Injectable photocrosslinkable acellular cartilage matrix hydrogel loaded with exosomes for promoting growth plate injury repair

The growth plate is vital for childhood development, and most of the injuries can formation of bone bridges on it, which has negative impact on limb development. Current biomaterial scaffolds often lack essential cartilage matrix components, which hurdles to get an acceptable regeneration. Additionally, stem cell transplantation faces challenges including high apoptosis rates and uncertain differentiation. Then, we designed an injectable composite hydrogel (Exo-AMG) loaded with exosomes (Exo) and composed of methacrylate-modified acellular cartilage matrix (ACMMA) and gelatin methacrylate (GelMA) to repair the growth plate for children and adolescents. The hydrogel is administered via minimally invasive injection and undergoes in-situ photocrosslinking to fill the growth plate defects. It exhibited suitable mechanical properties, biodegradation rates; it also could sustain exosome release. Moreover, it promoted M2 macrophage polarization and secretion of anti-inflammatory factors, and it enhanced bone mesenchymal stem cells (BMSCs) proliferation and chondrogenic differentiation in vitro. In vivo study, this Exo-AMG induced growth plate cartilage regeneration without bone bridge formation. Therefore, this injectable and in-situ photocrosslinkable composite hydrogel is promising on growth plate injury repair by alleviating inflammation and promoting chondrogenic differentiation.