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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Bibliographic Details
Main Authors: Leonie Berten-Schunk, Yvonne Roger, Heike Bunjes, Andrea Hoffmann
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/15/4/1303
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Summary: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.
ISSN:1999-4923