Biodegradable Polymer

Matrix Nanocomposites

For Tissue Engineering

Anand Singh 09MT3904

Nandan Kumar 09MT1027

Piyush Verma 09MT3018

Department of Metallurgical and

Materials Engineering

IIT Kharagpur

Tissue Engineering

• Use of cells to repair the damaged biological tissue, leaving only

natural substances to re-establish organ function.

• Challenge: appropriate design and fabrication of porous,

biodegradable, and biocompatible scaffolds.

What are Scaffolds?

• Cells are often implanted or 'seeded' into an artificial structure

capable of supporting 3-D tissue formation called Scaffolds.

• Scaffolds act as substrate for cellular growth, proliferation, and

support for new tissue formation.

Biomaterials

• Materials used for tissue engineering applications must be designed

to stimulate specific cell response at molecular level.

• Characteristics: Direct cell attachment, proliferation, differentiation,

and extracellular matrix production and organization.

Objective

• Fundamental requirements of biomaterials:

i. biocompatible surfaces

ii. favourable mechanical properties.

• Conventional single-component polymer materials cannot satisfy

these requirements.

• Multi-component polymer systems

Why Nanotechnology?

• Biological components, such as DNA, involve nano-dimensionality,

hence it has logically given rise to the interest in using

nanomaterials for tissue engineering.

• Enables the development of new systems that mimic the complex,

hierarchical structure of the native tissue.

• Nanomaterials have inherent high surface area-volume ratio

• Available polymeric porous scaffolds revealed insufficient stiffness

and compressive strength

Nanocomposites

• Nanocomposite materials often show an excellent balance between

strength and toughness

• Major Factor: Interface adhesion between nanoparticles and

polymer matrix

• Mechanical properties are dependant on

i. properties of the matrix

ii. properties and distribution of the fillers

iii. interfacial bonding

iv. synthesis or processing methods

• Surface modification of nanostructures is needed to promote better

dispersion of fillers and to enhance the interfacial adhesion.

Polymer Matrices For Bio-nanocomposites

• Polymers are the primary materials for scaffold fabrication

• Major Types:-

1) Natural-based materials: Biological recognition, poor mechanical

properties, limited in supply, costly. Eg. Polysaccharides (starch,

alginate, chitin/chitosan, hyaluronic acid derivatives) or proteins

(soy, collagen, fibrin gels, silk)

2) Synthetic polymers: relatively good mechanical strength, shape

and degradation rate can be easily modified, surfaces are

hydrophobic, lack of cell-recognition signals. Eg. Poly(lactic acid)

(PLA), poly(glycolic acid) (PGA), poly(3-caprolactone) (PCL), poly

(hydroxyl butyrate) (PHB)

Nanostructures For Bio-nanocomposites

Hydroxyapatite (HA)

• Hydroxyapatite (Ca10(PO4)6(OH)2) is the major mineral component

(69% wt.) of human hard tissues

• It possesses excellent biocompatibility with bones, teeth, skin and

muscles

• Promotes faster bone regeneration, and direct bonding to

regenerated bone without intermediate connective tissue.

• Problems:

i. brittleness of the HA

ii. lack of interaction with polymer

Contd..

Metal nanoparticles

• Nanoparticles of noble metals exhibit significantly distinct physical,

chemical and biological properties from their bulk counterparts

• Their electromagnetic, optical and catalytic properties of noble-metal

nanoparticles such as gold, silver and platinum, are strongly

influenced by shape and size

• Aim: To obtain small particle sizes, narrow size distributions and

well-stabilized metal particles.

• Silver (Ag) has been known to have a disinfecting effect and has

been commercially employed as antimicrobial agent.

• Problem: They are easily aggregated because of their high surface

free energy, and they can be oxidized or contaminated in air.

Contd..

Carbon nanostructures

• Fullerenes, carbon nanotubes (CNTs), carbon nanofibres (CNFs),

graphene and a wide variety of carbon related forms.

• Regular geometry gives CNT excellent mechanical and electrical

properties.

• By dispersing a small fraction of carbon nanotubes into a polymer,

significant improvements in the composite mechanical strength have

been observed.

a) Covalent Functionalization: Fluorine, radicals, amine groups, etc. are

attached to the CNT sidewall, play a determinant role in the mechanism of

interaction with cells.

b) Non-covalent attachment: SWCNTs is not damaged and their properties

remain intact, forces between the polymer and the SWCNTs are very weak

Processing Techniques

Electrospinning:

Contd..

• Electrospun using a high voltage power supply at 20 kV potential

between the solution and the grounded surface

• The PLLA/HA mixture was loaded in a 20mL glass syringe equipped

with a blunt 23 gauge needle

• The ground collector (9 cm in diameter) located at a fixed distance

of 15 cm from the needle.

• The flow rate of the solution and the spinning time were set to

0.85mL/h and 8 h, respectively

Contd..

Foaming Technology:

• Objective - To produce porous structure in matrix.

• Material used to produce porosity-Supercritical CO₂

• Matrix – Poly Lactic Acid (PLA)

• Reinforcement – Nano Hydroxy Apatite (nHA)

PLA Hydroxy Apatite

Contd..

Why PLA?

• Biodegradable

(Gradually transforms loads to the bone as organ heals)

(Medical implants in the form of screws, pins, rods, and as a mesh)

Why supercritical CO₂ ?

• Non-toxic, non- flammable , noncorrosive, abundant, inexpensive, commercially available in high

purity, and readily accessible supercritical conditions ( Critical Temperature = 31.1˚C and Critical

pressure = 7 37MPa)

Why nHA ?

• Nanocrystalline HA (nHA) enhances osteoblast adhesion and surface deposition of calcium-

containing materials. (with respect to Bone-tissue growth).

• Inorganic calcium-containing constituent of bone matrix and teeth, imparting rigidity to these

structures

Contd..

Steps involved:

• Firstly amorphous or semi-

crystalline polymer is saturated with

CO₂ at temperature 31.1 and

pressure 7.37 Mpa, with the

diffusion of gas into polymer matrix,

it forms single-phase polymer/CO₂solution.

• When the equilibrium is reached,

pressure is reduced or temperature

is increased or both, so that the

supercritical CO₂ turns into gas and

escape out of the polymer leaving

pores

Contd..

Applications

• Fracture fixation

• Interference Screws

• Meniscus Repair

• Suture anchors

• Suture coating

• Dental and orthopedic implants

• Drug delivery

References

• Z.C.Xing, S.J.Han, Y.S.Shin and I.K.Kang, Fabrication of

Biodegradable Polyester Nanocomposites by Electrospinning for

Tissue Engineering, Journal of Nanomaterials, v 2011, pp 1-18

• X.Shi, J.L.Hudson, P.P.Spicer, J.M.Tour, R.Krishnamoorti and

A.G.Mikos, Injectable Nanocomposites of Single-Walled Carbon

Nanotubes and Biodegradable Polymers for Bone Tissue

Engineering, Journal of Biomacromolecules, v 7, 2006, pp 2237-

2242

• Xia Liao, Haichen Zhang, and Ting He, Preparation of Porous

Biodegradable Polymer and Its Nanocomposites by Supercritical

CO2 Foaming for Tissue Engineering, Journal of Nanomaterials,

Volume 2012, Article ID 836394, pp 1-12.

Thank You