Dentistry and Biomaterials for Bone

Bioresorbable implant materials are in great demand for the repair of bone defects in reconstructive surgery. Many investigated biomaterials consist of calcium phosphates which excel in their biocompatibility, bioactivity and osteoconductivity. However, many commercially available products are limited for clinical applications because of their brittleness, incompressibility and difficulty to shape.

Dentistry

Root canal treatment is one of the major issues in dental science with more than 20 mio treatments per year in the USA. Conventional medications like calcium hydroxide are used for disinfection of the root canal (killing of bacteria). However, it attacks the dentine and makes the tooth more prone to fracture. A possible alternative to this material are bioactive glasses. This class of biomaterials does not only disinfect a root canal it forms also crystalline apatites, main component of the root canal, on its surface when immersed in simulated bodyfluids and it does not attack the dentine. Using nanotechnology the formation of this apatite and the reactivity of such bioactive glass can be enhanced via the high specific surface area. Bioactive glasses are tailored using the flame spray synthesis process in order to improve the current root canal treatment in collaboration with the dental hospital of the University of Zurich.

Bioactive glass doped with up to 50wt% bismuth oxide to render the particles visible on X-ray images.

Bioactive glass is mixed with a sterile NaCl solution (left) and applied into an artificial root canal by a lentulo spiral (right).

Cotton wool-like biomaterial

A highly bioactive network of fibers was synthesized by electrospinning using flame sprayed amorphous calcium phosphate (a-CaP) nanoparticles and biodegradable poly(lactide-co-glycolide) (PLGA). In vitro degradation in simulated body fluid (SBF) showed that significant deposition of a nano-featured hydroxyapatite layer occurred only on the surface of a-CaP doped PLGA as followed using scanning electron microscopy. This compressible and cotton-wool like biomaterial suggests application for complex shaped and non-load bearing bone defects as they appear for example in dental surgery. The in vivo bone regeneration of this easy applicable biomaterial was investigated in cooperation with the University Hospital in Zurich by creating calvarial defects in New Zealand White rabbits. Histological and micro-computed tomographic analysis after four weeks implantation showed a spongiosa-like structure of newly formed bone tissue. Furthermore we improved the material’s properties towards an antibacterial implant by using silver containing ATCP nanoparticles without influencing the bioactivity. A study in sheep using a drill hole defect model in the femur and humerus showed that both PLGA/a-CaP and PLGA/Ag-a-CaP scaffolds are biocompatible and that the fibrous material allows bone formation even at the center of former defects.

The cotton wool-like PLGA/a-CaP scaffolds enable fast mineralization when coming in contact with body fluid and are easy-to-apply by surgeons.

Anistropic a-CaP/Col/PLGA-PLGA layer

Electrospinning was used to produce a double membrane, which presents two different fronts. One front was made of a-CaP carrying collagen fibres strengthened with PLGA, the opposite front was composed of pure PLGA fibres. The mineral : collagen ratio was similar to the one in bone and hence not only the fibrous structure of bone tissue was mimicked but also its composition. In vitro biomineralisation was observed for the aCaP/Col/PLGA fibres in an SBF study. Incubation of hMSC for 4 weeks allowed for assessment of the proliferation and osteogenic differentiation of the cells on both sides of the double membrane.

The anisotropic pliable bilayer of a-CaP/Col/PLGA (dyed with Brilliant Blue) on pure PLGA could be given a spherical shape and was positioned on a femur head model. This flexibility indicates possible application as wound wrapping material.


Further reading:

• N. Hild, O.D. Schneider, D. Mohn, N.A. Luechinger, F.M. Koehler, S. Hofmann, J.R. Vetsch, B.W. Thimm, R. Müller, W.J. Stark, Two-layer membranes of calcium phosphate/collagen/PLGA nanofibres: in vitro biomineralisation and osteogenic differentiation of human mesenchymal stem cells, Nanoscale, 3(2), 401–9 (2011).
  DOI: 10.1039/C0NR00615G
• O.D. Schneider, A. Stepuk, D. Mohn, N.A. Luechinger, K. Feldmann, W.J. Stark, Light-curable polymer/calcium phosphate nanocomposite glue for bone defect treatment, Acta Biomater., 6(7), 2704-10 (2010).
  DOI: 10.1016/j.actbio.2010.01.033
  
• D. Mohn, M. Zehnder, T. Imfeld, W.J. Stark, Radio-opaque nanosized bioactive glass for potential root canal application: evaluation of radiopacity, bioactivity and alkaline capacity, Int. Endo. J., 43(3), 210-7 (2010).
  DOI: 10.1111/j.1365-2591.2009.01660.x
  
• D. Mohn, D. Ege, K. Feldman, O.D. Schneider, T. Imfeld, A.R. Boccaccini, W.J. Stark, Spherical calcium phosphate nanoparticle fillers allow polymer processing of bone fixation devices with high bioactivity, Polym. Eng. Sci., 50(5), 952-60 (2010).
  DOI: 10.1002/pen.21596
  
• O.D. Schneider, F. Weber, T.J. Brunner, S. Loher, M. Ehrbar, P.R. Schmidlin, W.J. Stark, In vivo and in vitro evaluation of flexible, cotton wool-like nanocomposites as bone substitute material for complex defects, Acta Biomater., 5, 1775-84 (2009).
  DOI: 10.1016/j.actbio.2008.11.030
  
• T. Waltimo, D. Mohn, F. Paqué, T.J. Brunner, W.J. Stark, T. Imfeld, M. Schätzle, M. Zehnder, Fine-tuning of Bioactive Glass for Root Canal Disinfection, J. Dent. Res., 88(3), 235-8 (2009).
  DOI: 10.1177/0022034508330315
  
• M. Gubler, T. J. Brunner, M. Zehnder, T. Waltimo, B. Sener, W. J. Stark, Do bioactive glasses convey a disinfecting mechanism beyond a mere increase in pH?, Int. Endo. J., 41(8), 670-8 (2008).
  DOI: 10.1111/j.1365-2591.2008.01413.x
  
• O.D. Schneider, S. Loher, T.J. Brunner, L. Uebersax, M. Simonet, R.N. Grass, H.P. Merkle, W.J. Stark, Cotton wool-like nanocomposite biomaterials prepared by electrospinning: In vitro bioactivity and osteogenic differentiation of human mesenchymal stem cells, J. Biomed. Mater. Res., 84B(2), 350-62 (2008).
  DOI: 10.1002/jbm.b.30878