Tissue engineering scaffolds for cleft palate

Nachanadar Rujimarmahasan

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content

I. Cleft lip and palate

II. Stem cell research

III. Tissue model constructs & lab techniques

IV. Craniofacial research

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Objectives• The ability to engineer anatomically correct pieces of viable and

functional human bone would have tremendous potential for bone reconstructions after congenital defects

• Design and Modifying Model to create Smart biomaterial scaffolds that improve tissue regeneration

• Biocompatible and biodegradable • Biomaterial scaffolds that are immunologically inert• Stem cell can be patient specific using their own isolated cells,

reducing risk of rejection

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Understanding cleft lip and palate. 1: An overview

• The normal anatomy of the face

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Anatomy

cleft palate

normal

cleft lip and cleft palate

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Cleft lip and palate

Patients with clefts: (A) incomplete unilateral cleft of the lip, (B) unilateral cleft of the lip, alveolus, and palate, (C) bilateral cleft of the lip, alveolus, and palate,

(D) isolated (median) cleft palate.

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Problems with Disorder • Breastfed• hearing (the Eustachian tube) glue ear• Speech• Functions• Cosmetic• Psychology• Dental• Swallowing• facial growth

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Obturator

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Care plan timetable• birth to 6 weeks: counseling for parents, hearing test and

feeding assessment • 3 months: surgery to repair a cleft lip • 6-12 months: surgery to repair a cleft palate • 18 months: speech assessment • 3 years: speech assessment • 5 years: speech assessment • 8-11 years: bone graft to the cleft in the gum area (alveolus) • 11-15 years: orthodontic treatment and monitoring jaw growth • 18 years+: if needed, jaw surgery, lip and nose revision surgery,

and final replacements for any missing teeth

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Problems

Be the angel for cleft lip and cleft palate children: What you can do to help?

If orthodontic and the oral surgeon treatment failure

Decreases the extent of surgery required for repairing the lip and palate.

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OUTCOME

• Developed a biomimetic scaffold for tissue engineering

• That provides a cell-instructive structural framework • For inducing differentiation of stem cells into

osteogenic cells. • This porous and matrix have increaded stiffness • Which can facilitate its use in load-bearing bone

tissue engineering.

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Hypothesis

Tissue engineering   

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Tissue model constructs &

lab techniques

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biomimetic

biomimetic of bone regeneration14

Biomimetic Scaffold Fabrication

                                                                                                                                       

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Engineering bone grafts

• Change stem cells into bone cells – with proper growth

factors in cell culture media

• This scaffold can’t be too big or the cells inside will die since they will not get enough oxygen

A 3D calcium phosphate scaffoldFrom Becton Dickinson

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Biomimetic Platforms for

Human Stem Cell Research

Gordana Vunjak-Novakovic,Volume 8, Issue 3, 4 March 2011, Pages 252–261

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stem cell science and bioengineering

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Biomimetic Paradigm Stem cell fate and function

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Scaffold-Bioreactor Systems for Human Stem Cells

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Craniofacial Bone regeneration

• clinically sized • anatomically shaped • viable human bone grafts stem cells• biomimetic” scaffold-bioreactor system.

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Engineering anatomically shaped human bone grafts

Warren L. Grayson, 2010

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Tissue engineering of anatomically shaped bone grafts.

Grayson W L et al. PNAS 2010;107:3299-3304

©2010 by National Academy of Sciences 23

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Grayson W L et al. PNAS 2010;107:3299-3304

©2010 by National Academy of Sciences

Tissue Development and Mineral Deposition

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Bone formation was markedly by perfusion

Grayson W L et al. PNAS 2010;107:3299-3304

©2010 by National Academy of Sciences 26

Architecture of the mineralized bone matrix

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Bone matrix morphology

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Biomaterials & scaffolds for tissue engineering

Fergal J. O'Brien, Volume 14, Issue 3, March 2011, Pages 88–95

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 Confocal micrograph

Fig. 1. Confocal micrograph showing osteoblast cells (green) attached to a highly porous collagen-GAG scaffold (red).

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 composite scaffolds

Fig. 2. Comparative SEM images of (a) collagen-GAG (CG) scaffold (b) hydroxyapatite (HA) and (c) composite collagen-HA (CHA) scaffold.

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collagen scaffolds for bone tissue engineering

Fig. 3. Effect of hydroxyapatite addition on (a) stiffness and (b) permeability of collagen scaffolds.

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cell-mediated mineralization

Fig. 4. Quantitative cell-mediated mineralization by osteoblasts on the CHA scaffolds containing differing amounts of HA

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degradation in rat calvarial defect

Fig. 5. Example of core degradation in a rat calvarial defect treated with a tissue engineered collagen-calcium phosphate scaffold 4 weeks post implantation.

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engineer microvasculature

Fig. 6. In vitro microvessel formation by endothelial cells on the scaffold.

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conclusion

Scaffold requirements• Biocompatibility• Biodegradability• Mechanical properties• Scaffold architecture

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conclusion• ideal scaffold should have several

characteristics: – (i) high porosity for cell/tissue growth,

nutrient diffusion, matrix production and vascularization;

– (ii) controllable degradation to match tissue growth once implanted in body and

– (iii) reasonable mechanical strength to match the tissues at the site of implantation

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