Release of TGF-β₃ from Surface-Modified PCL Fiber Mats Triggers a Dose-Dependent Chondrogenic Differentiation of Human Mesenchymal Stromal Cells

• Main Authors: Leonie Berten-Schunk (Author), Yvonne Roger (Author), Heike Bunjes (Author), Andrea Hoffmann (Author)
• Format: Book
• Published: MDPI AG, 2023-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics15041303; 1999-4923
• Keywords: TGF-β₃; chondrogenesis; chitosan nanoparticles; release; implant; tissue transition; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 15, Iss 4, p 1303 (2023)

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-β₃ (TGF-β₃) with increasing loading concentrations for the regeneration of the cartilage zone within direct entheses. Release experiments were performed, and the concentration of TGF-β₃ in the release medium was determined by ELISA. Chondrogenic differentiation of human mesenchymal stromal cells (MSCs) was analyzed in the presence of released TGF-β₃. The amount of released TGF-β₃ 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-β₃ by loading higher concentrations to the implant, which led to the desired biological effect.