Three-Dimensional Structured Hybrid Scaffolds for Enhanced Bone formation

Abstract

The most common clinical treatments for large bone deficiencies resulting from trauma, disease or infection are autograft, allograft or bone graft substitutes (BGS). However, these treatments still have limitations for clinical applications. Thus, this project aims to fabricate an optimal scaffold design for enhanced bone formation. Human bone is not solely hydroxyapatite (HA) but consists of multi-ionic substitutions in the HA lattice. Here, we have developed multi-substituted HA (SiCHA) nanopowders as bone substitute materials. SiCHA-2 was found to closely mirror the composition of the bone mineral content associated with the most enhanced proliferation and osteogenic activity.
An innovative coating materials assembly was then established using SiCHA-2 nanopowders in combination with hyaluronan and collagen type I by the Polyelectrolyte Multilayers (PEMs) technique. Increasing the number of deposition cycles resulted in linear increases of surface properties and cell activities up to 5-bilayers. One common problem in scaffold-based tissue engineering (TE) is the rapid formation of tissue on the outer edge of the scaffolds whereas inner regions of the scaffold undergo necrosis. In this study, we incorporated aligned channels on the structure of three-dimensional (3D) scaffolds by Rapid Prototyping (RP) technique using Poly (lactic acid) (PLA) followed by PEMs. We investigated the fate of human mesenchymal stem cells (hMSCs) on these scaffolds in a rotary bioreactor compared to static conditions using osteogenic and proliferation media. We demonstrate that the combination of appropriate substrates with aligned channels, biochemical cues from the osteogenic media and better mass transport provided by rotary bioreactor enhances bone formation. In order to create pre-vascularized 3DP hybrid scaffolds, proof of concept work introduces the co-culture model of human umbilical vein endothelial cells (HUVECs) and hMSCs into the best scaffold design. Co-culture shows enhanced expression of both proangiogenic markers, which is an early indication of an ability supporting vessel formation in vitro.