Injectable dual drug-loaded thermosensitive liposome-hydrogel composite scaffold for vascularised and innervated bone regeneration.

Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.

Triple-functional injectable liposome-hydrogel composite enhances bacteriostasis and osteo/angio-genesis for advanced maxillary sinus floor augmentation.

Bone-grafting biological materials are commonly used to increase the height of the alveolar bone in the maxillary posterior region during maxillary sinus floor augmentation. However, there has been little research on the development of an injectable bone-grafting material with bacteriostatic, angiogenic, and osteogenic properties. In this work, we developed a triple-functional vancomycin/deferoxamine/dexamethasone (Van/DFO/Dex) liposome-hydrogel composite with desirable injectability. The release kinetics confirmed orderly sustained release of Van (a bacteriostat), DFO (a vascularised small molecule), and Dex (an osteogenic small molecule). In vitro findings demonstrated the favourable cytocompatibility and antibacterial ability of this composite against Staphylococcus aureus. Additionally, the angiogenic ability of human umbilical vein endothelial cells and osteogenic differentiation activity of MC3T3-E1 cells were enhanced. An in vivo bacteriostasis assay and rabbit maxillary sinus floor augmentation model corroborated the enhanced bacteriostasis and vascularised bone regeneration properties of this functionalised composite. Overall, the favourable injectability to be fit for the minimally invasive procedure, locally sustained release property, and prominent biological functions underscore the clinical potential of Van/DFO/Dex as an ideal bone-grafting material for irregular bone defect repairs, such as maxillary sinus floor augmentation.