Bioactive Polymeric Composites Humberto Palza Departamento de Ingenieria Quimica y Biotecnologia, Facultad de Ciencias Físicas y Matemáticas, Universidad de Chile, Santiago, Chile.

Laboratory of Polymer Engineering Universidad de Chile

Dr. R. Quijada

Tailoring short chain branching 100 nm

Nanopartícles

Synthesis of novel fillers

Dr. H. Palza

Tacticity control in PP

Polyolefin synthesis via catalysis

Development of Novel Polymeric Materials Composites (melt and in-situ)

- Biomaterials - Conductive polymers - Structural appl. Applications - Packaging - Recycle

1 um 20 um

-Polyethylene -Polypropylene -Polyamides -etc

10 nm

Arcillas

Nanotubos de Carbono

Fillers: -Metallic particles (Cu, CuO) -Silices -Biomaterials -Carbon nanotubes - Grafites

Laboratory of Polymer Engineering Dr. R. Quijada

Mechanical

Universidad de Chile

Morphological

Thermal

Dr. H. Palza

Chemical recycle

Characterization Antimicrobial

Processing

Fundamental and Applied Research

Thermal stability

Rheological

Barrier Properties

Electrical

Laboratory of Polymer Engineering Dr. R. Quijada

Universidad de Chile

Dr. H. Palza

The concept: Reactor Engineering Catalyst

Filler Characterization

Pyrolisis

Catalyst

Processing

The General idea I: Synthesis

PP Copolymer

Atactic PP

Isotactic PP

Olefins + Catalytic System

Polar copolymers

cyclic olefin copolymers (COC)

Syndiotactic PP

PE Copolymer

Lineal PE

Micro-structure

Branching PE

Properties

The General idea II: Nanocomposites Natural Clay

Melt

+ In-situ Carbon based materials (CNT and graphites)

Silica Nanoparticles

Copper Nanoparticles

Polymer

What properties we can modify?

Tailor-made materials?

The General idea II: Nanocomposites 400

Polypropylene Antimicrobial

t50% [min]

300

Copper

200 100 0 0

5

10 15 CNP [vol %]

20

-3

10

Electrical Conductivity

-5

10

DC (S/cm)

CNT

-7

10

-9

10

-11

10

-13

10

Clay

Mechanical reinforcement

0

2

4 6 8 MWNT (wt%)

10

12

Introducción: Datos (1)

Poliolefinas: polietileno y polipropileno

Introducción: Datos (2) Poliolefinas

Introduction: Why this extraordinary growth?

Control of Microestructure

Flexibility!!!!!!

Composites Polymer + Another Material of different nature

Nanocomposites sPP

iPP aPP

Short chain branching PP

Polymer + Nanoparticle

Copper: Why not to use copper as filler?

For what ?

Copper as Filler ? (1): Materials based on Copper inhibit and/or kill bacteria Steel

Several studies show that copper and its alloys are antibacterial.

Zinc

Bronze (Cu-Zn) Copper

The 2008 Environmental Protection Agency U.S. (EPA) approved the use of more than 260 copper alloys recognizing its antibacterial property.

Keevil et al. Journal of Hospital Infection (2006).

Copper also inhibits or kills other microorganisms such as virus, fungi, and algae, among others

Copper as Filler ? (2): Hospital Applications Faucets

Beds / Bed guardrails

Today Copper represents:

Sinks

Bathroom equipment

Tray tables

Push plates

Door knobs

Carts

IV Poles

Computer keyboards

The world`s most effective antimicrobial touch surface material www.cobrebactericida.org

Why Copper is biocide?

a) Radicales:Reacción tipo Fenton: Cu+ + H2O2 → Cu2+ + OH– + •OH–

b) Iones cobre: En presencia de agua y oxígeno, por mecanismos de corrosión: 2Cu + H2O  Cu2O + 2H+ +2e-

Daño en la membrana celular : permeabilidad de la membrana celular. Daño en DNA: interactúa con el ADN previniendo la reproducción

Cu2O + 2H+  2Cu+2 + H2O +2eCu2O + H2O  2Cu+2 + 2OH- +2e-

The idea:

Polymer

Copper Nanoparticles

Polymeric Nano

Antimicrobial Plastic Material

Polypropylene/Copper (1): 10 nm copper nanoparticles

160 nm

Polymeric Composite

No evidence about oxidation processes on the particle during the processing

Polypropylene/Copper (2): After 90 minutes of contact, the composites eliminated the bacterial growth (E. coli) depending on the amount of copper 0%

Bacterial colony

5%

1%

10 %

20 %

Macromol. Rapid Comm. 31: 563, 2010.

