Tissue Scaffolding for Oral Mucosa

What is Tissue Scaffolding for Oral Mucosa?

Tissue scaffolding for oral mucosa is a set of cells and other materials (specifically textiles) that are made into a 3-dimensional replica of the oral mucosa [1]. Since this is something that goes in the oral cavity, the structure may change from person to person because every persons oral cavity is going to be slightly different. 

How do you know if you need it?

About 1.5 million Americans and 5 million people worldwide have some form of lupus. Lupus is a type of long-term disease that causes inflammation in any part of the body. It is also an autoimmune disease. Of the different types of lupus one subset is Cutaneous Lupus Erythematous (CLE). Of this subset, 50-85% of people will end up developing discoid lupus erythematosus (DLE). DLE is a chronic skin condition that affects the oral cavity. Symptoms of this condition include inflammation and scarring, red or white patches in the mouth, sores that do not heal properly or that bleed easily, lumps or thicker skin in the lining of the mouth and/or a chronic sore throat or voice loss. There may also be difficulty chewing or swallowing. 24% of people with DLE will develop oral mucosal lesions. Below is an image of what the oral cavity should look like and how it looks for a person with DLE. [2,3] 

The image above is of a normal oral mucosa [1].

[2]

In the image above, the left side is what a normal oral mucosa should look like. The image on the right shows how the oral mucosa changes once you have been affected by ulcers. Once you have been approved to have tissue scaffolding inserted, the scaffolding would be used to replace the soft defective skin tissue in the oral cavity. [2,3]

Available Products

Keystone Dental, and its parent company Cook Biotech, manufacture multiple tissue engineering products that are used in orthodontic and dental surgeries. One such product is the Dynamatrix Bioactive Membrane which can be used to promote the growth and healing of the soft tissues within the oral mucosa and ensure that the growth of tissue is happening where needed [4].

DynaMatrix is meant to remodel soft tissue and it does so by providing two of the three necessary components to tissue growth: scaffolding and signaling. Using porcine small intestinal submucosa, cells are removed from the mucosa leaving only the collagen and components of the extracellular matrix [4]. The collagen here creates the scaffold that is needed while components like hyaluronic acid, fibronectin, and other growth factors lead to the migration, cell adhesion, and division of the tissue cells that surround the implant [5]. Over time the cells of the surrounding tissue will invade the scaffold, leading to the tissue becoming completely healed [4].

Grafting Procedure

The procedure of the graft implementation can vary depending on why the graft is used. Cook Biotech and Keystone Dental typically show DynaMatix used to cover a large wound that results from a tooth extraction or an implant is placed. In these scenarios, there will be a wound caused by the removal of a tooth or tissue that will be filled with a medium to promote the growth of bone, DynaBlast is a graft that is meant to promote the growth of bone and manufactured by Keystone Dental [5]. After this graft is placed, DynaMatrix will be placed above this to contain the previous graft as well as promote the growth of the gingival tissue [4]. Following this, sutures will be placed to anchor the DynaBlast and DynaMatrix and allow for healing [5]. The below image depicts this procedure.

[5]

Studies on Oral Mucosa Scaffolding

The use of scaffolding and grafting is not very common in the treatment of ulcers and abrasion within the oral mucosa, however, research is currently being done to show the potential for scaffolding for the treatment of ulcers in animal trials. One such proposed method is through the use of in vitro scaffold construction. Samples of the oral mucosa are harvested and plasma samples are collected from the animals that will receive the graft. From here, the epithelial cells are extracted with enzymatic dissociation and the epithelial cells and fibroblasts are cultured in vitro [6]. Following this, the keratinocytes were placed on a plasma fibrin matrix and seeded with cultured fibroblasts [6]. This allowed for a scaffold that could easily be placed on an ulcer using sutures.

The grafts that were created through this process allowed for a greater re-epithelialization and reduced fibrosis or scarring when compared to a control group that did not have a scaffold [6]. In addition to this, the scaffold had the ability to stretch up to 200% without tearing and was able to be detached from the mucosa using only forceps [6]. Due to this, the scaffold is very versatile in its application and there is a possibility for a scaffold that can be reusable is some aspects for ulcers that are widespread. Lastly, this scaffold can be created within 3 weeks of the biopsy of the original oral mucosa sample [6] which allows for a relatively fast treatment in the event that other less invasive methods are not effective enough.

What types of materials are used?

Along with cells, there are some polymeric materials that are used in creating tissue scaffolding. Since it is going in the oral cavity, it is necessary that the polymers used do not dissolve with the fluids that constantly run through our oral cavity. Therefore, most natural polymers would be used such as collagen [4-7].

Alternative Therapies [8]

• C Officinalis extract in a gel form
• Calendula extract
• Matricaria chamomilla
• Aloe vera

There haven’t been enough trials using these types of alternative therapies to determine pros and cons. Because tissue scaffolding for oral mucosa is not heavily marketed, these alternative therapies are similar to what an average person who gets a mouth ulcer or sore would use to treat it. Until more studies and information is found on the tissue scaffolding product, studies for alternative therapies are not likely to take place because that is not the main goal in the production process. 

Current Market

Tissue scaffolding for oral mucosa is currently in the developmental stages of the production process. Because of this, there was no information found about the market for this product. From talking with a couple of professors at the Wilson College of Textiles at North Carolina State University, this product is currently being pursued more by the dental industry than others. It should be noted that while they are not used very often, Keystone Dental makes two different forms of DynaMatrix, the standard version and DynaMatrix Plus which is is a thicker version of the standard version due to the need and the small success of the standard version [4]. 

Sources

[1] “Oral mucosa tissue engineering,” Wikipedia, 26-Nov-2019. [Online]. Available: https://en.wikipedia.org/wiki/Oral_mucosa_tissue_engineering. [Accessed: 01-May-2020].

[2]A. L. Boros, “What is the difference between a vesicle and an ulcer?,” Online Dental Programs, 31-Jan-2020. [Online]. Available: https://ostrowon.usc.edu/2018/12/10/what-is-the-difference-between-a-vesicle-and-an-oral-ulcer/. [Accessed: 01-May-2020].

[3]“Oral Pathology Traverse City MI,” Traverse City MI. [Online]. Available: https://www.lakesideoralsurgery.com/procedures/oral-pathology/. [Accessed: 01-May-2020].

[4] Keystonedental.com, “DynaMatrix,” Keystone Dental. [Online]. Available: https://keystonedental.com/pages/dynamatrix. [Accessed: 01-May-2020].

[5] Keystonedental.com, “Resources,” Keystone Dental. [Online]. Available: https://keystonedental.com/pages/resources. [Accessed: 02-May-2020].

[6] J. Lee, D. Shin, and J. L. Roh, “Treatment of intractable oral ulceration with an oral mucosa equivalent,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 107, no. 6, pp. 1779–1785, 2018.

[7]G. Ceccarelli, R. Presta, L. Benedetti, M. G. C. D. Angelis, S. M. Lupi, and R. R. Y. Baena, “Emerging Perspectives in Scaffold for Tissue Engineering in Oral Surgery,” Stem Cells International, vol. 2017, pp. 1–11, 2017.

[8] A. Aghamohamamdi and S. J. Hosseinimehr, “Natural Products for Management of Oral Mucositis Induced by Radiotherapy and Chemotherapy,” Integrative Cancer Therapies, vol. 15, no. 1, pp. 60–68, 2015.

 

Final Version