Engineering a scaffold to control cell fates of stem cells for cartilage tissue engineering

Precise spatial and temporal control of the fates of mesenchymal stromal cells (MSCs) through dynamic microenvironmental cues is essential for MSC-based tissue engineering. Artificial niches that recapitulate the spatiotemporal regulation of cell fates have been regarded as ideal platforms. Here, we engineered an artificial niche scaffold by integrating growth and chondrogenic induction factors that exerted staged effects on MSCs to direct different phases of cartilage regeneration. The scaffold was prepared by immobilizing heparin-binding epidermal growth factor-like growth factor and matrix metalloproteinase-2-cleavable peptide-tethered kartogenin-loaded liposomes within a gelatin/heparin/γ-PGA scaffold. The immobilized growth factor initially promoted MSC proliferation. The upregulation of proliferation-associated signaling served as an autonomous trigger for the subsequent release of kartogenin, thereby inducing MSC chondrogenesis. The results indicated that this spatiotemporally programmed system was able to regulate cellular fates in a spatiotemporal manner and promote cartilage regeneration.