Novel bone wax based on poly(ethylene glycol)-calcium phosphate cement mixtures

Abstract

Classic bone wax is associated with drawbacks such as the risk of infection, inflammation and hindered osteogenesis. Here, we developed a novel self-setting bone wax on the basis of hydrophilic poly(ethylene glycol) (PEG) and hydroxyapatite (HA) forming calcium phosphate cement (CPC), to overcome the problems that are linked to the use of conventional beeswax systems. Amounts of up to 10 wt.% of pregelatinized starch were additionally supplemented as hemostatic agent. After exposure to a humid environment, the PEG phase dissolved and was exchanged by penetrating water that interacted with the HA precursor (tetracalcium phosphate (TTCP)/monetite) to form highly porous, nanocrystalline HA via a dissolution/precipitation reaction. Simultaneously, pregelatinized starch could gel and supply the bone wax with liquid sealing features. The novel bone wax formulation was found to be cohesive, malleable and after hardening under aqueous conditions, it had a mechanical performance (∼2.5 MPa compressive strength) that is comparable to that of cancellous bone. It withstood systolic blood pressure conditions for several days and showed antibacterial properties for almost one week, even though 60% of the incorporated drug vancomycin hydrochloride was already released after 8h of deposition by diffusion controlled processes.

Statement of significance: The study investigated the development of alternative bone waxes on the basis of a hydroxyapatite (HA) forming calcium phosphate cement (CPC) system. Conventional bone waxes are composed of non-biodegradable beeswax/vaseline mixtures that are often linked to infection, inflammation and hindered osteogenesis. We combined the usage of bioresorbable polymers, the supplementation with hemostatic agents and the incorporation of a mineral component to overcome those drawbacks. Self-setting CPC precursors (tetracalcium phosphate (TTCP), monetite) were embedded in a resorbable matrix of poly(ethylene glycol) (PEG) and supplemented with pregelatinized starch. This formulation was found to be malleable and cohesive underwater. While immersion in an aqueous environment, CPC precursors formed highly porous, nanocrystalline HA via dissolution/precipitation reaction as water penetrated the novel wax formulation and PEG molecules simultaneously dissolved. The bone wax further withstood blood pressure conditions. After hardening, mechanical performance was comparable to that of cancellous bone and we also successfully provided the bone wax with antibacterial properties. In our opinion, the described bone wax formulation outmatches conventional bone waxes, as it circumvents the detriments being associated with the term "bone wax". Our wax has a novel composition and would broaden the application of CPC and besides, the general interest in bone waxes will increase, as they were long considered as a "first-line treatment" to avoid.

Keywords: Bone wax; Cement; Poly(ethylene glycol); Tetracalcium phosphate.