SYNTHETIC BIOMATERIALS AND POLYMERS IN MEDICINE

Material Science Logic

Synthesis+processing

Structure

Performance/Application

Properties•Physical•Biological

Biomaterials

• Biomaterials are materials that are designed for in-vivo use

• The study of biomaterials focuses on controlling/understanding the performance and interaction of synthetic or modified biological materials in biological systems, especially at the interface between synthetic and biological materials (biocompatibility)

A biomaterial is "any substance (other than drugs) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system which treats, augments, or replaces any tissue, organ, or function of the body".

Biocompatibility — The ability of a material to perform with an appropriate host response in a specific application

Host Response — The response of the host organism (local and systemic) to the implanted material or device.

Definitions

• Biomaterial - Material for in-vivo use• Biocompatible - No adverse affects on biologic

al system• Bioinert - No interaction with biological system• Bioerodable - Dissolves in biological system o

ver time

KeywordsMetallic/glass/Polymeric/Ceramic/CompositeFracture/fatigue/creep/corrosion/degradationTissue

response/healing/biocompatibility/host response/carcinogenicity

Hard/soft tissue implantsVascular/Breast/Urological/Art. OrganMucosal contacting …

Biomaterial Selection Parameters

MechanicalThermal/Electrical ConductivityDiffusionWater AbsorptionBiostabilityBiocompatibility

Biomaterial Selection Criteria

• Specific Surface Interactions• Blood Contact• Need to Bear a Load• Structural Applications• Degradation Propensity• Permeability Responsiveness• Solubility under Physiological Conditions• Transparency Need• Bioenvironmental Responsiveness

Some Commonly Used Biomaterials

Material Applications Silicone rubber Catheters, tubing Dacron Vascular grafts Cellulose Dialysis membranes Poly(methyl methacrylate) Intraocular lenses, bone cement Polyurethanes Catheters, pacemaker leads Hydogels Opthalmological devices, Drug Delivery Stainless steel Orthopedic devices, stents Titanium Orthopedic and dental devices Alumina Orthopedic and dental devices Hydroxyapatite Orthopedic and dental devices Collagen (reprocessed) Opthalmologic applications, wound

dressings

Journals Biomaterials Biomaterials World News Materials Today Nature Journal of Biomedical Materials Research Cells and Materials Journal of Biomaterials Science Artificial Organs ASAIO Transactions Tissue Engineering Annals of Biomedical Engineering Medical Device Link … see: http://www.biomat.net/biomatnet.asp?group=1_5

A Little History on Biomaterials

• Chinese, Romans, and Aztecs used gold in dentistry over 2000 years ago, Cu not good.

• Ivory & wood teeth

• Aseptic surgery 1860 (Lister)

• Bone plates 1900, joints 1930

• Turn of the century, synthetic plastics came into use

– WWII, shards of PMMA unintentionally got lodged into eyes of aviators

– Parachute cloth used for vascular prosthesis

• 1960- Polyethylene (PE) and stainless steel being used for hip implants

Uses of Biomaterials

• Replace diseased part – dialysis• Assist in healing – sutures• Improve function – contacts• Correct function – spinal rods• Correct cosmetic – nose, ear• Aid dx – probe• Aid tx – catheter• Replace rotten – amalgam• Replace dead - skin

Problems/test for w Biomaterials

• Acute toxicity (cytotoxicity) arsenic• Sub chronic/chronic Pb• Sensitization Ni, Cu• Genotoxicity• Carcinogenicity• Reproductive &/or developmental Pb• Neurotoxicity• Immunotoxicity• Pyrogen, endotoxins

Evolution of Biomaterials

Structural

Functional Tissue Engineering Constructs

Soft Tissue Replacements

Biomaterials for Tissue Replacements

• Bioresorbable vascular graft

• Biodegradable nerve guidance channel

• Skin Grafts

• Bone Replacements

Biomaterials - An Emerging Industry

• Next generation of medical implants and therapeutic modalities

• Interface of biotechnology and traditional engineering

• Significant industrial growth in the next 15 years -- potential of a multi-billion dollar industry

Synthetic Biomaterial Classes

• METALS: Co-Cr alloys, Stainless steels, Gold, Titanium alloys, Vitallium, Nitinol (shape memory alloys) Uses: orthopedics, fracture fixation,dental and facial reconstruction,stents

• CERAMICS: Alumina, Zirconia, Calcium Phosphate, Pyrolitic Carbon Uses: orthopedics, heart valves, dental reconstruction

• COATINGS: Bioglasses, Hydroxyapatite, Diamond-like carbon Uses: orthopedics, in-growth

Synthetic Biomaterial Classes cont.

