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Scaffolding Materials for Scaffolding Materials for Tissue EngineeringTissue Engineering

Parisa Bahrami, Hailun(Helen) HuangParisa Bahrami, Hailun(Helen) Huang

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ContentContent

•• What is tissue scaffoldingWhat is tissue scaffolding•• History of tissue scaffoldingHistory of tissue scaffolding•• Types of tissue scaffoldingTypes of tissue scaffolding•• Materials used in tissue scaffolding, such as Materials used in tissue scaffolding, such as

metallic, polymers, natural materials and metallic, polymers, natural materials and etc.etc.

•• Future directionFuture direction•• ReferencesReferences

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What is tissue scaffolding?What is tissue scaffolding?

A permanent or temporary support to the A permanent or temporary support to the damaged tissues/organ until the damaged tissues/organ until the functionalities are restored. functionalities are restored. Used for reconstruction of skin, bone, Used for reconstruction of skin, bone, cartilage, enamel, dentin and periodontal cartilage, enamel, dentin and periodontal ligaments and even nerves, heart valves, ligaments and even nerves, heart valves, liver and bladder.liver and bladder.

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What is tissue scaffolding?What is tissue scaffolding?Example:

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History of Tissue ScaffoldingHistory of Tissue Scaffolding

2000 BC: reconstruction using gold in cranial 2000 BC: reconstruction using gold in cranial defectsdefects17th 17th century: using wood in making artificial century: using wood in making artificial legslegs1660s: tissue grafting1660s: tissue graftingIt was only during the last four decades the use It was only during the last four decades the use of materials in tissue scaffolding gained of materials in tissue scaffolding gained attention. attention.

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Types of tissue scaffoldingTypes of tissue scaffolding

Temporary: degrade over a period of time Temporary: degrade over a period of time with the regeneration of the organ or with the regeneration of the organ or tissue. useful especially in case of young tissue. useful especially in case of young patients patients Permanent: retain their shape and Permanent: retain their shape and strength through the process of strength through the process of regeneration/repair of the organ used regeneration/repair of the organ used older patients older patients

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Structure of scaffolds in generalStructure of scaffolds in generalAn interconnected, open pore network for passing An interconnected, open pore network for passing nutrients and cells to scaffold while ensuring waste nutrients and cells to scaffold while ensuring waste products can get out.products can get out.Mechanical properties close to the natural tissue.Mechanical properties close to the natural tissue.The scaffold must have a surface chemistry suitable for The scaffold must have a surface chemistry suitable for cell attachment and growth. cell attachment and growth. A scaffold material mustA scaffold material mustbe easily processed into be easily processed into a variety of shapes and sizes a variety of shapes and sizes

Pores can take different forms

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Some Techniques in Production of Some Techniques in Production of ScaffoldsScaffolds

•• Salt leaching technique: Salt leaching technique: -- salt crystals are put into a mold salt crystals are put into a mold

-- polymer is poured over the salt polymer is poured over the salt

-- polymer is hardened polymer is hardened

-- the salt is removed by dissolving it the salt is removed by dissolving it in a solvent in a solvent

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Some Techniques in Production of Some Techniques in Production of ScaffoldsScaffolds

•• Polymer foaming: Polymer foaming: --Polymer is stirred rapidly to create Polymer is stirred rapidly to create a foam.a foam.

--Polymer is Polymer is hardened, creating a hardened, creating a solid spongesolid sponge--like material.like material.

--FoamFoam’’s air bubbles form the pores s air bubbles form the pores of the final scaffold.of the final scaffold.

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Some Techniques in Production of ScaffoldsSome Techniques in Production of Scaffolds

•• Ink jet printing: Ink jet printing: --use of use of modified desktop printers filled with modified desktop printers filled with "thermo"thermo--reversible" gel instead of ink. reversible" gel instead of ink.

--printing alternate layers of the gel onto glass printing alternate layers of the gel onto glass slides, 3D structures such as tubes can be slides, 3D structures such as tubes can be

built upbuilt up

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Some Techniques in Production of Some Techniques in Production of Scaffolds:Scaffolds:•• CAD/CAM Technologies: CAD/CAM Technologies:

-- control of porosity and pore size is control of porosity and pore size is difficult, so difficult, so 3D structure is designed using CAD 3D structure is designed using CAD software.software.

-- This method is used in combination with This method is used in combination with other methods such as jet ink printing or other methods such as jet ink printing or SLS.SLS.

