Micro/Nanoporous Micro/Nanoporous Scaffolds for Tissue Scaffolds for Tissue

Engineering Engineering ApplicationsApplications

Department of Chemical Engineering and Department of Chemical Engineering and Materials ScienceMaterials Science

Amrita School of EngineeringAmrita School of Engineering

Coimbatore – 641 105Coimbatore – 641 105

October 2008October 2008

Zeroth ReviewZeroth Review

ByBy

Divya Haridas (CB105PE012)Divya Haridas (CB105PE012)

Karthikeyan G (CB105PE023)Karthikeyan G (CB105PE023)

Krishna Priya C (CB105PE025)Krishna Priya C (CB105PE025)

Premika G (CB105PE028)Premika G (CB105PE028)

GuideGuide

Dr. Murali Rangarajan. Ph.DDr. Murali Rangarajan. Ph.D

Co-GuideCo-Guide

Dr. Nikhil K Kothurkar. Ph.DDr. Nikhil K Kothurkar. Ph.D

Motivation of Tissue Motivation of Tissue EngineeringEngineering

… … Today around 80000 Indians are waiting for Today around 80000 Indians are waiting for Organ / Tissue TransplantationOrgan / Tissue Transplantation

Many children suffer from crippling diseases and Many children suffer from crippling diseases and deformities deformities

Current therapies like bone grafting has many Current therapies like bone grafting has many limitations limitations additional cost of the harvesting procedureadditional cost of the harvesting procedure pain and infection at the harvesting sitepain and infection at the harvesting site

Concept of Tissue EngineeringConcept of Tissue Engineering

Life science and Life science and Engineering dealing Engineering dealing with the with the development of development of biological biological substitutes that substitutes that restore, maintain restore, maintain and improve tissue and improve tissue functions or a whole functions or a whole organorgan

Polymeric ScaffoldsPolymeric Scaffolds Three dimensional Three dimensional

scaffolds play important scaffolds play important roles as extracellular roles as extracellular matrices onto which matrices onto which cells can attach, grow, cells can attach, grow, and form new tissuesand form new tissues

Modeling, design and Modeling, design and fabrication of scaffolds fabrication of scaffolds are always a difficult are always a difficult task in the regenerative task in the regenerative tissue engineeringtissue engineering

Scaffolds – Bone FormationScaffolds – Bone Formation

Scaffold ConsiderationsScaffold Considerations

Matrix Material CharacteristicsMatrix Material Characteristics Bioactive and Biocompatible Bioactive and Biocompatible

Slow degradabilitySlow degradability For stable scaffold morphologyFor stable scaffold morphology For homogeneity of new tissuesFor homogeneity of new tissues

High Porosity & interconnectivityHigh Porosity & interconnectivity To minimize the amount of implanted polymer To minimize the amount of implanted polymer To increase specific surface area for cell attachment & To increase specific surface area for cell attachment &

tissue in growthtissue in growth

Scaffold ConsiderationsScaffold Considerations

Pore Size Pore Size 150 – 500 150 – 500 µµm for bones, < 50 m for bones, < 50 µµm for organsm for organs

3D Pore architecture3D Pore architecture Allows for cell attachment , proliferation and Allows for cell attachment , proliferation and

differentiationdifferentiation Provides pathways for bio-fluids Provides pathways for bio-fluids Pore architecture influences mechanical strengthPore architecture influences mechanical strength

Tailoring possibilities Tailoring possibilities Controllable pore size, porosityControllable pore size, porosity Control of matrix designControl of matrix design

Fabrication TechniquesFabrication Techniques

Electrospinning - Electrospinning - High voltage electrostatic field is High voltage electrostatic field is applied to polymer solution to form non-woven scaffold applied to polymer solution to form non-woven scaffold fibersfibers

Solid Freeform Fabrication - Solid Freeform Fabrication - 3D scaffold is constructed 3D scaffold is constructed from 2D layers (CAD/CAM methodologies) using 3D from 2D layers (CAD/CAM methodologies) using 3D positioning system and extrusion headpositioning system and extrusion head

Fiber Bonding - Fiber Bonding - Polymer fibers are immersed in polymer Polymer fibers are immersed in polymer solution. On heating, the fibers weld together and polymer solution. On heating, the fibers weld together and polymer melts and fills the voids. Removal of polymer results in melts and fills the voids. Removal of polymer results in porous scaffoldporous scaffold

