An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering
[Display omitted] Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alo...
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| Veröffentlicht in: | Acta biomaterialia 2018-01, Vol.66, p.141-156 |
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| creator | Zhang, Can Wang, Xianliu Zhang, Erchen Yang, Long Yuan, Huihua Tu, Wenjing Zhang, Huilan Yin, Zi Shen, Weiliang Chen, Xiao Zhang, Yanzhong Ouyang, Hongwei |
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Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.
Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of “translating |
| doi_str_mv | 10.1016/j.actbio.2017.09.036 |
| format | Article |
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Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.
Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of “translating the biological knowledge learned from cell-material interaction into optimizing biomaterials (from Biomat-to-Biomat)”.</description><identifier>ISSN: 1742-7061</identifier><identifier>EISSN: 1878-7568</identifier><identifier>DOI: 10.1016/j.actbio.2017.09.036</identifier><identifier>PMID: 28963019</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Achilles tendon ; Alignment ; Biocompatibility ; Biomaterials ; Biomedical materials ; Cells (biology) ; Composite materials ; Differentiation ; Electrospun aligned fibers ; Fibers ; Histone acetylation ; Histone deacetylase ; Histone deacetylase inhibitor ; Implantation ; Lactic acid ; Mechanical properties ; Molecular chains ; Nanofibers ; Polylactic acid ; Progenitor cells ; Scaffolds ; Stem cell transplantation ; Stem cells ; Studies ; Surgical implants ; Tendon differentiation ; Tendons ; Tissue engineering ; Tissue regeneration ; Topography ; Transplants & implants ; Trichostatin A ; Ultrastructure</subject><ispartof>Acta biomaterialia, 2018-01, Vol.66, p.141-156</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Ltd.</rights><rights>Copyright Elsevier BV Jan 15, 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-fb9d83ee914c213175723be9d5e06af4ab5f47cb57e0870ede31787734f9b6243</citedby><cites>FETCH-LOGICAL-c427t-fb9d83ee914c213175723be9d5e06af4ab5f47cb57e0870ede31787734f9b6243</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.actbio.2017.09.036$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,777,781,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28963019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Can</creatorcontrib><creatorcontrib>Wang, Xianliu</creatorcontrib><creatorcontrib>Zhang, Erchen</creatorcontrib><creatorcontrib>Yang, Long</creatorcontrib><creatorcontrib>Yuan, Huihua</creatorcontrib><creatorcontrib>Tu, Wenjing</creatorcontrib><creatorcontrib>Zhang, Huilan</creatorcontrib><creatorcontrib>Yin, Zi</creatorcontrib><creatorcontrib>Shen, Weiliang</creatorcontrib><creatorcontrib>Chen, Xiao</creatorcontrib><creatorcontrib>Zhang, Yanzhong</creatorcontrib><creatorcontrib>Ouyang, Hongwei</creatorcontrib><title>An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering</title><title>Acta biomaterialia</title><addtitle>Acta Biomater</addtitle><description>[Display omitted]
Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.
Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of “translating the biological knowledge learned from cell-material interaction into optimizing biomaterials (from Biomat-to-Biomat)”.</description><subject>Achilles tendon</subject><subject>Alignment</subject><subject>Biocompatibility</subject><subject>Biomaterials</subject><subject>Biomedical materials</subject><subject>Cells (biology)</subject><subject>Composite materials</subject><subject>Differentiation</subject><subject>Electrospun aligned fibers</subject><subject>Fibers</subject><subject>Histone acetylation</subject><subject>Histone deacetylase</subject><subject>Histone deacetylase inhibitor</subject><subject>Implantation</subject><subject>Lactic acid</subject><subject>Mechanical properties</subject><subject>Molecular chains</subject><subject>Nanofibers</subject><subject>Polylactic acid</subject><subject>Progenitor cells</subject><subject>Scaffolds</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Surgical implants</subject><subject>Tendon differentiation</subject><subject>Tendons</subject><subject>Tissue engineering</subject><subject>Tissue regeneration</subject><subject>Topography</subject><subject>Transplants & implants</subject><subject>Trichostatin A</subject><subject>Ultrastructure</subject><issn>1742-7061</issn><issn>1878-7568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kU1vFSEUhonR2C__gTEkbtzMlK8ZmI1J02g1aeLGrgkDhys3c2EEpk3_fWludeHCFWfxvO8BHoTeU9JTQsfLfW9snUPqGaGyJ1NP-PgKnVIlVSeHUb1usxSsk2SkJ-islD0hXFGm3qITpqaREzqdovUqYljDDiLUYHHra63hHrBNhzWVUAEXa7xPi8MPof7CD7AsnVnCLoLD0cTkwwy5YJ8y9lts4RTNgitElyKuoZQNMMRdiAA5xN0FeuPNUuDdy3mO7r5--Xn9rbv9cfP9-uq2s4LJ2vl5cooDTFRYRjmVg2R8hskNQEbjhZkHL6SdBwlESQIOGqOk5MJP88gEP0efjr1rTr83KFUfQrHt8iZC2oqmkxgYlUSQhn78B92nLbdXFM2IoJQPgg6NEkfK5lRKBq_XHA4mP2pK9LMRvddHI_rZiCaTbkZa7MNL-TYfwP0N_VHQgM9HANpv3AfIutgA0YILGWzVLoX_b3gCzZ2fvA</recordid><startdate>20180115</startdate><enddate>20180115</enddate><creator>Zhang, Can</creator><creator>Wang, Xianliu</creator><creator>Zhang, Erchen</creator><creator>Yang, Long</creator><creator>Yuan, Huihua</creator><creator>Tu, Wenjing</creator><creator>Zhang, Huilan</creator><creator>Yin, Zi</creator><creator>Shen, Weiliang</creator><creator>Chen, Xiao</creator><creator>Zhang, Yanzhong</creator><creator>Ouyang, Hongwei</creator><general>Elsevier Ltd</general><general>Elsevier BV</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20180115</creationdate><title>An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering</title><author>Zhang, Can ; Wang, Xianliu ; Zhang, Erchen ; Yang, Long ; Yuan, Huihua ; Tu, Wenjing ; Zhang, Huilan ; Yin, Zi ; Shen, Weiliang ; Chen, Xiao ; Zhang, Yanzhong ; Ouyang, Hongwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-fb9d83ee914c213175723be9d5e06af4ab5f47cb57e0870ede31787734f9b6243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Achilles tendon</topic><topic>Alignment</topic><topic>Biocompatibility</topic><topic>Biomaterials</topic><topic>Biomedical materials</topic><topic>Cells (biology)</topic><topic>Composite materials</topic><topic>Differentiation</topic><topic>Electrospun aligned fibers</topic><topic>Fibers</topic><topic>Histone acetylation</topic><topic>Histone deacetylase</topic><topic>Histone deacetylase inhibitor</topic><topic>Implantation</topic><topic>Lactic acid</topic><topic>Mechanical properties</topic><topic>Molecular chains</topic><topic>Nanofibers</topic><topic>Polylactic acid</topic><topic>Progenitor cells</topic><topic>Scaffolds</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Studies</topic><topic>Surgical implants</topic><topic>Tendon differentiation</topic><topic>Tendons</topic><topic>Tissue engineering</topic><topic>Tissue regeneration</topic><topic>Topography</topic><topic>Transplants & implants</topic><topic>Trichostatin A</topic><topic>Ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Can</creatorcontrib><creatorcontrib>Wang, Xianliu</creatorcontrib><creatorcontrib>Zhang, Erchen</creatorcontrib><creatorcontrib>Yang, Long</creatorcontrib><creatorcontrib>Yuan, Huihua</creatorcontrib><creatorcontrib>Tu, Wenjing</creatorcontrib><creatorcontrib>Zhang, Huilan</creatorcontrib><creatorcontrib>Yin, Zi</creatorcontrib><creatorcontrib>Shen, Weiliang</creatorcontrib><creatorcontrib>Chen, Xiao</creatorcontrib><creatorcontrib>Zhang, Yanzhong</creatorcontrib><creatorcontrib>Ouyang, Hongwei</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Aluminium