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Materials used in tissue scaffoldingMaterials used in tissue scaffolding

•• Synthetic: Synthetic: --MetallicMetallic--CeramicsCeramics--PolymersPolymers

•• Natural:Natural:--CollagenCollagen--Alginate Alginate

--OthersOthers

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Metallic & Ceramic ScaffoldsMetallic & Ceramic Scaffolds

Stainless steel was widely used in Stainless steel was widely used in orthopedics and dentistry.orthopedics and dentistry.CoCo––Cr and Ti alloys are used in joint Cr and Ti alloys are used in joint prostheses, dentistry and cardioprostheses, dentistry and cardio--vascular vascular applications.applications.Ceramics was a good alternative to Ceramics was a good alternative to metallic butmetallic but……

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Metallic & Ceramic Scaffolds (Cont.)Metallic & Ceramic Scaffolds (Cont.)

Advantages: biocompatible and bio inertAdvantages: biocompatible and bio inertDisadvantages: failure due to wear and wear assisted Disadvantages: failure due to wear and wear assisted corrosioncorrosionExample: difference in modulus compared to the natural Example: difference in modulus compared to the natural bone. bone.

--The modulus of hard bone varies fromThe modulus of hard bone varies from77––30 GPa. 30 GPa.

--Typical modulus of ceramic and metallic Typical modulus of ceramic and metallic lies above 70 GPa.lies above 70 GPa.

--RResults in stress shielding effect on bones and esults in stress shielding effect on bones and tissues tissues

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Example of Polymeric ScaffoldsExample of Polymeric Scaffolds

•• Which polymer? Which polymer? Polycaprolactone Polycaprolactone (PCL) a bioresorbable (PCL) a bioresorbable polymer polymer

•• Potential applications: Potential applications: bone and cartilage bone and cartilage repair.repair.

(a) STL design .le for the 1.75mm x=y=z porous scaffold. (b) 1.75mm x=y=z PCL scaffold fabricated by SLS.

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Example of Polymeric Scaffolds (cont.)Example of Polymeric Scaffolds (cont.)

•• Is it a good choice? Is it a good choice? -- more stable in ambient conditions more stable in ambient conditions -- less expensive and is readily available less expensive and is readily available in large quantities in large quantities

-- can be fabricated with can be fabricated with selective laser sintering (SLS), so…

- precise mechanical properties close to physiological range

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Example of Polymeric Scaffolds (cont.)Example of Polymeric Scaffolds (cont.)

•• Method of fabrication of Method of fabrication of PCL: selective laser PCL: selective laser sintering (SLS) sintering (SLS)

•• SLS constructs scaffolds SLS constructs scaffolds from 3from 3--D digital data by D digital data by sequentially fusing sequentially fusing regions in a powder bed, regions in a powder bed, layer by layer, via a layer by layer, via a computer controlled computer controlled scanning laser beam.scanning laser beam.

(a) An isometric view of a surface rendering of the STL design .le for the subcutaneous-size scaffold, (b) bottom view, (c) side view, (d) topview of mCT bone surface rendering data combined with a surface rendering of the STL design .le. PCL scaffold is shown in blue and mineralizedmatrix is shown in white.

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Example of Polymeric Scaffolds (cont.)Example of Polymeric Scaffolds (cont.)

•• Advantages of using SLS technique:Advantages of using SLS technique:-- allows construction of scaffolds with allows construction of scaffolds with

complex internal & external geometriescomplex internal & external geometries

-- any powdered biomaterial that will fuse any powdered biomaterial that will fuse but not decompose under a laser beam but not decompose under a laser beam can be usedcan be used

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Example of Polymeric Scaffolds (cont.)Example of Polymeric Scaffolds (cont.)

•• Other Advantages of using SLS technique:Other Advantages of using SLS technique:

-- SLS does not require the use of SLS does not require the use of organic solvents, so intricate scaffold organic solvents, so intricate scaffold geometries can be madegeometries can be made

-- Fast and cost effective Fast and cost effective

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Example of Polymeric Scaffolds (cont.)Example of Polymeric Scaffolds (cont.)

•• How they have tested this How they have tested this polymer?polymer?

-- Fabricate the scaffoldFabricate the scaffold-- Seed the scaffold with Seed the scaffold with bone morphogenetic bone morphogenetic proteinsproteins

-- Implant the tissue to Implant the tissue to evaluate the evaluate the biological propertiesbiological properties

An actual pig condyle, (b) surface rendering of STL design .le for pig condyle scaffold, (c) front view, and (d) back view of pig condyle PCL scaffold fabricated by SLS.

