1 3.051J/20.340J Lecture 1: Intro. to Biomaterials: Structural Hierarchy in Materials & Biology What are “biomaterials”? A good working definition from the text is: “A nonviable material used in a medical device, intended to interact with biological systems.”* MEDICAL DEVICE EXAMPLES ANNUAL # (U.S.)* Sutures (temporary or bioresorbable) 250 M** Catheters (fluid transport tubes) 200 M Blood Bags 40 M Contact Lenses 30 M Intraocular Lenses 2.5 M Coronary Stents 1.2 M*** Knee and Hip Prostheses 0.5 M Breast Prostheses (cancer or cosmetic) 0.25 M Dental Implants 0.9 M Renal Dialyzers (patients) 0.3 M Oxygenators/CPB’s (cardiopulmonary bypass system— 0.3 M facilitates open heart surgery) Vascular Grafts 0.3 M Pacemakers (pulse generators) 0.4 M Biomaterials are defined by their application, NOT chemical make-up Ex. Intraocular lenses Composition: poly(methyl methacrylate) PMMA, a.k.a. “acrylic” Properties: • High refractive index Used as auto • Easily processed taillight covers for the same reasons! • Environmentally stable (relatively inert) • Good mechanical properties *from Biomaterials Science: An Introduction to Materials in Medicine, 2nd ed., B.D. Ratner et al., eds., Elsevier, NY 2004 **from Biomaterials Science: An Introduction to Materials in Medicine, 1st ed., B.D. Ratner et al., eds., Elsevier, NY 1996 ***from Introduction to Biomedical Engineering, 2nd ed., J. Enderle et al,, eds., Elsevier, NY 200523.051J/20.340J Biomaterials cover all classes of materials – metals, ceramics, polymers PLA = polylactide PGA= polyglycolide PDO=poly(p-dioxanone) PUR = polyurethane ePTFE = expanded polytetrafluoroethylene polyethylene PET=polyethylene terephthalate Ear: HA, Al2O3, Ti, silicone Ti, Ti-Al-V, Al2O3, HA, Bioglass acrylic 2O3, HA, TCP, HA/PLA, Bioglass, Ti, Ti-Al-V Cranial: 316L SS, Ti, acrylic, HA, TCP Blood vessels: ePTFE, PET C, ePTFE, PET, PUR PLA, PGA, PCL, PTMC, PDO Ocular lenses: acrylates, silicone Bone Fixation: 316L SS, Co-Cr-Mo, Ti, Ti-Al-V, PLA/HA., PLA, PGA Load-bearing Orthopedic: Al2O3, Zirconia, 316L SS, Ti, Ti-Al-V, PTMC=polytrimethylenecarbonate UHMWPE = ultrahigh mol. wt. Dental: acrylic, gold, 316L SS, Co-Cr-Mo, Prosthetic joints: 316L SS, Co-Cr-Mo, Ti, Ti-Al-V, silicone, UHMWPE, Maxillofacial reconstruction: AlHeart: Co-Cr-Mo, Ti-Al-V, pyrolytic Pacemaker: 316L SS, Pt, PUR, silicone, PET Degradable Sutures: copolymers of Tendon & Ligments: PLA/C fiber, ePTFE, PET, UHMWPE Co-Cr-Mo, UHMWPE Spinal: Co-Cr-Mo, Ti, HA, UHMWPE HA = hydroxyapatite SS = stainless steel Figure by MIT OCWinterface 33.051J/20.340J What governs materials choice? Historically ⇒ Today Today ⇒ Future 1. Bulk properties: matched to those of natural organs • Mechanical (ex., modulus) • Chemical (ex., degradation) • Optical (ex., whiteness, clarity) 2. Ability to Process 3. Federal Regulations: Medical Device Amendment of ’76 (all new biomaterials must undergo premarket approval for safety and efficacy) Engineering Paradigm ? Rational design of better understanding of material/biological Adoption of the Materials biomaterials based on natural materials and the organism interface Application (Performance) Properties Structure Processing What is “structure”? the arrangement of matter Both synthetic materials & biological systems have many length scales of structural importance.3.051J/20.340J 4Structural Hierarchies Synthetic Materials Living Organisms Chemical Primary Structure 10-10m Molecules (H2O, peptides, salts…) Higher Order Structure Organelles (lysosomes, nucleus, mitochondria) Microstructure Cells Composites 10-3m Tissues Parts Organs Devices Individuals Biomaterials Engineering spans ~8 orders of magnitude in structure! The realm of biomaterials engineering C a + + C a + + C a + + C a + + C a + + C a + + C a + + C a + + C a + +C a + + C a + C a + + extracellular environment lipid membrane cytosol Fibroblast cells aligned on micro-patterned surface Engineered length scale: 10-3 to 10-6 mCell adheres to RGD peptide clusters linked to comb copolymer chain ends Engineered length scale: 10-7 to 10-8 m Cell adhesion receptors embedded in membrane interact with RGD sequence Engineered length scale: 10-9 to 10-10 m53.051J/20.340J LENGTH SCALES OF STRUCTURE 1. Primary Chemical Structure (Atomic & Molecular: 0.1–1 nm) Length scale of bonding – strongly dictates biomaterial performance Primary • Ionic: e-donor, e-acceptor ceramics, glasses (inorganic) • Covalent: e-sharing glasses, polymers • Metallic: e-“gas” around lattice of + nuclei Secondary/Intermolecular • Electrostatic • H-bonding • Van der Waals (dipole-dipole, dipole-induced dipole, London dispersion) • Hydrophobic Interactions (entropy-driven clustering of nonpolar gps in H2O) • Physical Entanglement (high MW polymers) Ex. 1: alumina Al2O3 used for hard tissue replacement – (corundum) e.g., dental implants Properties: • corrosion resistant • high strength derived from • wear resistant ionic bonding Electrostatic interactions w/ charges on • “biocompatible” proteins ⇒ non-denatured adsorbed protein layer ⇒ “camouflage” www.biocon.com from Biocon, Inc. website: Courtesy of BICON, LLC. (http://www.bicon.com). Used with permission.3.051J/20.340J 6 Ex. 2: polyethylene oxide (PEO) (CH2CH2O)n used for protein resistant coatings, hydrogels Properties: • flexible • • water soluble • bioinert secondary bonding Strong H-bonding, unique 3 n.n. coordination w/ H2O ⇒ ⇒hydrolysable Derived from primary & water-like layer “camouflage” protein grafted PEO denatured protein Take Home Message: “Biocompatibility” is strongly determined by primary chemical structure! Biocompatibility: “ability of a material to perform with an appropriate host response” Protein Adsorption Cell Attachment Cell Secretion Chemical Structure Host Response73.051J/20.340J 2. Higher Order Structure (1 – 100 nm) Crystals: 3D periodic arrays of atoms or molecules metals, ceramics, polymers (semicrystalline) crystallinity decreases solubility and bioerosion (biogradable polymers & bioresorbable ceramics) Networks: exhibit short range order & characteristic lengths inorganic glasses, gels Ex. 1: Bioactive Glasses used for hard connective tissue replacement Network formers