Сучасний стан та перспективи біоматеріалів і нанотехнологій в

Сучасний стан та перспективи біоматеріалів і нанотехнологій в медицині. . В. Б. Максименко 2010

Отчёт ЦРУ Глобальная технологическая революция намечена на ближайш лет В очередном свободно доступном отчете ЦРУ, посвященном тенденциям технологического развития общества до 2015 г. (The Global Technology Revolution), утверждается, что глобальное влияние на развитие земной цивилизации в этот период окажут био-, нано- и информационные технологии, а также прикладные исследования в области физики материалов. Все эти сферы тесно переплетутся друг с другом и с большой долей вероятности увеличат разрыв между развитыми и развивающимися странами.

ШТУЧНЕ СЕРЦЕ

ELECTROMECHANICALLY ACTIVE POLYMERS Italy Abstract— Electroactive polymers(EAPs) consist of synthetic materials capable of changing dimensions and/or shape in response to an electrical input. Fig. 2. DE pulsatile chamber: (a) schematic drawing of the structure; (b), (c) sample made of a silicone elastomer, shown at rest and under an electrical activation, respectively.

Biodegradable suture Intraocular Lens Wound dressing Vascular grafts INTRODUCTION TO BIOMATERIALS BMEN 343 Contact Lens Prof. Melissa Grunlan bone plates Biodegradablest ent Nose implants knee & hip replacement

What are MATERIALS? a. Solids b. Liquids c. Gases d. All of the above

Біосумісність

Metals and Alloy Devices Advantages: Disadvantages: Examples: Joint replacement Dental root implants Orthopedic fixation – bone plates Knee replacement Shoulder replacement Dental implant (“root”) Bone plate

What is a Ceramic? • Example in biomaterials: Aluminum Oxide/ Alumina (Al 2 O 3) Femoral ball liner (occasionally) Acetabular cup liner (occasionally)

Ceramic Devices Advantages: Disadvantages: (*these terms will be defined later) Examples: Dental implant (looks like bone/tooth) Some joint replacement articulating surfaces Bone cement filler to encourage bone in-growth (older patients) Dental implant (“root”) Hip joint Elbow joint Cemented hip joint

What is a Polymer? Example in biomaterials: UHMWPE -[CH 2 -CH 2]MW = 2 -3 million g/mols (n = ~107, 143) n acetabular cup liner (most common)

Polymer Devices Advantages: Examples: Some joint replacement articulating surfaces Spinal cages Biodegradable bone plates for low load regions Biodegradable sutures Hip joint Spinal cage for spine fusion Bone plates

BIOMATERIALS CAN BE USED TO FORM: Exoprothesis – Endoprothesis - Artificial Skin Artificial Liver Vascular Graft

How do biomaterials fit into biomedical engineering? implementation idea ACTION Identify a need -Treat disease -Replace organ -Cosmetic Device Design Biomaterials Selection Biomaterials Development Biomaterials Testing patient FACILITATOR Physician Engineer/Scientist Engineer Physician Engineer Scientist Fabrication, sterilization, device testing, regulatory, clinical use

1. Identify a Need: Replacement of Deteriorated Hip Joint Osteoarthritis: loss of cartilage The hip joint is the largest load-bearing joint. A hip joint is lined with articular cartilage: a layer of tissue that provides low-friction and shock-absorbing properties. Arthritis and injury can damage this protective layer of cartilage, causing extreme pain for a patient performing even simple activities.

2. Design Device: Total Hip Replacement

3. Biomaterial Selection

Ø > 250, 00 per year in USA Ø By 2030, > 750, 000 per year in USA Ø Average age: 66 years Ø 57% women

Ø “Modern” design: Late 1960’s, John Charnly Ø Success rate: After 10 years: 90% function well After 20 years: 80% function well After 30 years: 50% function well Failure is related to the limitations of the current biomaterials used for the components (as well as design issues).

