An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study
Background: Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a brid...
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| Veröffentlicht in: | The American journal of sports medicine 2020-11, Vol.48 (13), p.3233-3244 |
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| creator | Yan, Wenqiang Xu, Xingquan Xu, Qian Sun, Ziying Lv, Zhongyang Wu, Rui Yan, Wenjin Jiang, Qing Shi, Dongquan |
| description | Background:
Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic.
Hypotheses:
(1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment.
Study Design:
Controlled laboratory study.
Methods:
48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests.
Results:
The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects.
Conclusion:
(1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects.
Clinical Relevance:
This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important pro |
| doi_str_mv | 10.1177/0363546520957346 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2456821686</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sage_id>10.1177_0363546520957346</sage_id><sourcerecordid>2456821686</sourcerecordid><originalsourceid>FETCH-LOGICAL-c365t-2c75bbdb2f3c813356e88821aaf43735e195c8c516c7c4a08fa5e9f4dcbf31633</originalsourceid><addsrcrecordid>eNp1kEtLAzEUhYMotj72riTgOppMJpnUXSm-8IkPXA6ZTFKnpMmYzCD9Cf5rU1oVBFcX7jnnu9wDwAHBx4QUxQmmnLKcswyPWEFzvgGGhLEMUcrZJhguZbTUB2AnxhnGmBRcbIMBpTjjguIh-Bw7eOVmWnWyshpeLurgp9rCJyWN8baGr033Bq9l6NLaNQ6dOSXb2FvZ6RreSefbpDXK6giND_DBB9U4DSfLrZVTDR91Cuogu8a7UziGJEO33iXoubfWf6C-hU9dXy_2wJaRNur99dwFL-dnz5NLdHN_cTUZ3yCVnupQpgpWVXWVGaoEoZRxLYTIiJQmpwVlmoyYEooRrgqVSyyMZHpk8lpVhhJO6S44WnHb4N97Hbty5vvg0skyyxlPKC54cuGVSwUfY9CmbEMzl2FRElwuuy__dp8ih2twX811_RP4LjsZ0MoQUy-_V_8FfgH0sYxj</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2456821686</pqid></control><display><type>article</type><title>An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study</title><source>MEDLINE</source><source>SAGE Complete</source><source>Alma/SFX Local Collection</source><creator>Yan, Wenqiang ; Xu, Xingquan ; Xu, Qian ; Sun, Ziying ; Lv, Zhongyang ; Wu, Rui ; Yan, Wenjin ; Jiang, Qing ; Shi, Dongquan</creator><creatorcontrib>Yan, Wenqiang ; Xu, Xingquan ; Xu, Qian ; Sun, Ziying ; Lv, Zhongyang ; Wu, Rui ; Yan, Wenjin ; Jiang, Qing ; Shi, Dongquan</creatorcontrib><description>Background:
Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic.
Hypotheses:
(1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment.
Study Design:
Controlled laboratory study.
Methods:
48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests.
Results:
The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects.
Conclusion:
(1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects.
Clinical Relevance:
This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.</description><identifier>ISSN: 0363-5465</identifier><identifier>EISSN: 1552-3365</identifier><identifier>DOI: 10.1177/0363546520957346</identifier><identifier>PMID: 33026830</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Anilides ; Animals ; Biomechanics ; Bones ; Cartilage ; Cartilage, Articular - diagnostic imaging ; Cartilage, Articular - injuries ; Cartilage, Articular - surgery ; Defects ; Follow-Up Studies ; Hydrogels ; Hydrogels - pharmacology ; Magnetic resonance imaging ; Nanoparticles ; Phthalic Acids ; Rabbits ; Regeneration ; Sports medicine ; Swine ; Swine, Miniature ; Tissue engineering ; Viscosupplements - pharmacology ; X-Ray Microtomography</subject><ispartof>The American journal of sports medicine, 2020-11, Vol.48 (13), p.3233-3244</ispartof><rights>2020 The Author(s)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c365t-2c75bbdb2f3c813356e88821aaf43735e195c8c516c7c4a08fa5e9f4dcbf31633</citedby><cites>FETCH-LOGICAL-c365t-2c75bbdb2f3c813356e88821aaf43735e195c8c516c7c4a08fa5e9f4dcbf31633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.sagepub.com/doi/pdf/10.1177/0363546520957346$$EPDF$$P50$$Gsage$$H</linktopdf><linktohtml>$$Uhttps://journals.sagepub.com/doi/10.1177/0363546520957346$$EHTML$$P50$$Gsage$$H</linktohtml><link.rule.ids>314,776,780,21798,27901,27902,43597,43598</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33026830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, Wenqiang</creatorcontrib><creatorcontrib>Xu, Xingquan</creatorcontrib><creatorcontrib>Xu, Qian</creatorcontrib><creatorcontrib>Sun, Ziying</creatorcontrib><creatorcontrib>Lv, Zhongyang</creatorcontrib><creatorcontrib>Wu, Rui</creatorcontrib><creatorcontrib>Yan, Wenjin</creatorcontrib><creatorcontrib>Jiang, Qing</creatorcontrib><creatorcontrib>Shi, Dongquan</creatorcontrib><title>An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study</title><title>The American journal of sports medicine</title><addtitle>Am J Sports Med</addtitle><description>Background:
Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic.
