Lecture 4:�
Biomaterials Surfaces: Chemistry�
Hydrolysis�
Supporting notes�
3.051J/20.340J Materials for Biomedical Applications,
Spring 2006
1
Hydrolysis�
• Hydrolysis is a kind of “Solvolysis”,
solvent + lysis: cleavage by the solvent.
H2O
OH
+ HBr
Hydoloysis
+ HBr
Methanolysis
+ HBr
Formic acidolysis
CH3OH
OCH3
Br
HCOOH
OCOH
2-Bromo-2-methyl propane
2
Polymer Hydrolysis�
•�Polymers prepared by polycondensation can
be susceptible to hydrolysis.
O
nH
O
O
+
H
OH
n HO
O
Succinic acid
1,4-Butanediol
O
As, Zn catalysts, Δ
*
O
O
H+, OH-, or enzyme
O
*
n
+ nH2O
Poly(butylene succinate), PBS
3
Hydrolysable is “degradable”.�
Synthetic polymers�
Naturally-occurring polymers
· Polyesters
· Proteins and polyamides
· Polyamides
· Polyanhydrides
· Polyethers
· Polyurethanes
· Polycarbonates
· Polyureas
Material properties can
be tuned readily.
Cheaper!
Collagen
Fibrinogen and fibrin
Gelatin
Casein
· Polysaccharides
Cellulose
Starch and amylose
Chitin and chitosan
Dextran
· Polynucleotides
DNA and RNA
4
Biodegradation:�
An event which takes place through the action of enzymes
and/or chemical decomposition associated with living
organisms (bacteria, fungi, etc.) or their secretion products.
Albertsson and Karlsson, in Chemistry and Technology of Biodegradable Polymers 1994
O
R
O
H
C
N
Polyester
O
C
O
R
O
C
O
Polyamide
R
O
R
O
C
N
O
C
Polycarbonate
R
O
O
R'
O
O
O
R"
P
R'
Polyanhydride
R
Polyphosphazene
Poly(ortho ester)
Typical examples of synthetic biodegradable polymers
5
Key factors in hydrolysis�
1. Bond stability
δ+
Example: Hydrolysis of polyester
C
O
δ-
Base-catalyzed polyester hydrolysis
δO
R
C
δ
O
O-
O
OH-
R'
+
R
C-
H
O
O
R'
R
C
H
O
O
R'
O
H+
R
C
OH
+
R’OH
6
Acid-catalyzed polyester hydrolysis
δO
R
C
δ+
O+ H
H+
O
R'
R
C
O
O
C+ O
R
R'
H
R'
R
O
H
C
O+ R'
O
H
H2O
O
H
R
C
O
H
O+
R'
H
O
-H+
R
C
+
OH
R’OH
H
Polyamide hydrolysis
O
R
C
O
H2O
N
R'
R
C
OH
+
H2N-R’
H
7
Key factors in hydrolysis�
2. Hydrophobicity
3. Molecular weight & architecture
4. Morphology
Crystallinity, porosity
5. Tg Mobility of polymer chain
Chance to contact with H2O
8
120
Amorphous PLLA
�a (degrees)
110
Crystalline PLLA
108
113
100
90
80
0
12
24
36
Alkaline Treatment Time (h)
48
0
12
24
36
Alkaline Treatment Time (h)
48
Orthorhombic crystal structure of α-PLLA�
Figures removed for copyright reasons.
6.1
dcrystal: 1.290 g/cm3
damorphous: 1.248 g/cm3
28.8
10.5 Å
10
Hydrolysable polymers�
O
Polyanhydride
R
O
C
O
C
R'
O
Polyester
R
Polyamide
R
Polyether
O
H2O
R
C
O
O
H
C
N
+
OH
R'
R
C
R'
R'
O
H
O
C
N
H
O
H
N
C
N
Polyether urethane
R
Polyurea
R
R
C
R
+
HO
R'
OH
+
H2N
R'
HO
R'
O
H
R'
C
N
H2O
O
Polycarbonate
R
O
C
R
R
OH
H
O
N
C
R'
+
HO
R'
OH
+
H2N
R'
OH
+
HO
R' 11
O
H2O
O
+
OH
H2O
R'
R'
O
H2O
O
C
OH
H2O
R
HO
O
H2O
C
O
R
O
C
Poly(sebacic anhydride)�
Properties: rapid degradation, Tg: 50 °C, Tm : 80 °C
Uses: drug delivery matrices
O
O
O
Table. Half-lives of hydrolyzable polymers
Polymer class
Half-life
Polyanhydrides
0.1 h
Incorporation of
hydrophobic segment
O
C
PLLA
O
O C3H6 O
O
O
O
C8H16
O
3.3 years
Polyamides
83,000 years
Poly(bis-(p-carboxyphenoxy)propane-co-sebacic anhydride)
Tabata et al., Pharm. Res., 10, 391, 1993
Göpferich, Biomater., 17, 103, 1996
12
Poly(glycolide-co-lactide) (polyglactide)
Properties: rapid degradation, amorphous*, Tg: 45-55 °C
Uses: bioresorbable sutures, controlled release matrices,
tissue engineering scaffolds
*Depending
on composition
O
O
O
O
Glycolate
(GA)
Lactate
(DL-LA)
Dexon®: the first synthetic bioresorbable suture in 1960s.