Useful Definitions Foreign Body Reaction – host response to biomaterial “some biomaterial”

BMEN 343: Introduction to Biomaterials Fundamental Material Science & Engineering Concepts: Introduction to the structure-property relationships of engineering materials. Structure: Atomic structure and bonding; crystal structures; imperfections in solids; diffusion; structures of metals, ceramics and polymers. Mechanical Properties mechanical properties of metals, ceramics, and polymers : The (including processing and failure) and their relationship to material structure. Atomic Structure Crystal Structure Dislocations in Ti alloy Modulus, strength, failure

Mechanical Properties is important to study for all biomaterials? : Why Determines how well it will work (or not work) for a given device. One major factor is modulus the material. the of metal polymer Toe implant _______ hydrogel polymer ______

Mechanical Properties of Biomaterials • CASE 1: Modulus of device > Modulus of tissue higher modulus of the bone plate vs. the surrounding bone tissue leads to __________ bone loss implant loosening possible fracture Stainless Steel 316 L (bone plate): E = 193 GPa Cortical Bone: 17 -24 GPa

Mechanical Properties of Biomaterials • CASE 2: Modulus of device < Modulus of tissue Can only be used in “low loadbearing applications” (e. g. wrist; not femoral fractures) PLLA (bone plate): E = 2. 7 GPa Cortical Bone: E =17 -24 GPa

Some other devices…. KNEE REPLACEMENT The healthy human knee joint is aslo lined with articular cartilage. Arthritis and injury can similarly damage this protective layer of cartilage causing extreme pain. wear UHMWPE http: //tc. engr. wisc. edu/UER/uer 01/author 1/content. html

Mechanical Properties of Biomaterials • CASE 1: Modulus of device > Modulus of tissue Stainless Steel 316 L (Stent): E = 193 GPa Artery: E = ~0. 1 MPa

POLYMERS IN OPHTHALMICS 1. Intraocular Lens: replace opaque crystalline lens (“cataract”) of the eye Inflexible IOL: Foldable IOL: Tg = 105 C: ____ Tg (PDMS) = -125 C _____ Larger incision needed PMMA PDMS + PMMA Silicone Acrylates Smaller incision

POLYMERS IN OPHTHALMICS 2. Soft Contact Lenses: placed on cornera to correct vision Hydrogels:

Some Allotropes of Carbon diamond graphite C 60 Buckyball Pyrolytic carbon (Py. C) carbon nanotube Montreal’s 1067 Expo: American pavilion at night

FYI

Nanotechnology Growth S. Milunovich, J. Roy. United States Technology Strategy. Merrill Lynch. 4 Sept. 2001

ПОШИРЕНІ НАНОТЕХНОЛОГІЧНІ ПОХІДНІ КВАНТОВІ КРАПКИ n ОКСИД ЗАЛІЗА n ВУГЛЕЦЕВІ НАНОТРУБКИ n КОМПОЗИТНІ НАНООБОЛОНКИ n ДВУОКИС ТИТАНУ n СІЛІКОНОВІ СТРУКТУРИ n НАНОКРИСТАЛІЧНЕ СРІБЛО n ФОТОННІ ЗОНДИ n

НАНОСТРУКТУРОВАНІ МАТЕРІАЛИ НАНОПОРИСТІ МАТЕРІАЛИ Проростання тканинами, транспорт НАНОКРИСТАЛІЧНІ МАТЕРІАЛИ Фізичні, електричні, оптичні, механічні властивості НАНОПІДСИЛЕНІ Механічні властивості МОДИФІКОВАНІ ПОВЕРХНІ Біосумісність

СПЕЦИФІКА БІОЛОГІЧНОГО НАНОВПЛИВУ СИСТЕМА ІМУННОГО ЗАХИСТУ n ФІЗІОЛОГІЧНІ ТА ПАТОЛОГІЧНІ СТРУКТУРИ ТА ПРОЦЕСИ n НАНОІНДУКОВАНІ ПОБІЧНІ КЛІТИННІ РЕАКЦІЇ n РАЦІОНАЛЬНИЙ ДИЗАЙН ТА ІНЖЕНЕРІЯ ПОВЕОРХНІ

