Biomaterials & Tissue Engineering · Biomaterials & Tissue Engineering Prof. Lesley Chow Materials...
Transcript of Biomaterials & Tissue Engineering · Biomaterials & Tissue Engineering Prof. Lesley Chow Materials...
Biomaterials & Tissue Engineering
Prof. Lesley ChowMaterials Science and Engineering & Bioengineering
Society for Biomaterials
The Chow Lab: Modular Biomaterials thechowlab.com
Explore how combination of physical and biochemical cues
influence cell behavior and tissue function
Design versatile building blocks to create
multicomponent, biomimetic materials
thechowlab
thechowlab
The Chow Lab: Modular Biomaterials thechowlab.com
What are biomaterials?
‘‘any substance or combination of substances, other than
drugs, synthetic or natural in origin, which can be used for
any period of time, which augments or replaces partially or
totally any tissue, organ, or function of the body, in order to
maintain or improve the quality of life of the individual’’
*official definition from the National Institutes of Health
What are biomaterials?
a natural or synthetic material that is
suitable for introduction into living tissue to
augment or replace any tissue, organ, or
function in the body
What are biomaterials?
a natural or synthetic material that is
suitable for introduction into living tissue to
augment or replace any tissue, organ, or
function in the body
• metals
• ceramics
• polymers
What are biomaterials?
a natural or synthetic material that is
suitable for introduction into living tissue
to augment or replace any tissue, organ, or
function in the body
• metals
• ceramics
• polymers
• bioinert
• biocompatible
• bioactive
• regenerative
What are biomaterials?
a natural or synthetic material that is
suitable for introduction into living tissue
to augment or replace any tissue, organ,
or function in the body
• metals
• ceramics
• polymers
• bioinert
• biocompatible
• bioactive
• regenerative
• mechanical
• chemical
• biological
• electrical
History of biomaterials
Gold used in dentistry
thousands of years ago by
Romans, Chinese, and Aztecs
images: Science Museum, London
Glass used as artificial eyes in
the early 20th century
Plants, animal
hair/tendons/arteries/muscles/nerv
es/intestines, silk all used as
sutures (earliest reported suture in
3000 B.C.)
http://www.kvsupply.com/
http://www.kruuse.com/
History of biomaterials
Rayner
Poly(methyl methacrylate)
aka PMMA used for
intraocular lens after WWII
Biomaterial design criteria
• tissue or organ type
• functions
• size and scale of
defect
• age of the patient
• disease conditions
• etc...
image adapted from Stupp, MRS Bulletin 2005
Ratner, Hoffman, Schoen, & Lemons, Biomaterials Science: An Introduction to Materials in Medicine, Academic Press, 3rd Ed.
Biomaterials for vascular applications
What properties would we want in our biomaterial?
• suturable and works immediately
• no leaking
• flexible
• compatible with blood
• avoids clots/blockages
• resist bursting and repeated stress
poly(ethylene terepthalate)
aka Dacron
aka PET
www.uahealth.com
Biomaterials for hip replacement
What properties would we want in our biomaterial?
What are the limitations?
polyethylene
titanium
Common problems with hip implants
http://www.radiologyassistant.nl/
• stress shielding = reduction in bone
density due to removal of stress
• bones need stress/loading to be
healthy and remodel
• bone-material integration critical
for implant success
How materials science can help
Porosity to encourage bone ingrowth
and bone-material integration
Murr et al., International Journal of Biomaterials, 2012
Traditional biomaterials
Stryker
hip implants
St. Jude’s Medical
heart valve
Perouse Medical
vascular grafts
intraocular lens
Rayner
Traditional biomaterials
Stryker
hip implants
St. Jude’s Medical
heart valve
Perouse Medical
vascular grafts
intraocular lens
Rayner
• traditional engineering solutions
• inert
• long-lasting, non-biodegradable
• acellular
• require replacement after 10-20 years
The evolution of biomaterials
BIOINERT
minimal reaction/interaction
BIOACTIVE
controlled reaction with tissue,
bioresorbable
REGENERATIVE
biointeractive, integrative, resorbable,
stimulates specific cell response, etc.
