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Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies

Objective Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. Th...

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Published in:Cartilage 2021-12, Vol.13 (2_suppl), p.386S-397S
Main Authors: Styczynska-Soczka, Katarzyna, Amin, Anish K., Simpson, A. Hamish W., Hall, Andrew C.
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container_end_page 397S
container_issue 2_suppl
container_start_page 386S
container_title Cartilage
container_volume 13
creator Styczynska-Soczka, Katarzyna
Amin, Anish K.
Simpson, A. Hamish W.
Hall, Andrew C.
description Objective Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. Design Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco’s modified Eagle’s medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. Results Chondrocyte viability remained at >95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to 0.05). Conclusions In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. This human model could prove invaluable for the exploration, development, and assessment of preclinical cartilage repair and regenerative therapies.
doi_str_mv 10.1177/1947603520934534
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Hamish W. ; Hall, Andrew C.</creator><creatorcontrib>Styczynska-Soczka, Katarzyna ; Amin, Anish K. ; Simpson, A. Hamish W. ; Hall, Andrew C.</creatorcontrib><description>Objective Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. Design Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco’s modified Eagle’s medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. Results Chondrocyte viability remained at &gt;95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to &lt;35% at 10 weeks with deeper zones being relatively unaffected. In DMEM + 10% HS at 10 weeks, the number of chondrocytes possessing cytoplasmic processes increased compared with DMEM (P = 0.017). Alcian blue labeling decreased (P = 0.02) and cartilage thinned (P ≤ 0.05); however, there was no change to surface roughness, chondrocyte density, chondrocyte volume, or picrosirius red labeling (P &gt; 0.05). Conclusions In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. This human model could prove invaluable for the exploration, development, and assessment of preclinical cartilage repair and regenerative therapies.</description><identifier>ISSN: 1947-6035</identifier><identifier>EISSN: 1947-6043</identifier><identifier>DOI: 10.1177/1947603520934534</identifier><identifier>PMID: 32567330</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Clinical Research papers</subject><ispartof>Cartilage, 2021-12, Vol.13 (2_suppl), p.386S-397S</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020 2020 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c434t-b7baa28b90b5fae4cb44937bf67039cecc4a59c659b439a0e2c17edb1d1e403e3</citedby><cites>FETCH-LOGICAL-c434t-b7baa28b90b5fae4cb44937bf67039cecc4a59c659b439a0e2c17edb1d1e403e3</cites><orcidid>0000-0001-8015-9473</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721618/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8721618/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,21966,27853,27924,27925,44945,45333,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32567330$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Styczynska-Soczka, Katarzyna</creatorcontrib><creatorcontrib>Amin, Anish K.</creatorcontrib><creatorcontrib>Simpson, A. Hamish W.</creatorcontrib><creatorcontrib>Hall, Andrew C.</creatorcontrib><title>Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies</title><title>Cartilage</title><addtitle>Cartilage</addtitle><description>Objective Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. Design Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco’s modified Eagle’s medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. Results Chondrocyte viability remained at &gt;95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to &lt;35% at 10 weeks with deeper zones being relatively unaffected. In DMEM + 10% HS at 10 weeks, the number of chondrocytes possessing cytoplasmic processes increased compared with DMEM (P = 0.017). Alcian blue labeling decreased (P = 0.02) and cartilage thinned (P ≤ 0.05); however, there was no change to surface roughness, chondrocyte density, chondrocyte volume, or picrosirius red labeling (P &gt; 0.05). Conclusions In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. 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Hamish W.</creator><creator>Hall, Andrew C.</creator><general>SAGE Publications</general><scope>AFRWT</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8015-9473</orcidid></search><sort><creationdate>20211201</creationdate><title>Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies</title><author>Styczynska-Soczka, Katarzyna ; Amin, Anish K. ; Simpson, A. Hamish W. ; Hall, Andrew C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c434t-b7baa28b90b5fae4cb44937bf67039cecc4a59c659b439a0e2c17edb1d1e403e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Clinical Research papers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Styczynska-Soczka, Katarzyna</creatorcontrib><creatorcontrib>Amin, Anish K.</creatorcontrib><creatorcontrib>Simpson, A. Hamish W.</creatorcontrib><creatorcontrib>Hall, Andrew C.</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cartilage</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Styczynska-Soczka, Katarzyna</au><au>Amin, Anish K.</au><au>Simpson, A. Hamish W.</au><au>Hall, Andrew C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies</atitle><jtitle>Cartilage</jtitle><addtitle>Cartilage</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>13</volume><issue>2_suppl</issue><spage>386S</spage><epage>397S</epage><pages>386S-397S</pages><issn>1947-6035</issn><eissn>1947-6043</eissn><abstract>Objective Articular cartilage is incapable of effective repair following injury or during osteoarthritis. While there have been developments in cartilage repair technologies, there is a need to advance biologically relevant models for preclinical testing of biomaterial and regenerative therapies. This study describes conditions for the effective ex vivo culture of the whole human femoral head. Design Fresh, viable femoral heads were obtained from femoral neck fractures and cultured for up to 10 weeks in (a) Dulbecco’s modified Eagle’s medium (DMEM); (b) DMEM + mixing; (c) DMEM + 10% human serum (HS); (d) DMEM + 10% HS + mixing. The viability, morphology, volume, and density of fluorescently labelled in situ chondrocytes and cartilage surface roughness were assessed by confocal microscopy. Cartilage histology was studied for glycosaminoglycan content using Alcian blue and collagen content using picrosirius red. Results Chondrocyte viability remained at &gt;95% in DMEM + 10% HS. In DMEM alone, viability remained high for ~4 weeks and then declined. For the other conditions, superficial zone chondrocyte viability fell to &lt;35% at 10 weeks with deeper zones being relatively unaffected. In DMEM + 10% HS at 10 weeks, the number of chondrocytes possessing cytoplasmic processes increased compared with DMEM (P = 0.017). Alcian blue labeling decreased (P = 0.02) and cartilage thinned (P ≤ 0.05); however, there was no change to surface roughness, chondrocyte density, chondrocyte volume, or picrosirius red labeling (P &gt; 0.05). Conclusions In this ex vivo model, chondrocyte viability was maintained in human femoral heads for up to 10 weeks in culture, a novel finding not previously reported. This human model could prove invaluable for the exploration, development, and assessment of preclinical cartilage repair and regenerative therapies.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>32567330</pmid><doi>10.1177/1947603520934534</doi><orcidid>https://orcid.org/0000-0001-8015-9473</orcidid><oa>free_for_read</oa></addata></record>
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title Optimization and Validation of a Human Ex Vivo Femoral Head Model for Preclinical Cartilage Research and Regenerative Therapies
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