Biomaterials & Tissue Engineering Society for Biomaterials Prof. Lesley Chow Materials 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 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 • 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 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/ 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 Medicine, 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 stress www.uahealth.com poly(ethylene terepthalate) aka Dacron aka PET Biomaterials for hip replacement titanium polyethylene What properties would we want in our biomaterial? What are the limitations? Common problems with hip implants • 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 http://www.radiologyassistant.nl/ How materials science 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 Human body 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 decellularization 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 peptide-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, polymer 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 peptides 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.