Biomedical Engineering Series

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Biomedical Engineering Series
What I do as a Craniofacial Plastic Surgeon

• John A. van Aalst, MD, MA, FACS
• Director Pediatric and Craniofacial Plastic
  Surgery
• UNC Childrens Hospital

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Overview

• Patient care
• Cleft lip and palate
• Craniosynostosis
• Distraction
• Microtia
• Basic Science
• Nanofibers
• Stem cells
• Overseas work
• West Bank/Gaza

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Incidence

• Cleft Lip /- Cleft palate (Primary Palate)
• 1/400 500 American Indian, Asian
• 1/700 900 Caucasian
• 1/2000 African American
• Cleft Palate (Secondary Palate)
• 1/2000
• gt 400 Syndromes
• Multifactorial
• Genes
• gt 400 single gene causes of cleft lip/palate
• Environment

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Embryologic Timeline
22-27 d
27 d
30 d
28 d
42 d
50 d
21 d
Birth
Palate fusion
Lip fusion
Branchial Arch formation
Nasal Placode formation
Neural Crest migration
Neural Tube closure
Gastrulation
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In-Utero Diagnosis
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Advancement
Rotation
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Normal Suture Closure

• Time in years
• Metopic 2
• Sagittal 22
• Coronal 24
• Lambdoid 26
• Palatal 30 35
• Frontonasal 68
• Frontozygomatic 72

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Growth Perpendicular to Sutures
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Incidence of Craniosynostosis

• US incidence 0.04 - 0.1 of general population
• 1/1,900 live births
• 2 - 8 have primary craniosynostosis
• Remaining are secondary craniosynostoses
• Accompanied by microcephaly
• Sagittal 50 - 58
• Coronal 20 - 29
• Metopic 4 - 10
• Lambdoid 2 - 4.

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Microtia

• Microtia
• 1/6,000 Westerners
• 1/3,000 Japanese
• 1/1,200 Navajo Indians
• Reconstruction
• Rib cartilage
• 5-7 years of age
• 3 or 4 stages

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• Birth
• Multi-disciplinary evaluation
• Airway and feeding problems
• 14 days
• Bronchoscopy/laryngoscopy
• Grade IV view of larynx
• 24 days
• Distraction initiated

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24 days
Left
Right
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Day 1
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Day 15
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5 months
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Soft Tissue Evaluation
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Evaluation of Movement
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Distinguishing Between Soft Tissue and Bone
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Craniosynostosis
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Craniosynostosis

• Cranial database
• Determine ideal shape/size

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Tissue-Engineering

• Structural mimicry of native tissues
• Scaffolds
• Biologically derived
• Acellular dermal matrix
• Manufactured
• Nanofibers
• Stem cells
• Embryonic (totipotent)
• Non-embryonic
• Adult (multipotent, progenitor cells)
• Natal (embryonic-like)
• Stimuli for differentiation
• Growth factors (Bone Morphogenetic proteins
  BMPs, VEGF)
• Physical (loading forces, shear stress)
• Specific nutrients (Ascorbic acid)

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Nanofibers

• Submicron size
• Large surface area-to-volume ratio
• Manufactured from multiple compounds
• Synthetics
• Polycaprolactone (PCL)
• Poly (lactic-co-glycolytic) acid (PLGA)
• Natural
• Collagen, fibrin, chitin, silk
• Controlled degradation rates
• Manufacturing techniques
• Electrospinning
• Versatile
• Cost-effective
• Fiber uniformity

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Cell Incorporation into PVA Nanofibers
Scanning Electron Microscopy
Fibroblasts
Stem cells
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CD90()
CD105()
SSEA4()
CD73()
Nikon Eclipse Ti-S Inverted Microscope (80/20)
with a 40X, 0.6 mm WD CFI Plan Fluor ELWD
Objective and a DS Cooled Monochromatic Camera
Head DS-QI1
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Osteoinduction of hADAS
Adipose Tissue
CD73 CD105 CD166
Growth
Digestion
Positive Immunostaining
Centrifugation
Seeding onto Nanofiber Scaffolds (Cell ID83940
Passage 3 2 x 105 cell seeding density per
well?5 x 104 cells/cm2)
PCL
PLGA
21 days Osteoinduction
21 days Osteoinduction
Viability Staining
Viability Staining
Alizarin Red Staining
Alizarin Red Staining
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IHC Staining for Chondrogenesis on Chitosan
Nanofibers
Chondrogenic
Control
10x
20x
10x
20x
2 3 1 1
Aggrecan
Collagen I
Collagen II
Collagen X
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www.palestiniancleftsociety.com
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What do I need?

• A way to track facial movement
• In order to show adequate muscle function
• A distractor that is resorbable and reliable
• A better ear mold/model
• A way to adequately predict bone movements for
  craniosynostosis
• Transportable technology

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