Hypotheses:
(1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment.
Study Design:
Controlled laboratory study.
Methods:
48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests.
Results:
The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects.
Conclusion:
(1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects.
Clinical Relevance:
This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.</description><subject>Anilides</subject><subject>Animals</subject><subject>Biomechanics</subject><subject>Bones</subject><subject>Cartilage</subject><subject>Cartilage, Articular - diagnostic imaging</subject><subject>Cartilage, Articular - injuries</subject><subject>Cartilage, Articular - surgery</subject><subject>Defects</subject><subject>Follow-Up Studies</subject><subject>Hydrogels</subject><subject>Hydrogels - pharmacology</subject><subject>Magnetic resonance imaging</subject><subject>Nanoparticles</subject><subject>Phthalic Acids</subject><subject>Rabbits</subject><subject>Regeneration</subject><subject>Sports medicine</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Tissue engineering</subject><subject>Viscosupplements - pharmacology</subject><subject>X-Ray Microtomography</subject><issn>0363-5465</issn><issn>1552-3365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtLAzEUhYMotj72riTgOppMJpnUXSm-8IkPXA6ZTFKnpMmYzCD9Cf5rU1oVBFcX7jnnu9wDwAHBx4QUxQmmnLKcswyPWEFzvgGGhLEMUcrZJhguZbTUB2AnxhnGmBRcbIMBpTjjguIh-Bw7eOVmWnWyshpeLurgp9rCJyWN8baGr033Bq9l6NLaNQ6dOSXb2FvZ6RreSefbpDXK6giND_DBB9U4DSfLrZVTDR91Cuogu8a7UziGJEO33iXoubfWf6C-hU9dXy_2wJaRNur99dwFL-dnz5NLdHN_cTUZ3yCVnupQpgpWVXWVGaoEoZRxLYTIiJQmpwVlmoyYEooRrgqVSyyMZHpk8lpVhhJO6S44WnHb4N97Hbty5vvg0skyyxlPKC54cuGVSwUfY9CmbEMzl2FRElwuuy__dp8ih2twX811_RP4LjsZ0MoQUy-_V_8FfgH0sYxj</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Yan, Wenqiang</creator><creator>Xu, Xingquan</creator><creator>Xu, Qian</creator><creator>Sun, Ziying</creator><creator>Lv, Zhongyang</creator><creator>Wu, Rui</creator><creator>Yan, Wenjin</creator><creator>Jiang, Qing</creator><creator>Shi, Dongquan</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></search><sort><creationdate>202011</creationdate><title>An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study</title><author>Yan, Wenqiang ; Xu, Xingquan ; Xu, Qian ; Sun, Ziying ; Lv, Zhongyang ; Wu, Rui ; Yan, Wenjin ; Jiang, Qing ; Shi, Dongquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c365t-2c75bbdb2f3c813356e88821aaf43735e195c8c516c7c4a08fa5e9f4dcbf31633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Anilides</topic><topic>Animals</topic><topic>Biomechanics</topic><topic>Bones</topic><topic>Cartilage</topic><topic>Cartilage, Articular - diagnostic imaging</topic><topic>Cartilage, Articular - injuries</topic><topic>Cartilage, Articular - surgery</topic><topic>Defects</topic><topic>Follow-Up Studies</topic><topic>Hydrogels</topic><topic>Hydrogels - pharmacology</topic><topic>Magnetic resonance imaging</topic><topic>Nanoparticles</topic><topic>Phthalic Acids</topic><topic>Rabbits</topic><topic>Regeneration</topic><topic>Sports medicine</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>Tissue engineering</topic><topic>Viscosupplements - pharmacology</topic><topic>X-Ray Microtomography</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, Wenqiang</creatorcontrib><creatorcontrib>Xu, Xingquan</creatorcontrib><creatorcontrib>Xu, Qian</creatorcontrib><creatorcontrib>Sun, Ziying</creatorcontrib><creatorcontrib>Lv, Zhongyang</creatorcontrib><creatorcontrib>Wu, Rui</creatorcontrib><creatorcontrib>Yan, Wenjin</creatorcontrib><creatorcontrib>Jiang, Qing</creatorcontrib><creatorcontrib>Shi, Dongquan</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><jtitle>The American journal of sports medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, Wenqiang</au><au>Xu, Xingquan</au><au>Xu, Qian</au><au>Sun, Ziying</au><au>Lv, Zhongyang</au><au>Wu, Rui</au><au>Yan, Wenjin</au><au>Jiang, Qing</au><au>Shi, Dongquan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study</atitle><jtitle>The American journal of sports medicine</jtitle><addtitle>Am J Sports Med</addtitle><date>2020-11</date><risdate>2020</risdate><volume>48</volume><issue>13</issue><spage>3233</spage><epage>3244</epage><pages>3233-3244</pages><issn>0363-5465</issn><eissn>1552-3365</eissn><abstract>Background:
