A Structured Scaffold Featuring Biomimetic Heterogeneous Architecture for the Regeneration of Critical-Size Bone Defects

Abstract

The regeneration of critical-size bone defects on long bones has remained a significant challenge because of the complex anatomical structure and vascular network. In such circumstances, current biomaterial forms with homogeneous structure and function can hardly satisfy the need for both osteogenesis and angiogenesis. In the current study, a heterogeneous biomimetic structured scaffold was constructed with the help of a 3D printed mold to simultaneously mimic the outer/inner periosteum and intermediate bone matrix of a natural long bone. Because of the reinforcement via modified mesoporous bioactive glass nanoparticles (MBGNs), enhanced structural stability and adequate osteogenic capacity could be achieved for the intermediate layer of this scaffold. Conversely, GelMA incorporated with VEGF-loaded liposome exhibiting controlled release of the angiogenic factor was applied to the inner and outer layers of the scaffold. The resulting heterogeneous structured scaffold was shown to successfully guide bone regeneration and restoration of the natural bone anatomic structure, rendering it a promising candidate for future orthopedic clinical studies.

Proliferative and Osteogenic Supportive Effect of VEGF-Loaded Collagen-Chitosan Hydrogel System in Bone Marrow Derived Mesenchymal Stem Cells

“…Our results showed that all the HGs showed a better drug-releasing ability of VEGF over the incubation time and higher VEGF drug release was observed with a higher concentration of VEGF-loaded HGs. The drug release profile further demonstrates that the HG could start releasing quantifiable VEGF after 6 h incubation and a significant release of VEGF by HGs was achieved on day 3 onwards, which is contradictory to the previous studies [52][53][54]. This could be due to the influence of the polymer's nature, such as the type, composition, and chemical bonding of the polymers, on the drug-releasing behavior of hydrogels.…”

“…Previous studies also proved the osteogenic stimulatory effect of HGs fabricated with nano-hydroxyapatite/collagen [6,65], chitosan/collagen [17,48], and hyaluronic acid/collagen [66]. Similarly, the osteogenic stimulatory effect of VEGF loaded in HGs was also demonstrated in several reports [37,54,67,68]. Several pieces of empirical evidence elucidated the actual signaling mechanism of VEGF in the osteogenesis of MSCs.…”