BIODEGRADABLE POLYMER

Reporter: AGNES Purwidyantri

Student ID no: D0228005

Biomedical Engineering Dept.

Definition

Biodegradable A “biodegradable” product has the ability to break

down, safely, reliably, and relatively quickly, by biological means, into raw materials of nature and disappear into nature.

Biomaterial A biomaterial can be defined as a material intended to interface with biological systems to evaluate, treat, augment or replace any tissue, organ or function of

the body [1].

Degradation time

Cotton rags 1-5 months Paper 2-5 months Rope 3-14 months Orange peels 6 months Wool socks 1 to 5 years Cigarette butts 1 to 12 years Plastic coated paper milk cartons 5 years Plastic bags 10 to 20 years Nylon fabric 30 to 40 years Aluminum cans 80 to 100 years Plastic 6-pack holder rings 450 years Glass bottles 1 million years Plastic bottles May be never

What is Polymer Degradation?

                                                             

polymers were synthesized from glycolic acid in 1920s

At that time, polymer degradation was viewed negatively as a process where properties and

performance deteriorated with time.

Biodegradable Polymers as Medical Device Material

No need a second surgery for removal

More physiological repair

Avoid stress shielding Potential as the basis

for controlled drug delivery

Temporary sport during tissue recovery

Less invasive repair

BONE+PLATE

BONE PLATE

Time

Mec

han

ical

Str

engt

h

Degradable Polymer Plate

Natural Biodegradable Polymer

1. Polysaccharides Starch Cellulose

Chitin & Chitosan Hyaluronic acid Alginic acid

2. Polypeptides Collagen Gelatin

3. Bacterial Polyesters EXPENSIVE Poly-b-hydroxybutyrate (PHB)

Synthetic Biodegradable Polymer

Polymer with hydrolyzable backbones Poly-lactic acid (PLA) and its isomers

& copolymers Poly-glycolic acid (PGA) Poly-lactide-co-glycolide (PLGA) Poly-caprolactone (PCL) long

degradation time Polydioxanone

Polymers with carbon backbones Poly (vinyl alcohol) and poly

(vinyl acetate) Polyacrylates

Biodegradable Polymers

Carbonyl bond toONS

R1 C X

O

R2

OH2

R1 C OH

O

+ HX R2

Where X= O, N, S

R1 C O

O

R2

Ester

R1 C NH

O

R2

Amide

R1 C S

O

R2

A.

Where X = O, N, S

Ester Amide Thioester

X C X'

O

R2R1

OH2

+ HX' R2X C OH

O

R1

Where X and X’= O, N, S

B.

O C O

O

R2R1 NH C O

O

R2R1 NH C NH

O

R2R1

Carbonate Urethane Urea

C. R1 C X

O

C

O

R2

OH2

+R1 C OH

O

HX C

O

R2

R1 C NH

O

C

O

R2 R1 C O

O

C

O

R2

Imide Anhydride

Where X and X’= O, N, S

Biodegradable Polymers

Biodegradable Polymers

Acetal:

Hemiacetal:

Ether

Nitrile

Phosphonate

Polycyanocrylate

OH2+C

O

H H

R' OHO C O

H

H

R R' R OH +

OC

C

C C

C

OH

OH

OH

OH

OH OHC

C

C C

OH

OH

OH

OH

H2O+

C==O

H

H2O

R C O C R'

H H

H HOH2

R C OH

H

H

R' C OH

H

H

+

R C R

C N

H

R C R

C O

H

NH2

R C R

C O

H

OH

OH2 OH2

RO P OR'

O

OR''

OH P OH

O

OR''

OH2+ +R OH OH R'

R C C C C R'

CN

C

OR''

CNH

H O C

OR'''

O

H

H

OH2R C C C

CN

C

OR''

H

H O

H

H

OH C R'

CN

C

OR'''

O

+

Degradation Mechanisms Enzymatic degradation Hydrolysis

(depend on main chain structure: anhydride > ester > carbonate)

Homogenous degradation Heterogenous degradation

Degradation Steps

Water-sorption

Reduction of mechanical properties (modulus & strength)

Molar mass

reduction

Loss of weight

Degradation Steps

Polymer Degradation by Erosion

Degradation Schemes

Surface erosion (poly(ortho)esters & polyanhydrides) Sample is eroded from the surface Mass loss is faster than the ingress of water

into the bulk Bulk degradation (PLA,PGA,PLGA, PCL)

Degradation takes place throughout the whole of the sample

Ingress of water is faster than the rate of degradation

Erodible Matrices or Micro/Nanospheres

(a)Bulk-eroding system

(b)Surface-eroding system

Comparison [7]Comparison [7]

Properties PLA PS PVC PPYield Strength, MPa 49 49 35 35

Elongation, % 2.5 2.5 3.0 10

Tensile Modulus, GPa 3.2 3.4 2.6 1.4

Flexural Strength, MPa

70 80 90 49

Factors Influence the Degradation Behavior

Chemical Structure and Chemical Composition

Distribution of Repeat Units in Multimers

Molecular Weight Polydispersity Presence of Low Mw

Compounds (monomer, oligomers, solvents, plasticizers, etc)

Presence of Ionic Groups Presence of Chain

Defects Presence of Unexpected

Units Configurational

Structure

Morphology (crystallinity, presence of

microstructure, orientation and residue

stress) Processing methods & Conditions

Method of Sterilization Annealing

Storage History Site of Implantation

Absorbed Compounds Physiochemical Factors (shape, size) Mechanism of Hydrolysis (enzymes

vs water)

Poly(lactide-co-glycolide) (PLGA) [8]

Factors for Polymer Degradation Acceleration

More hydrophilic backbone. More hydrophilic endgroups. More reactive hydrolytic groups in the backbone. Less crystallinity. More porosity. Smaller device size.

Medical Applications of Biodegradable Polymers

Wound Management

• Staples• Sutures

• Clips• Surgical Meshes

• Adhesives

Orthopedic Devices• Pins• Rods

• Screws• Tacks

• Ligament

Dental Applications

•Tissue regeneration membrane

• Void filler for after tooth extraction

Cardiovascular

applications Stents

Intestinal ApplicationAnastomosis

Ring

Drug, Gene Delivery System

Tissue Engineering

Tissue Engineering

PLLA, PCL, PGA, poly(glycolide) & poly[d,l-(lactide-co-glycolide)] have excellent biocompatibility and good mechanical properties and have been licensed by FDA for in vivo applications for tissue engineering scaffolds [2].

Cells are cultured on a scaffold to form a natural

tissue, and then the formed tissue is implanted in the

defect part in the patients. In some cases, a scaffold or a

scaffold with cells is implanted in vivo directly,

and the host’s body works as a bioreactor to construct new

tissues [3].

Gene Delivery System [4]

Poly(l-lysine)-based degradable polymers

Poly(β-amino ester)s-based degradable polymers

Polyphosphoester-based degradable polymers

Polyethylenimine modified with degradable polymers

Degradable polymers in siRNA delivery

Gene Delivery System

Barriers to gene delivery. Design requirements for gene delivery systems

include the ability to (I) package therapeutic genes, (II) gain entry into

cells,(III) escape from the endo-lysosomal pathway,(IV) affect DNA/vector release,(V)travelthrough the cytoplasm and into

the nucleus, and (VI) enable gene expression [5].

TSP50 was immobilized onto biodegradable

polymer fibers.ThenTSP50-immobilized polymer fibers

could selectivelyadsorb the anti-TSP50 [6].

Conclusion

Synthetic biodegradable polymers

no immunogenicity

easier to be chemically modified &functionalized. The developing trends in the functionalization of

synthetic biodegradable polymers

(1) Easier functionalization processes with mild

reaction conditions and without harmful effects on bulk

properties of polymers are pursued

(2) Functionalization will be related to biomimetics

(3) Promising potential for in vivo applications.

References

1. Nair LS,Laurencin CT. Biodegradable polymers as biomaterials. Prog Polym Sci. 2007;32:762–98

2 Rezwan K, Chen QZ, Blaker JJ, Boccaccini AR. Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials 2006;27:3413–31

3. Place ES, George JH, Williams CK, Stevens MM. Synthetic polymer scaffolds for tissue engineering. Chem Soc Rev 2009;38:1139–51.

4. H. Tian et al. Progress in Polymer Science 37 (2012) 237–280

5. Wong SY, Pelet JM, Putnam D. Polymer systems for gene delivery—past, present, and future. Prog Polym Sci 2007;32:799–837

6. Shi Q, Chen X, Lu T, Jing X. The immobilization of proteins on biodegradable polymer fibers via click chemistry. Biomaterials 2008;29:1118–26

7. Mobley, D. P. Plastics from Microbes. 1994

8. Robert A. Miller, John M. Brady, Duane E. Cutright. Degradation rates of oral resorbable implants (polylactates and polyglycolates): Rate modification with changes in PLA/PGA copolymer ratios. Journal of Biomedical Materials Research. Vol 11 issue 5 pages 711–719, September 1977

Thank you