Abstract
Summary Statement
This work features a new approach to overcome drawbacks of commercial calcium phosphate cements in terms of application by on-site preparation and bone ingrowth by introduction of macropores in the material using a hydrofluoroalkane based aerosol foam.
Introduction
The application of calcium phosphate bone cements (CPCs) into a void for example of an osteoporotic bone is very difficult as the cement paste is made outside the application site and subsequently applied into the damaged bone. A common drawback of especially apatitic cements is a very low resorption rate due to small pore size Therefore different approaches have been described to add macropores into the cement2, leading to bone ingrowth and tissue penetration. The aim of this project is the use of two separate formulations in pressurised systems – a suspension and an emulsion – which can be mixed in a specially developed device and can be applied easily and efficiently into a bone directly during surgery leading to a self-hardening macro porous CPC foam. The intention is to fill voids in osteoporotic bones to ensure stability for implants like e.g. screws for femur neck fractures. An increased stability for implants can allow the possibility of a less invasive femur neck preserving therapy in contrast to a femur neck replacement. Other indications for such foam (i.e. kyphoplasty) are under evaluation.
Methods
As suggested above two separate formulations for the components are developed to prevent premature hardening. Hydrofluoroalkanes were preferred as propellants to propane, butane or isobutane, due to their superior safety profile. The hardener component was formulated as propellant-in-water emulsion. Several parentally approved emulsifiers (e.g. Poloxamer 188) were tested in view of solubility at the given salt and binder concentration. The stability of resulting emulsions in pressurised containers, the corresponding foams as well as the foam expansion volume was analyzed. Porous hydroxyapatite is formed after addition of tetra-calciumphosphate, di-calciumphosphate dihydrate and tri-sodiumcitrat dehydrate incorporated in the suspension component. To overcome quick sedimentation of these solids, particle size was reduced by dry or non-aqueous wet milling, respectively. Changes in particle size distribution and enthalpy changes during processes were analyzed. Hardening properties of both components were tested particularly with regard to compressive strength. In order to apply the components, a suitable application system was developed and the hardened product analyzed using x-ray diffraction.
Results
The optimised Ca2+/(PO4)3− component is a submicron-sized suspension in a mixture of ethanol and HFA 134a. The development of the suspension led to new knowledge with regard to milling effects on the Ca2+/(PO4)3− components. The optimised hardener component contains an aqueous solution of sodium phosphates, Povidone 90 and Poloxamer 188 emulsified in HFA 227. Both components are formulated in pressurised cans.
Discussion/Conclusion
A two component bone foam for stabilisation in osteoporotic bones including a new mixing / application system, which allows actuation of the components and leads to a hardening process that results in hydroxyapatite in a suitable test setup, was developed. The new application system.
Further steps i.e. proof of concept (in-vitro and in-vivo) are being taken.
