteointegration. The results showed that given this in vivo model BMP-2 influences osteointegration at the microscale, but not at the macroscale, but not at the macroscale. Cell density was higher in the rod micropores for scaffolds containing BMP-2 compared with controls at all time points, but BMP-2 was not required for bone formation in micropores. In contrast, there was essentially no difference in the fraction of bone in macropores for scaffolds with BMP-2 compared with controls. Additionally, bone in macropores seemed to have reached steady-state by 3weeks. Multiscale osteointegration results in bone-scaffold composites that are fully osteointegrated, with no ‘dead space’. These composites are likely to contain a continuous cell network as well as the potential for enhanced load transfer and improved mechanical properties.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>20176148</pmid><doi>10.1016/j.actbio.2010.02.026</doi><tpages>9</tpages></addata></record> |
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subjects | Animals Bone and Bones - cytology Bone and Bones - diagnostic imaging Bone and Bones - drug effects Bone ingrowth Bone Morphogenetic Protein 2 - pharmacology Calcium phosphate Calcium Phosphates - pharmacology Cell Count Gelatin - pharmacology Humans Microscopy, Electron, Scanning Microspheres Organ Size - drug effects Osseointegration - drug effects Osteogenesis - drug effects Osteointegration Porosity Porosity - drug effects Robotics Scaffold Sus scrofa Tissue Scaffolds - chemistry Tomography, X-Ray Computed |
title | The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity |
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