Thermosensitive nanocomposite hydrogel composed of PVPylated poly(D, L-alanine) and laponite as an injectable and bioactive biomaterial

Development of regenerative medicine requires multifunctional and bioactive materials/devices. Herein, we exploit a thermosensitive bioactive nanocomposite hydrogel composed of non-thermogelable poly(N-vinyl pyr-rolidone)-b-poly(D,L-alanine) (PVP-PA) and laponite nanoclay, which displays a sol-gel transition with warming. The incorporation of PVP-PA and laponite in water first triggers self-assembly driven by hydrogen bonding and electrostatic interactions to form nanocomposite assemblies, and then turns into a physical hydrogel upon heating due to the assembly aggregation plus the partial conformation transformation of PA and PVP segments. Meanwhile, the gelation behavior of the composite system can be easily modulated by simply changing the concentration of either component. The presence of bioactive laponite and the improvement of mechanical and physiological stability enable the nanocomposite hydrogel to remain intact in vivo for over 90 days and exhibit good biological activity, which not only facilitates cell infiltration and vascularization inside the gel but also achieves rapid hemostasis within 10 s in rat bleeding models. Finally, thanks to the efficient complexation be-tween PVP and poorly water-soluble iodine, an injectable iodophor hydrogel is conveniently obtained. The long-lasting antibacterial activity induced by continuously released iodine makes the multifunctional bioactive nanocomposite system promising for rapid wound hemostasis and accelerated wound/tissue repair while pre-venting infection.