ОСНОВНІ МЕДИЧНО ОРІЄНТОВАНІ НАПРЯМКИ ДОСЛІДЖЕНЬ “STELTH TECHNOLOGIES” n “INVISIBLE MEN TECHNOLOGIES” n “RED OCTOBER TECHNOLOGIES” n

РОЗПОДІЛ НАНЧАСТОК В ОРГАНІЗМІ n< 5 nm – виводять нирки n 10 -20 nm – адгезія до клітин n < 50 nm - гіпертермічний вплив n 5 -100 nm - підвищена рухливість n 200 – 500 nm – ендоцитоз та затримка в РЕС

Знаменитая любовница короля Франции Генриха II, умершая в возрасте 66 лет, выглядела на 30 Чтобы оставаться молодой, женщина регулярно его употребляла. Видимо, пила напитки с частичками золота. Патологоанатом Филипп Шарлье (Philippe Charlier) из Объединения парижских госпиталей и токсиколог Жоэль Пупон (Joel Poupon) на днях сообщили об этом в журнале British Medical Journal. Содержание золота в волосах фаворитки было превышенным (в 250 раз)

ПЕРФЛЮОРОКАРБОН (“ПЕРФТОРАН”) Размер частиц 0. 07 -0. 15 mkm Осмолярность 280 -340 m. Osm Вязкость 2. 5 s. P р. H 7. 4 -7. 6 Растворимость О 2 (760 mm Hg) 7. 0 vol. % Растворимость СО 2(760 mm Hg) 60 vol. % LD 50 140 m. L/kg

BIO-MECHANICAL EVALUATION OF A 3 D PRINTED COMPOSITE MATERIAL Dundee, UK Abstract— Composite materials such as ceramic are now widely used in the field of Tissue Engineering. The material was formed into a 3 D scaffold. This research paper evaluates the mechanical properties and biocompatibility of the Rapid Prototyped material. Fig. 4 a Images of Control experiment with Fibroblast cells on Day 2

STRATEGIES COMBINING CELLS AND SCAFFOLDS FOR BONE TISSUE ENGINEERING Italy Abstract Engineering bone typicallyuses highly porous scaffolds, osteoblasts or cells that can become osteoblasts, and regulating factors that promote cell attachment, differenti ation, and mineralized bone formation. Fig. 1 Scanning electron microscopy observation of an unseeded 3 D titanium scaffold at 25× magnification (A) and at 100× magnification (B) Fig. 3 Immunolocalization of type-I collagen (green) in the static (A) andelectromagnetic (B) cultures Fig. 2 Scanning electron microscopy observation of a seeded 3 D titanium scaffold at 50× magnification in static (A) and dynamic culture (B)

ENHANCEMENT OF A CULTURE OF HUMAN OSTEOBLASTS INSIDE HYDROXYAPATITE SCAFFOLDS VIA [2 MT; 75 HZ]-ELECTROMAGNETIC BIOREACTOR Italy Abstract In this study we have followed a biomimetic strategy where electromagnetically stimulated human osteoblasts prolif erated and built their extracellular matrix inside porous hydroxyapatite. Fig. 1 Electromagnetic bioreactor Fig. 3 Immunolocalization of type-I collagen (A) and cellular nuclei (B) in the static culture, bar equal to 80 m Fig. 4 Immunolocalization of type-I collagen (A) and cellular nuclei (B) in the electromagnetic culture, bar equal to 80 m