Fabrication TechniquesFabrication Techniques

Phase Separation - Phase Separation - A homogeneous multi-component A homogeneous multi-component system phase separates (polymer rich - polymer lean system phase separates (polymer rich - polymer lean phase) under certain conditions. Removal of solvent results phase) under certain conditions. Removal of solvent results in solidification of polymer rich phase which forms porous in solidification of polymer rich phase which forms porous scaffoldscaffold

Solvent Casting and Particulate Leaching - Solvent Casting and Particulate Leaching - Polymer Polymer solution is cast into the particle assembly (salt, paraffin). solution is cast into the particle assembly (salt, paraffin). Vacuum is applied to evaporate the solvent. Particles are Vacuum is applied to evaporate the solvent. Particles are leached using solvent. Pore architecture resembles the leached using solvent. Pore architecture resembles the particles particles

Technique Advantages Disadvantages

ElectrospinningGood mechanical

strength, highly porous structure

Costly process, poor control over internal

architecture

Solid Freeform Fabrication

Good mechanical strength, solvent free

High processing temperature

Fiber Bonding High porosityLimited range of

polymer, Residual solvent, lack mechanical

strength

Phase SeparationHighly porous

structure, permit incorporation of bioactive agents

Poor internal architecture, limited range of pore size

Solvent Casting/Particulate

Leaching

Large range of pore size, good control of

porosity and pore size

Poor control over internal architecture

Focus of the ProjectFocus of the Project

Preparation of Scaffold from the feasible Preparation of Scaffold from the feasible Fabrication TechniqueFabrication Technique

Incorporation of Hydroxyapatite for Bone Tissue Incorporation of Hydroxyapatite for Bone Tissue Engineering ApplicationEngineering Application

Characterization of Fabricated ScaffoldsCharacterization of Fabricated Scaffolds

Modeling and Simulation of HAp incorporated Modeling and Simulation of HAp incorporated ScaffoldsScaffolds

MethodologyMethodology

Step 1Step 1

Identification of Fabrication MethodIdentification of Fabrication Method

The Particulate Leaching method is identified The Particulate Leaching method is identified through Literature Survey during August – through Literature Survey during August – September 2008 by considering the constraints September 2008 by considering the constraints like do-ability in the Institution, with limited like do-ability in the Institution, with limited financial resources, in limited timefinancial resources, in limited time

MethodologyMethodology

Step 2Step 2

Fabrication of Scaffolds by Particulate Leaching Fabrication of Scaffolds by Particulate Leaching TechniqueTechnique

Preparation of Solid Paraffin

Spheres

Ma PX, Ji-Won Choi. Biodegradable Polymer Scaffolds with Well Defined Interconnected Spherical Pore Network. Tissue Engineering 2001;7(1):23-33.

MethodologyMethodology

Step 2Step 2

Fabrication of Scaffolds by Particulate Leaching Fabrication of Scaffolds by Particulate Leaching TechniqueTechnique

Preparation ofPolymer Foam

Ma PX, Ji-Won Choi. Biodegradable Polymer Scaffolds with Well Defined Interconnected Spherical Pore Network. Tissue Engineering 2001;7(1):23-33.

MethodologyMethodology

Step 3Step 3

Incorporation of Hydroxyapatite and fabricating Incorporation of Hydroxyapatite and fabricating ScaffoldsScaffolds

The major mineral phase in the bone is The major mineral phase in the bone is Hydroxyapatite. Incorporating them in Polymer Hydroxyapatite. Incorporating them in Polymer Scaffolds offers bone regeneration potentialScaffolds offers bone regeneration potential

Literature Survey on HAp incorporation in Literature Survey on HAp incorporation in Polymeric Scaffolds and its fabricationPolymeric Scaffolds and its fabrication

MethodologyMethodology

Step 4Step 4

CharacterizationCharacterization

Density Density PorosityPorosity Morphology to be studied using SEMMorphology to be studied using SEM Compressive Modulus using a Mechanical TesterCompressive Modulus using a Mechanical Tester

MethodologyMethodology

Step 5Step 5

Modeling and SimulationModeling and Simulation

To study the kinetics of Hydroxyapatite (HAp) To study the kinetics of Hydroxyapatite (HAp) incorporationincorporation

Physical /chemical absorption of HApPhysical /chemical absorption of HAp

Resulting morphology changes in scaffoldResulting morphology changes in scaffold

Project CalendarProject Calendar

Aug

Sep Oct Nov

Dec Jan Feb Mar

Apr

Literature Survey

Materials Purchase

Experimental Process

HAp Incorporation

Characterization

Modeling and Simulation

Final Report

Thank youThank you