An artificial membrane binding protein-polymer surfactant nanocomplex facilitates stem cell adhesion to the cartilage extracellular matrix

One of the major challenges within the emerging field of injectable stem cell therapies for articular cartilage (AC) repair is the retention of sufficient viable cell numbers at the site of injury. Even when delivered via intra-articular injection, the number of stem cells retained at the target is often low and declines rapidly over time. To address this challenge, an artificial plasma membrane binding nanocomplex was rationally designed to provide human mesenchymal stem cells (hMSCs) with increased adhesion to articular cartilage tissue. The nanocomplex comprises the extracellular matrix (ECM) binding peptide of a placenta growth factor-2 (PlGF-2) fused to a supercharged green fluorescent protein (scGFP), which was electrostatically conjugated to anionic polymer surfactant chains to yield [S-]scGFP_PlGF2. The [S-]scGFP_PlGF2 nanocomplex spontaneously inserts into the plasma membrane of hMSCs, is not cytotoxic, and does not inhibit differentiation. The nanocomplex-modified hMSCs showed a significant increase in affinity for immobilised collagen II, a key ECM protein of cartilage, in both static and dynamic cell adhesion assays. Moreover, the cells adhered strongly to bovine ex vivo articular cartilage explants resulting in high cell numbers. These findings suggest that the re-engineering of hMSC membranes with [S-]scGFP_PlGF2 could improve the efficacy of injectable stem cell-based therapies for the treatment of damaged articular cartilage.