Polypropylene/Copper (3): 400

t50: needy time to eliminate 50% of bacteria

8

10

300

10

t50% [min]

CFU/ml

7

6

10

0 vol % 1 vol% 5 vol% 10 vol% 20 vol%

5

10

0

50

100 0

4

10

200

100 150 Time [min]

200

250

0

5

10 15 CNP [vol %]

20

The biocide behaviour can be tailored by the amount of filler

Composites with the highest incorporation kill or eliminate 99.9% of bacteria after just 4 hours of contact Macromol. Rapid Comm. 31: 563, 2010. Letters in Applied Microbiology.53;50-54, 2011

Polypropylene/Copper (3): Why copper particles embedded in a non-polar polymer matrix release ions?

vs Particles on the surface

Particles from the bulk

Evidence of copper particles on the surface was not detected by XPS

Copper

Copper particles in the bulk are responsable for the ion release!!!!! H. Palza, et al.Macromol. Rapid Comm. 31: 563, 2010.

0

Polypropylene/Copper (4): X-ray difractions

Oxide layer

Original Composite Composite after 100 days submerged in water

50

60 º

70

80 Cu2O

Cu

+ Water + Oxygen

Cu

Corrosion process!!!

Cu2O

Water and oxigen molecules are able to go through the composite and oxidate the metallic copper particles in the bulk of the material

Polypropylene/Copper (5): 1) Water and oxygen molecules diffuse through the polymeric composite water H2O + O2

nanoparticles/polymer

Cu+2

2) Oxidation processes on the metallic copper surface (corrosion)

3) Release of copper ions from the oxide layer 4) Diffusion-out of ions to the water solution

4Cu + 2H2O  2Cu2O+ 4H+ + 4e2Cu2O + O2 CuO Cu2O + 1/2 O2 + 2H2O  2Cu+2 + 4OH-

Polypropylene/Copper (6): Estudio de citotoxicidad:

Efecto de la matriz: Alginato

células de corteza cerebral de ratón

Imágenes de Microscopio de Fluorescencia Ensayo Live/Dead para células UCHT1 para I) Polipropileno Blanco, (II) Polipropileno con 10% de NPCu, (III) Polipropileno con 20% de NPCu, (IV) Polybond con 50% de NPCu. a- Fluorescencia Verde para células vivas; b- Fluorescencia Roja para células muertas.

Polypropylene/Copper Oxide(1):

Particles 200 nm

Composites 1 µm

Polypropylene/Copper Oxide(2): Actividad Antibacterial de PP/NPCu y PP/NPCuO. Conteo de Colonias Bacterianas Bacteria E. Coli .(G-) 10

10

8

10

90%

CFU/ml

6

10

PP 5% vol NPCu 5% vol NPCuO

4

10

2

10

99.9% 0

10

0

100

200

Time [min]

300

Polyethylene/TiO2:

10 nm sol-gel nanoparticles

a

b

c

In-situ polymerization with a metallocene catalyt 1 m

1 m

500 nm

TEM images of PE/TiO2 Nps nanocomposite with (a) 5 wt% of TiO2Nps; and (b and c) with 5 wt% of Mod-TiO2Nps. P. Zapata et al. J. Polymer Science: Chemistry. In press 2012

Polyethylene/TiO2:

P. Zapata et al. J. Polymer Science: Chemistry. In press 2012

Polypropylene/ceramic: Cerámicos bioactivos: – SiO2-CaO-P2O5, en proporciones similares al mineral del hueso humano. – Para un enlace con el hueso, se debe formar una capa superficial de apatita biológicamente activa (Ca10(PO4)6(OH)2) en la interface material/hueso. – Los cerámicos bioactivos por sol-gel presentan mayor bioactividad (formación HA).

http://www.rsc.org/education/eic/issues/2006nov/glassbones.asp

Polypropylene/ceramic: Infecciones centradas en el implante

 El factor esencial en la evolución y persistencia de la infección es la formación de biopelículas bacterianas en la superficie del implante.

