Lecture Biomaterials Surfaces: Chemistry Hydrolysis

Transcription

1 Lecture Biomaterials Surfaces: Chemistry ydrolysis Supporting notes 1

2 ydrolysis ydrolysis is a kind of Solvolysis, solvent + lysis: cleavage by the solvent. 2 + Br ydoloysis Br C 3 C 3 + Br Methanolysis C C + Br Formic acidolysis 2-Bromo-2-methyl propane 2

3 Polymer ydrolysis Polymers prepared by polycondensation can be susceptible to hydrolysis. n n + 1,4-Butanediol Succinic acid As, Zn catalysts, Δ +, -, or enzyme * * n + n2 Poly(butylene succinate), PBS 3

4 ydrolysable is degradable. Synthetic polymers Polyesters Polyamides Polyanhydrides Polyethers Polyurethanes Polycarbonates Polyureas Material properties can be tuned readily. Cheaper! Naturally-occurring polymers Proteins and polyamides Collagen Fibrinogen and fibrin Gelatin Casein Polysaccharides Cellulose Starch and amylose Chitin and chitosan Dextran Polynucleotides DNA and RNA 4

5 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 R C N R C R C Polyester Polyamide Polycarbonate R R R' C R C N P R' R" Polyanhydride Polyphosphazene Poly(ortho ester) Typical examples of synthetic biodegradable polymers 5

6 Key factors in hydrolysis 1. Bond stability Example: ydrolysis of polyester C δ + δ - Base-catalyzed polyester hydrolysis δ - δ + R C R' - R C - R' - R C R' + R C + R 6

7 Acid-catalyzed polyester hydrolysis δ R C R' δ + R C R' R C + R' R C + R' 2 R C R' R C + R Polyamide hydrolysis R C N R' 2 R C + 2 N-R 7

8 Key factors in hydrolysis 2. ydrophobicity 3. Molecular weight & architecture 4. Morphology Crystallinity, porosity 5. T g Mobility of polymer chain Chance to contact with 2 8

9 120 Amorphous PLLA Crystalline PLLA Θ a (degrees) Alkaline Treatment Time (h) Alkaline Treatment Time (h)

10 ydrolysable polymers Polyanhydride R C C R' 2 R C + C R' Polyester R C R' 2 R C + R' Polyamide R C N R' 2 R C + 2 N R' Polyether 2 R R' R + R' Polyether urethane R C N R' 2 R + C N R' Polyurea R N C N R' 2 R N C + 2 N R' Polycarbonate R C R' 2 R C + R' 11

11 Poly(sebacic anhydride) Properties: rapid degradation, T g : 50 C, T m : 80 C Uses: drug delivery matrices Table. alf-lives of hydrolyzable polymers Polymer class alf-life Polyanhydrides 0.1 h Incorporation of hydrophobic segment PLLA 3.3 years C C 3 6 C 8 16 Polyamides 83,000 years Poly(bis-(p-carboxyphenoxy)propane-co-sebacic anhydride) Göpferich, Biomater., 17, 103, 1996 Tabata et al., Pharm. Res., 10, 391,

12 Poly(glycolide-co-lactide) (polyglactide) Properties: rapid degradation, amorphous *, T g : C Uses: bioresorbable sutures, controlled release matrices, tissue engineering scaffolds * Depending on composition Glycolate (GA) Lactate (DL-LA) Dexon : the first synthetic bioresorbable suture in 1960s. (PGA) istological response can be predictable in comparison to nonsynthetic materials. igh-crystalline nature limits processability. 13

13 Poly(L-lactide), poly(l-lactic acid) (PLLA) Properties: rapid degradation, semicrystalline, T g : 60 C, T m : 180 C Uses: fracture fixation, ligament augmentation * PLLA D-glucose from agricultural product; corn, potato, rice Fermentation microorganisms e.g. Lactobacilli - 2 * * L-lactic acid - 2 * * PLLA L-lactide 14

14 Physical properties of various plastics PLLA PET PS PP Density/g/cm Tensile strength/mpa Yong s modulus/mpa Elongation@break/% Cost/$/lb *Polymeric materials were non-oriented (as prepared). Tsuji, Polylactic acid, JPS press, Kyoto, 1997, Ikada, Macromol. Rapid Commun., 21, 117,

15 Polyethylene oxide (PE) Properties: water soluble, semicrystalline, T g : -60 C, T m : 60 C Uses: hydrogel, protein-resistant coatings PE 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): Rate of hydrolysis: anhydride > ester >> amide >>>> ether etc. Matrices for drug delivery 16

16 ydrolysis of polymeric materials Acid- or base-catalyzed hydrolysis MW Time Enzymatic hydrolysis -surface erosion- MW Time 17

17 Application of biodegradable polymers and minimal requirements of biomaterials Minimal Requirements of Biomaterials Medical Application PDLLA PGA PGALA xidized cellulose PCA PPZ PE PAA yaluronate Collagen Fibrin PLLA Chitin PCL Starch Ecological Application PBS PES PEC PEA Cellulose PA (PB) 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 CW. PAA: PBS: PCA: PCL: PEA: PGA: PGALA: PDLLA: Poly(acid anhydride) PA: Poly(butylene succinate) PB: Poly(α-cyanoacrylate) PLLA: Poly(ε-caprolactone) Poly(ester amide) PE: Poly(glycolide), PEC: Poly(glycolic acid) PES: Poly(glycolide-co-lactide), Poly(glycolic acid-co-lactic acid) Poly(DL-lactide), Poly(DL-lactic acid) Poly(hydroxyalkanoate Poly(3-hydroxybutyrate) Poly(L-lactide), Poly(L-lactic acid) Poly(orthoester) Poly(ester carbonate) Poly(ethylene succinate) Application of Biodegradable Polymers Figure by MIT CW. 19

18 Enzymatic degradation -Lipase- Lipase: an esterase (EC ) stable in organic high temp. lipase R C R' + 2 R C + R' In toluene at 90 C MW of the polyester is usually low (< 10 k). Poor mechanical properties. Brzozowski, et al., Nature 1991, 351,