Biomaterials

Dr. Rajendran JC Bose M.Pharm. PhD

The reason why we are doing?

“A material intented to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of the body.

Biomaterials-An Interdisciplinary field

Evolution of Biomaterial Science .

1st generation (since 1950s)

Objective: Bioinertness.

2nd generation (since 1980s)

Objective : Bioactivity

3rd generation (since 2000s)

Objective : Regenerate functional tissue

Biomaterials

20

17

201

2CAGR

15%

$44.0 billion

$88.4 billion

20000

15000

10000

5000Reve

nue

in $

Mill

ion

Metals

Ceramics

Polymers Others

USA EuropeAsia ROW

Reve

nue

in $

Mill

ion

2009 2014

Orthopedic38%

Cardio vascu-

lar37%

Wound care

9%

Plastic surger

y8%

Urological4%

Gastro2% Others

2%

Biomaterial Product Market

Biomaterial market status,

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

Cell-biomaterial interaction

Biocompatibility

• The application of engineering disciplines to either maintain existing tissue structures or ti enable tissue growth.

• From a material engineering pint of view, tissues are considered to be cellular composites representing mltiphase system:

Three main structural components:

1. Cells organised into functional units 2. The extracellular matrix 3. Scaffolding architecture

Tissue engineering-a biomaterial perspective

Nature Nanotechnology  6, 13–22 (2011)

Tissue engineering-scaffold concept

• Biodegradable• Fast spread on wet (wound) surface• Adequate working time• Adequate bonding strength• Hemostasis• Biocompatible• Easy cell penetration, distribution,

proliferation• Permeability of culture medium• In vivo vascularization (once implanted)• Maintenance of cell phenotypes• Adequate mechanical properties• Controlled biodegradation• Ease of fabrication

Requirements of Biomaterials as Tissue engineering Scaffold.

Advanced Drug Delivery Reviews, Volume 65, Issue 4, 2013, 581 - 603

Metals

Biocomposite

Ceramics

Polymers

BIOMATERIALS

Orthopedic screws/fixation

Dental Implants

Dental Implants

Heart valves

Bone replacements

Biosensors

Implantable Microelectrodes

Skin/cartilageDrug Delivery

DevicesOcular implants

Biomaterials –Classical sources

Natural biomaterialsProteins• Silk• Keratin• Collagen• Gelatin• Fibronogen• Elastin• Actin• MyosinPolysaccharides• Cellulose• Amylose• Dextron• Chitin• GlysaminoglyconsPoly neucleotites• DNA• RNA

Synthetic biomaterials• PMMA-Poly(methyl methacrylate) • PVC- polyvinyl chloride• PLA/PGA- Poly lactic acid/poly glycolic acid• PE-Polyethylene• PP-Poly propylene• PA-Poly amides• PTFE -Polytetrafluoroethylene• PET-Polyethylene terephthalate• PUR-Polyurethane• Silicones

Advantages• Easy to make complicated

items• Tailorable physical &

mechanical properties• Surface modification• Immobilize cell etc.• Biodegradable

Disadvatages• Leachable compounds• Absorb water & proteins etc.• Surface contamination• Wear & breakdown• Biodegradation• Difficult to sterilize

Polymeric Biomaterials

Chem. Soc. Rev., 2009,38, 1139-1151

Polymeric Biomaterials-Tissue engineering

Scaffolds

Advantages • High compression strength• Wear & corrosion resistance• Can be highly polished• Bioactive/inert

Disadvantage • High modulus (mismatched with

bone)• Low strength in tension• Low fracture toughness• Difficult to fabricate

• Alumina• Zirconia (partially stabilized)• Silicate glass• Calcium phosphate (apatite)• Calcium carbonate

Bioceramic-biomaterials

• Stainless steel (316L)

• Co-Cr alloys• Ti6Al4V• Au-Ag-Cu-Pd alloys• Amalgam

(AgSnCuZnHg)• Ni-Ti• Titanium

Advantages.• High strength• Fatigue resistance• Wear resistance• Easy fabrication• Easy to sterilize• Shape memoryDisadvantages• High moduls• Corrosion• Metal ion sensitivity and toxicity• Metallic looking

Metallic-biomaterials

• Mechanical and chemicals properties• No undersirable biological effects carcinogenic, toxic, allergenic or

immunogenic• Possible to process, fabricate and sterilize with a godd reproducibility• Acceptable cost/benefit ratio

General Criteria for materials selection

Material Properties• Compresssive strength• Tensile strength• Bending strength• E-Modulus• Coefficient of thermal expansion• Coefficient of thermal coductivity

• Surface tension• Hardness and density• Hydrophobic/philic• Water sorption/solubility• Surface friction• Creep• Bonding properties

Deterioration of Biomaterials• Corrossion• Degradation• Calcification• Mechanical loading• Combined

Valve cells Collagen scaffold of heart valve

Heart valve post- implantation

Heart valve tissue engineering

The promise of Biomaterials

Intraocular Lens

Vascular Grafts

Substitute Heart Valves

Artificial Hip Joints

Matrix-based ACI using a collagen type I hydrogel..(A) Articular cartilage defect (3 × 2 cm) at the medial femoral condyle in a 31-year old male. (B) Debridement was performed down to the subchondral bone and the shape of the chondrocyte-laden colla...

Advanced Drug Delivery Reviews, Volume 65, Issue 4, 2013, 581 - 603

Collagen material for articular cartilage defect

• Physical and mechanical • Biological• In vitro assessment• in vivo assessment• Functional assessment• Clincal assessment

Testing method

• Cell culture, cytotoxicity (Mouse L929 cell line)

• Hemolysis (rabbit or human blood)• Mutagenicity (Ames test)• Systemic injection, acute toxicity

(Mouse)• Sensitization (Guinea pig)• Pyrogenicity (Rabbit)• Intramuscular implnatation (Rat,

rabbit)• Blood compatibility• Long-term implatation.

Testing of Biomaterials

General Problems with Biomaterials

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

Pb• Neurotoxicity• Immunotoxicity• Pyrogen, endotoxins

• Amalgam• Dental composite• Ceramics• Other metals

General criteria for tooth filling materials• Non-irritation to pulp and gingival • Low systemic toxicity• Cariostatic• Bonding to tooth substance without marginal leakage (20 u)• Not dissolved or erode in saliva• Mechanical strength, wear resistance, modules matching.• Good aesthetic properties• Thermal propertiesy (expansion & conductivity)• Minimal dimensional changes on setting and adequate working time and radio opacity

Tooth fillings materials

• Cell matrices for 3-D growth and tissue reconstruction

• Biosensors, Biomimetic , and smart devices• Controlled Drug Delivery/ Targeted delivery• Biohybrid organs and Cell immunoisolation• New biomaterials - bioactive, biodegradable,

inorganic• New processing techniques

Advances in Biomaterials Technology