First
generation
Second
generation
Third
generation
1940
now/future
Bioglass to promote bonding to bone
Prosidyan
• ceramic composed of SiO2, Na2O, CaO, P2O5 that interacts with
soft tissues and bone
• enhances strong bond to bone and can induce new bone
formation
The evolution of biomaterials
BIOINERT
minimal reaction/interaction
BIOACTIVE
controlled reaction with tissue,
bioresorbable
REGENERATIVE
biointeractive, integrative, resorbable,
stimulates specific cell response, etc.
First
generation
Second
generation
Third
generation
1940
now/future
The evolution of biomaterials
BIOINERT
minimal reaction/interaction
BIOACTIVE
controlled reaction with tissue,
bioresorbable
REGENERATIVE
biointeractive, integrative, resorbable,
stimulates specific cell response, etc.
First
generation
Second
generation
Third
generation
now/future
1940
What about the body’s ability to heal itself?
Human body has capacity to repair and regenerate
image adapted from Stupp, MRS Bulletin 2005
skin
bone
intestine
liver
Repair vs regeneration
Repair = reestablishing lost or damaged tissue to retain continuity
MIT
Regeneration = replacement of lost or damaged tissue with an
exact copy so that morphology and function are restored
ASSH
Biomaterials for tissue engineering
Isolate cells
from patient
Expand cells in
the labSeed cells on
biomaterials
Grow
engineered
tissue
Implant
engineered
tissue into
patient
Decellularized heart maintains tissue architecture
• composed of native ECM molecules
• biodegradable and biocompatible after decellularization
Ott et al, Nature Medicine 2008.
Recellularized heart beats again!
Ott et al, Nature Medicine 2008.
• composed of native ECM molecules
• biodegradable and biocompatible after decellularization
• requires donor…
Bonzani, George, Stevens. Curr Opin Chem Biol 10:568-575, 2005.
Biological tissues are complex
tissue composition and organization linked to biological function
Bonzani, George, Stevens. Curr Opin Chem Biol 10:568-575, 2005.
Biological tissues are complex
tissue composition and organization linked to biological function
Can we create biomaterials that drive
functional, native-like tissue formation?
thechowlab.com
The Chow Lab: Modular Biomaterials thechowlab.com
Explore how combination of physical and biochemical cues
influence cell behavior and tissue function
Design versatile building blocks to create
multicomponent, biomimetic materials
peptide exposed
on fiber surface
peptide exposed
on fiber surface
PCL block remains
with bulk scaffold
as ink extrudes,
solvent evaporates,
polymer solidifies,
and peptide emerges
on surface
ink: peptide-PCL conjugate mixed
with unmodified PCL in volatile
solvent prior to printing
peptidepeptide poly(caprolactone) (PCL)
Chow, et al. Adv Healthc Mater 3(9): 1381-1386, 2014; Harrison, et al. Adv Funct Mater 25(36): 5748-5757, 2015; Campagnolo, et al. Adv Healthc
Mater 5(23): 3046-3055, 2016; Chow, Methods Mol Biol 1758: 27-39, 2018; Camacho*, Busari*, et al. Biomater Sci 7: 4237-3247, 2019.
peptide-functionalized
3D-printed scaffold
200 µmCy3
3D printing peptide-functionalized biodegradable polymers
Camacho*, Busari*, Seims, Schwarzenberg, Dailey, Chow. Biomaterials Science 7: 4237-4347, 2019.
FITC/Cy3
Alternating Layers Alternating Fibers
FITC/Cy3= RGDS(biotin)-PCL
= RGES(azide)-PCL
Cells detect spatially organized peptides and
preferentially spread on RGDS vs RGES
Spatial deposition of multiple peptides in one step
bone-promoting
peptide-PCL
cartilage-promoting
peptide-PCL
3D printing cartilage- and bone-promoting conjugates
100 µmFITC-HA
100 µm
Cy3100 µm100 µm
Change print pattern to control scaffold architecture
A B
200 µm
C
Scaffold architecture AND peptide
functionalization can be tuned
independently and simultaneously
HA
bin
d-P
CL
E3-P
CL
200 µm
200 µm200 µm
200 µm
120 µm 260 µm
Scaffold architecture can be varied
within a continuous construct
200 µm
120 µm
260 µm
200 µm200 µm
Print with multiple peptide-PCL conjugates to control porosity
and peptide functionalization in a single scaffold
Groen et al. J Orthop Res 35(10): 2089-2097, 2017.
GOAL: highly tunable, continuous, spatially
organized scaffold to guide in situ regeneration
of the osteochondral tissue