Mechanically enhanced lipo-hydrogel with controlled release of multi-type drugs for bone regeneration

Abstract Hydrogel is an excellent candidate in the field of drug delivery and tissue regeneration. However, hydrogel used as drug carriers is facing several problems including limited optional drug and burst drug release, besides hydrogel is still confronting some challenges in mechanical property involving decreased hydrogel's strength caused by interface separation between hydrogel and other solid composition. In this research, we designed a mechanical enhanced and release-controlling liposome modified hydrogel via hydrogen bone and hydrogel network micro-cross-linking double network as artificial scaffold for promoting the angiogenesis and osteogenesis in bone regeneration. Specifically, photo-cross linkable gelatin derivative (GelMA) was combined with drug loaded liposome by bonding effects, which lead to double improvement in mechanical property, such as compression, stretching, torsion and resiliency. Furthermore, the ability to control phased release was observed in the composite hydrogel including the early release of hydrophilic drug (deferoxamine), mid-term release of bioactive macromolecule (bovine serum albumin and bone morphogenetic protein 2) and long-term release of liposoluble medicine (paclitaxel). In vitro study revealed that, this composite hydrogel significantly promoted osteogenic and angiogenesis differentiation without significant influence on cell adhesion, proliferation. Finally, the composite hydrogel demonstrated a superior capacity in accelerating new and mature lamellar bone formation in distal femoral defect of Sprague-Dawley rats. Thus, the liposome modified hydrogel could supply a promising strategy for extending the application of hydrogel in drug delivery and tissue reconstruction.