bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing
Background: Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and...
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| Veröffentlicht in: | The American journal of sports medicine 2016-08, Vol.44 (8), p.1972-1982 |
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| container_issue | 8 |
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| container_title | The American journal of sports medicine |
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| creator | Zhang, Chenghao Li, Qi Deng, Senlin Fu, Weili Tang, Xin Chen, Gang Qin, Tingwu Li, Jian |
| description | Background:
Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and tissue engineering,
Hypothesis:
Modified fibrin clots can improve the bioactivity of the tendon-bone interface and histological appearance.
Study Design:
Controlled laboratory study.
Methods:
A total of 27 male New Zealand White rabbits were used. Of these, 3 were used for cell isolation, and the remaining 24 rabbits were divided into 2 groups (12 per group) for an in vivo partial patellectomy study. The setting time, degradation time, and basic fibroblast growth factor (bFGF) and ceramide-activated protein phosphatase (CaPP) release kinetics of bFGF- and CaPP-loaded fibrin clots were modified appropriately for early tendon-to-bone healing. In an in vitro experiment, the bFGF- and CaPP-loaded fibrin clots were assessed for cell migration and proliferation by microscopy, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, and DAPI (4′,6-diamidino-2-phenylindole) assay. Quantitative real-time reverse transcription polymerase chain reaction and a Western blot assay were performed to test for an induction effect of the bFGF- and CaPP-loaded fibrin clots. Finally, for the in vivo experiment, the rabbits were divided into 2 treatment groups: one with bFGF- and CaPP-loaded fibrin clots and one without bFGF- and CaPP-loaded fibrin clots after partial patellectomy in patella–patellar tendon sutured sites. A histological evaluation was performed at 2, 4, and 6 weeks after surgery.
Results:
The sitting time and degradation time of the bFGF- and CaPP-loaded fibrin clots were set at 15 seconds and more than 2 weeks, respectively, and the porosity was minimized to achieve the highest levels of cell migration and growth. In the bFGF-CaPP group of the in vitro experiment, cell proliferation increased to a greater extent relative to the control group (P < .05); the mRNA expression of osteopontin, alkaline phosphatase, runt-related transcription factor 2, vascular endothelial growth factor, and collagen type I was upregulated (P < .05); and the relative protein expression of these factors was enhanced (P < .05). In vivo, hematoxylin and eosin staining showed that the tendon-to-bone connections were more mature and more arranged when treated with bFGF- and C |
| doi_str_mv | 10.1177/0363546516637603 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1811875066</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0363546516637603</sage_id><sourcerecordid>1811875066</sourcerecordid><originalsourceid>FETCH-LOGICAL-c468t-a60a770c1807de355d8a048b834468665b82363004837b4142bd79af7521c61c3</originalsourceid><addsrcrecordid>eNqFkc1Lw0AQxRdRtFbvnmTBi5fVmeynRy1WhYI96Dlskk1NSXc1mwj-926tigjiaWDeb94w8wg5QjhD1PocuOJSKIlKca2Ab5ERSpkxzpXcJqO1zNb6HtmPcQkAqJXZJXuZRnnBAUdkWUxvpoxaX9GJnc_ZLNjKVXTaFF3j6aQNfaTX_sn60tH-ydGrJtiyb16b_o2G-qP14HwVPLsK3tE737uutms40MthsXK-p7fOto1fHJCd2rbRHX7WMXmcXj9Mbtns_uZucjljpVCmZ1aB1RpKNKArx6WsjAVhCsNF0pWShcnSXZB6XBcCRVZU-sLWWmZYKiz5mJxufJ-78DK42OerJpauba13YYg5GkSjJaSf_Y-CUSCkgISe_EKXYeh8OiRRXGAmlMBEwYYquxBj5-r8uWtWtnvLEfJ1ZPnvyNLI8afxUKxc9T3wlVEC2AaIduF-bP3L8B2aKpkG</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1834124641</pqid></control><display><type>article</type><title>bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing</title><source>MEDLINE</source><source>SAGE Complete</source><source>Alma/SFX Local Collection</source><creator>Zhang, Chenghao ; Li, Qi ; Deng, Senlin ; Fu, Weili ; Tang, Xin ; Chen, Gang ; Qin, Tingwu ; Li, Jian</creator><creatorcontrib>Zhang, Chenghao ; Li, Qi ; Deng, Senlin ; Fu, Weili ; Tang, Xin ; Chen, Gang ; Qin, Tingwu ; Li, Jian</creatorcontrib><description>Background:
Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and tissue engineering,
Hypothesis:
Modified fibrin clots can improve the bioactivity of the tendon-bone interface and histological appearance.
Study Design:
Controlled laboratory study.