• POLYMERS: Silicones, Gore-tex (ePTFE), Polyethylenes(LDPE,HDPE,UHMWPE,) Polyurethanes, Polymethylmethacrylate,Polysulfone, Delrin Uses:orthopedics, artificial tendons,catheters, vascular grafts, facial and soft tissue reconstruction

• COMPOSITES: CFRC, self reinforced, hybrids Uses:orthopedics, scaffolds

• HYDROGELS: Cellulose, Acrylic co-polymers Uses:drug delivery, vitreous implants,wound healing

• RESORBABLES: Polyglycolic Acid, Polylactic acid, polyesters Uses: sutures,drug delivery, in-growth, tissue engineering

Metals• Metals are (mostly) crystalline solids composed of elemental,

positively charged ions in a cloud of electrons

– Properties are a function of grain size, imperfections in crystal

structure

– Metals comprised of more than one element are alloys

– The surface of metals are often oxides, if inert leads to

protection, if active is corrosion

• Typical metal properties include:

– High melting points

– High stiffness and strength

– High conductivities

– isotropic properties

Why Use Metals as Biomaterials

• Properties and fabrication well known

• Stiff and strong

• Bioinert

• Joining technologies known

• Metals commonly used

– Titanium

– Stainless steel

Figure 4.1 These titanium-alloy joint replacements are an example of the many applications for metal biomaterials for implantations. (from http://www.spirebiomedical.com)

金屬材料 (1).具有高強度及導電度等特性，在需要機械性強度或電傳導 ，則需使用金屬材料。 (2).如人工骨骼、關節及心臟節律器 (3).常用的金屬材料的種類及其應用列於表三

表三 金屬生醫材料及其應用金 屬 生 醫 材 料 應 用汞齊 (Amalgam) 牙科膺復物鈦 - 鋁 - 釩合金 (Ti-Al-V alloy)

骨科 - 牙科 駐植體

鈷 - 鉻合金 (Co-Cr alloy) 骨科 - 牙科 駐植體鎳合金 (Nickel alloy) 牙科膺復物鉑 - 銥合金 (Platinum-Iridium)

電導體

不銹鋼 (Stainless steel) 骨科 - 牙科 駐植體

Ceramics

• Ceramics are compounds characterized by ionic or covalent bonding

• Ceramics are generally crystalline, crystalline SiO2 is quartz

• Glasses are the amorphous “ceramics” common glass is amorphous SiO2

• Properties

– Properties function of grain size, imperfections in crystal structure

– Many ceramics comprised of more than one compound

– Low conductivities (semi-conductors, insulators)

– Stiff and Brittle

Why Use Ceramics as Biomaterials

• Properties and fabrication well known• Stiff and strong• Bioinert• Obvious fix for teeth and bones

陶瓷材料 (1).陶瓷材料是種無機非金屬固體，具有強的抗壓性質及很好 的生物相容性等優點，故常應用於生醫材料中 (2).常用的陶瓷材料的種類及其應用列於表四

表四 陶瓷類生醫材料及其應用 陶 瓷 生 醫 材 料 應 用氧化鋁 (Alumina) 人工骨骼、關節、牙套玻璃陶瓷 (Glass-Ceramics， Bioglass， Ceravital)

骨骼修復

氫氧磷灰石 (Hydroxyapatite) 骨骼修復低溫均質碳纖維 (Low temperature isotropic carbon)

人工心瓣膜

Metals

Semiconductor Materials

Ceramics

Polymers

Synthetic BIOMATERIALS

Orthopedic screws/fixation

Dental Implants Dental Implants

Heart valves

Bone replacements

BiosensorsImplantable Microelectrodes

Skin/cartilageDrug Delivery Devices

Ocular implants

複合材料

(1).即几種材料，取其優點組合而成。 (2).一般而言，複合材料具生物相容性佳、抗腐蝕、高強度等 優點；其缺點是因為組合而成，故為不均質。 (3).常用的複合材料的種類及其應用列於表五。

