Sustained Release SDF-1α/TGF-β1-Loaded Silk Fibroin-Porous Gelatin Scaffold Promotes Cartilage Repair

Abstract

Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1α (SDF-1α)/transforming growth factor-β1 (TGF-β1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1α and TGF-β1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1α and TGF-β1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-β1-loaded scaffolds (GSTS or GST: loading TGF-β1 only) and the conditioned medium from SDF-1α-loaded scaffolds (GSTS or GSS: loading SDF-1α only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1α and TGF-β1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1α and TGF-β1 releasing GSTS have promising therapeutic potential in cartilage repair.

miR‐23a‐3p‐abundant small extracellular vesicles released from Gelma/nanoclay hydrogel for cartilage regeneration

“…The embedded specimens were cut into 6 μm thick sections which were analysed by Safranin-O & fast green-stained, haematoxylin and eosin (H&E) staining, immunohistochemical staining. Immunohistochemical staining was carried out as previously described [34]. The sections were treated with sodium citrate solution to epitope retrieval and then incubated with a primary antibody like collagen II (Abcam, USA) overnight at 4°C.…”

Simultaneous Recruitment of Stem Cells and Chondrocytes Induced by a Functionalized Self-Assembling Peptide Hydrogel Improves Endogenous Cartilage Regeneration

“…In recent years, in situ cartilage regeneration by recruiting endogenous stem cells has received more attention (Williams and Harnly, 2007;Dai et al, 2016;Chen et al, 2019). It utilizes the body's own regeneration capacity to repair cartilage tissue while avoiding exogenous cell-associated limitations.…”

“…By bypassing the aforementioned disadvantages, in situ cartilage regeneration by recruiting endogenous stem cells (especially bone marrow mesenchymal stem cells, BMSCs) into the damaged sites might be a promising alternative. Excitingly, many approaches based on this concept, such as bone marrow stimulation and the use of inductive bioscaffold alone or in combination with chemoattractants, have been shown to largely regenerate damaged cartilage tissue (Williams and Harnly, 2007;Dai et al, 2016;Chen et al, 2019). However, in most studies, the integration of neo-cartilage with the surrounding host cartilage is poor or problematic (Poole, 2003).…”

Nanotextured silk fibroin/hydroxyapatite biomimetic bilayer tough structure regulated osteogenic/chondrogenic differentiation of mesenchymal stem cells for osteochondral repair

“…HAp short nanowires were synthesized according to our previous method 17 . Degumming process was in accordance with a previous study 32 . Degumming SF and CS were added into formic acid solution containing CaCl 2 to form SF‐CS solution.…”