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A three-dimensional tissue-engineered oral mucosal model for the investigation of the implant-soft tissue interfaces.


Dental endosseous implant therapy has been established for more than 4 decades since its discovery by Dr Per-Ingvar Branemark in the late 1960s. Ever since then, more than 2000 types of implant systems varying in terms of the implant surface morphology, materials, design, surgical approaches were available in the market. Before the introduction of any new implant system to the market, the peri-implant tissue responses were normally tested using an animal model or in vitro monolayer cell culture models. However, we know that there are limitations in both study models, such as a strict ethical issue involved when using the animal model and the lack of information on cell to cell modulations in monolayer cell culture model. Our team has successfully developed an in vitro three-dimensional tissue-engineered oral mucosal model (3D OMM) for the investigation of the implant-soft tissue interfaces. This tissue-engineered oral mucosa equivalent (OME) consists of both epithelium and connective tissue layers that resembled the normal oral mucosa (Figure 1).

Briefly, the 3D OMM was constructed by co-culturing the primary or cell line oral keratinocytes together with oral fibroblasts on an acellular dermis scaffold. The implant test surface was incorporated into the model in a disk form. After 10-14 days of culturing, this tissue-engineered oral mucosa forms a peri-implant like epithelium attachment on the tested implant surface (Figure 2) as seen under light microscopy examination. The evidence of cell attachment on the implant tested surface could be further observed under the scanning electron microscopy (Figure 3) and transmission electron microscopy (Figure 4) examinations.
 

Figure 2. A light microscopy examination of a ground section. The white arrow depicts the presence of peri-implant like epithelium attached on a tested implant surface.


Figure 3. a) The scanning electron micrograph showing a partially detached tissue-engineered oral mucosa equivalent from the tested implant surface.


Figure 3. b) A magnification of the interface area as shown in the black arrow in Figure 3a, showing condensed cell attachment on the implant surface.


Figure 4. A transmission electron micrograph of the interface between the titanium implant test surface and the tissue-engineered oral mucosa equivalent (OME). A hemidesmosome like attachment (black arrow) was noted adjacent to the titanium oxide layer (white arrows).
 
In summary, the use of the 3D OMM provides more information on the soft tissue response to new implant surfaces when compared to the monolayer cell culture model. It may help to reduce the use of animal model for future studies on new implant surfaces as well as on biomaterial biocompatibility. This is because to date, there have been several studies using the 3D OMM for biocompatibility test of dental materials [1,2] and drug permeability/diffusion tests [3] that proved to be reliable.
  1. Moharamzadeh K, Franklin KL, Brook IM, van Noort R. Biologic assessment of antiseptic mouthwashes using a three-dimensional human oral mucosal model. Journal of periodontology 2009;80:769-775.
  2. Vande Vannet BM, Hanssens JL. Cytotoxicity of two bonding adhesives assessed by three-dimensional cell culture. Angle Orthod 2007;77:716-722.
  3. Hearnden V, Lomas H, Macneil S, et al. Diffusion studies of nanometer polymersomes across tissue engineered human oral mucosa. Pharmaceutical research 2009;26:1718-1728.


For more information on the research, Please contact: ASSOCIATE PROF. DR. CHAI WEN LIN
Last Update: July 03, 2012