Radioprotection and cross-linking of allograft bone in the presence of vitamin E.

Jeremy V Suhardi,Orhun K Muratoglu,Ebru Oral,David F A Morgan

doi:10.1002/jbm.b.34569

Abstract

Bone allografts are the preferred method for bone augmentation in over 500,000 orthopedic surgical procedures in the US. Sterilization by ionizing radiation is the most effective method of minimizing the bioburden of bone allografts; however, radiation causes chain scission of collagen, resulting in the reduction of the allografts' mechanical strength. In this study, we doped bone allografts with vitamin E as radioprotectant using a novel two-step process to protect the collagen architecture against radiation damage and to preserve the mechanical strength of the construct. In addition, combining the radioprotectant with a cross-linking agent further minimized collagen degradation and further preserved the mechanical strength of the allografts. Both vitamin E and combined vitamin E/genipin-treated allograft were less cytotoxic to both osteoblasts and osteoclasts when compared to irradiated-only allografts. Host bone-allograft unionization was faster in a rat calvaria defect model with vitamin E-treated and combined vitamin E and genipin-treated allograft when compare to irradiated-only allografts. This method can enable the efficient and uniform radioprotective treatment of bone allograft of desired shapes for sterilization with improved mechanical strength and biointegration.

Highlights

The fracture toughness of samples doped using emulsion of the radioprotectant vitamin E and irradiated to 25 kGy (VE-e) showed a measurable but not statistically significant increase compared to the 25 kGy irradiated native bone (Irr) (Figure 2a)
The work to failure of both vitamin E and irradiated to kGy (VE-e) and vitamin E and homogenized by supercritical CO2 (VE/SC) samples were higher than into three groups: a control group (Irr) (Figure 2b) and were comparable to that of unirradiated native bone (Figure 2b)
Samples doped first with a cross-linking agent, with the pure radioprotectant followed by supercritical homogenization and 25 kGy irradiation (Gen/VE/SC) had statistically significant higher fracture toughness (Figure 2a) and work to failure (Figure 2b) compared to that of control irradiated without treatment

Summary

Chapter I Introduction

I.I Bone Graft Bone augmentation using natural bone grafts is routinely used in orthopaedic fracture, tumor and joint replacement surgeries to support the repair of defects. X Osteoinductivity: A material can be considered osteoinductive when it is able to induce migration of mesenchymal stem cells from the surrounding tissue, and subsequently differentiate into bone-forming osteoblasts[12] This process is usually facilitated by presence of growth factors within the graft, such as bone morphogenetic proteins (BMP)[13]. The poor revascularization of the cortical allograft resulted in increased quantity of necrotic bone that remains even after full incorporation of the allograft and poor ability of the allograft to heal from fatigue-generated microfractures [17] These observations correlates with clinical studies that shows allograft fracture occurred more frequently during second year after implantation[53, 54]. In addition to the reduced mechanical strength and increased clinical fracture rate of radiation sterilized bone allograft, higher delayed union rate was observed with irradiated bone allograft as compared to unirradiated bone allograft[70]. We hypothesized that vitamin E impregnated bone allograft will enhance fracture healing in vivo

Chapter II Materials and Methods

Results

Chapter IV Discussion

IV.VI Study limitation and future works