Translation of bone wax and its substitutes: History, clinical status and future directions

Abstract

Bone wax, primarily composed of beeswax and softening agent, is a century-old material used to control bleeding of disrupted bone surfaces by acting as a mechanical barrier to seal the wound. The current bone wax products are commonly packed in easy-to-open foil in the form of sterile sticks or plates, with excellent malleability and smooth consistency, enabling cost-effective and easy handling approach for bleeding control. It has also been reported that the inert nature of bone wax causes complications including foreign body reaction, infection promotion and bone healing inhibition. With the advances in biomaterials and the market boost of bone haemostatic materials, the arena of bone wax substitute research has expanded to a wide spectrum of material formulations and forms. However, the development of substitutes of bone wax for translation is a pivotal yet challenging topic because currently a potential candidate is recommended to be just as simple to use, effective and inexpensive to produce as traditional bone wax but also be absorbable and osteogenic. This review provides an overview of bone wax including its history, clinical applications and associated complication. In addition, emerging substitutes of bone wax and outlooks of future directions including the standardised evaluation methods are also discussed as an effort to catalyse the innovation and translation of bone haemostatic agents in the near future. The translational potential of this article: Occurrence of osseous haemorrhage is common in surgically incised or traumatically fractured bone. It is essential to stop bone bleeding to avoid further pathologic consequences such as tissue necrosis and eventually mortalities due to blood loss. Medical sterile bone wax is a classical material for haemostasis of bone during orthopaedic surgeries, thoracic surgeries, neurological surgeries and so on. Along with its widespread use, complications such as foreign body reaction, bone healing inhibition and infection promotion associated with bone wax are observed. With the growing knowledge in biomaterials and the boost of market of bone haemostatic materials, bone wax substitute research is thriving. An overview of bone and its substitutes together with evolution of their design criteria is carried out in this work, providing information for the innovation and translation of bone haemostatic agents in the near future.

Keywords: Biocompatible materials; Bone regeneration; Bone wax; Haemostatic.

Figure 1

Operating process of bone wax. (A) Bone wax is a sterile and flat slice wrapped in a tiny bag; (B), (C) and (D) softened bone wax is malleable and easy to be shaped.

Figure 2

Summary of reported complications caused by bone wax in the body.

Figure 3

The rabbit tibia model was inoculated with Staphylococcus aureus, introduced into the intramedullary canal through a defect created at the anteromedial facet of the proximal tibia. After 4 weeks, the cross section of the rabbit tibia shows normal bone development in the cortical window of the Ostene and control samples. The bone wax cross section shows signs of osteomyelitis with no sign of bone healing .

Figure 4

Traditional calcium phosphate cement (CPC) requires the addition of a liquid curing agent and manual mixing to finally form HA, whereas ready-to-use bone wax substitute can be much simpler and easier to use . After exposure to blood, the PEG phase dissolved and was exchanged by penetrating blood, which stimulates HA matrix formation in situ. HA, hydroxyapatite; PEG, polyethylene glycol.