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Naturally Derived Materials for Naturally Derived Materials for Tissue ScaffoldingTissue Scaffolding

Collagen Collagen Alginate Alginate Other materials such as acecellular tissue Other materials such as acecellular tissue

matrices, silk from silkworm and hydrogelsmatrices, silk from silkworm and hydrogels

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CollagenCollagen

The main protein of The main protein of connective tissue in connective tissue in animals and the most animals and the most abundant protein in abundant protein in mammals, making up mammals, making up about 40% of the about 40% of the total.total.

Collagentriplehelix

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Properties of CollagenProperties of Collagen

One of the long, fibrous structural proteins One of the long, fibrous structural proteins whose functions are quite different from whose functions are quite different from those of globular proteins such as those of globular proteins such as enzymes. enzymes.

Tough and inextensible, with great tensile Tough and inextensible, with great tensile strength.strength.

The main component of cartilage, The main component of cartilage, ligaments, tendons, bone and teeth.ligaments, tendons, bone and teeth.

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Medical UsagesMedical Usages

May readily be purified from both animal May readily be purified from both animal and human tissues with enzyme treatment and human tissues with enzyme treatment and salt/acid extraction.and salt/acid extraction.

Wound dressing and artificial skin Wound dressing and artificial skin Cosmetic surgery Cosmetic surgery Burns surgeryBurns surgerySold commercially as a joint mobility Sold commercially as a joint mobility

supplement.supplement.

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Advantages Advantages DisadvantagesDisadvantages

Minimize inflammatory Minimize inflammatory and antigenic reponsesand antigenic reponses

Exhibits high tensile Exhibits high tensile strength and flexibility strength and flexibility and can be further and can be further enhancedenhanced

Can be processed into Can be processed into a wide variety of a wide variety of structures like fibers, structures like fibers, films, etc.films, etc.

Fairly high rate of allergic Fairly high rate of allergic reactions causing reactions causing prolonged redness and prolonged redness and requiring inconspicuous requiring inconspicuous patch testing prior to patch testing prior to cosmetic usecosmetic use

Derived from cows, posing Derived from cows, posing the risk of transmitting the risk of transmitting prion diseases like BSEprion diseases like BSE

Alternatives using the Alternatives using the patient's own fat is patient's own fat is readily available.readily available.

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AlginateAlginate

A polysaccharide A polysaccharide isolated from isolated from seaweed, often seaweed, often brown algea.brown algea.

Brown Algea

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Medical UsagesMedical Usages

Due to alginate's biocompatibility and Due to alginate's biocompatibility and simple gelation with divalent cations, it is simple gelation with divalent cations, it is widely used for cell widely used for cell transplantation,immobilization and transplantation,immobilization and encapsulation and other tissue engineering encapsulation and other tissue engineering application. application.

Calcium alginate is used in burn dressings Calcium alginate is used in burn dressings that promote healing and can be removed that promote healing and can be removed painlessly.painlessly.

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Pros and ConsPros and Cons

Possess many favourable properties Possess many favourable properties required in biomaterials but are unable to required in biomaterials but are unable to specifically interact with mammalian cell.specifically interact with mammalian cell.

Hence, a new biomaterial called chitosan Hence, a new biomaterial called chitosan is emering cause chitosan can be directed to is emering cause chitosan can be directed to assemble in response to locally applied assemble in response to locally applied electrical signals, and its backbone provides electrical signals, and its backbone provides sites that can be employed for the assembly sites that can be employed for the assembly of proteins, nucleic acids, and virus particles. of proteins, nucleic acids, and virus particles.

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Other MaterialsOther MaterialsAcecellular tissue matrices Acecellular tissue matrices

-- collagen rich matrices prepared by collagen rich matrices prepared by mechanical and chemical manipulation of a mechanical and chemical manipulation of a segment of bladder tissue. segment of bladder tissue. -- matrices slowly degrade upon implantation matrices slowly degrade upon implantation -- replaced and remodeled by Extra Celluar replaced and remodeled by Extra Celluar Matrices(ECM) proteins synthesized and Matrices(ECM) proteins synthesized and secreted by transplanted or in growing cells.secreted by transplanted or in growing cells.