Methods:
A total of 27 male New Zealand White rabbits were used. Of these, 3 were used for cell isolation, and the remaining 24 rabbits were divided into 2 groups (12 per group) for an in vivo partial patellectomy study. The setting time, degradation time, and basic fibroblast growth factor (bFGF) and ceramide-activated protein phosphatase (CaPP) release kinetics of bFGF- and CaPP-loaded fibrin clots were modified appropriately for early tendon-to-bone healing. In an in vitro experiment, the bFGF- and CaPP-loaded fibrin clots were assessed for cell migration and proliferation by microscopy, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, and DAPI (4′,6-diamidino-2-phenylindole) assay. Quantitative real-time reverse transcription polymerase chain reaction and a Western blot assay were performed to test for an induction effect of the bFGF- and CaPP-loaded fibrin clots. Finally, for the in vivo experiment, the rabbits were divided into 2 treatment groups: one with bFGF- and CaPP-loaded fibrin clots and one without bFGF- and CaPP-loaded fibrin clots after partial patellectomy in patella–patellar tendon sutured sites. A histological evaluation was performed at 2, 4, and 6 weeks after surgery.
Results:
The sitting time and degradation time of the bFGF- and CaPP-loaded fibrin clots were set at 15 seconds and more than 2 weeks, respectively, and the porosity was minimized to achieve the highest levels of cell migration and growth. In the bFGF-CaPP group of the in vitro experiment, cell proliferation increased to a greater extent relative to the control group (P < .05); the mRNA expression of osteopontin, alkaline phosphatase, runt-related transcription factor 2, vascular endothelial growth factor, and collagen type I was upregulated (P < .05); and the relative protein expression of these factors was enhanced (P < .05). In vivo, hematoxylin and eosin staining showed that the tendon-to-bone connections were more mature and more arranged when treated with bFGF- and CaPP-loaded fibrin clots than when untreated, and the histological scores were higher.
Conclusion:
bFGF- and CaPP-loaded fibrin clots enhanced cell migration and proliferation and the expression of related genes and proteins, which increased the bioactivity of the tendon-bone interface and resulted in the histological improvement of tendon-to-bone healing.
Clinical Relevance:
As fibrin clots have already been used in clinical practice, bFGF- and CaPP-loaded fibrin clots can be further used to augment healing in the early stages of tendon-to-bone healing.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546516637603</identifier><identifier>PMID: 27159301</identifier><identifier>CODEN: AJSMDO</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Animals ; Biological activity ; Bone and Bones - metabolism ; Bone and Bones - physiopathology ; Cell adhesion & migration ; Fibrin - metabolism ; Fibroblast Growth Factor 2 - metabolism ; Growth factors ; Humans ; Knee ; Male ; Phosphatase ; Phosphoprotein Phosphatases - metabolism ; Rabbits ; Sports medicine ; Tendon Injuries - metabolism ; Tendon Injuries - physiopathology ; Tendon Injuries - surgery ; Tendons - enzymology ; Tendons - metabolism ; Tendons - physiopathology ; Tendons - surgery ; Vascular Endothelial Growth Factor A - metabolism ; Wound Healing</subject><ispartof>The American journal of sports medicine, 2016-08, Vol.44 (8), p.1972-1982</ispartof><rights>2016 The Author(s)</rights><rights>2016 The Author(s).</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-a60a770c1807de355d8a048b834468665b82363004837b4142bd79af7521c61c3</citedby><cites>FETCH-LOGICAL-c468t-a60a770c1807de355d8a048b834468665b82363004837b4142bd79af7521c61c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0363546516637603$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0363546516637603$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,780,784,21818,27923,27924,43620,43621</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27159301$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Chenghao</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Deng, Senlin</creatorcontrib><creatorcontrib>Fu, Weili</creatorcontrib><creatorcontrib>Tang, Xin</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Qin, Tingwu</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><title>bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background:
Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and tissue engineering,
Hypothesis:
Modified fibrin clots can improve the bioactivity of the tendon-bone interface and histological appearance.
Study Design:
Controlled laboratory study.
Methods:
A total of 27 male New Zealand White rabbits were used. Of these, 3 were used for cell isolation, and the remaining 24 rabbits were divided into 2 groups (12 per group) for an in vivo partial patellectomy study. The setting time, degradation time, and basic fibroblast growth factor (bFGF) and ceramide-activated protein phosphatase (CaPP) release kinetics of bFGF- and CaPP-loaded fibrin clots were modified appropriately for early tendon-to-bone healing. In an in vitro experiment, the bFGF- and CaPP-loaded fibrin clots were assessed for cell migration and proliferation by microscopy, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, and DAPI (4′,6-diamidino-2-phenylindole) assay. Quantitative real-time reverse transcription polymerase chain reaction and a Western blot assay were performed to test for an induction effect of the bFGF- and CaPP-loaded fibrin clots. Finally, for the in vivo experiment, the rabbits were divided into 2 treatment groups: one with bFGF- and CaPP-loaded fibrin clots and one without bFGF- and CaPP-loaded fibrin clots after partial patellectomy in patella–patellar tendon sutured sites. A histological evaluation was performed at 2, 4, and 6 weeks after surgery.