Industry Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Ceramic Abstracts</collection><collection>Computer and Information Systems Abstracts</collection><collection>Corrosion Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Materials Business File</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Engineering Research Database</collection><collection>Aerospace Database</collection><collection>Copper Technical Reference Library</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Acta biomaterialia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Can</au><au>Wang, Xianliu</au><au>Zhang, Erchen</au><au>Yang, Long</au><au>Yuan, Huihua</au><au>Tu, Wenjing</au><au>Zhang, Huilan</au><au>Yin, Zi</au><au>Shen, Weiliang</au><au>Chen, Xiao</au><au>Zhang, Yanzhong</au><au>Ouyang, Hongwei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering</atitle><jtitle>Acta biomaterialia</jtitle><addtitle>Acta Biomater</addtitle><date>2018-01-15</date><risdate>2018</risdate><volume>66</volume><spage>141</spage><epage>156</epage><pages>141-156</pages><issn>1742-7061</issn><eissn>1878-7568</eissn><abstract>[Display omitted]
Poor tendon repair is often a clinical challenge due to the lack of ideal biomaterials. Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. Here, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), an HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. We found that TSA incorporated aligned fibers of PLLA had an additive effect in directing tenogenic differentiation. Moreover, the in situ implantation study in rat model further confirmed that A-TSA scaffold promoted the structural and mechanical properties of the regenerated Achilles tendon. This study demonstrated that HDAC was involved in the teno-differentiation with aligned fiber topography, and the combination of HDAC with aligned topography might be a more efficient strategy to promote tenogenesis of stem cells.
Electrospun aligned fibers, resembling the ultrastructure of tendon, have been previously reported to promote tenogenesis. However, the underlying mechanism is unclear and the aligned fibers alone are not capable enough to commit teno-differentiation of stem cells. The uniqueness of our studies are as follows, based on our observation of reduced expression of histone deacetylases (HDACs) in tendon stem/progenitor cells (TSPCs) cultured on aligned fibers, we proposed a strategy to enhance the tenogenesis effect of aligned fibers by using a small molecule Trichostatin A (TSA), a HDAC inhibitor. Such a TSA-laden poly (l-lactic acid) (PLLA) aligned fiber (A-TSA) scaffold was successfully fabricated by a stable jet electrospinning method, and demonstrated its sustained capability in releasing TSA. The incorporation and subsequent release of bioactive small molecule TSA into electrospun aligned fibers allows a controllable manner for both biochemical and physical regulation of tenogenesis of stem cells both in vitro and in vivo. Collectively, the present study provides a model of “translating the biological knowledge learned from cell-material interaction into optimizing biomaterials (from Biomat-to-Biomat)”.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28963019</pmid><doi>10.1016/j.actbio.2017.09.036</doi><tpages>16</tpages></addata></record> |
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| subjects | Achilles tendon Alignment Biocompatibility Biomaterials Biomedical materials Cells (biology) Composite materials Differentiation Electrospun aligned fibers Fibers Histone acetylation Histone deacetylase Histone deacetylase inhibitor Implantation Lactic acid Mechanical properties Molecular chains Nanofibers Polylactic acid Progenitor cells Scaffolds Stem cell transplantation Stem cells Studies Surgical implants Tendon differentiation Tendons Tissue engineering Tissue regeneration Topography Transplants & implants Trichostatin A Ultrastructure |
| title | An epigenetic bioactive composite scaffold with well-aligned nanofibers for functional tendon tissue engineering |
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