Abstract
Purpose
Traditionally, the gold standard for bone grafting has been either autografts or allografts. Whilst autografts are still widely used, drawbacks such as donor site morbidity are shifting the market rapidly toward the use of orthobiologic bone graft substitutes. This study investigated the in vivo performance of a novel (W02008096334) collagen-hydroxyapatite (CHA) bone graft substitute material as an osteoinductive tissue engineering scaffold. This highly porous CHA scaffold offers significantly increased mechanical strength over collagen-only scaffolds while still exhibiting an extremely high porosity (≈ 99%), and an osteoinductive hydroxyapatite phase [1]. This study assessed the ability of the CHA scaffolds to heal critical-sized (15 mm) long bone segmental defects in vivo, as a viable alternative to autologous bone grafts.
Method
Collagen-HA (CHA) composite scaffolds were fabricated based on a previously-described freeze-drying technique [1]. After freeze-drying, these scaffolds were subjected to a dehydrothermal treatment and subsequently chemically crosslinked using EDAC. In vivo performance was assessed using a critical size segmental radial defect (15 mm) introduced into 16 young adult New Zealand White Rabbits under Irish Government license. Animals were divided into three groups; (i) an empty defect group (negative control), (ii) an autogenous bone graft group (positive control) and (iii) a CHA scaffold group (CHA). Segmental defect healing in all animals was assessed using plain X-Ray analysis, at four time-points (0, 6, 12 and 16 weeks). MicroCT and histological analysis were carried out at week 16.
Results
Empty defect groups at all time points resulted in non-union of the segmental defect bone ends. Autogenous bone graft groups exhibited good filling of the segmental defect with extensive callus formation but even after 16 weeks showed poor remodelling. Although autogenous bone graft groups showed evidence of mineralized tissue within the defect, tissue healing appeared relatively uncontrolled (Figure 1a). CHA scaffold groups exhibited extensive bone healing as early as 6 weeks. By week 16, CHA defects showed complete bridging across the entire defect (figures 1b, 2b, 3b, 4b), development of a continuous marrow cavity (Figures 2b, 3b, 4b) and evidence of remodelling.
Conclusion
The results of this study provide clear evidence that Collagen-HA scaffolds, can perform at least as well as autogenous bone grafts. This study provides strong evidence that after a relatively short time in vivo, CHA scaffolds can result in a more complete and homogenous bone healing response and have the potential to offer improved bone tissue formation above that of autogenous bone. More importantly, this study provides strong evidence that the use of low stiffness, organic, biodegradable scaffolds in fully load-bearing defects is not only successful but arguably produces significantly improved results when compared with the current Gold Standard, autogenous bone grafting.