N engl j med, 350;14, 2004. Current Medicinal Chemical , 2005, 12, 2163-2175

Ceramic particles: Síntesis Sol-Gel de los Biovidrios a partir de TEOS Comp. Biovidrio (%mol)

Nombre

SiO2

CaO

P2O5

Ag2O

CuO

SiO2 - P2O5 - CaO

BG

64%

26%

10%

-

-

SiO2 - P2O5 - CaO - Ag2O

AgBG

64%

26%

5%

5%

-

SiO2 - P2O5 - CaO - CuO

CuBG

64%

26%

5%

-

5%

Superficie especifica BET: 260 m2/g

Material

d50% [µm]

BG

115

AgBG

95

CuBG

104

- arrow in BG shows the peak related with Ca(SiO4) crystals; - arrows in CuBG2 show the peaks related with CuO crystals; - arrows in AgBG2 show: Ag (letter a); Ag2CO3 (letter b); SiP2O/SiO2-P2O5 (letter c) and AgO (letter d) crystals.

Ceramic particles: Biocompatibilidad partículas in vitro después de 14 días en SBF

The arrows indicate the characteristic peaks of polycrystalline hidroxy carbonate apatite

Scanning electron micrographs of: a) original BG sample; and b) BG; c) CuBG2 and d) AgBG2 samples immersed 10 days in SBF.

Ceramic particles: Partículas bioactivas y antimicrobianas Material

E.coli (24 h cultivo)

E. coli (48 h cultivo)

S. mutans (48 h cultivo)

BG [mg/mL]

>300

No ensayado

No ensayado

AgBG [mg/mL]

1–5

0,3 – 0,5

0,5 – 2

CuBG [mg/mL]

100 – 150

5 – 10

5 – 10

Concentración fostatos (ppm)

8 6 4 2 0

0

50

100 150 Tiempo (h)

200

250

Metal ion ppm/g de biovidrio

BG CuBG AgBG

10

CuBG AgBG

140 120 100 80 60 40 20 0

0

50

100 150 200 Tiempo (horas)

250

Polypropylene/ceramic: Original sample:

After 14 days inmersed in SBF-BG/PP:

PP BG/PP CuBG/PP AgBG/PP

Concentración fosforo (ppm)

10 8 6 4 2 0

0

50

100 150 Tiempo (h)

200

250

Metal ion ppm/g de compuesto

Polypropylene/ceramic: CuBG/PP AgBG/PP

6

4

2

0

0

50

100

150

200

250

Tiempo (horas)

Polypropylene/ceramic composites could promote the formation of HA and at the same time be antimicrobial

Polypropylene/ceramic: Estudio de citotoxicidad: Partículas: DMEM+ BG + CuBG + AgBG + Células CNh1 Células CNh1 Células CNh1 Células CNh1 100%

59,7%

23,5%

28,3%

Composito: DMEM+ PP+ BG/PP+ CuBG/PP+ AgBG/PP+ Células CNh1 Células CNh1 Células CNh1 Células CNh1 Células CNh1 100%

96,5%

99,5%

células de corteza cerebral de ratón

77,6%

86,4%

Agradecimientos:

Laboratorio de Terapia Celular Dr. Pablo Caviedes

Dr. Mario Diaz-Dosque Facultad de Odontología Universidad de Chile Dra. Paula Zapata Facultad de Química y Biología Universidad de Santiago

Estudiantes: Macarena Beltran (Ingeniería Química) Natalia Galarce (Ingeniería Química) Julian Bejarano (doctorado en Ciencias de los Materiales) Katherine Delgado (doctorado en Ciencias de los Materiales)