Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy
Identifieur interne : 005314 ( Ncbi/Merge ); précédent : 005313; suivant : 005315Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy
Auteurs : Isaac A. Rodriguez [États-Unis] ; Emily A. Growney Kalaf [États-Unis] ; Gary L. Bowlin [États-Unis] ; Scott A. Sell [États-Unis]Source :
- BioMed Research International [ 2314-6133 ] ; 2014.
Abstract
Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both
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DOI: 10.1155/2014/392398
PubMed: 25050347
PubMed Central: 4094865
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy</title>
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<author><name sortKey="Growney Kalaf, Emily A" sort="Growney Kalaf, Emily A" uniqKey="Growney Kalaf E" first="Emily A." last="Growney Kalaf">Emily A. Growney Kalaf</name>
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<series><title level="j">BioMed Research International</title>
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<front><div type="abstract" xml:lang="en"><p>Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both <italic>in vitro</italic>
and <italic>in vivo</italic>
scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.</p>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomed Res Int</journal-id>
<journal-id journal-id-type="iso-abbrev">Biomed Res Int</journal-id>
<journal-id journal-id-type="publisher-id">BMRI</journal-id>
<journal-title-group><journal-title>BioMed Research International</journal-title>
</journal-title-group>
<issn pub-type="ppub">2314-6133</issn>
<issn pub-type="epub">2314-6141</issn>
<publisher><publisher-name>Hindawi Publishing Corporation</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25050347</article-id>
<article-id pub-id-type="pmc">4094865</article-id>
<article-id pub-id-type="doi">10.1155/2014/392398</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Platelet-Rich Plasma in Bone Regeneration: Engineering the Delivery for Improved Clinical Efficacy</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Rodriguez</surname>
<given-names>Isaac A.</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Growney Kalaf</surname>
<given-names>Emily A.</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Bowlin</surname>
<given-names>Gary L.</given-names>
</name>
<xref ref-type="aff" rid="I1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sell</surname>
<given-names>Scott A.</given-names>
</name>
<xref ref-type="aff" rid="I2"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="I1"><sup>1</sup>
Department of Biomedical Engineering, The University of Memphis and Joint University of Memphis-UTHSC-Memphis Biomedical Engineering Program, 330 Engineering Technology, Memphis, TN 38152, USA</aff>
<aff id="I2"><sup>2</sup>
Department of Biomedical Engineering, Parks College of Engineering, Aviation, and Technology, Saint Louis University, 3507 Lindell Boulevard, St. Louis, MO 63103, USA</aff>
<author-notes><corresp id="cor1">*Scott A. Sell: <email>ssell@slu.edu</email>
</corresp>
<fn fn-type="other"><p>Academic Editor: Li Wu Zheng</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>23</day>
<month>6</month>
<year>2014</year>
</pub-date>
<volume>2014</volume>
<elocation-id>392398</elocation-id>
<history><date date-type="received"><day>24</day>
<month>2</month>
<year>2014</year>
</date>
<date date-type="rev-recd"><day>18</day>
<month>5</month>
<year>2014</year>
</date>
<date date-type="accepted"><day>1</day>
<month>6</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2014 Isaac A. Rodriguez et al.</copyright-statement>
<copyright-year>2014</copyright-year>
<license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract><p>Human bone is a tissue with a fairly remarkable inherent capacity for regeneration; however, this regenerative capacity has its limitations, and defects larger than a critical size lack the ability to spontaneously heal. As such, the development and clinical translation of effective bone regeneration modalities are paramount. One regenerative medicine approach that is beginning to gain momentum in the clinical setting is the use of platelet-rich plasma (PRP). PRP therapy is essentially a method for concentrating platelets and their intrinsic growth factors to stimulate and accelerate a healing response. While PRP has shown some efficacy in both <italic>in vitro</italic>
and <italic>in vivo</italic>
