Abstract
Hydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.
Highlights
Articular cartilage (AC) plays important roles in load bearing, mechanical stress resistance and shock absorption[1,2]
We developed a p-hydroxybenzene propanoic acid (PA)-modified chitosan (PC)/Silk fibroin (SF) hydrogel containing stromal cell-derived factor-1 (SDF-1) and microspheres loaded with KGN
The PC was subjected to 1H-NMR spectroscopy (Fig. 2B) and infrared spectroscopy (Fig. 2C). 1H-NMR showed that the chemical shifts of δ 7.11–7.13 and δ 6.79–6.81 in PA spectra were attributable to proton absorption peaks at intersite and ortho sites of the benzene ring, indicating that PA was successfully grafted into the CS molecular chain
Summary
Articular cartilage (AC) plays important roles in load bearing, mechanical stress resistance and shock absorption[1,2]. If cartilage defects are not treated adequately, the joints will show irreversible deterioration, even leading to disability. A significant target of TE is the construction of biomimetic extracellular matrix (ECM) biomaterials, which can provide mechanical support and a suitable microenvironment for cell survival. Hydrogels are very good ECM biomimetic materials with three-dimensional crosslinked structures and high water contents[10]. Injectable hydrogels used as drug carriers can be adapted to defects of any size or shape and allow the
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