(PGA)� Histological response can be predictable in comparison to nonsynthetic materials.
High-crystalline nature limits processability.
13
Poly(L-lactide), poly(L-lactic acid) (PLLA)
Properties: rapid degradation, semicrystalline, Tg: 60 °C, Tm: 180 °C
Uses: fracture fixation, ligament augmentation
*
O
O
PLLA
H OH
HO
HO
H
H
O
Fermentation
H O
HO
H
OH
OH
microorganisms
e.g. Lactobacilli
*
-H2O
H
*
O
O
L-lactic
acid
PLLA
D-glucose
from agricultural product;
corn, potato, rice
O
O
-H2O
O
*
*
O
O
L-lactide
14
Physical properties of various plastics�
PLLA
PET
PS
Density/g/cm3
1.27
1.34
1.04
0.90
Tensile strength/MPa
66.7
55.9
43.1
37.3
Yong’s modulus/MPa
3300
2600
3300
2100
Elongation@break/%
4
300
2
700
1-5
0.75
0.55
-
Cost/$/lb
PP�
*Polymeric materials were non-oriented (as prepared).
Tsuji, Polylactic acid, JPS press, Kyoto, 1997,
Ikada, Macromol. Rapid Commun., 21, 117, 2000
15
Polyethylene oxide (PEO)
Properties: water soluble, semicrystalline, Tg: -60 °C, Tm: 60 °C
Uses: hydrogel, protein-resistant coatings
O
PEO
Two photos removed for copyright reasons.
Figure 6 in Irvine, D., et al. "Nanoscale Clustering of RGD Peptides at
Surfaces Using Comb Polymers. 1. Synthesis and Characterization of
Comb Thin Films." Biomacromolecules 2, no. 1 (2001): 85 -94.
Rate of hydrolysis:
anhydride > ester >> amide >>>> ether
Matrices for drug delivery
16
etc.
Hydrolysis of polymeric materials�
Acid- or base-catalyzed hydrolysis
MW
Time
Enzymatic hydrolysis -surface erosionMW
Time
17
Hydrolysis of
Bionole® (PBS)�
O
*
O
O
*
O
Photos removed for copyright reasons.
Alkaline treated
Lipase PS treated
Taniguchi I., unp ub lished results
18
Application of biodegradable polymers
and minimal requirements of biomaterials
Minimal Requirements of Biomaterials
Medical Application
PDLLA
PGA
PGALA
Oxidized
cellulose
PCA
PPZ
POE
PAA
Hyaluronate
Collagen
Fibrin
PLLA
Chitin
PCL
Starch
Ecological Application
PBS
PES
PEC
PHA
(PHB)
PEA
Cellulose
A) Non-toxic (biosafe)
Non-pyrogenic, Non-hemolytic, Chronically noninflammative, Non-allergenic, Non-carcinogenic,
Non-teratogenic, etc.
B) Effective
Functionality, Performance, Durability, etc.
C) Sterilizable
Ethylene oxide, Θ-Irradiation, Electron beams,
Autoclave, Dry heating, etc.
D) Biocompatible
Interfacially, Mechanically, and Biologically
Figure by MIT OCW.
PHA: Poly(hydroxyalkanoate
Poly(acid anhydride)
PHB: Poly(3-hydroxybutyrate)
Poly(butylene succinate)
PLLA: Poly(L-lactide),
Poly(�-cyanoacrylate)
Poly(L-lactic acid)
Poly(�-caprolactone)
POE: Poly(orthoester)
Poly(ester amide)
PEC: Poly(ester carbonate)
Poly(glycolide),
PES: Poly(ethylene succinate)
Poly(glycolic acid)
PGALA: Poly(glycolide-co-lactide),
Poly(glycolic acid-co-lactic acid)
PDLLA: Poly(DL-lactide), Poly(DL-lactic acid)
PAA:
PBS:
PCA:
PCL:
PEA:
PGA:
Application of Biodegradable Polymers
Figure by MIT OCW.
19
Microbial degradation of PLLA (rare case)�
With S. waywayandensis JC M 9114
C ontrol
Photos removed for copyright reasons.
With A. orientalis subsp. Orientalis IFO 12362
*
O
O
Hydrolysable polymer
Esterases do not degrade
except proteinase K.
PLLA�
Figure. SEM images of PLLA film treated with microbe
Jarerat et al., Macromol. Biosci., 2, 420, 2002
20�
Enzymatic degradation -Lipase-
Lipase: an esterase (EC3.1.1.3)
stable in organic solvents @ high temp.
O
R
Two figures removed for copyright reasons.
C
O
lipase
O
R'
+
H2O
R
C
OH
+
HO
In toluene at 90 °C
MW of the polyester is usually low (< 10 k).
Poor mechanical properties.
21
Brzozowski, et al., Nature 1991, 351, 491
R'