Osteoinduction and -conduction through absorbable bone substitute materials based on calcium sulfate: in vivo biological behavior in a rabbit model
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Calcium sulfate (CS) can be used as an antibiotically impregnated bone substitute in a variety of clinical constellations. Antibiotically loaded bone substitutes find specific application in orthopedic and trauma surgery to prevent or treat bone infections especially in relation to open bone defects. However, its use as a structural bone graft reveals some concerns due to its fast biodegradation. The addition of calcium carbonate and tripalmitin makes CS formulations more resistant to resorption leaving bone time to form during a prolonged degradation process. The aim of the present study was the evaluation of biocompatibility and degradation properties of newly formulated antibiotically impregnated CS preparations. Three different types of CS bone substitute beads were implanted into the tibial metaphysis of rabbits (CS dihydrate with tripalmitin, containing gentamicin (Group A) or vancomycin (Group B); Group C: tobramycin-loaded CS hemihydrate). Examinations were performed by means of x-ray, micro-computed tomography (micro-CT) and histology after 4, 6, 8 and 12 weeks. Regarding biocompatibility of the formulations, no adverse reactions were observed. Histology showed formation of vital bone cells attached directly to the implanted materials, while no cytotoxic effect in the surrounding of the beads was detected. All CS preparations showed osteogenesis associated to implanted material. Osteoblasts attached directly to the implant surface and revealed osteoid production, osteocytes were found in newly mineralized bone. Group C implants (Osteoset®) were subject to quick degradation within 4 weeks, after 6–8 weeks there were only minor remnants with little osteogenesis demonstrated by histological investigations. Group A implants (Herafill®-G) revealed similar degradation within atleast 12 weeks. In contrast, group B implants (CaSO4-V) were still detectable after 12 weeks with the presence of implant-associated osteogenesis atlatest follow-up. In all of these preparations, giant cells were found during implant degradation on surface and inside of resorption lacunae. None of the analyzed CS preparations triggered contact activation. All implants demonstrated excellent biocompatibility, with implants of Group A and B showing excellent features as osteoconductive and -inductive scaffolds able to improve mechanical stability.
At first, we would like to thank Mr. Dr. H. Büchner and Mr. Dr. S. Vogt (Heraeus Medical GmbH, Werheim, Germany) for their kind supply of bone substitute materials (Herafill®-G, as well as CaSO4-V). Second, many thanks to the central pre-clinical research division (ZPF) of the Klinikum rechts der Isar at the Technical University of Munich for their excellent support in performing the animal study. Especially, many thanks to Mrs. Dr. M. Rößner and Prof. Dr. H. Gollwitzer for their guidance in surgical procedure. Also, many thanks to Mrs. Dr. S. Kerschbaumer for generating and interpreting histological slices. Moreover, special thanks to Prof. Dr. P. Augat (Department of Biomechanics at the Unfallklinik Murnau) for his kind support in micro-CT investigations. Finally, many thanks to Mr. F. Seidl (M.A. Interpreting and Translating, MBA) for his kind support due to his perfect command of scientific English.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest
- 1.Lalidou F, Kolios G, Drosos GI. Bone infections and bone graft substitutes for local antibiotic therapy. Surg Technol Int. 2014;24:353–62.Google Scholar
- 7.Slater N, Dasmah A, Sennerby L, Hallman M, Piattelli A, Sammons R. Back-scattered electron imaging and elemental microanalysis of retrieved bone tissue following maxillary sinus floor augmentation with calcium sulphate. Clin Oral Implant Res. 2008;19:814–22. https://doi.org/10.1111/j.1600-0501.2008.01550.x CrossRefGoogle Scholar
- 9.Stubbs D, Deakin M, Chapman-Sheath P, et al. In vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials. 2004;25:5037–44. https://doi.org/10.1016/j.biomaterials.2004.02.014 CrossRefGoogle Scholar
- 10.Fan X, Ren H, Luo X, et al. Mechanics, degradability, bioactivity, in vitro, and in vivo biocompatibility evaluation of poly(amino acid)/hydroxyapatite/calcium sulfate composite for potential load-bearing bone repair. J Biomater Appl. 2016;30:1261–72. https://doi.org/10.1177/0885328215620711 CrossRefGoogle Scholar
- 14.J Borrelli, Jr., Prickett WD, Ricci WM. Treatment of nonunions and osseous defects with bone graft and calcium sulfate. Clin Orthop Relat Res. 2003:245–54. https://doi.org/10.1097/01.blo.0000069893.31220.6f
- 21.Lebourg L, Biou. C. [The imbedding of plaster of paris in surgical cavities of the maxilla]. Sem Med Prof Med Soc. 1961;37:1195–7.Google Scholar
- 22.Geldmacher J. [Therapy of enchondroma with a plaster implant--renaissance of a treatment principle]. Handchir Mikrochir Plast Chir. 1986;18:336–8.Google Scholar
- 25.Lillo R, Peltier LF. The substitution of plaster of Paris rods for portions of the diaphysis of the radius in dogs. Surg Forum. 1956;6:556–8.Google Scholar
- 27.Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson JT, Kim PT. The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop Relat Res. 2001:42–50. http://graphics.tx.ovid.com/ovftpdfs/FPDDNCJCCBGBCB00/fs046/ovft/live/gv023/00003086/00003086-200101000-00008.pdf.
- 28.Blaha JD. Calcium sulfate bone-void filler. Orthopedics. 1998;21:1017–9.Google Scholar
- 31.Walsh WR, Morberg P, Yu Y, et al. Response of a calcium sulfate bone graft substitute in a confined cancellous defect. Clin Orthop Relat Res. 2003;228–36. https://doi.org/10.1097/01.blo.0000030062.92399.6a.