Results:
The sitting time and degradation time of the bFGF- and CaPP-loaded fibrin clots were set at 15 seconds and more than 2 weeks, respectively, and the porosity was minimized to achieve the highest levels of cell migration and growth. In the bFGF-CaPP group of the in vitro experiment, cell proliferation increased to a greater extent relative to the control group (P < .05); the mRNA expression of osteopontin, alkaline phosphatase, runt-related transcription factor 2, vascular endothelial growth factor, and collagen type I was upregulated (P < .05); and the relative protein expression of these factors was enhanced (P < .05). In vivo, hematoxylin and eosin staining showed that the tendon-to-bone connections were more mature and more arranged when treated with bFGF- and CaPP-loaded fibrin clots than when untreated, and the histological scores were higher.
Conclusion:
bFGF- and CaPP-loaded fibrin clots enhanced cell migration and proliferation and the expression of related genes and proteins, which increased the bioactivity of the tendon-bone interface and resulted in the histological improvement of tendon-to-bone healing.
Clinical Relevance:
As fibrin clots have already been used in clinical practice, bFGF- and CaPP-loaded fibrin clots can be further used to augment healing in the early stages of tendon-to-bone healing.</description><subject>Animals</subject><subject>Biological activity</subject><subject>Bone and Bones - metabolism</subject><subject>Bone and Bones - physiopathology</subject><subject>Cell adhesion & migration</subject><subject>Fibrin - metabolism</subject><subject>Fibroblast Growth Factor 2 - metabolism</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Knee</subject><subject>Male</subject><subject>Phosphatase</subject><subject>Phosphoprotein Phosphatases - metabolism</subject><subject>Rabbits</subject><subject>Sports medicine</subject><subject>Tendon Injuries - metabolism</subject><subject>Tendon Injuries - physiopathology</subject><subject>Tendon Injuries - surgery</subject><subject>Tendons - enzymology</subject><subject>Tendons - metabolism</subject><subject>Tendons - physiopathology</subject><subject>Tendons - surgery</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Wound Healing</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1Lw0AQxRdRtFbvnmTBi5fVmeynRy1WhYI96Dlskk1NSXc1mwj-926tigjiaWDeb94w8wg5QjhD1PocuOJSKIlKca2Ab5ERSpkxzpXcJqO1zNb6HtmPcQkAqJXZJXuZRnnBAUdkWUxvpoxaX9GJnc_ZLNjKVXTaFF3j6aQNfaTX_sn60tH-ydGrJtiyb16b_o2G-qP14HwVPLsK3tE737uutms40MthsXK-p7fOto1fHJCd2rbRHX7WMXmcXj9Mbtns_uZucjljpVCmZ1aB1RpKNKArx6WsjAVhCsNF0pWShcnSXZB6XBcCRVZU-sLWWmZYKiz5mJxufJ-78DK42OerJpauba13YYg5GkSjJaSf_Y-CUSCkgISe_EKXYeh8OiRRXGAmlMBEwYYquxBj5-r8uWtWtnvLEfJ1ZPnvyNLI8afxUKxc9T3wlVEC2AaIduF-bP3L8B2aKpkG</recordid><startdate>201608</startdate><enddate>201608</enddate><creator>Zhang, Chenghao</creator><creator>Li, Qi</creator><creator>Deng, Senlin</creator><creator>Fu, Weili</creator><creator>Tang, Xin</creator><creator>Chen, Gang</creator><creator>Qin, Tingwu</creator><creator>Li, Jian</creator><general>SAGE Publications</general><general>Sage Publications 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>7TS</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>U9A</scope><scope>7X8</scope></search><sort><creationdate>201608</creationdate><title>bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing</title><author>Zhang, Chenghao ; Li, Qi ; Deng, Senlin ; Fu, Weili ; Tang, Xin ; Chen, Gang ; Qin, Tingwu ; Li, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-a60a770c1807de355d8a048b834468665b82363004837b4142bd79af7521c61c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Biological activity</topic><topic>Bone and Bones - metabolism</topic><topic>Bone and Bones - physiopathology</topic><topic>Cell adhesion & migration</topic><topic>Fibrin - metabolism</topic><topic>Fibroblast Growth Factor 2 - metabolism</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Knee</topic><topic>Male</topic><topic>Phosphatase</topic><topic>Phosphoprotein Phosphatases - metabolism</topic><topic>Rabbits</topic><topic>Sports medicine</topic><topic>Tendon Injuries - metabolism</topic><topic>Tendon Injuries - physiopathology</topic><topic>Tendon Injuries - surgery</topic><topic>Tendons - enzymology</topic><topic>Tendons - metabolism</topic><topic>Tendons - physiopathology</topic><topic>Tendons - surgery</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Chenghao</creatorcontrib><creatorcontrib>Li, Qi</creatorcontrib><creatorcontrib>Deng, Senlin</creatorcontrib><creatorcontrib>Fu, Weili</creatorcontrib><creatorcontrib>Tang, Xin</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Qin, Tingwu</creatorcontrib><creatorcontrib>Li, Jian</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Chenghao</au><au>Li, Qi</au><au>Deng, Senlin</au><au>Fu, Weili</au><au>Tang, Xin</au><au>Chen, Gang</au><au>Qin, Tingwu</au><au>Li, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2016-08</date><risdate>2016</risdate><volume>44</volume><issue>8</issue><spage>1972</spage><epage>1982</epage><pages>1972-1982</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><coden>AJSMDO</coden><abstract>Background:
