Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells
The design of implants for tissue transitions remains a major scientific challenge. This is due to gradients in characteristics that need to be restored. The rotator cuff in the shoulder, with its direct osteo-tendinous junction (enthesis), is a prime example of such a transition. Our approach towar...
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1303 |
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| author | Leonie Berten-Schunk Yvonne Roger Heike Bunjes Andrea Hoffmann |
| author_facet | Leonie Berten-Schunk Yvonne Roger Heike Bunjes Andrea Hoffmann |
| author_sort | Leonie Berten-Schunk |
| collection | DOAJ |
| description | The design of implants for tissue transitions remains a major scientific challenge. This is due to gradients in characteristics that need to be restored. The rotator cuff in the shoulder, with its direct osteo-tendinous junction (enthesis), is a prime example of such a transition. Our approach towards an optimized implant for entheses is based on electrospun fiber mats of poly(ε-caprolactone) (PCL) as biodegradable scaffold material, loaded with biologically active factors. Chitosan/tripolyphosphate (CS/TPP) nanoparticles were used to load transforming growth factor-β<sub>3</sub> (TGF-β<sub>3</sub>) with increasing loading concentrations for the regeneration of the cartilage zone within direct entheses. Release experiments were performed, and the concentration of TGF-β<sub>3</sub> in the release medium was determined by ELISA. Chondrogenic differentiation of human mesenchymal stromal cells (MSCs) was analyzed in the presence of released TGF-β<sub>3</sub>. The amount of released TGF-β<sub>3</sub> increased with the use of higher loading concentrations. This correlated with larger cell pellets and an increase in chondrogenic marker genes (<i>SOX9</i>, <i>COL2A1</i>, <i>COMP</i>). These data were further supported by an increase in the glycosaminoglycan (GAG)-to-DNA ratio of the cell pellets. The results demonstrate an increase in the total release of TGF-β<sub>3</sub> by loading higher concentrations to the implant, which led to the desired biological effect. |
| first_indexed | 2024-03-11T04:36:54Z |
| format | Article |
| id | doaj.art-032e1e3a91e24e87b611ecff39a8b835 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:36:54Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-032e1e3a91e24e87b611ecff39a8b8352023-11-17T20:55:36ZengMDPI AGPharmaceutics1999-49232023-04-01154130310.3390/pharmaceutics15041303Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal CellsLeonie Berten-Schunk0Yvonne Roger1Heike Bunjes2Andrea Hoffmann3Technische Universität Braunschweig, Institut für Pharmazeutische Technologie und Biopharmazie, 38106 Braunschweig, GermanyHannover Medical School, Department of Orthopedic Surgery, Graded Implants and Regenerative Strategies, Laboratory of Biomechanics and Biomaterials, 30625 Hannover, GermanyTechnische Universität Braunschweig, Institut für Pharmazeutische Technologie und Biopharmazie, 38106 Braunschweig, GermanyHannover Medical School, Department of Orthopedic Surgery, Graded Implants and Regenerative Strategies, Laboratory of Biomechanics and Biomaterials, 30625 Hannover, GermanyThe design of implants for tissue transitions remains a major scientific challenge. This is due to gradients in characteristics that need to be restored. The rotator cuff in the shoulder, with its direct osteo-tendinous junction (enthesis), is a prime example of such a transition. Our approach towards an optimized implant for entheses is based on electrospun fiber mats of poly(ε-caprolactone) (PCL) as biodegradable scaffold material, loaded with biologically active factors. Chitosan/tripolyphosphate (CS/TPP) nanoparticles were used to load transforming growth factor-β<sub>3</sub> (TGF-β<sub>3</sub>) with increasing loading concentrations for the regeneration of the cartilage zone within direct entheses. Release experiments were performed, and the concentration of TGF-β<sub>3</sub> in the release medium was determined by ELISA. Chondrogenic differentiation of human mesenchymal stromal cells (MSCs) was analyzed in the presence of released TGF-β<sub>3</sub>. The amount of released TGF-β<sub>3</sub> increased with the use of higher loading concentrations. This correlated with larger cell pellets and an increase in chondrogenic marker genes (<i>SOX9</i>, <i>COL2A1</i>, <i>COMP</i>). These data were further supported by an increase in the glycosaminoglycan (GAG)-to-DNA ratio of the cell pellets. The results demonstrate an increase in the total release of TGF-β<sub>3</sub> by loading higher concentrations to the implant, which led to the desired biological effect.https://www.mdpi.com/1999-4923/15/4/1303TGF-β<sub>3</sub>chondrogenesischitosan nanoparticlesreleaseimplanttissue transition |
| spellingShingle | Leonie Berten-Schunk Yvonne Roger Heike Bunjes Andrea Hoffmann Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells Pharmaceutics TGF-β<sub>3</sub> chondrogenesis chitosan nanoparticles release implant tissue transition |
| title | Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells |
| title_full | Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells |
| title_fullStr | Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells |
| title_full_unstemmed | Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells |
| title_short | Release of TGF-β<sub>3</sub> from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells |
| title_sort | release of tgf β sub 3 sub from surface modified pcl fiber mats triggers a dose dependent chondrogenic differentiation of human mesenchymal stromal cells |
| topic | TGF-β<sub>3</sub> chondrogenesis chitosan nanoparticles release implant tissue transition |
| url | https://www.mdpi.com/1999-4923/15/4/1303 |
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