Introduction: Bone wax based on mixtures of beeswax and vaseline is commonly used as physical barrier to treat bleeding of cancellous bone during surgery. Although it is easy to handle and cost-effective, disadvantages such as foreign body reactions, infections, tissue damage and a hindered osteogenesis in vivo are observed[1]. Previous approaches to overcome these problems are waxes consisting of biodegradable polymers (poly(ethylene glycol), PEG) and hemostatic agents (pregelatinized starch) to create an intrinsically hemostatic bone sealant[2]. Here, we additionally incorporated osteoconductive hydroxyapatite (HA) forming calcium phosphate cement (CPC) precursors to create a malleable system, which initially can seal bone wounds and hardens after contact with physiological fluids due to diffusion exchange of PEG and water molecules.
Materials and Methods: 4 g tetracalcium phosphate (TTCP)/monetite were mixed with 1 g NaH2PO4 and up to 10 wt.% corn starch and dispersed in 3 g of a molten PEG 1,500/400 mixture. After hardening, the bone wax was softened and kneaded until a homogeneous texture was reached. Cuboidal samples (6x6x12 mm) were deposited in phosphate buffered saline for up to 24 d at 37°C. Compressive strength, porosity, mass loss, phase composition, PEG release, water sealing duration, antibiotic release and antibacterial properties via vancomycin hydrochloride addition were tested.
Results: The compressive strength of the tested bone waxes varied between 2.0-2.9 (no starch) and 2.4-2.6 MPa (10 % starch) with corresponding porosities of 66 and 63 %. The 10 % probes lost about 3 % of their initial weight while an overall mass loss of 9 % occurred for the starch-less samples. After 24 d, a matrix of nanocrystalline HA was formed with small residues of unreacted TTCP. After 6 d of deposition, possible PEG residues were beyond the detection limit of FTIR analysis. Under blood pressure conditions, all bone waxes had a liquid sealing duration of 47 h at most. Concerning the cumulative vancomycin release, an initial burst was observed with a quantitative release being reached after 6 d. Testing against Staphylococcus aureus proved antibacterial activity.
Discussion: We could show that PEG-CPC bone wax almost completely converted to HA without organic residues. HA is known to be biocompatible, osteoconductive and similar to biological apatite[3] and the obtained strengths were comparable to those of cancellous bone[4]. Furthermore, a sealing ability of almost 2 d confirms its suitability as mechanically effective hemostatic agent. Furthermore, such novel bone waxes can be modified with antibiotics without affecting the activity of the released drug.
Conclusion: To the best of our knowledge, a PEG-CPC bone wax system is a novel and sophisticated approach to create a bone wax with ameliorated properties being osteoconductive, self-setting, partially degradable, hemostatic and antibacterial if necessary.
We gratefully acknowledge financial support by: DFG State Major Instrumentation Programme, funding the crossbeam scanning electron microscope Zeiss CB 340 (INST 105022/58-1 FUGG)
References:
[1] Schonauer C. et al., Eur. Spine J. 13:89-96, 2004.
[2] Suwanprateeb J. et al., J. Mater. Sci.-Mater. Med. 24:2881-2888, 2013.
[3] Bohner M., Injury. 31: D37-D47, 2000
[4] Galante, J. et al., Calcif. Tissue Res. 5:236-246, 1970