scenarios, to date its use and delivery have not been optimized for bone regeneration. Issues remain with the effective delivery of the platelet-derived growth factors to a localized site of injury, the activation and temporal release of the growth factors, and the rate of growth factor clearance. This review will briefly describe the physiological principles behind PRP use and then discuss how engineering its method of delivery may ultimately impact its ability to successfully translate to widespread clinical use.</p>
</abstract>
</article-meta>
</front>
<floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label>
<caption><p>Preparation of autologous bone-platelet gel. Autologous bone particles mixed with PRP followed by activation. This gel-consistency scaffold can be easily handled [<xref rid="B71" ref-type="bibr">64</xref>
]. Reprinted with permission from Elsevier.</p>
</caption>
<graphic xlink:href="BMRI2014-392398.001"></graphic>
</fig>
<fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label>
<caption><p>Gross examination of rabbit tibia healing after 11 weeks with (a) control group, no platelet gel or Coragraft; (b) platelet gel; (c) Coragraft; and (d) platelet gel and Coragraft [<xref rid="B81" ref-type="bibr">74</xref>
]. Reprinted with permission from Elsevier.</p>
</caption>
<graphic xlink:href="BMRI2014-392398.002"></graphic>
</fig>
<fig id="fig3" orientation="portrait" position="float"><label>Figure 3</label>
<caption><p>Photographs and 3D images of rabbit calvarial defects before and after 8 weeks of implantation with (a) gelatin hydrogel + PRP, (b) platelet gel, (c) gelatin hydrogel without PRP, and (d) no treatment. Complete bone regeneration was only observed in the gelatin hydrogels with PRP. Reprinted with permission from Mosby, Inc.</p>
</caption>
<graphic xlink:href="BMRI2014-392398.003"></graphic>
</fig>
<table-wrap id="tab1" orientation="portrait" position="float"><label>Table 1</label>
<caption><p>Some PRP bioactive molecules and their physiologic roles [<xref rid="B25" ref-type="bibr">127</xref>
]. Reprinted with permission from John Wiley and Sons.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">General category</th>
<th align="left" rowspan="1" colspan="1">Specific molecules</th>
<th align="left" rowspan="1" colspan="1">Physiologic role</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Adhesive proteins</td>
<td align="left" rowspan="1" colspan="1">Fibrinogen, fibronectin, vitronectin, thrombospondin-1, von Willebrand factor, and laminin-8</td>
<td align="left" rowspan="1" colspan="1">Cell contact interactions, cellular adhesion, chemotaxis, ECM composition, and clotting</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Clotting factors and associated proteins</td>
<td align="left" rowspan="1" colspan="1">Factor V, factor XI, protein S, antithrombin, and tissue factor pathway inhibitor</td>
<td align="left" rowspan="1" colspan="1">Thrombin activation and its regulation, eventual fibrin clot formation</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Fibrinolytic factors and associated proteins</td>
<td align="left" rowspan="1" colspan="1">Plasminogen, plasminogen activator inhibitor, <italic>α</italic>
-2 antiplasmin, and thrombin-activatable fibrinolysis inhibitor</td>
<td align="left" rowspan="1" colspan="1">Plasmin production and regulation</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Proteases and antiproteases</td>
<td align="left" rowspan="1" colspan="1">Tissue inhibitor of metalloproteases 1-4 (TIMP 1-4), MMP-1, -2, -4, and -9, and <italic>α</italic>
-1 antitrypsin</td>
<td align="left" rowspan="1" colspan="1">Regulation of matrix degradation, regulation of cellular behavior, and so forth</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Growth factors, cytokines, and chemokines</td>
<td align="left" rowspan="1" colspan="1">TGF-<italic>β</italic>
, PDGF, insulin like growth factors (IGF) I and II, FGF, EGF, VEGF, ECGF, KGF, GM-CSF, hepatocyte GF, TNF<italic>α</italic>
, RANTES, IL-8, IL-1<italic>β</italic>
, and BMP-2, -4, and -6</td>
<td align="left" rowspan="1" colspan="1">Chemotaxis, cell proliferation and differentiation, promotion of ECM production, regulation of inflammation, and angiogenesis</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Antimicrobial proteins</td>
<td align="left" rowspan="1" colspan="1">Thrombocidins and kinocidins</td>
<td align="left" rowspan="1" colspan="1">Bactericidal and fungicidal properties</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Membrane glycoproteins</td>
<td align="left" rowspan="1" colspan="1"><italic>α</italic>
IIb<italic>β</italic>
3, <italic>α</italic>
v<italic>β</italic>
3, CD-40 ligand, P-selectin, tissue factor, PECAM-1, tissue factor, and CD63</td>
<td align="left" rowspan="1" colspan="1">Platelet aggregation and adhesion, inflammation, and platelet-leukocyte interactions</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Lipids</td>
