Scaffolding Materials for Tissue Engineering Parisa Bahrami, Hailun(Helen) Huang 1
Content What is tissue scaffolding History of tissue scaffolding Types of tissue scaffolding Materials used in tissue scaffolding, such as metallic, polymers, natural materials and etc. Future direction References 2
What is tissue scaffolding? A permanent or temporary support to the damaged tissues/organ until the functionalities are restored. Used for reconstruction of skin, bone, cartilage, enamel, dentin and periodontal ligaments and even nerves, heart valves, liver and bladder. 3
What is tissue scaffolding? Example: 4
History of Tissue Scaffolding 2000 BC: reconstruction using gold in cranial defects 17th century: using wood in making artificial legs 1660s: tissue grafting It was only during the last four decades the use of materials in tissue scaffolding gained attention. 5
Types of tissue scaffolding Temporary: degrade over a period of time with the regeneration of the organ or tissue. useful especially in case of young patients Permanent: retain their shape and strength through the process of regeneration/repair of the organ used older patients 6
Structure of scaffolds in general An interconnected, open pore network for passing nutrients and cells to scaffold while ensuring waste products can get out. Mechanical properties close to the natural tissue. The scaffold must have a surface chemistry suitable for cell attachment and growth. A scaffold material must be easily processed into a variety of shapes and sizes Pores can take different forms 7
Some Techniques in Production of Scaffolds Salt leaching technique: - salt crystals are put into a mold - polymer is poured over the salt - polymer is hardened - the salt is removed by dissolving it in a solvent 8
Some Techniques in Production of Scaffolds Polymer foaming: -Polymer is stirred rapidly to create a foam. -Polymer is hardened, creating a solid sponge-like material. -Foam s s air bubbles form the pores of the final scaffold. 9
Some Techniques in Production of Scaffolds Ink jet printing: -use of modified desktop printers filled with "thermo-reversible" reversible" gel instead of ink. -printing alternate layers of the gel onto glass slides, 3D structures such as tubes can be built up 10
Some Techniques in Production of Scaffolds: CAD/CAM Technologies: - control of porosity and pore size is difficult, so 3D structure is designed using CAD software. - This method is used in combination with other methods such as jet ink printing or SLS. 11
Materials used in tissue scaffolding Synthetic: Natural: -Metallic -Ceramics -Polymers -Collagen -Others -Alginate Alginate 12
Metallic & Ceramic Scaffolds Stainless steel was widely used in orthopedics and dentistry. Co Cr Cr and Ti alloys are used in joint prostheses, dentistry and cardio-vascular applications. Ceramics was a good alternative to metallic but 13
Metallic & Ceramic Scaffolds (Cont.) Advantages: biocompatible and bio inert Disadvantages: failure due to wear and wear assisted corrosion Example: difference in modulus compared to the natural bone. -The modulus of hard bone varies from 7 30 GPa. -Typical modulus of ceramic and metallic lies above 70 GPa. -Results in stress shielding effect on bones and tissues 14
Example of Polymeric Scaffolds Which polymer? Polycaprolactone (PCL) a bioresorbable polymer Potential applications: bone and cartilage 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. 15
Example of Polymeric Scaffolds (cont.) Is it a good choice? - more stable in ambient conditions - less expensive and is readily available in large quantities - can be fabricated with selective laser sintering (SLS), so - precise mechanical properties close to physiological range 16
Example of Polymeric Scaffolds (cont.) Method of fabrication of PCL: selective laser sintering (SLS) SLS constructs scaffolds from 3-D 3 D digital data by sequentially fusing regions in a powder bed, layer by layer, via a computer controlled 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) top view of mct bone surface rendering data combined with a surface rendering of the STL design.le. PCL scaffold is shown in blue and mineralized matrix is shown in white. 17
Example of Polymeric Scaffolds (cont.) Advantages of using SLS technique: - allows construction of scaffolds with complex internal & external geometries - any powdered biomaterial that will fuse but not decompose under a laser beam can be used 18
Example of Polymeric Scaffolds (cont.) Other Advantages of using SLS technique: - SLS does not require the use of organic solvents, so intricate scaffold geometries can be made - Fast and cost effective 19
