Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep

TL;DR

This study evaluates silicon-substituted hydroxyapatite scaffolds with VEGF for bone regeneration in osteoporotic sheep, finding crystalline structures with VEGF promote effective bone growth, unlike nanocrystalline variants.

Contribution

It introduces VEGF-decorated crystalline SiHA scaffolds as effective bone grafts for osteoporotic conditions, optimizing microstructure for enhanced regeneration.

Findings

Crystalline SiHA with VEGF promotes bone regeneration.

Nanocrystalline SiHA induces fibrous tissue and inflammation.

VEGF enhances vascularization and osteoblast activity.

Abstract

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis.