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Biomaterials &

Society for Biomaterials

Prof. Lesley Chow Science and Engineering & Bioengineering

[email protected] 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 The Chow Lab: Modular Biomaterials thechowlab.com

thechowlab What are biomaterials?

‘‘any substance or combination of substances, other than , 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 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

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

• bioinert • metals • biocompatible • ceramics • bioactive • polymers • 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

• bioinert • mechanical • metals • biocompatible • chemical • ceramics • bioactive • biological • polymers • regenerative • electrical History of biomaterials

Gold used in dentistry thousands of years ago by Romans, Chinese, and Aztecs

Glass used as artificial eyes in the early 20th century

images: Science Museum, London History of biomaterials

Plants, animal /tendons/arteries/muscles/nerv es/intestines, all used as sutures (earliest reported suture in 3000 B.C.)

http://www.kvsupply.com/

http://www.kruuse.com/

Poly(methyl methacrylate) aka PMMA used for intraocular lens after WWII

Rayner 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 , Academic Press, 3rd Ed. St. Jude’s Medical Perouse Medical

Stryker 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

www.uahealth.com

poly(ethylene terepthalate) aka Dacron aka PET Biomaterials for replacement

titanium

What properties would we want in our biomaterial?

What are the limitations? Common problems with hip implants

• stress shielding = reduction in density due to removal of stress

need stress/loading to be healthy and remodel

• bone-material integration critical for success

http://www.radiologyassistant.nl/ How can help

Porosity to encourage bone ingrowth and bone-material integration

Murr et al., International Journal of Biomaterials, 2012 Traditional biomaterials hip implants vascular grafts

Perouse Medical

Stryker intraocular lens heart valve

St. Jude’s Medical Rayner Traditional biomaterials hip implants vascular grafts

• traditional engineering solutions

• inert

• long-lasting, non-biodegradable Perouse Medical

Stryker • acellular intraocular lens heart valve • require replacement after 10-20 years

St. Jude’s Medical Rayner The evolution of biomaterials

1940 First BIOINERT generation minimal reaction/interaction

BIOACTIVE Second controlled reaction with tissue, generation bioresorbable

REGENERATIVE Third biointeractive, integrative, resorbable, generation stimulates specific cell response, etc. 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

1940 First BIOINERT generation minimal reaction/interaction

BIOACTIVE Second controlled reaction with tissue, generation bioresorbable

REGENERATIVE Third biointeractive, integrative, resorbable, generation stimulates specific cell response, etc. now/future The evolution of biomaterials

1940 First BIOINERT generation minimal reaction/interaction What about the body’s ability to heal itself?

BIOACTIVE Second controlled reaction with tissue, generation bioresorbable

REGENERATIVE Third biointeractive, integrative, resorbable, generation stimulates specific cell response, etc. now/future has capacity to repair and regenerate

skin

bone

intestine

liver

image adapted from Stupp, MRS Bulletin 2005 Repair vs regeneration

Repair = reestablishing lost or damaged tissue to retain continuity

MIT 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

Expand cells in Seed cells on the lab biomaterials

Isolate cells from patient

Implant Grow engineered engineered tissue into tissue patient Decellularized heart maintains tissue architecture

• composed of native ECM molecules • biodegradable and biocompatible after

Ott et al, Nature Medicine 2008. Decellularized heart can be recellularized

Ott et al, Nature Medicine 2008. Recellularized heart beats again!

• composed of native ECM molecules • biodegradable and biocompatible after decellularization • requires donor…

Ott et al, Nature Medicine 2008. Biological tissues are complex

Bonzani, George, Stevens. Curr Opin Chem Biol 10:568-575, 2005. tissue composition and organization linked to biological function Biological tissues are complex

Can we create biomaterials that drive functional, native-like tissue formation?

Bonzani, George, Stevens. Curr Opin Chem Biol 10:568-575, 2005. tissue composition and organization linked to biological function 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.com 3D printing -functionalized biodegradable polymers

peptidepeptide exposed poly(caprolactone)PCL block remains (PCL) peptidepeptide exposed on fiber surface with bulk scaffold on fiber surface

ink: peptide-PCL conjugate mixed with unmodified PCL in volatile as ink extrudes, solvent prior to printing solvent evaporates, solidifies, and peptide emerges on surface

Cy3 200 µm peptide-functionalized 3D-printed scaffold

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. Spatial deposition of multiple in one step

Alternating Layers Alternating Fibers

Cells detect spatially organized peptides and FITC/Cy3 FITC/Cy3 = RGDS(biotin)-PCL preferentially spread on RGDS vs RGES = RGES(azide)-PCL

Camacho*, Busari*, Seims, Schwarzenberg, Dailey, Chow. Biomaterials Science 7: 4237-4347, 2019. 3D printing cartilage- and bone-promoting conjugates

100 µm 100 µm FITC-HA

100 µm Cy3 100 µm bone-promoting cartilage-promoting peptide-PCL peptide-PCL Change print pattern to control scaffold architecture

A B C

200 µm 200 µm 200 µm

120 µm 260 µm

Scaffold architecture can be varied PCL

within a continuous construct - 120 µm

200 µm 200 µm 260 µm HAbind

Scaffold architecture AND peptide PCL

functionalization can be tuned -

200 µm 3

independently and simultaneously E 200 µm 200 µm

Print with multiple peptide-PCL conjugates to control porosity and peptide functionalization in a single scaffold GOAL: highly tunable, continuous, spatially organized scaffold to guide in situ regeneration of the osteochondral tissue

Groen et al. J Orthop Res 35(10): 2089-2097, 2017. The evolution of biomaterials

1940 First BIOINERT generation minimal reaction/interaction

BIOACTIVE Second controlled reaction with tissue, generation bioresorbable

REGENERATIVE Third biointeractive, integrative, resorbable, generation stimulates specific cell response, etc. now/future