Dual growth factor delivery using PLGA nanoparticles in silk fibroin/PEGDMA hydrogels for articular cartilage tissue engineering

Degeneration of articular cartilage due to damages, diseases, or age-related factors can significantly decrease the mobility of the patients. Various tissue engineering approaches which take advantage of stem cells and growth factors in a three-dimensional constructs have been used for reconstructing articular tissue. Proliferative impact of basic fibroblast growth factor (bFGF) and chondrogenic differentiation effect of transforming growth factor-beta 1 (TGF-beta 1) over mesenchymal stem cells have previously been verified. In this study, silk fibroin (SF) and of poly(ethylene glycol) dimethacrylate (PEGDMA) were used to provide a versatile platform for preparing hydrogels with tunable mechanical, swelling and degradation properties through physical and chemical crosslinking as a microenvironment for chondrogenic differentiation in the presence of bFGF and TGF-beta 1 releasing nanoparticles (NPs) for the first time. Scaffolds with compressive moduli ranging from 95.70 +/- 17.82 to 338.05 +/- 38.24 kPa were obtained by changing both concentration PEGDMA and volume ratio of PEGDMA with 8% SF. Highest cell viability was observed in PEGDMA 10%-SF 8% (1:1) [PEG10-SF8(1:1)] hydrogel group. Release of bFGF and TGF-beta 1 within PEG10-SF8(1:1) hydrogels resulted in higher DNA and glycosaminoglycans amounts indicating synergistic effect of dual release over proliferation and chondrogenic differentiation of dental pulp stem cells in hydrogels, respectively. Our results suggested that simultaneous delivery of bFGF and TGF-beta 1 through utilization of PLGA NPs within PEG10-SF8(1:1) hydrogel provided a novel and versatile means for articular cartilage regeneration as they allow for dosage- and site-specific multiple growth factor delivery.