Biomaterials & Tissue Engineering · Biomaterials & Tissue Engineering Prof. Lesley Chow Materials Science and Engineering & Bioengineering [email protected] Society for Biomaterials

Biomaterials & Tissue Engineering

Prof. Lesley ChowMaterials Science and Engineering & Bioengineering

[email protected]

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.

Stryker

Perouse Medical

St. Jude’s Medical

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

Coat metal implants with bioglass to improve bonding

Qiu et al, Regenerative Biomaterials 2014.

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

MIT

Repair = reestablishing lost or damaged tissue to retain continuity

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.

Decellularized heart can be recellularized

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

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