表五 複合生醫材料及其應用複 合 生 醫 材 料 應 用碳纖維 - 聚四氟乙烯 (Proplast) 人工關節、人工中耳生醫陶瓷 - 樹脂 ( 複合樹脂 ) 牙科補綴物生醫陶瓷 - 金屬、合金 人工關節、人工骨骼生醫陶瓷 - 高密度聚乙烯 人工關節

Issues• Understanding and controlling performance

– Physical

– Chemical

– Biological

• Relevant material performance is under biological conditions

– 37 C, aqueous, saline, extracelluar matrix (ECM)

– Material properties as a function of time

• Initial negative biological response - toxicity

• Long term biological response – rejection

• Biology is a science of surfaces and interfaces

– Seldom (never) at equilibrium

Materials Lessons from Biology

• Polymer based• Nanoscaled• Energy efficient• Self-healing• Ecologically sound• Self-improving• Smart!

Biology represents a material/ part/system strategy that works

A Brief Introduction of Polymer

A polymer is generally named based on the monomer it is synthesized from. F

or example, ethylene is used to produce poly(ethylene) (PE). For both glycolic aci

d and lactic acid, an intermediate cyclic dimer is prepared and purified, prior to pol

ymerization. These dimers are called glycolide and lactide, respectively. Although

most references in the literature refer to polyglycolide or poly(lactide), you will also

find references to poly(glycolic acid) and poly(lactic acid). Poly(lactide) exists in tw

o stereo forms, signified by d or l for dexorotary or levorotary, or by dl for the race

mic mix.

HOMOPOLYMER(one monomer)

Polymers

• Terminology (contn):– copolymer: polymers of two mer types

• random · · ·-B-A-B-A-B-B-A-· · ·• alternating· · ·-A-B-A-B-A-B-A-· · · • block · · ·-A-A-A-A-B-B-B-· · ·

– heteropolymer: polymers of many mer types

COPOLYMER

Polymers Structure

Linear

Branched

Crosslinked

PolyurethanesA urethane has an ester group and amide group bonded to the same carbon. Urethanes can be prepare by treating an isocyanate with an alcohol.

RN C O ROH RNH C

O

OR+

an isocyanate an alcohol a urethane

Polyurethanes are polymers that contain urethane groups.

O C NCH3

N C O

toluene-2,6-diisocyanate

+ HOCH2CH2OH

ethylene glycol

C

O

NHCH3

NH C

O

OCH2CH2O C

O

NH NH C

O

OCH2CH2O C

OCH3

n

a polyurethane

I. Biodegradable Polymers

O

O

n O

O

nO

O

O

On m

PGA

Tm= 225C

Tg = 36C

PPL

Tm= 80C

Tg = -24C

PCL

Tm= 61C

Tg = -60C

PLA

Tm= 180C

Tg = 60C

PLGA

Tg ~ 50 C

O

O

nO

O

n

Synthetic Polymers

Biodegradable Synthetic Polymers

• Poly(alkylene ester)s

• PLA, PCL, PLGA

• Poly(aromatic/aliphatic ester)s

• Poly(amide-ester)s

• Poly(ester-urethane)s

• Polyanhydrides

• Polyphosphazenes

Biostable Polymers

• Polyamides

• Polyurethanes

• Polyethylene

• Poly(vinylchloride)

• Poly(hydroxyethylmethacrylate)

• Poly(methylmethacrylate)

• Poly(tetrafluoroethylene)

• Poly(dimethyl siloxane)

• Poly(vinylalcohol)

• Poly(ethylenglycol)

Stimuli Responsive Poly(ethylene oxide-co-propilene oxide) Poly(methylvinylether) Poly(N-alkyl acrylamide)s Poly(phosphazone)s

生物医用高分子材料的分类

生物降解型非降解型包括

要求

用途

聚乙烯、聚丙烯、芳香 胶原、纤维素、聚氨

酸脂、聚硅氧烷等长期保持稳定，不发生降解具有良好的机械性能

氨基酸、甲壳素等降解产物能被机体正常吸收、利用或排出体外

人体软、硬组织修复体，人工器官粘合剂，管腔等的制造

药物释放、送达载体、非永久性植入装置

高分子在医学领域中的应用

Polymers: Biomedical Applications

• Polyethylene (PE)

– five density grades: ultrahigh, high, low, linear low and very low density

– UHMWPE and HDPE more crystalline

– UHMWPE has better mechanical properties, stability and lower cost

– UHMWPE can be sterilized

Polymers: Biomedical Applications

• UHMWPE: acetabular caps in hip implants and p

atellar surface of knee joints

• HDPE used as pharmaceutical bottles, fabrics

• Others used as bags, pouches, tubes etc.

