Abstract
An ideal tissue-engineered bone graft should have both excellent pro-osteogenesis and pro-angiogenesis properties to rapidly realize the bone regeneration in vivo. To meet this goal, in this work a porcine bone scaffold was successfully used as a Trojan horse to store growth factors produced by mesenchymal stem cells (MSCs). This new scaffold showed a time-dependent release of bioactive growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), in vitro. The biological effect of the growth factors-adsorbed scaffold on the in vitro commitment of MSCs into osteogenic and endothelial cell phenotypes has been evaluated. In addition, we have investigated the activity of growth factor-impregnated granules in the repair of critical-size defects in rat calvaria by means of histological, immunohistochemical, and molecular biology analyses. Based on the results of our work bone tissue formation and markers for bone and vascularization were significantly increased by the growth factor-enriched bone granules after implantation. This suggests that the controlled release of active growth factors from porcine bone granules can enhance and promote bone regeneration.
Highlights
Bone healing is a tightly regulated process that involves different cell types
An increased bone density, often due to a significant increase in the trabecular number, seems to guarantee an improved strength of the defect, a starting point favorable to the success of the implant. In light of such consideration, in the present work, we have investigated the biological basis supporting this evidence, starting from the hypothesis that a porcine-derived bone scaffold could act as a Trojan horse to entrap growth factors released by mesenchymal stem cells (MSCs) migrated to the injured site to start the regeneration process
Porcine-derived bone granules were loaded with MSCs, in particular those isolated from human dental pulp
Summary
Bone healing is a tightly regulated process that involves different cell types. During the first hours after a trauma, there is the formation of a hematoma and an acute inflammatory response. Leukocytes derived from blood and bone marrow leukocytes express pro-inflammatory cytokines and start the healing process. Mesenchymal stem cells (MSCs) migrate from the surrounding tissue, become osteoprogenitor cells [1,2,3]. Tissue engineering offers a revolutionary approach to restore critical-sized defects and, traditionally, this occurs by means of biomaterials, cells, and biologicals. Biomaterials provide a three-dimensional (3D) substrate with specific engineered characteristics for cells to attach and proliferate. In order to improve the migration and differentiation into the required tissue type growth factors supply essential signaling cues for these kind of cells
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