Synthetic Scaffolds for

Tissue Engineering

Antonios G. Mikos

Rice University

25 Years Celebration of

Institute of Chemical Engineering and

High Temperature Chemical Processes

July 3, 2009

Currently Investigated Tissues

bone

cartilage, ligament

cartilage

cornea, vitreous

muscle, skin

esophagus

heart muscle

liver

bladder

blood vessel

lungnerve

Tissue Engineering Paradigm

Scaffold Drugs

Cells

3D Polymer Scaffolds

500 m

Particulate Leaching

100 m

High Internal Phase Emulsion

10 m

Electrospinning

3D Cell/Scaffold Constructs

Ectopic bone formation by mesenchymal stem cell

transplantation in a rat model.

Carbon Nanotube Composites

Functionalization improves carbon nanotube

dispersion into fumarate-based polymers.

500 nm

100 nm

3D Nanocomposite Scaffolds

Bone tissue induction into US-tube nanocomposite

scaffolds in a rabbit femoral condyle model.

US-tube NanocompositePPF Polymer

Distilled Water (Reference)

0.04 mM of Gd3+

Gd-nanotubes

Gd-fullerenes

Gd@C60[C(COOH)2]10

Conventional Gd-DTPA

(Magnevist™)

Gd@(Carbon Nanostructures) show very large

signal enhancements suitable for cellular MRI.

Nanotubes as MR Contrast Agents

3D Micro- and Nanofiber

Layered Scaffolds

Number, location, and thickness of nanofiber layers

can be controlled by electrospinning.

AB

C

D

B

C

D

100 m

25 m

Sheep Model for Bone Engineering

Molded Tissue Chamber

Periosteum

Rib

Periosteum

Molded Tissue Chamber Scaffold Material

Tissue IngrowthIntercostal Blood Vessels

Vascularized Tissue Flaps

Formation of vascularized bone flaps for reconstructive

surgery by guided tissue growth in a sheep model.

Vascularized Tissue Flaps

Tissue engineered autologous bone flap technology

has been translated for clinical applications.

Plastic and Reconstructive Surgery, 2006

Peristaltic

Pump

Media

Reservoirs

Flow

Chamber

Mitigates nutrient and waste

transport limitations

Provides mechanical stimulation

in the form of fluid shear stresses

Flow Perfusion Bioreactor

Stem cells exposed to generated ECM differentiated

based upon the factors present in the matrix.

*, # p < 0.05

* #

*

*

g C

a2

+/

co

ns

tru

ct

Days of in vitro culture

Ti/ECM Scaffold

Ti Mesh Scaffold

50 m

In Vitro Generated ECM

Biomimetic Hydrogels

Modulation of mesenchymal stem cell function using

biomimetic peptide-modified hydrogels.

20 m

Particulate Polymer Carriers

Biodegradable polymer microparticles used

for the delivery of bioactive molecules.

Growth Factor Carriers/Scaffolds

Bone regeneration by TP508 release from PPF-based

scaffolds in a rabbit radius segmental defect model.

Animal Model Development

Micro-CT imaging of bone and blood vessel formation

within a rabbit mandibular critical size defect.

Bone Regeneration

Vessel Regeneration

Rabbit CSD

Buccal Lingual

Sagittal Sagittal Coronal

Multiple Growth Factor Carriers

Controlled release of VEGF and BMP-2

within a rat cranial critical size defect.

Micro-CT Imaging at 4 Weeks

PPF VEGF

BMP-2 VEGF + BMP-2

0

10

20

30

40

50

60

EMPTY PPF VEGF BMP-2 VEGF +BMP-2

4 weeks

12 weeks

% o

bje

ct

vo

lum

e

# #

*

Multiple Growth Factor Carriers

Controlled release of VEGF and BMP-2

within a rat cranial critical size defect.

Micro-CT Imaging at 12 Weeks

PPF VEGF

BMP-2 VEGF + BMP-2

0

10

20

30

40

50

60

EMPTY PPF VEGF BMP-2 VEGF +BMP-2

4 weeks

12 weeks

# #

*

% o

bje

ct

vo

lum

e

Ceramic/Polymer Scaffolds

Bone formation by rhBMP-2 release from Ca-P/PLGA

scaffolds in a rat cranial critical sized defect model.

Cell/Scaffold Constructs

Bone regeneration using genetically modified MSCs

in a rat cranial critical sized defect model.

1.0 mmUnmodified Cells

Genetically Modified Cells

Injectable Plasmid DNA Carriers

Plasmid DNA is released from biodegradable

OPF scaffolds in a controlled manner.

Day

OO

OH

O

O

OH

n n m

Cum

ula

tive F

raction D

NA

Rele

ase

No DNA Expression

Plasmid DNA Expression

(Antibiotic Resistance Gene)

Fast Degrading OPF: Total DNA

Fast Degrading OPF: Double-Stranded DNA

Slow Degrading OPF: Total DNA

Slow Degrading OPF: Double-Stranded DNA

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

0 10 20 30 40 50 60

100 m

Day 7

Day 28

MSCs produce calcified matrix over 28 days in vitro.

OO

OH

O

O

OH

n n m

Blank

Hydrogel

Hydrogel with

Embedded MSCs

Injectable Cellular Constructs

Encapsulated chondrocytes attach to gelatin

microparticles and proliferate over 3 wks in culture.

100 m

Cells Only Cells + TGF- 1-Loaded MPs

100 m

Cell and Growth Factor Carriers

Injectable Growth Factor Carriers

Cartilage repair using a

growth factor carrier in a

rabbit osteochondral

defect model.

1.0 mm

H & E

1.0 mm

Safranin O

Synthetic Scaffolds for

Tissue Engineering

• Matrices for cell culture and transplantation

• Conduits for guided tissue growth

• Substrates for targeted cell adhesion

• Stimulants for desired cellular response

• Carriers for controlled drug delivery

Acknowledgments

www.ruf.rice.edu/~mikosgrp/