Treatment of cartilage lesions is clinically challenging. A previous study demonstrated that a hyaluronic acid hydrogel (m-HA) with kartogenin (KGN)-loaded PLGA nanoparticles (m-HA+KGN treatment) achieved superior cartilage repair in a rabbit model. However, large animals serve as a bridge to translate animal outcomes into the clinic.
Hypotheses:
(1) m-HA+KGN treatment could facilitate hyaline cartilage and subchondral bone tissue repair in a porcine model. (2) Defect size and type (full-thickness chondral vs osteochondral) influence the therapeutic efficacy of m-HA+KGN treatment.
Study Design:
Controlled laboratory study.
Methods:
48 minipigs were randomized into 3 treatment groups: m-HA hydrogel with KGN-loaded PLGA nanoparticles (m-HA+KGN treatment), m-HA hydrogel (m-HA treatment), and untreated (blank treatment). Full-thickness chondral (6.5 mm or 8.5 mm in diameter) or osteochondral (6.5 mm or 8.5 mm in diameter; 5-mm depth) defects were prepared in the medial femoral condyle. At 6 and 12 months postoperatively, defect repair was assessed by macroscopic appearance, magnetic resonance imaging (MRI), micro–computed tomography (µCT), and histologic and biomechanical tests.
Results:
The m-HA+KGN group exhibited superior gross and histological healing after evaluation at 6 and 12 months postoperatively. Improved quality of the repaired cartilage demonstrated by MRI and better subchondral bone reconstruction assessed by µCT were observed in the m-HA+KGN group. The m-HA+KGN group showed more hyaline-like cartilage exhibited by histological staining in terms of extracellular matrix, cartilage lacuna, and type II collagen. The biomechanical properties were improved in the m-HA+KGN group. With m-HA+KGN treatment, defects with a diameter of 6.5 mm or full-thickness chondral-type defects possessed significantly higher ICRS macroscopic and histological scores compared with diameter 8.5 mm or osteochondral-type defects.
Conclusion:
(1) m-HA+KGN treatment facilitated hyaline cartilage and subchondral bone tissue repair in a porcine model at the 12-month follow-up. (2) m-HA+KGN treatment demonstrated better therapeutic efficacy in defects with a diameter of 6.5 mm or full-thickness chondral-type defects.
Clinical Relevance:
This study verified the efficacy of this innovative KGN release system on cartilage repair. The KGN release system can be injected into defect sites arthroscopically. This convenient and minimally invasive operation holds important prospects for clinical application.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>33026830</pmid><doi>10.1177/0363546520957346</doi><tpages>12</tpages></addata></record> |
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| subjects | Anilides Animals Biomechanics Bones Cartilage Cartilage, Articular - diagnostic imaging Cartilage, Articular - injuries Cartilage, Articular - surgery Defects Follow-Up Studies Hydrogels Hydrogels - pharmacology Magnetic resonance imaging Nanoparticles Phthalic Acids Rabbits Regeneration Sports medicine Swine Swine, Miniature Tissue engineering Viscosupplements - pharmacology X-Ray Microtomography |
| title | An Injectable Hydrogel Scaffold With Kartogenin-Encapsulated Nanoparticles for Porcine Cartilage Regeneration: A 12-Month Follow-up Study |
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