CYTOLOGICAL EVALUATION OF A POROUS IMPLANT MADE FROM TPU German Abstract— Thermoplastic polyurethane (TPU) was widely used in medical area such as implants or medical devices. In this study an implant made from TPU was treated by plasma activation and Ti. O 2 -coating. Figure 1: Model of the implant with an inner porous and an outer nonporous surface. The green line is the Nitinol-ring embedded in the implant. Figure 5: SEM images of the surface of the implant with/without treatment after 7 day incubation

STRESS - STRAIN SIMULATIONS FOR OPTIMISING THE DESIGN OF SHAPE - MEMORY POLYMER BASED ANNULOPLASTY RINGS A. Díaz Lantada 1, P. Lafont 1, J. M. Munoz-Guijosa 1, J. Echavarri 1, H. Lorenzo 1 Spain

TISSUE ENGINEERING OF HEART VALVE LEAFLET BY SELFASSEMBLY OF TISSUE SPHEROIDS BIOFABRICATED FROM HUMAN FAT TISSUE DERIVED STEM CELLS. USA Approximately 1000 tissue spheroids was then placed on specially designed complaint electrospun scaffold. After 24 hours tissue spheroid fused into heart valve leaflet. Mechanically properties of tissue engineered heart valve leaflets (stress train curves) were estimated before and after using method of accelerated tissue maturation.

UNCOATED AND COATED HOLLOW FIBER MEMBRANE SURFACES FOR ARTIFICIAL LUNG

THE INFLUENCES OF REUSE SOLUTION AND THE HEMODIALYSIS ENVIRONMENT ON THE HIGH FLUX POLYAMIDE HOLLOW FIBER MEMBRANES Turkey

THERMO-RESPONSIVE POLYMER COATINGS FOR THE CONTROL OF CELL ADHESION Germany Abstract— In various fields of biotechnology, the control of cell adhesion to culture substrates is an important issue.

A MOBILE BIOSENSOR USING LIVING CELLS FOR WATER QUALITY ANALYSIS Germany Various biohybride sensor chips equipped with sensors for measuring p. H, p. O 2, temperature and impedance in parallel. The left one is made of glass to allow microscopy imaging; the middle sensor chip is made of silicon; the right one is made upon a ceramic carrier (Bio. Chip-C). Cell signal data processing loop with user interface Impact of the pesticide “Metamitron” on the cell vitality parameters p. H and oxygen consumption.

AUTOMATED 24 WELL NEURO-SCREENING SYSTEM WITH LIFE SUPPORT Germany Abstract— Pharmacological research requires devices capable of performing parallel analyses to deliver a high quantity of comparable data for statistical evaluation.

Can conception, the most intimate of human experiences, be automated? 26 July 2007 Womb-on-a-chip may boost IVF successes Teruo Fujii of the University of Tokyo in Japan and his colleagues are building a microfluidic chip to nurture the first stages of pregnancy. Embryo-on-a-chip From the movie MATRIX RELOADED New Line Cinema

APPLICATION OF CARBONYL IRON POWDER AS A NOVEL MEDIATOR FOR ARTERIAL EMBOLIZATION China Abstract— In this study, we proposed carbonyl iron(CIP) as a novel mediator for arterial powder embolization hyperthermia (AEH).

April ПОДОВЖЕННЯ ЖИТТЯ Life extension Life extension consists of attempts to extend human life beyond the natural lifespan. So far none has been proven successful in humans. Several aging mechanisms are known, and anti-aging therapies aim to correct one or more of these: Dr. Leonard Hayflick discovered that mammalian cells divide only a fixed number of times. This "Hayflick limit" was later proven to be caused by telomeres on the ends of chromosomes that shorten with each cell-division. When the telomeres are gone, the DNA can no longer be copied, and cell division ceases. In 2001, experimenters at Geron Corp. lengthened the telomeres of senescent mammalian cells by introducing telomerase to them. They then became youthful cells. Sex and some stem cells regenerate the telomeres by two mechanisms: Telomerase, and ALT (alternative lengthening of telomeres). At least one form of progeria (atypical accelerated aging) is caused by premature telomeric shortening. In 2001, research showed that naturally occurring stem cells must sometimes extend their telomeres, because some stem cells in middle-aged humans had anomalously long telomeres. A strain of mice that have lived . . . more than three normal lifespans Should humans live 200 years?

