Pre-vascularization in fibrin Gel/PLGA microsphere scaffolds designed for bone regeneration

Blood supply plays a central role in alveolar bone regeneration within a large bone defect filled with a cell-laden scaffold material, as it provides sufficient oxygen and nutrition to cells inside the scaffold. To address the issue of insufficient vascularization within scaffolds designed to promote bone regeneration, we developed a pre-vascularized scaffold to enable the repair of large alveolar bone defects. Peripheral blood-derived mesenchymal stem cells (PBMSCs) and endothelial colony-forming cells (ECFCs) were collected from peripheral blood and incorporated into fibrin gel, which was then mixed with poly(lactic-co-glycolic acid) (PLGA) microspheres to form a fibrin gel/PLGA microsphere (FP) scaffold. The induction of osteogenic differentiation of PBMSCs and the pre-vascularization in the FP scaffold were achieved separately under different conditions. PBMSCs seeded into the FP scaffolds with fibrin gel tended to migrate to the surface of PLGA microspheres and express high levels of osteogenic markers. ECFCs co-cultured with PBMSCs in FP scaffolds were inclined to form a capillary-like structure in the gel substrate. These capillary-like structures penetrated the space among the microspheres and are supposed to anastomosis with blood capillaries in vivo. Together these results indicate that the pre-vascularized FP scaffold may overcome the shortages of oxygen and nutrition inside conventional scaffolds, leading to a better clinical effect. Regeneration of bones that support human teeth may occur more quickly with a tissue engineering scaffold designed to enhance blood supply. The slow growth of blood vessels often limits the survival of cells transplanted into bone defects. Feimin Zhang at China’s Nanjing Medical University and colleagues have developed a cell growth medium containing capillary structures that can accelerate blood vessel development. The team co-cultured the precursor cells of blood vessel lining and stem cells from peripheral blood in a gel scaffold made from fibrin proteins, and then integrated polymer microspheres into this structure. The rigid microspheres proved ideal for anchoring stem cells during differentiation into new bone cells, while the soft gel helped the lining cells and stem cells form capillary structures. The scaffold could be customized into shapes including that of a tooth root. A composite of fibrin gel/PLGA microspheres, as well as cells from peripheral blood can be used to generate a pre-vascularized scaffold in vitro for improved repair of alveolar bone defects. The capillary-like structures formed in the scaffolds are supposed to anastomose with host blood capillaries to supply oxygen and nutrition to the cells inside the scaffold.