NANOFIBER%20TECHNOLOGY:%20DESIGNING%20THE%20NEXT%20GENERATION%20OF%20TISSUE%20ENGINEERING%20SCAFFOLDS - PowerPoint PPT Presentation

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NANOFIBER%20TECHNOLOGY:%20DESIGNING%20THE%20NEXT%20GENERATION%20OF%20TISSUE%20ENGINEERING%20SCAFFOLDS

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Title: NANOFIBER%20TECHNOLOGY:%20DESIGNING%20THE%20NEXT%20GENERATION%20OF%20TISSUE%20ENGINEERING%20SCAFFOLDS


1
NANOFIBER TECHNOLOGY DESIGNING THE NEXT
GENERATION OF TISSUE ENGINEERING SCAFFOLDS
C.P. Barnes1, S.A. Sell1, E.D. Boland1, D.G.
Simpson2, G.L. Bowlin11Department of Biomedical
Engineering, 2Department of Anatomy and
NeurobiologyVirginia Commonwealth University,
Richmond, VA
MARK HWANG
2
EXTRACELLULAR MATRIX
Signalling - cell adhesion - programmed cell
death - migration - cytokine/growth factor
activity - growth - differentiation
3
TISSUE ENGINEERING SCAFFOLDS - BACKGROUND
Premise - ECM microenvironment key to tissue
regeneration - Cell not viewed as self-contained
unit Role of ECM - ECM mediates biochemical and
mechanical signalling - Ideal ECM
non-immunogenic promote growth maintain
3-D structure only native tissues remain
post-treatment
Research emphases to-date - Biocompatibility -
Degradability
4
TISSUE ENGINEERING SCAFFOLDS - BACKGROUND
Overall Goals - Design scaffold with maximum
control over biocompatibility
(chemical) biodegradability (mechanical) -
Utilize natural and synthetic polymers - Future
directions tissue regeneration drug delivery
EFFECTIVE SCAFFOLD DESIGN BEGINS WITH ACCURATE
SCALING
Current Focus - Nanofiber synthesis
5
NANOFIBERS - INTRODUCTION
ECM fibers 50-500 nm in diameter Cell
several-10 um Fibers 1-2 orders of magnitude lt
cell
3 techniques to achieve nanofiber scale - self
assembly - phase separation - electrospinning
6
NANOFIBERS SELF-ASSEMBLY
  • Definition spontaneous organization into stable
    structure without covalent bonds
  • Biologically relevant processes
  • DNA, RNA, protein organization
  • - can achieve small diameter

