3D Printed Integrated Bionic Oxygenated Scaffold for Bone Regeneration

Abstract

The repair of large bone defects remains a challenging problem in bone tissue engineering. Ischemia and hypoxia in the bone defect area make it difficult for seed cells to survive and differentiate, which fail to perform effective tissue regeneration. Current oxygen-producing materials frequently encounter problems such as a rapid degradation rate, insufficient mechanical properties, difficult molding, and cumbersome fabrication. Here, a novel three-dimensional (3D) printed integrated bionic oxygenated scaffold was fabricated with gelatin-CaO2 microspheres, polycaprolactone (PCL), and nanohydroxyapatite (nHA) using low-temperature molding 3D printing technology. The scaffold had outstanding mechanical properties with bionic hierarchical porous structures. In vitro reports showed that the scaffold exhibited excellent cytocompatibility and could release O2 sustainably for more than 2 weeks, which significantly enhanced the survival, growth, and osteogenic differentiation of bone marrow mesenchymal stem cells under hypoxia. In vivo experiments revealed that the scaffold facilitated efficient bone repair after it was transplanted into a rabbit calvarial defect model. This result may be due to the scaffolds reducing hypoxia-inducible factor-1α accumulation, improving the expression of osteogenic regulatory transcription factors, and accelerating osteogenesis. In summary, the integrated bionic PCL/nHA/CaO2 scaffold had excellent capabilities in sustainable O2 release and bone regeneration, which provided a promising clinical strategy for bone defect repair.

Cellular modifications and biomaterial design to improve mesenchymal stem cell transplantation

“…Compared to non-oxygenated scaffolds, the oxygenated scaffolds exhibit favourable mechanical properties, promote MSC survival in hypoxic conditions, and enhance MSC proliferation and osteogenic differentiation, resulting in enhanced bone regeneration at 4 and 12 weeks after implantation in a rabbit cranial defect. 231…”

“…Compared to nonoxygenated scaffolds, the oxygenated scaffolds exhibit favourable mechanical properties, promote MSC survival in hypoxic conditions, and enhance MSC proliferation and osteogenic differentiation, resulting in enhanced bone regeneration at 4 and 12 weeks after implantation in a rabbit cranial defect. 231 A major therapeutic mechanism of MSCs is their secretion of extracellular vesicles (EV), which carry a range of intercellular signalling factors. Scaffolds can be designed to not only improve cell retention and survival, but also promote EV secretion.…”

Progress in microsphere-based scaffolds in bone/cartilage tissue engineering

“…Another study demonstrated that nHA/chitosan composite microspheres added to chitosan membranes can significantly enhance the mechanical strength of materials with strong spatial maintenance ability and bionic function, and effectively promote the recovery of bone defects [64]. Recently, a bionic oxygenated scaffold was fabricated using gelatin-CaO 2 microspheres, polycaprolactone, and nHA, which could release oxygen continuously for more than 2 weeks, thus improving the survival, growth and osteogenic differentiation of MSCs under hypoxic conditions [65]. Moreover, gelatin/CaO 2 microspheres acted as a pressure dispersion conductor within the scaffold, approaching the compressive strength of the natural bone cortex at week 12.…”

Biodegradable Nanoflowers with Abaloparatide Spatiotemporal Management of Functional Alveolar Bone Regeneration

“…30,31 The NFs structure has been widely studied in the field of catalysis and chemistry; 10 however, it is less reported in regard to biomedical applications. Most highlighted is the bioactive capacity of the NFs, with the constituents of calcium, phosphate and gelatin, which resemble components of bone tissue and might be "bionic" 32 for the bone remodeling procedure. Interestingly, this flower-like structure could release bioactive ions including Ca 2+ and PO 4 3− for the joint bone remodeling process.…”

“…Flower-like structures are defined as hierarchical morphologies, with high specific surface area, porous structure, and capacity of substance adsorption and capture. , The NFs structure has been widely studied in the field of catalysis and chemistry; however, it is less reported in regard to biomedical applications. Most highlighted is the bioactive capacity of the NFs, with the constituents of calcium, phosphate and gelatin, which resemble components of bone tissue and might be “bionic” for the bone remodeling procedure. Interestingly, this flower-like structure could release bioactive ions including Ca 2+ and PO 4 3– for the joint bone remodeling process. , The Ca 2+ released from flower also could create the in situ biomineralization layer, thus providing an “osteogenic microenvironment” for the BMSCs’ osteogenic induction .…”