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Liu Nanobionics Lab



       Biomaterials
       Tissue Engineering
       Nanotechnology
Biomaterials
   Biomaterials encompasses aspects of
    medicine, biology, chemistry,
    engineering and materials science.
   Biomaterials are : “Non-viable
    materials used in a medical devices
    intended to interact with biological
    systems” [D.F. Williams, 1987]
Human Tissue Damage
   Disease (e.g cancer, infection, degenerative
    diseaes).
   Trauma (e.g accidental, surgery).
   Congenital abnormalities (e.g birth defects).

   Current clinical treatment based on:
    Grafts and Transplants

Artificial Biomaterials
   Tissue loss as a result of injury or
    disease, in an increasing ageing
    population, provides reduced quality
    of life for many at significant
    socioeconomic cost.

   Thus a shift is needed from tissue
    replacement to tissue regeneration by
    stimulation the body’s natural
    regenerative mechanisms.
Biomaterials: Examples
   Joint replacements
   Bone plates
   Bone cement
   Hip Joint
   Artificial ligaments
    and tendons
   Dental implants for    Heart valve   Hip joint
    tooth fixation
   Blood vessel
    prostheses
   Heart valves
   Skin repair devices
   Cochlear
    replacements           Knee joint       Skin
   Contact lenses
Biomaterials
   Prostheses have significantly
    improved the quality of life for
    many ( Joint replacement, Cartilage
    meniscal repair, Large diameter
    blood vessels, dental)

   However, incompatibility due to
    elastic mismatch leads to
    biomaterials failure.
Tissue Engineering
   National Science Foundation first defined
    tissue engineering in 1987 as “ an
    interdisciplinary field that applies the
    principles of engineering and the life
    sciences towards the development of
    biological substitutes that restore,
    maintain or improve tissue function”
Tissue engineering
   Potential advantages:
    unlimited  supply
    no rejection issues

    cost-effective
Tissue Engineering
                                        Expand number in culture


                                                                   Remove cells from the
                                                                   body.
Seed onto an appropriate
scaffold with suitable growth
factors and cytokines



                                                                       Re-implant engineered
                                                                       tissue repair damaged
                                                                       site

                          Place into culture
 SCAFFOLDS
Synthetic polymers
   More controllable from a
    compositional and materials
    processing viewpoint.

   Scaffold architecture are widely
    recognized as important parameters
    when designing a scaffold

   They may not be recognized by cells
    due to the absence of biological
    signals.
Natural polymers
   Natural materials are readily
    recognized by cells.



   Interactions between cells and
    biological materials are catalysts to
    many critical functions in tissues

   These materials have poor
    mechanical properties.
Tissue engineering scaffold:
Self-assembly
   Self-aggregation of
    hydrophilic, lipophilic
    groups
   First layer creates
    template for growth of
    second layer
   Ions can be deposited on
    charged sites
   This kind of self-
    aggregation leads to
    ordered, heirarchical
    structures
Supramolecular Chemistry




http://www.chm.bris.ac.uk/webprojects2003/lee/supra1.jpg
Tissue engineering scaffold:
    controlled architecture




Featured with:
Pre-defined channels;
with highly porous
structured matrix;
With suitable chemistry
for tissue growth –
Collagen or HA
No toxic solvent involved,
it offers a strong potential
to integrate cells/growth
factors with the scaffold
fabrication process.
Architecture of Hard Tissue
   Staggered mineral platelets
    (hydroxyapataite) embedded in a
    collagen matrix

   Arrangement of platelets in
    preferred orientations makes
    biocomposites intrinsically
    anisotropic

   Under an applied tensile stress,
    the mineral platelets carry most
    of the tensile load

   Protein matrix transfers the load
    between mineral crystals via
    shear

   Biocomposites can be described
    through tension-shear model
    described by Ji et. al.
Tissue engineering scaffold:
          Electrospinning




   This process involves the ejection of a charged polymer fluid onto an oppositely
    charged surface.
   Multiple polymers can be combined
   Control over fiber diameter and scaffold architecture
Printing Techniques for Tissue Engineering
Techniques to study scaffolds:
      Scanning Probe Microscopy
   Atomic Force
    Microscopy :Surface
    irregularities

   Scanning Tunneling
    Microscopy:
    Conducting Surfaces

   Adhesion Force
    Microscopy:
    Functionalised tips
Surface Modification of Biomaterials
Enhanced intrinsic biomechanical properties of osteoblastic
    mineralized tissue on roughened titanium surface




       Nano-indentation

       Acid-etched vs. Machined
        surfaces

       culturing osteoblasts on
        rougher titanium surfaces
        enhances hardness and
        elastic modulus of the
        mineralized tissue
Surface modification of SPU


           Segmented Polyurethane
            – common biocompatible
            elastomer

           2-methacryloyloxyethyl
            phosphorylcholine added
            to create nano-domains
            on surface

           Nano-scale domains
            reduce platelet adhesion
            to biomaterial surface




Nano-scale surface modification of a segmented polyurethane with a phospholipid polymer, Biomaterials 25 (2004) 5353–5361
Protecting Bionic Implants
Immunoisolation for Cell-encapsulation
         therapy
   Liver Dysfunction: Encapsulation of
    Hepatic Cells

   Pancreas Dysfunction: Encapsulation of
    Islets of Langerham

   Disorders of the CNS: Parkinson’s,
    Alzheimer’s

   Pre-requisites for cell encapsulation

        continued and optimal tissue/cell
         supply
        maintenance of cell viability and
         function
        successful prevention of immune
         rejection

   Nanoporous Silicone-based biocapsules
    serves as Artificial Pancreas(Desai et
    al. 2001)

   What are the drawbacks of such an
    artificial pancreas?
Nanoengineering Bio-analogous
Structures

   Bone-cartilage
    composite ?

