Salivary Gland Tissue Engineering:

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Salivary Gland Tissue Engineering

• TSI Award Overview

Christopher A. Sullivan, M.D. January 10, 2007
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Slobber
Spittle
Salivate
Saliva
Dribble
Drool
Spit
Slaver
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Xerostomia
Dry mouth
Uninspired
Unexciting
Dehydrated
Uninteresting
Waterless
Dull
Boring
Dreary
Monotonous
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Aim
Slaver your attention in a
Dull talk about dribble
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Grant Aims

• Scientific
• Educational

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Salivary Fluid

• Essential role in upper GI function
• 1.5 liter daily
• Swallowing lubricant
• -amylase digestion of starch
• Neutralizes oral pH
• Maintains dental enamel
• Immune function (IgA)
• Facilitates speech

a
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Acinus
Parotid Gland
Duct
Submandibular Gland
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Salivary Cell Loss

• Acinar cell loss leads to loss of functional
  salivary gland tissue
• Sjogrens Syndrome (1 million , USA)
• Radiation therapy for upper aerodigestive cancer
  (40,000/y, USA)
• Age related degeneration
• Tumor
• Surgery

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Salivary Hypofunction

• Loss of normal salivary flow
• Dry mouth
• Dental decay
• Swallowing dysfunction
• Nutritional deficits
• Decreased quality of life

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(No Transcript)
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Management

• No cure for salivary hypofunction
• Saliva substitutes
• Transient effect, frequent administration
• Oral sialogogues
• Stimulate salivary flow
• Not reliable
• Primary side effect (sweating)

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Salivary Tissue Engineering

• Physiologic solution
• Steady source of saliva
• Eliminates need for saliva substitutes and
  sialogogues
• Autologous cells eliminate need for systemic
  immunosuppression.

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Hypothesis

• Creation of functional salivary gland tissue
  that is composed of a patient's own glandular
  cells could provide a physiologic solution to
  salivary gland hypofunction.

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Clinical Scenario
Cells are grown and expanded
Cells are seeded on scaffolds
Implantation into salivary bed
Autologous salivary cell harvest
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Proof of Concept
Human Clinical Trial
Disease Model
Autologous Animal Model
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Scientific Aims

• Specific Aim 1 Optimize a culture system of
  human salivary gland cells.
• Specific Aim 2 Create a salivary gland
  hypofunction model in a rodent.
• Specific Aim 3 Engineer human salivary gland
  tissue in-vivo.

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Educational Aims

• Develop and refine scientific methods
• Learn to manage a budget
• Develop working understanding of the rules of
  intellectual property
• Commercialization strategies

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Execution of Grant Aims

• Scientific Meeting Weekly
• Optimize salivary cell culture system
• Optimize animal disease model
• Engineer salivary tissue in-vivo
• Education 2008
• WFIRM/OTO/CCC tutorials and education
  opportunities local/regional national
• Spring 2008 WFUHS Innovation Commercialization
  at Babcock School
• Presentation of findings June 2008 at American
  Head and Neck Society

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Execution of Grant Aims

• Commercialization
• US patent application filed 2/1/05
• US patent supplemental amendment filed 12/282007
• Working with OTAM on potential industrial
  partners