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Tissue engineering scaffolds
for cleft palate

Nachanadar Rujimarmahasan

1
content
I.
II.
III.
IV.

Cleft lip and palate
Stem cell research
Tissue model constructs & lab techniques
Craniofacial research

2
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

3
Understanding cleft lip and
palate. 1: An overview
• The normal anatomy of the face

4
Anatomy

cleft palate

normal

cleft lip and cleft palate
5
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.
6
Problems with Disorder
•
•
•
•
•
•
•
•
•

Breastfed
hearing the Eustachian tube glue ear
Speech
Functions
Cosmetic
Psychology
Dental
Swallowing
facial growth
7
Obturator

8
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

9
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.

10
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.

11
Hypothesis
Tissue engineering

12
Tissue model
constructs &
lab techniques

13
biomimetic

biomimetic of bone regeneration
14
Biomimetic Scaffold Fabrication

15
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 scaffold
From Becton Dickinson
16
Biomimetic Platforms for
Human Stem Cell Research
Gordana Vunjak-Novakovic,Volume 8, Issue 3, 4 March 2011, Pages 252–261

17
stem cell science and bioengineering

18
Biomimetic Paradigm Stem cell fate and function

19
Scaffold-Bioreactor Systems
for Human Stem Cells

20
Craniofacial Bone regeneration
•
•
•
•

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

21
Engineering anatomically shaped
human bone grafts
Warren L. Grayson, 2010

22
Tissue engineering of anatomically shaped bone grafts.

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

©2010 by National Academy of Sciences

23
24
Tissue Development and Mineral Deposition

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

©2010 by National Academy of Sciences

25
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

27
Bone matrix morphology

28
Biomaterials & scaffolds for
tissue engineering
Fergal J. O'Brien, Volume 14, Issue 3, March
2011, Pages 88–95

29
Confocal micrograph

Fig. 1. Confocal micrograph showing osteoblast cells (green) attached to
a highly porous collagen-GAG scaffold (red).
30
composite scaffolds

Fig. 2. Comparative SEM images of (a) collagen-GAG (CG) scaffold (b)
hydroxyapatite (HA) and (c) composite collagen-HA (CHA) scaffold.
31
collagen scaffolds for
bone tissue engineering

Fig. 3. Effect of hydroxyapatite addition on (a) stiffness and (b) permeability
of collagen scaffolds.
32
cell-mediated mineralization

Fig. 4. Quantitative cell-mediated mineralization by osteoblasts on the CHA
scaffolds containing differing amounts of HA
33
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.
34
engineer microvasculature

Fig. 6. In vitro microvessel formation by endothelial cells on the scaffold.
35
conclusion
Scaffold requirements
•
•
•
•

Biocompatibility
Biodegradability
Mechanical properties
Scaffold architecture

36
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
37
38

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Seminar

Editor's Notes

  1. เรื่องการรักษาผู้ป่วยปากแหว่งเพดานโหว่โดยใช้หลักการทางด้านวิศวกรรมเนื้อเยื่อ
  2. palate, in vertebrate anatomy, the roof of the mouth, separating the oral and nasal cavities. It consists of an anterior hard palate of bone and, in mammals, a posterior soft palate that has no skeletal support and terminates in a fleshy, elongated projection called the uvula.The hard palate, which composes two-thirds of the total palate area, is a plate of bone covered by a moist, durable layer of mucous-membrane tissue, which secretes small amounts of mucus. This layer forms several ridges that help grip food while the tongue agitates it during chewing
  3. glue earis fluid replace air flow in middle ear can reduce hearing,
  4. การแก้ปัญหาเกิดเป็นที่มาของงานวิจัย if orthodontic and the oral surgeon failure