Artificial Hip Joints (UHMWPE)

http://www.totaljoints.info/Hip.jpg

Polymers: Biomedical Applications

• Polymethylmethacrylate (PMMA, lucite, acrylic,plexiglas)

– acrylics

– transparency

– tough

– biocompatible

• Used in dental restorations, membrane for dialysis, ocular len

ses, contact lenses, bone cements

Intraocular Lens3 basic materials - PMMA, acrylic, silicone

Polymers: Biomedical Applications

• Polyamides (PA, nylon)

– high degree of crystallinity

– interchain hydrogen bonds provide superior mechanical str

ength (Kevlar fibers stronger than metals)

– plasticized by water, not good in physiological environment

• Used as sutures

Polymers: Biomedical Applications

• Polyvinylchloride (PVC) (monomer residue must be very low)

– Cl side chains

– amorphous, hard and brittle due to Cl

– metallic additives prevent thermal degradation

• Used as blood and solution bags, packaging, IV sets, dialysis

devices, catheter, bottles, cannulae

Polymers: Biomedical Applications

• Polypropylene (PP)

– properties similar to HDPE

– good fatigue resistance

• Used as syringes, oxygenator membranes, sutures, fabrics, vascula

r grafts

• Polyesters (PET)

– hydrophobic (beverage container PET)

– molded into complex shapes

• Used as vascular grafts, sutures, heart valves, catheter housings

Polymers: Biomedical Applications

• Polytetrafluoroethylene (PTFE, teflon)

– low coefficient of friction (low interfacial forces between its

surface and another material)

– very low surface energy

– high crystallinity

– low modulus and strength

– difficult to process

• catheters, artificial vascular grafts

Synthetic vascular grafts from W.L.Gore

Polymers: Biomedical Applications

• Rubbers

– latex, silicone

– good biocompatibility

• Used as maxillofacial prosthetics

Figure 4.3 This artificial heart valve is coated with Silizone, a biocompatible material that allows the body to accept the implant. (from http://www.sjm.com/devices/).

Polymers: Biomedical Applications

• Polyurethanes

– block copolymer structure

– good mechanical properties

– good biocompatibility

• tubing, vascular grafts, pacemaker lead insulation, heart

assist balloon pumps

高 分 子 生 醫 材 料 應 用

聚甲基丙烯酸甲酯 (Polymethylmethacrylate) 牙齒膺復物隱形眼鏡、人工水晶體骨泥

聚羥乙基丙烯酸甲酯(Polyhydroxyethylmethacrylate)

隱形眼鏡、釋藥系統

聚丙烯酸 (Polyacrylic acid) 牙科黏著劑聚醯胺 ( 尼龍 )(Polyamides) 縫線、人造血管高密度聚乙烯 (High Density Polyethylene) 關節、人工瓣膜聚丙烯 (Polypropylene) 縫線、注射筒、導管聚脲化物 (Polyurethanes) 人造血管、導管、人造心室矽膠 (Silicons) 組織取代品 ( 整型用 ) 、導管纖維素乙醯酸 (Cellulose acetate) 透析膜四氟化碳 (Fluorocarbons) 人工血液聚四氟乙烯 (Polytetrafluoroethylene) 血管聚碳酸酯 (Polycarbonates) 導管、容器聚氯乙烯 (Polyvinyl chloride) 血袋、導管聚羥基乙酸 (Polyglycolic acid) 縫線聚丙烯腈 (Polyacrylonitrile) 滲透膜聚乙烯對苯二甲酯 ( 達克龍 )(Polyethylene terephthalates)

血管

聚硫化物 (Polysulfide) 牙科印模材

Substitute Heart Valves

Polymers in the body