   Muscle ?

   Brain-machine
    Interface ?
An Ink-Jet Printer for Tissue Engineering?

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Liu Nanobionics Lab: Tissue Engineering and Biomaterials Research

  • 1. Liu Nanobionics Lab Biomaterials Tissue Engineering Nanotechnology
  • 2. Biomaterials  Biomaterials encompasses aspects of medicine, biology, chemistry, engineering and materials science.  Biomaterials are : “Non-viable materials used in a medical devices intended to interact with biological systems” [D.F. Williams, 1987]
  • 3. Human Tissue Damage  Disease (e.g cancer, infection, degenerative diseaes).  Trauma (e.g accidental, surgery).  Congenital abnormalities (e.g birth defects).  Current clinical treatment based on: Grafts and Transplants Artificial Biomaterials
  • 4. Tissue loss as a result of injury or disease, in an increasing ageing population, provides reduced quality of life for many at significant socioeconomic cost.  Thus a shift is needed from tissue replacement to tissue regeneration by stimulation the body’s natural regenerative mechanisms.
  • 5. Biomaterials: Examples  Joint replacements  Bone plates  Bone cement  Hip Joint  Artificial ligaments and tendons  Dental implants for Heart valve Hip joint tooth fixation  Blood vessel prostheses  Heart valves  Skin repair devices  Cochlear replacements Knee joint Skin  Contact lenses
  • 6. Biomaterials  Prostheses have significantly improved the quality of life for many ( Joint replacement, Cartilage meniscal repair, Large diameter blood vessels, dental)  However, incompatibility due to elastic mismatch leads to biomaterials failure.
  • 7. Tissue Engineering  National Science Foundation first defined tissue engineering in 1987 as “ an interdisciplinary field that applies the principles of engineering and the life sciences towards the development of biological substitutes that restore, maintain or improve tissue function”
  • 8. Tissue engineering  Potential advantages: unlimited supply no rejection issues cost-effective
  • 9. Tissue Engineering Expand number in culture Remove cells from the body. Seed onto an appropriate scaffold with suitable growth factors and cytokines Re-implant engineered tissue repair damaged site Place into culture
  • 11. Synthetic polymers  More controllable from a compositional and materials processing viewpoint.  Scaffold architecture are widely recognized as important parameters when designing a scaffold  They may not be recognized by cells due to the absence of biological signals.
  • 12. Natural polymers  Natural materials are readily recognized by cells.  Interactions between cells and biological materials are catalysts to many critical functions in tissues  These materials have poor mechanical properties.
  • 13.
  • 14.
  • 15.
  • 16.
  • 17.
  • 18.
  • 19. Tissue engineering scaffold: Self-assembly  Self-aggregation of hydrophilic, lipophilic groups  First layer creates template for growth of second layer  Ions can be deposited on charged sites  This kind of self- aggregation leads to ordered, heirarchical structures
  • 21. Tissue engineering scaffold: controlled architecture Featured with: Pre-defined channels; with highly porous structured matrix; With suitable chemistry for tissue growth – Collagen or HA No toxic solvent involved, it offers a strong potential to integrate cells/growth factors with the scaffold fabrication process.
  • 22. Architecture of Hard Tissue  Staggered mineral platelets (hydroxyapataite) embedded in a collagen matrix  Arrangement of platelets in preferred orientations makes biocomposites intrinsically anisotropic  Under an applied tensile stress, the mineral platelets carry most of the tensile load  Protein matrix transfers the load between mineral crystals via shear  Biocomposites can be described through tension-shear model described by Ji et. al.
  • 23. Tissue engineering scaffold: Electrospinning  This process involves the ejection of a charged polymer fluid onto an oppositely charged surface.  Multiple polymers can be combined  Control over fiber diameter and scaffold architecture
  • 24. Printing Techniques for Tissue Engineering
  • 25. Techniques to study scaffolds: Scanning Probe Microscopy  Atomic Force Microscopy :Surface irregularities  Scanning Tunneling Microscopy: Conducting Surfaces  Adhesion Force Microscopy: Functionalised tips
  • 26. Surface Modification of Biomaterials
  • 27. Enhanced intrinsic biomechanical properties of osteoblastic mineralized tissue on roughened titanium surface  Nano-indentation  Acid-etched vs. Machined surfaces  culturing osteoblasts on rougher titanium surfaces enhances hardness and elastic modulus of the mineralized tissue
  • 28. Surface modification of SPU  Segmented Polyurethane – common biocompatible elastomer  2-methacryloyloxyethyl phosphorylcholine added to create nano-domains on surface  Nano-scale domains reduce platelet adhesion to biomaterial surface Nano-scale surface modification of a segmented polyurethane with a phospholipid polymer, Biomaterials 25 (2004) 5353–5361
  • 30. Immunoisolation for Cell-encapsulation therapy  Liver Dysfunction: Encapsulation of Hepatic Cells  Pancreas Dysfunction: Encapsulation of Islets of Langerham  Disorders of the CNS: Parkinson’s, Alzheimer’s  Pre-requisites for cell encapsulation  continued and optimal tissue/cell supply  maintenance of cell viability and function  successful prevention of immune rejection  Nanoporous Silicone-based biocapsules serves as Artificial Pancreas(Desai et al. 2001)  What are the drawbacks of such an artificial pancreas?
  • 31. Nanoengineering Bio-analogous Structures  Bone-cartilage composite ?  Muscle ?  Brain-machine Interface ?
  • 32. An Ink-Jet Printer for Tissue Engineering?