<td align="left" rowspan="1" colspan="1">Sphingosine-1-phosphate, HETEs, thromboxane B<sub>2</sub>
, prostaglandin F<sub>2</sub>
<italic>α</italic>
, leukotriene B<sub>4</sub>
, and lipoxin A<sub>4</sub>
</td>
<td align="left" rowspan="1" colspan="1">Inflammation modulation, cell migration and proliferation, and so forth</td>
</tr>
<tr><td align="center" colspan="3" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Basic proteins and others</td>
<td align="left" rowspan="1" colspan="1">Platelet factor 4, <italic>β</italic>
-thromboglobulin, endostatins, connective tissue activating peptide III, chondroitin-4 sulfate, albumin, and immunoglobulins G and M</td>
<td align="left" rowspan="1" colspan="1">Regulation of endothelial cell chemotaxis and angiogenesis, vascular modeling, platelet activation, and so forth</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab2" orientation="portrait" position="float"><label>Table 2</label>
<caption><p>Role of PRP components in bone remodeling.</p>
</caption>
<table frame="hsides" rules="groups"><tbody><tr><td align="left" rowspan="1" colspan="1">PDGF</td>
<td align="left" rowspan="1" colspan="1">Mesenchymal stem cell (MSC) and progenitor cell recruitment, proliferation, migration, and osteogenic differentiation. Osteoblast proliferation and ECM ossification [<xref rid="B27" ref-type="bibr">25</xref>
, <xref rid="B26" ref-type="bibr">128</xref>
, <xref rid="B28" ref-type="bibr">129</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">TGF-<italic>β</italic>
</td>
<td align="left" rowspan="1" colspan="1">MSC recruitment and differentiation. Increased production of collagen and mineral matrix. Inhibits osteoclast formation and bone resorption [<xref rid="B26" ref-type="bibr">128</xref>
–<xref rid="B29" ref-type="bibr">130</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">TGF-<italic>β</italic>
1</td>
<td align="left" rowspan="1" colspan="1">MSC recruitment, proliferation, and osteogenic differentiation [<xref rid="B27" ref-type="bibr">25</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">IGF-1</td>
<td align="left" rowspan="1" colspan="1">Stimulates bone formation via cellular proliferation, differentiation, and synthesis of Type I collagen [<xref rid="B27" ref-type="bibr">25</xref>
, <xref rid="B26" ref-type="bibr">128</xref>
, <xref rid="B28" ref-type="bibr">129</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">IL-1, IL-6, TNF-<italic>α</italic>
</td>
<td align="left" rowspan="1" colspan="1">Promotes early responses of bone repair, endochondral bone formation, and bone remodeling [<xref rid="B28" ref-type="bibr">129</xref>
, <xref rid="B30" ref-type="bibr">131</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Basic FGF</td>
<td align="left" rowspan="1" colspan="1">MSC growth and differentiation. Osteoblast proliferation [<xref rid="B31" ref-type="bibr">132</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Fibronectin, vitronectin</td>
<td align="left" rowspan="1" colspan="1">Enhances formation of focal adhesions by osteoblasts, osteoblast migration [<xref rid="B32" ref-type="bibr">133</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">VEGF</td>
<td align="left" rowspan="1" colspan="1">Promotes angiogenesis and endochondral ossification [<xref rid="B27" ref-type="bibr">25</xref>
]</td>
</tr>
<tr><td align="center" colspan="2" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">VGF, platelet microparticles</td>
<td align="left" rowspan="1" colspan="1">Promotes angiogenesis [<xref rid="B30" ref-type="bibr">131</xref>
]</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab3" orientation="portrait" position="float"><label>Table 3</label>
<caption><p>Summary of studies which used PRP in its inactive form. </p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Authors</th>
<th align="center" rowspan="1" colspan="1">Study</th>
<th align="center" rowspan="1" colspan="1">Platelet concentration</th>
<th align="left" rowspan="1" colspan="1">Results</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Nikolidakis et al. (2006) [<xref rid="B34" ref-type="bibr">27</xref>
], Nikolidakis et al. (2008) [<xref rid="B35" ref-type="bibr">28</xref>
]</td>
<td align="center" rowspan="1" colspan="1">CaP + Ti implants</td>
<td align="center" rowspan="1" colspan="1">8–12 × 10<sup>5</sup>
/<italic>μ</italic>
L </td>
<td align="left" rowspan="1" colspan="1">Significantly increased bone contact percentage with Ti + PRP (liquid) implants <break></break>
Significantly higher endosteal bone formation length in CaP + PRP (gel) coated implants</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Yun et al. (2013) [<xref rid="B38" ref-type="bibr">31</xref>
]</td>