Drawbacks more complex in vitro - limited to 1)
several polymers and - 2) hydrophobic/philic
interactions - small size larger unstable
7
NANOFIBERS PHASE SEPARATION
Definition thermodynamic separation of polymer
solution into polymer-rich/poor layers - similar
to setting a gel - control over macroporous
architecture using porogens, microbeads,
salts 98 porosity achieved! - consistent
Drawbacks - limited to several polymers - small
production scale
8
NANOFIBERS ELECTROSPINNING
Definition electric field used to draw polymer
stream out of solution
D- electric field overcomes solution surface
tension polymer stream generated
E- fibers 1) collected and 2) patterned on plate
9
NANOFIBERS ELECTROSPINNING
- simple equipment - multiple polymers can be
combined at 1) monomer level 2) fiber
level 3) scaffold level
- control over fiber diameter alter
concentration/viscosity - fiber length unlimited
- control over scaffold architecture target
plate geometry target plate rotational speed
10
NANOFIBERS ELECTROSPINNING
Drawbacks - natural fibers 50-500 nm spun
fibers closer to 500 nm - architecture very
random
LACK OF GOLD STANDARD
Current approaches combined techniques - usually
electrospinning phase separation - fibers woven
over pores
11
NANOFIBERS OVERVIEW
12
ELECTROSPINNING POLYMERS
Synthetics - Polyglycolic acid (PGA) - Polylactic
acid (PLA) - PGA-PLA - Polydioxanone (PDO) -
Polycaprolactone - PGA-polycaprolactone -
PLA-polycaprolactone - Polydioxanone-polycaprolact
one Natural - Elastin - Gelatin collagen -
Fibrillar collagen - Collagen blends - Fibrinogen
13
POLYGLYCOLIC ACID (PGA)
- biocompatible - consistent mechanical
properties hydrophilic predictable
bioabsorption (2-4 wks) - electrospinning yields
diameters 200 nm
Parameters - surface area to volume ratio -
spinning orientation affects scaffold elastic
modulus
Drawbacks - rapid hydrolitic degradation pH
change tissue must have buffering capacity
14
POLYGLYCOLIC ACID (PGA)
Random fiber collection (L), aligned collection
(R)
15
POLYGLYCOLIC ACID (PGA)
Fiber collection Orientation affects stress /
strain
16
POLYLACTIC ACID (PLA) 200 nm
- aliphatic polyester - L optical isomer
used by-product of L isomer degradation
lactic acid - methyl group decreases
hydrophilicity - predictable bioabsorption,
slower than PGA (30 wks) - half-life ideal for
drug delivery
Parameters (similar to PGA) - surface area to
volume ratio - spinning orientation affects
scaffold elastic modulus
Compare to PGA - low degradation rate less pH
change
17
POLYLACTIC ACID (PLA) 200 nm
Thickness controlled by electrospin solvent
Chloroform solvent (L) 10 um HFP (alcohol)
solvent (R) 780 nm Both fibers randomly
collected
18
PGAPLA PLGA
- tested composition at 25-75, 50-50, 75-25
ratios - degradation rate proportional to
composition - hydrophilicity proportional to
composition
Recent Study - delivered PLGA scaffold cardiac
tissue in mice - individual cardiomyocytes at
seeding - full tissue (no scaffold) 35 weeks
later - scaffold loaded with antibiotics for
wound healing
19
PGAPLA PLGA
PLGA modulus proportional to composition
20
POLYDIOXANONE (PDO)
- crystalline (55) - degradation rate between
PGA/PLA close to 40-60 ratio - shape memory -
modulus 46 MPa compare collagen 100
MPa elastin 4 MPa
Advantages - PDO ½ way between collagen/elastin,
vascular ECM components - cardiac tissue
replacement (like PLGA) - thin fibers (180nm)
Drawbacks - shape memory less likely to adapt
with developing tissue
21
POLYCAPROLACTONE (PCL)
- highly elastic - slow degradation rate (1-2
yrs) - gt 1 um - similar stress capacity to PDO,
higher elasticity
Advantages - overall better for cardiac tissue
no shape retention bc elastic
Previous Applications Loaded with - collagen ?
cardiac tissue replacement - calcium carbonate ?
bone tissue strengthening - growth factors ?
mesenchymal stem cell differentation
22
POLYCAPROLACTONE PGA
- PGA high stress tolerance - PCL high
elasticity - optimized combination PGA/PCL
3/1 - bioabsorption at least 3 mths (PCL-2 yrs,
PGA 2-4 wks) Clinical Applications none yet
POLYCAPROLACTONE PLA
- PLA highly biocompatible (natural by
products) - PCL high elasticity - more elastic
than PGA/PCL - strain limit increases 8x with
just 5 PCL
23
POLYCAPROLACTONE PLA
- PCL elastic however, decreasing PLA/PCL
ratios decreases strain capacity - strain
capacity optimized at 955 - still ideal in vivo
mostly PLA natural by products
24
POLYCAPROLACTONE PLA
Clinical Applications - several planned - all
vasculature tissue - high PLA tensile
strength react (constrict) to sudden pressure
increase - increased elasticity with
PCL passively accommodate large fluid flow
OVERALL passive expansion, controlled
constriction best synthetic ECM combination
for cardiac application
25
POLYCAPROLACTONE POLYDIOXANONE PCL PDO
Recall - PCL high elasticity - PDO approx
PLA/PGA - PDO shape memory limits use in
vascular tissue
Findings - hybrid structure NOT hybrid
properties - lower tensile capacity than PDO -
low elasticity than PDO - larger diameter
- NOT clinically useful
This will be further investigated by our
laboratory
In other words- not publishable, but 1 years
worth of work and good enough for a masters
thesis
26
POLYCAPROLACTONE POLYDIOXANONE PCL PDO
Principle Drawbacks Large fiber diameter Low
tensile/strain capacity
Possible Cause? PDO is the only crystalline
structure polymer
27
ELASTIN
- highly elastic biosolid (benchmark for PDO) -
hydrophobic - present in vascular walls skin
Synthesis of Biosolid? - 81 kDa recombinant
protein (normal 64 kDa) - repeated regions were
involved in binding - 300 nm (not as small as PDO
180 nm) - formed ribbons, not fibers diameter
varies
Findings - not as elastic as native elastin -
currently combined with PDO to increase tensile
strength - no clinical applications yet
28
COLLAGENS GELATIN
- highly soluble, biodegradable (very rapid) -
current emphasis on increasing lifespan
Type II - 100-120 nm (consistent) - found in
cartilage - pore size and fiber diameter easily
controlled by dilution
29
COLLAGENS FIBRIL FORMING
Type I (inconsistent fibers)
30
COLLAGENS FIBRIL FORMING
Type III - preliminary studies - appears
consistent 250 nm
None of the electrospun collagens have clinical
application yet
31
COLLAGENS BLENDS
In context vasculature - intima collagen type
IV elastin - media thickest, elastin,
collagen I, III, SMC - adventia collagen I
32
RECONSTRUCTING THE MEDIA
- SMC seeded into tube - average fiber 450
nm slightly larger ECM fibers - incorporation of
GAG carbohydrate ECM collagen
crosslinker mediate signalling
33
COMBINING COLLAGEN WITH PDO
Observations - collagen I highest tensile
capacity - 7030 collagen-PDO optimal ratio for
all collagens
34
FIBRINOGEN
- smallest diameter (both synthetic and bio) 80,
310, 700 nm fibers possible - high surface area
to volume ratio increase surface
interaction used in clot formation
Stress capacity comparable to collagen (80-100
MPa)
35
HEMOGLOBIN
- hemoglobin mats - clinical applications drug
delivery hemostatic bandages - fiber sizes 2-3
um - spun with fibrinogen for clotting/healing -
high porosity high oxygenation
36
OVERVIEW
- Electrospinning viable for both synthetic and
biological scaffolds/mats - Wide range of fiber
sizes necessary and possible ECM ideally 150-500
nm cell mats 2-3 um - Hybridizing polymers can,
but not necessarily, lead to hybrid properties
Specifics - PGA, PLA, PLGA most commonly used
scaffold materials - PDO exhibits
elastincollagen functionality in 1 synthetic
polymer BUT inhibited by shape memory - PCL
most elastic synthetic frequently mixed with
other synthetics
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