Building Osteogenic Microenvironments with a Double-Network Composite Hydrogel for Bone Repair

The critical factor determining the in vivo effect of bone repair materials is the microenvironment,which greatly depends on their abilities to promote vascularization and bone formation.However,implant materials are far from ideal candidates for guiding bone regeneration due to their deficient angiogenic and osteogenic microenvironments.Herein,a double-network composite hydrogel combining vascular endothelial growth factor(VEGF)-mimetic peptide with hydroxyapatite(HA)precursor was developed to build an osteogenic microenvironment for bone repair.The hydrogel was prepared by mixing acrylatedβ-cyclodextrins and octacalcium phosphate(OCP),an HA precursor,with gelatin solution,followed by ultraviolet photo-crosslinking.To improve the angiogenic potential of the hydrogel,QK,a VEGF-mimicking peptide,was loaded in acrylatedβ-cyclodextrins.The QK-loaded hydrogel promoted tube formation of human umbilical vein endothelial cells and upregulated the expression of angiogenesis-related genes,such as Flt1,Kdr,and VEGF,in bone marrow mesenchymal stem cells.Moreover,QK could recruit bone marrow mesenchymal stem cells.Furthermore,OCP in the composite hydrogel could be transformed into HA and release calcium ions facilitating bone regeneration.The double-network composite hydrogel integrated QK and OCP showed obvious osteoinductive activity.The results of animal experiments showed that the composite hydrogel enhanced bone regeneration in skull defects of rats,due to perfect synergistic effects of QK and OCP on vascularized bone regeneration.In summary,improving the angiogenic and osteogenic microenvironments by our double-network composite hydrogel shows promising prospects for bone repair.

Three-dimensional biofabrication of nanosecond laser micromachined nanofibre meshes for tissue engineered scaffolds

There is a high demand for bespoke grafts to replace damaged or malformed bone and cartilage tissue.Three-dimensional(3D)printing offers a method of fabricating complex anatomical features of clinically relevant sizes.However,the construction of a scaffold to replicate the complex hierarchical structure of natural tissues remains challenging.This paper reports a novel biofabrication method that is capable of creating intricately designed structures of anatomically relevant dimensions.The beneficial properties of the electrospun fibre meshes can finally be realised in 3D rather than the current promising breakthroughs in two-dimensional(2D).The 3D model was created from commercially available computer-aided design software packages in order to slice the model down into many layers of slices,which were arrayed.These 2D slices with each layer of a defined pattern were laser cut,and then successfully assembled with varying thicknesses of 100μm or 200μm.It is demonstrated in this study that this new biofabrication technique can be used to reproduce very complex computer-aided design models into hierarchical constructs with micro and nano resolutions,where the clinically relevant sizes ranging from a simple cube of 20 mm dimension,to a more complex,50 mm-tall human ears were created.In-vitro cell-contact studies were also carried out to investigate the biocompatibility of this hierarchal structure.The cell viability on a micromachined electrospun polylactic-co-glycolic acid fibre mesh slice,where a range of hole diameters from 200μm to 500μm were laser cut in an array where cell confluence values of at least 85%were found at three weeks.Cells were also seeded onto a simpler stacked construct,albeit made with micromachined poly fibre mesh,where cells can be found to migrate through the stack better with collagen as bioadhesives.This new method for biofabricating hierarchical constructs can be further developed for tissue repair applications such as maxillofacial bone injury or nose/ear cartilage replacement in the future.

3D bioactive composite scaffolds for bone tissue engineering

Bone is the second most commonly transplanted tissue worldwide,with over four million operations using bone grafts or bone substitute materials annually to treat bone defects.However,significant limitations affect current treatment options and clinical demand for bone grafts continues to rise due to conditions such as trauma,cancer,infection and arthritis.Developing bioactive three-dimensional(3D)scaffolds to support bone regeneration has therefore become a key area of focus within bone tissue engineering(BTE).A variety of materials and manufacturing methods including 3D printing have been used to create novel alternatives to traditional bone grafts.However,individual groups of materials including polymers,ceramics and hydrogels have been unable to fully replicate the properties of bone when used alone.Favourable material properties can be combined and bioactivity improved when groups of materials are used together in composite 3D scaffolds.This review will therefore consider the ideal properties of bioactive composite 3D scaffolds and examine recent use of polymers,hydrogels,metals,ceramics and bio-glasses in BTE.Scaffold fabrication methodology,mechanical performance,biocompatibility,bioactivity,and potential clinical translations will be discussed.