<td align="center" rowspan="1" colspan="1">HA + BMMSCs + Ti implants</td>
<td align="center" rowspan="1" colspan="1">Adjusted to 1 × 10<sup>6</sup>
/<italic>μ</italic>
L</td>
<td align="left" rowspan="1" colspan="1">No significance found</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Chang et al. (2009) [<xref rid="B39" ref-type="bibr">32</xref>
]</td>
<td align="center" rowspan="1" colspan="1">HA/collagen type I bone graft formation</td>
<td align="center" rowspan="1" colspan="1">9.25–12.5 × 10<sup>5</sup>
/<italic>μ</italic>
L </td>
<td align="left" rowspan="1" colspan="1">Significant bone tissue in HA/collagen + PRP (liquid injection)</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Han et al. (2009) [<xref rid="B40" ref-type="bibr">33</xref>
]</td>
<td align="center" rowspan="1" colspan="1">DBM + active versus inactive PRP</td>
<td align="center" rowspan="1" colspan="1">8x over baseline∗</td>
<td align="left" rowspan="1" colspan="1">PRP (liquid) significantly increased osteoconductivity of DBM </td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn><p>Note (∗) that the study by Han et al. [<xref rid="B40" ref-type="bibr">33</xref>
] did not give exact platelet counts.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab4" orientation="portrait" position="float"><label>Table 4</label>
<caption><p>Summary of studies that used PRP via incorporating into nanofiber matrices. </p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="1" colspan="1">Authors</th>
<th align="center" rowspan="1" colspan="1">Study</th>
<th align="center" rowspan="1" colspan="1">Platelet concentration</th>
<th align="left" rowspan="1" colspan="1">Results</th>
</tr>
</thead>
<tbody><tr><td align="left" rowspan="1" colspan="1">Berner et al. (2012) [<xref rid="B128" ref-type="bibr">121</xref>
]</td>
<td align="center" rowspan="1" colspan="1">Allogenic PRP + BMP-7 + CaP coated electrospun PCL</td>
<td align="center" rowspan="1" colspan="1">Unknown</td>
<td align="left" rowspan="1" colspan="1">Significantly increased bone volume and biomechanical properties</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Sell et al. (2011) [<xref rid="B129" ref-type="bibr">122</xref>
]</td>
<td align="center" rowspan="1" colspan="1">PRGF scaffold characteristics and effects on human macrophages and ADSCs</td>
<td align="center" rowspan="1" colspan="1">955 × 10<sup>3</sup>
/<italic>μ</italic>
L (quantified elsewhere)</td>
<td align="left" rowspan="1" colspan="1">Increased macrophage chemotaxis, increased proliferation, and infiltration of ADSCs. Sustained protein release discovered</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Wolfe et al. (2011) [<xref rid="B122" ref-type="bibr">115</xref>
]</td>
<td align="center" rowspan="1" colspan="1">PRGF scaffold characteristics and effects on human ADSCs and hSMCs</td>
<td align="center" rowspan="1" colspan="1">955 × 10<sup>3</sup>
/<italic>μ</italic>
L (quantified elsewhere)</td>
<td align="left" rowspan="1" colspan="1">Cell integration into the scaffold after 3 days</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Yoshimi et al. (2009) [<xref rid="B126" ref-type="bibr">119</xref>
]</td>
<td align="center" rowspan="1" colspan="1">Self-assembling peptide “PuraMatrix” nanofiber scaffolds + PRP + dMSCs</td>
<td align="center" rowspan="1" colspan="1">Unknown</td>
<td align="left" rowspan="1" colspan="1">PRP alone did not promote bone regeneration, but it was facilitated with addition to dMSCs + PM</td>
</tr>
<tr><td align="left" rowspan="1" colspan="1">Kohgo et al. (2011) [<xref rid="B127" ref-type="bibr">120</xref>
]</td>
<td align="center" rowspan="1" colspan="1">Osseointegration of dental implants with PM + PRP + dMSCs</td>
<td align="center" rowspan="1" colspan="1">Unknown</td>
<td align="left" rowspan="1" colspan="1">PM + dMSCs + PRP showed significant osseointegration over other groups</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Missouri (État)</li>
<li>Tennessee</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Tennessee"><name sortKey="Rodriguez, Isaac A" sort="Rodriguez, Isaac A" uniqKey="Rodriguez I" first="Isaac A." last="Rodriguez">Isaac A. Rodriguez</name>
</region>
<name sortKey="Bowlin, Gary L" sort="Bowlin, Gary L" uniqKey="Bowlin G" first="Gary L." last="Bowlin">Gary L. Bowlin</name>
<name sortKey="Growney Kalaf, Emily A" sort="Growney Kalaf, Emily A" uniqKey="Growney Kalaf E" first="Emily A." last="Growney Kalaf">Emily A. Growney Kalaf</name>
<name sortKey="Sell, Scott A" sort="Sell, Scott A" uniqKey="Sell S" first="Scott A." last="Sell">Scott A. Sell</name>
</country>
</tree>
</affiliations>
</record>
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