Mechanically Enhanced Lipo-hydrogel With Controlled Release Of Multi-type Drugs For Bone Regeneration

Objectives: To construct 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.Methods: Deferoxamine-Lipoosome,Paclitaxel-Liposome,Thrombin-Liposome and Bone morphogenetic protein 2-Liposome were prepared by film dispersion method and reverse evaporation method,then these liposomes were combined with Gel MA to fabricated multifuncational composited hydrogel.Above liposomes and composited hydrogel were investigated by SEM,TEM,FT-IR,universal mechanical tester,rheometer and DLS,moreover the release characteristics of DFO,PTX and THR were examined by HPLC and BCA kit.In order to examine the biocompatibility of these materials,Live/dead assay and Cell Counting Kit-8(CCK-8)were used according to the product's instruction.The ability to induce osteogenic differentiation was examined by ALP activity and Alizarin Red S staining,and the capbility to promote angiogenesis was observed by CLSM.Composite scaffolds were implanted into the rat distal femoral defect to test bone formation ability by Micro-CT and histological analysis.Results: photo-crosslinkable gelatin derivative(Gel MA)was combined with drug loaded liposome by bonding effects,which lead to double improvement in mechanical property for over four times,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(Thrombin 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.Conclusion: This compisited hydrogel could promote the osteogenesis and angiogenesis differentiation both in vitro and in vivo,because early neovascularization and sustained promoting osteogenesis were crucial to bone regeneration.Thus,the liposome modified hydrogel could supply a promising strategy for extending the application of hydrogel in drug delivery and tissue reconstruction...