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Other Materials Cont.Other Materials Cont.Silk from the silkworm Silk from the silkworm

-- used as biomedical suture material for used as biomedical suture material for centuries centuries -- unique mechanical properties of these fibers unique mechanical properties of these fibers provided important clinical repair options for provided important clinical repair options for many applications. many applications.

Hydrogels: Hydrogels: -- crosscross--linked hydrophilic polymers, represents an linked hydrophilic polymers, represents an important class of biomaterials in biotechnology important class of biomaterials in biotechnology and medicine and medicine -- many hydrogels exhibit excellent many hydrogels exhibit excellent biocompatability, causing minimal inflammatory biocompatability, causing minimal inflammatory reponses, and tissue damage. reponses, and tissue damage.

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Future Direction Future Direction -- ChitosanChitosan

A linear BetaA linear Beta--1,41,4--linked polysaccharide linked polysaccharide (similar to cellulose) that is obtained by the (similar to cellulose) that is obtained by the partial deacetylation of chitin partial deacetylation of chitin

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BiofabricationBiofabrication

•• Directed assembly Directed assembly -- electrodeposition electrodeposition in response to in response to electrical stimuli electrical stimuli

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Research @ MacResearch @ Mac

•• Metallic implant of a Metallic implant of a bone bone –– bioinertbioinert

•• Hydroxyapatite Hydroxyapatite (Ca10(PO4)6(OH)2)(Ca10(PO4)6(OH)2)deposition on deposition on surface surface –– bioactivebioactive

•• Sintering problem Sintering problem @ 1000C, cracking@ 1000C, cracking

•• Chitosan as a Chitosan as a polymer to adherepolymer to adhere

Figure shows that a human long bone cell growing on the surface of a hydroxyapatite foam.

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Other ResearchOther Research

•• Antibacterial Antibacterial •• Dispose of waste Dispose of waste

waterwater

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ConclusionConclusion

•• Method for restoring the damaged tissue Method for restoring the damaged tissue •• Different tissues Various methods and Different tissues Various methods and

materials materials •• Future...? Future...?

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Thanks for your attentions.

Any question?

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ReferencesReferenceshttp://www.uweb.engr.washington.edu/research/tutorials/porousscahttp://www.uweb.engr.washington.edu/research/tutorials/porousscaffolds.htmlffolds.htmlhttp://www.nature.com/nmat/journal/v4/n7/full/nmat1421.htmlhttp://www.nature.com/nmat/journal/v4/n7/full/nmat1421.htmlhttp://www.npl.co.uk/materials/biomaterials/mpp42_overview.htmlhttp://www.npl.co.uk/materials/biomaterials/mpp42_overview.htmlhttp://www.newscientist.com/article.ns?id=dn3292http://www.newscientist.com/article.ns?id=dn3292http://en.wikipedia.org/wiki/Tissue_engineeringhttp://en.wikipedia.org/wiki/Tissue_engineeringhttp://www.sfgate.com/cgihttp://www.sfgate.com/cgi--bin/article.cgi?f=/c/a/2006/04/04/MNGQ0I2P2B1.DTLbin/article.cgi?f=/c/a/2006/04/04/MNGQ0I2P2B1.DTLhttp://en.wikipedia.org/wiki/Collagenhttp://en.wikipedia.org/wiki/Collagenhttp://en.wikipedia.org/wiki/Brown_algaehttp://en.wikipedia.org/wiki/Brown_algaeJ. M. Williamsa, A. Adewunmib et al.,J. M. Williamsa, A. Adewunmib et al.,““Bone tissue engineering using Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sinterpolycaprolactone scaffolds fabricated via selective laser sinteringing””, , Biomaterials, Volume 26, pp. 4818 Biomaterials, Volume 26, pp. 4818 –– 48274827H. Yi, L. Q. Wu, W. E. Bentley et al., H. Yi, L. Q. Wu, W. E. Bentley et al., ““Biofabrication with ChitosanBiofabrication with Chitosan””, , Biomacromolecules, Volume 6, Number 6Biomacromolecules, Volume 6, Number 6

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References(cont.)References(cont.)P. K.D.V Yarlagadda, M. Chandrasekharan and J. Y. M. Shyan, P. K.D.V Yarlagadda, M. Chandrasekharan and J. Y. M. Shyan, ““Recent adcances and current developments in tissue scaffoldingRecent adcances and current developments in tissue scaffolding””, , BioBio--Medical Materials and Engineering 15 (2005) 159Medical Materials and Engineering 15 (2005) 159--177177