Oxygen-Releasing Scaffolds for Accelerated Bone Regeneration

Abstract

Hypoxia, the result of disrupted vasculature, can be categorized in the main limiting factors for fracture healing. A lack of oxygen can cause cell apoptosis, tissue necrosis, and late tissue healing. Remedying hypoxia by supplying additional oxygen will majorly accelerate bone healing. In this study, biphasic calcium phosphate (BCP) scaffolds were fabricated by robocasting, an additive manufacturing technique. Then, calcium peroxide (CPO) particles, as an oxygen-releasing agent, were coated on the BCP scaffolds. Segmental radial defects with the size of 15 mm were created in rabbits. Uncoated and CPO-coated BCP scaffolds were implanted in the defects. The empty (control) group received no implantation. Repairing of the bone was investigated via X-ray, histological analysis, and biomechanical tests at 3 and 6 months postoperatively, with immunohistochemical examinations at 6 months after operation. According to the radiological observations, formation of new bone was augmented at the interface between the implant and host bone and internal pores of CPO-coated BCP scaffolds compared to uncoated scaffolds. Histomorphometry analysis represented that the amount of newly formed bone in the CPO-coated scaffold was nearly two times higher than the uncoated one. Immunofluorescence staining revealed that osteogenic markers, osteonectin and octeocalcin, were overexpressed in the defects treated with the coated scaffolds at 6 months of postsurgery, demonstrating higher osteogenic differentiation and bone mineralization compared to the uncoated scaffold group. Furthermore, the coated scaffolds had superior biomechanical properties as in the case of 3 months after surgery, the maximal flexural force of the coated scaffolds reached to 134 N, while it was 92 N for uncoated scaffolds. The results could assure a boosted ability of bone repair for CPO-coated BCP scaffolds implanted in the segmental defect of rabbit radius because of oxygen-releasing coating, and this system of oxygen-generating coating/scaffold might be a potential for accelerated repairing of bone defects.

Targeting Endogenous Hydrogen Peroxide at Bone Defects Promotes Bone Repair

“…[ 27 ] In another study, biphasic calcium phosphate scaffolds coated with oxygen‐releasing calcium peroxide particles markedly facilitated bone repair. [ 28 ] Oxygen‐releasing materials can also enhance angiogenesis and augment the survival of implanted bone marrow mesenchymal stem cells (BMSCs). [ 29 ] Taken together, these studies show that improving the hypoxic microenvironment by enhancing the oxygen supply can facilitate bone repair.…”

3D-Bioprinting Strategies Based on In Situ Bone-Healing Mechanism for Vascularized Bone Tissue Engineering

“…Harrison et al synthesized an oxygen-generating compound, sodium percarbonate, resulting in decreased tissue necrosis and cell apoptosis in murine skin flaps [ 83 ]. Recently, 3D modeling of biphasic calcium phosphate scaffolds integrated with calcium peroxide particles showed an increase in ALP activity compared to normal scaffolds with oxygen-poor status, which cause a decrease in ALP activity, inhibiting differentiation of both MSCs and osteoblasts, and bone formation [ 84 ]. The byproducts of chemical oxygen production are resistant to bacteria; rather, they can sometimes present oxidative stress to cells [ 85 ].…”

Hypoxia in Bone and Oxygen Releasing Biomaterials in Fracture Treatments Using Mesenchymal Stem Cell Therapy: A Review

“…Ischemia-induced cells apoptosis and dysfunction were prevented by suppression of cell stress pathways activation and shifting to anaerobic metabolism ( Lee et al, 2006 ). Additionally, scaffolds have been used with CaO 2 to better modulate oxygen release ( Touri et al, 2020 ). These CaO 2 -coated scaffolds were found to augment bone formation at the regions between the scaffolds and the host’s bone.…”