Tendon-to-bone healing is a complex and slow process, and the rate of poor healing remains high. In recent years, several new strategies have been developed that enhance tendon-to-bone healing by increasing the bioactivity. Fibrin clots have been widely used to improve tissue healing and tissue engineering,
Hypothesis:
Modified fibrin clots can improve the bioactivity of the tendon-bone interface and histological appearance.
Study Design:
Controlled laboratory study.
Methods:
A total of 27 male New Zealand White rabbits were used. Of these, 3 were used for cell isolation, and the remaining 24 rabbits were divided into 2 groups (12 per group) for an in vivo partial patellectomy study. The setting time, degradation time, and basic fibroblast growth factor (bFGF) and ceramide-activated protein phosphatase (CaPP) release kinetics of bFGF- and CaPP-loaded fibrin clots were modified appropriately for early tendon-to-bone healing. In an in vitro experiment, the bFGF- and CaPP-loaded fibrin clots were assessed for cell migration and proliferation by microscopy, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay, and DAPI (4′,6-diamidino-2-phenylindole) assay. Quantitative real-time reverse transcription polymerase chain reaction and a Western blot assay were performed to test for an induction effect of the bFGF- and CaPP-loaded fibrin clots. Finally, for the in vivo experiment, the rabbits were divided into 2 treatment groups: one with bFGF- and CaPP-loaded fibrin clots and one without bFGF- and CaPP-loaded fibrin clots after partial patellectomy in patella–patellar tendon sutured sites. A histological evaluation was performed at 2, 4, and 6 weeks after surgery.
Results:
The sitting time and degradation time of the bFGF- and CaPP-loaded fibrin clots were set at 15 seconds and more than 2 weeks, respectively, and the porosity was minimized to achieve the highest levels of cell migration and growth. In the bFGF-CaPP group of the in vitro experiment, cell proliferation increased to a greater extent relative to the control group (P < .05); the mRNA expression of osteopontin, alkaline phosphatase, runt-related transcription factor 2, vascular endothelial growth factor, and collagen type I was upregulated (P < .05); and the relative protein expression of these factors was enhanced (P < .05). In vivo, hematoxylin and eosin staining showed that the tendon-to-bone connections were more mature and more arranged when treated with bFGF- and CaPP-loaded fibrin clots than when untreated, and the histological scores were higher.
Conclusion:
bFGF- and CaPP-loaded fibrin clots enhanced cell migration and proliferation and the expression of related genes and proteins, which increased the bioactivity of the tendon-bone interface and resulted in the histological improvement of tendon-to-bone healing.
Clinical Relevance:
As fibrin clots have already been used in clinical practice, bFGF- and CaPP-loaded fibrin clots can be further used to augment healing in the early stages of tendon-to-bone healing.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>27159301</pmid><doi>10.1177/0363546516637603</doi><tpages>11</tpages></addata></record> |
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| subjects | Animals Biological activity Bone and Bones - metabolism Bone and Bones - physiopathology Cell adhesion & migration Fibrin - metabolism Fibroblast Growth Factor 2 - metabolism Growth factors Humans Knee Male Phosphatase Phosphoprotein Phosphatases - metabolism Rabbits Sports medicine Tendon Injuries - metabolism Tendon Injuries - physiopathology Tendon Injuries - surgery Tendons - enzymology Tendons - metabolism Tendons - physiopathology Tendons - surgery Vascular Endothelial Growth Factor A - metabolism Wound Healing |
| title | bFGF- and CaPP-Loaded Fibrin Clots Enhance the Bioactivity of the Tendon-Bone Interface to Augment Healing |
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