Background

Properties of an
Ideal Scaffold

Scaffold Fabrication
Main Discussion
Methods

Material Used
Within BTE

Barriers to Clinical
Translation
 Background
• Bone is the second most commonly transplanted
tissue worldwide.

• Developing 3D bioactive scaffolds to support bone

regeneration.

• Considering the ideal properties of bioactive 3D

scaffolds.
 Clinical Demand of an Ideal
Scaffold
• Capacity for bone to self-regenerate has prompted
study and intrigue since the times oh Hippocrates and
Galen

• Congenital and acquired pathologies including trauma,

infection, neoplasm and failed arthroplasty remain
capable of leaving patients with bone defects beyond a
critical-size which body cannot heal

• Porous 3D scaffolds fabricated through a variety of

methods and including a range of biomaterials have
been utilised to aid and direct bone regeneration
 Properties of an Ideal
Scaffold
Ideal 3D Scaffold should be like these :

• Composed of a biocompatible, biodegradable

material
• Facilitate host cells to deposit ECM
• Easily manipulated into different shapes and sizes
• Nontoxic to cells and easily eliminated from the body
 Desirable Scaffold Properties
Biocompatibility
• Non-toxic breakdown products
• Non inflammatory scaffold components, avoiding immune
rejection

Biodegradability
• Controlled scaffold degradation which can complement
tissue ingrowth whilst maintaining sufficient support
• Degradable by host enzymatic or biological processes
• Allows invading host cells to produce their own
extracellular matrix
Bioactivity
• Scaffold materials that can interact with and bind to host
tissue
• Osteosoncductive and osteinductive properties
• Inclusion of biological cues and growth factors to stimulate
cell ingrowth, attachment, and differentiation

Scaffold Architecture
• Interconnected pores allowing diffusion and cell migration
• Microporosity to present a large surface area for cell-
scaffold interactions
• Macroporosity to allow cell migration and invasion of
vasculature
• Pore size tailored to target tissue and cells
• Sufficient porosity to facilitate cell ingrowth without
weakening mechanical properties
Mechanical Properties
• Inbuilt vascular channels to enhance angiogenesis in vivo
• Compressive, elastic and fatigue strength comparable to
host tissue allowing cell mechanoregulation to occur and
structural integrity to remain in vivo
• Scaffold material that can be readily manipulated in the
clinical environment to treat individual patient bone
defects
Ideal scaffold specification :

• Compressive strength approx.

100 – 230 MPa
• Young’s modulus close to 7 – 30
GPa
• Tensile strength of 50 - 151 MPa
• Porosity between 60% until
90%
• Average pore size > 150 um
Scaffold Fabrication Methods

Conventional 3D Printing

• Solvent Casting • SLA/SLS

• Gas Foaming • FDM
• Emulsification Freeze- • Ink-jet
Drying
• Phase Separation
• Electrospinning
 Conventional Scaffold Printing

• This technique uses porogens, a substance that can be

dispersed into a moulded structure and subsequently
dissolved once the structure has set

• Polymer is subsequently hardened as the solvent

evaporates

• Hardened polymer scaffold with a porous network is left

behind, although it’s difficult to control pore shape and
pore interconnectivity
• Gas foaming eliminates the use of
solvents deployed in solvent
casting leaching methods

• Compression moulding is first

used to create solid discs of a
scafflod material

• The discs are saturated with high

pressure CO2 gas, make the CO2
gas clump together

• Difficult to control pore

connectivity and pore sizes by
gas foaming
• Freeze-drying begins with
freezing of a polymer solution

• The surrounding pressure is

then reduced via vacuum to a
level lower than the
equilibrium vapor pressure of
the frozen solvent

• The frozen emulsion is then

freeze-dried to remove the
solvent and dispersed water,
creating pores in a solidified
scaffold
• Phase separation scaffold manufacture begins with dissolution of
a polymer in a high-boiling, low molecular weight solvent at an
elevated temperature

• The solution then cast into a desired scaffold shape and cooled in
a controlled manner to induce phase separation and precipitation

• It creates a porous scaffold as a removal of the solvent leaves

pores behind in the polymer matrix
• Electrospinning method uses
an externally applied electric
field to draw charged
threads of polymer solutions
or polymer melts as thin jets
from a capillary tube
towards a collector plate.

• Fibres in the micrometre and

nanometre range can be
created and deposited
sequentially to create a
scaffold
3D Scaffold Printing
• Stereolitography (SLA) is
one of the earliest 3D
printing techniques to
have been developed

• SLA can quickly produce

scaffolds but there was a
limited number of
materials applicable to
this costly technique
• Fused deposition Modelling
(FDM) uses a temperature
controlled printhead to
deposit thermoplastic
material onto a platform in a
layer by layer manner to
build up a 3D construct

• FDM has been successfully

adapted into BTE as method
of producing synthetic
scaffolds, although the
elevated temperatures
involved limit the inclusion of
biomolecules and hydrogels
• Selective Laser Sintering (SLS) involves the use of a
computer controlled laser beam to fuse layer-upon-layer of
a powder

• The elevated temperatures involved the process limit the

inclusion of cells and biomaterials directly into SLS
scaffolds
Materials Used Within Bone
Tissue Engineering

Metals Bioceramics Hydrogels

Bioactive Glasses Polymer

 Comparison of Scaffold Materials
HYDROGELS
BENEFITS LIMITATIONS

• High water content/growth

• Mechanical properties limit use
media inclusion for cell
in load bearing constructs
encapsulation and growth
• Optimising printing conditions
• Mechanical properties can be
for individual hydrogels can be
modified through crosslinking
time consuming
• Controlled drug/growth factor
• Physical manipulation constructs
release possible
can be difficult
• Ease of patterning via 3D
• Loading evenly with cells can be
printing to mimic tissue
challenging
microarchitectures.
 POLYMERS
BENEFITS
• Natural polymers can be
derived from extracelluler
matrix, ensuring high
biocompatibility and low
toxicity
• Biodegradable
• Often contain biofunctional
molecules on their surface
• Synthetic polymers offer
improved control over
physical properties
LIMITATIONS
• Natural and synthetic
polymers generally lack
mechanical properties for
load bearing
• Pathological impurities such
as endotoxin may be
present in natural polymers
• Synthetic polymers are
often hydrophobic and lack
cell recognition sites
 CERAMICS
BENEFITS
• Osteoconductibe and
osteoinductive properties
allow strong integration
with hot tissue
• Similar composition to host
bone mineral content
• Can be delivered as
granules, paste or in an
injectable format
LIMITATIONS
• Hard and brittle when used
alone
• May display inappropriate
degradation/resorption
rates, with dicline in
mechanical properties as a
result
 BIOACTIVE GLASS

BENEFITS LIMITATIONS
• Osteoconductive, • Inherent brittleness
osteoinductive properties
• Difficult to tune resorption
• Adapted into clinical rate
prosthesis already
• Manipulation of constructs
into 3D shaped to treat
specific defects challenging

• Potential for release of toxic

metal ions
 METALS
BENEFITS
• Biocompatible
• Superior strength
• Superior mechanical
properties can be
advantageous in situations
where slow bone growth
likely
LIMITATIONS
• Superior modulus can lead
to stress-shielding
• Poor biodegradability may
result in further
surgery/impairment of
tissue ingrowth
• Secondary release of metal
ions may cause local and
distal toxicity
 Barriers to Clinical
Translation

• Scientifics and Technological Challenges

• Translational Challenge
• Ethical Issues