FLUORESCENT GOLD NANOCLUSTERS FOR BIOMEDICAL APPLICATIONS Taipei, Taiwan, R. O. C Abstract— Synthesis, characterization, and bioconjugation fluorescent gold of nanoclusters (FGNCs) are reported. When the gold nanocluster is capped with reduced lipoic acid (DHLA, dihydrolipoic acid) that the nanocluster has the fluorescent Uptake of fluorescent Au nanoclusters by HAEC cells

Roger Tsien Nobel Laureate in Chemistry 2008 “For the discovery and development of the green fluorescent protein, GFP”

МЕМС XACTIX CONVENTIONAL

SIMULATION OF DRUG RELEASE FOR THE DEVELOPMENT OF DRUGELUTING STENTS – INFLUENCE OF DESIGN AND MANUFACTURING PARAMETERS ON DRUG RELEASE KINETICS N. Grabow 1 al. , Germany et

DESIGN AND PERFORMANCE OF AN IMPROVED ACTIVE SUBRETINAL CHIP Germany Abstract— The aim of the subretinal implant is to visual perception in blind restore patients suffering from retinitis pigmentosa (RP) and – at a later stage – agerelated macular degeneration (AMD). Fig. 2 Retina Chip with 1600 pixels

Tapered Atraumatic Tip IROX Coated Electrodes @120° Dual Steroid Collar Spiral Fixation RX Marker 6 Fr lead body Silicone/PET

Artificial Ear

ВПЛИВ НАНОТЕХНОЛОГІЙ

ВИСНОВКИ: 1. ВИКЛАДАЧІ І СТУДЕНТИ - БІОНАНОТЕХНОЛОГИ МАЮТЬ ІДЕНТИФІКУВАТИ СЕБЕ ЯК ПРЕДСТАВНИКИ НОВОЇ ГАЛУЗІ ЗНАНЬ І МАТИ ВІДПОВІДНИЙ МЕДИКОІНЖЕНЕРНИЙ СВІТОГЛЯД; 2. В ПЕРСПЕКТИВІ, ТАМ ДЕ ВИКОРИСТОВУЮТЬСЯ НАНОБІОМАТЕРІАЛИ І НАНОТЕХНОЛОГІЇ ЗНИКНЕ МЕЖА В ДІЯЛЬНОСТІ ІНЖЕНЕРІВ І ЛІКАРІВ; 3. СЬОГОДНІ, НЕОБХІДНО ОБ’ЄДНАТИ ЗУСИЛЛЯ ВИКЛАДАЧІВ І СТУДЕНТІВ НАВКОЛО МЕДИКО-ІНЖЕНЕРНИХ РОЗРОБОК В МЕЖАХ АСОЦІАЦІЇ БІОМЕДИЧНИХ ІНЖЕНЕРІВ І ТЕХНОЛОГІВ ТА ПОСТІЙНО ДІЮЧИХ МІЖФАКУЛЬТЕТСЬКИХ СЕМІНАРІВ З МЕТОЮ ВІДРОДЖЕННЯ ВІТЧИЗНЯНОГО МЕДИЧНОГО ВИОБНИЦТВА НАНОМАТЕРІАЛІВ. 4. ВІДРОДЖЕНА ВЛАСНА МЕД. ПРОМИСЛОВІСТЬ - ЦЕ ГОЛОВНА УМОВА СТАБІЛЬНОГО ФІНАНСУВАННЯ НОВИХ НАУКОВИХ МЕДИКО-ІНЖЕНЕРНИХ ДОСЛІДЖЕНЬ.

ДЯКУЮ ЗА УВАГУ!