Example of Polymeric Scaffolds (cont.) How they have tested this polymer? - Fabricate the scaffold - Seed the scaffold with bone morphogenetic proteins - Implant the tissue to evaluate the biological 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. 20
Naturally Derived Materials for Tissue Scaffolding Collagen Alginate Other materials such as acecellular tissue matrices, silk from silkworm and hydrogels 21
Collagen The main protein of connective tissue in animals and the most abundant protein in mammals, making up about 40% of the total. Collagentriplehelix 22
Properties of Collagen One of the long, fibrous structural proteins whose functions are quite different from those of globular proteins such as enzymes. Tough and inextensible, with great tensile strength. The main component of cartilage, ligaments, tendons, bone and teeth. 23
Medical Usages May readily be purified from both animal and human tissues with enzyme treatment and salt/acid extraction. Wound dressing and artificial skin Cosmetic surgery Burns surgery Sold commercially as a joint mobility supplement. 24
Advantages Disadvantages Minimize inflammatory and antigenic reponses Exhibits high tensile strength and flexibility and can be further enhanced Can be processed into a wide variety of structures like fibers, films, etc. Fairly high rate of allergic reactions causing prolonged redness and requiring inconspicuous patch testing prior to cosmetic use Derived from cows, posing the risk of transmitting prion diseases like BSE Alternatives using the patient's own fat is readily available. 25
Alginate A polysaccharide isolated from seaweed, often brown algea. Brown Algea 26
Medical Usages Due to alginate's biocompatibility and simple gelation with divalent cations, it is widely used for cell transplantation,immobilization and encapsulation and other tissue engineering application. Calcium alginate is used in burn dressings that promote healing and can be removed painlessly. 27
Pros and Cons Possess many favourable properties required in biomaterials but are unable to specifically interact with mammalian cell. Hence, a new biomaterial called chitosan is emering cause chitosan can be directed to assemble in response to locally applied electrical signals, and its backbone provides sites that can be employed for the assembly of proteins, nucleic acids, and virus particles. 28
Other Materials Acecellular tissue matrices - collagen rich matrices prepared by mechanical and chemical manipulation of a segment of bladder tissue. - matrices slowly degrade upon implantation - replaced and remodeled by Extra Celluar Matrices(ECM) proteins synthesized and secreted by transplanted or in growing cells. 29
Other Materials Cont. Silk from the silkworm - used as biomedical suture material for centuries - unique mechanical properties of these fibers provided important clinical repair options for many applications. Hydrogels: - cross-linked hydrophilic polymers, represents an important class of biomaterials in biotechnology and medicine - many hydrogels exhibit excellent biocompatability, causing minimal inflammatory reponses, and tissue damage. 30
Future Direction - Chitosan A linear Beta-1,4 1,4-linked polysaccharide (similar to cellulose) that is obtained by the partial deacetylation of chitin 31
Biofabrication Directed assembly - electrodeposition in response to electrical stimuli 32
Research @ Mac Figure shows that a human long bone cell growing on the surface of a hydroxyapatite foam. Metallic implant of a bone bioinert Hydroxyapatite (Ca10(PO4)6(OH)2) deposition on surface bioactive Sintering problem @ 1000C, cracking Chitosan as a polymer to adhere 33
Other Research Antibacterial Dispose of waste water 34
Conclusion Method for restoring the damaged tissue Different tissues Various methods and materials Future...? 35
Thanks for your attentions. Any question? 36
References http://www.uweb.engr.washington.edu/research/tutorials/poroussca ffolds.html http://www.nature.com/nmat/journal/v4/n7/full/nmat1421.html http://www.npl.co.uk/materials/biomaterials/mpp42_overview.html http://www.newscientist.com/article.ns?id=dn3292 http://en.wikipedia.org/wiki/tissue_engineering http://www.sfgate.com/cgi- bin/article.cgi?f=/c/a/2006/04/04/mngq0i2p2b1.dtl http://en.wikipedia.org/wiki/collagen http://en.wikipedia.org/wiki/brown_algae J. M. Williamsa, A. Adewunmib et al., Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering ing, Biomaterials, Volume 26, pp. 4818 4827 H. Yi, L. Q. Wu, W. E. Bentley et al., Biofabrication with Chitosan, Biomacromolecules, Volume 6, Number 6 37
References(cont.) P. K.D.V Yarlagadda, M. Chandrasekharan and J. Y. M. Shyan, Recent adcances and current developments in tissue scaffolding, Bio-Medical Materials and Engineering 15 (2005) 159-177 177 38