Tissue Engineering

http://www.youtube.com/watch?v=PEc7QXAjsL4&feature=related

Mouse Ears

1997 MIT

http://www.youtube.com/watch?v=WvSxZ4JKQAY&feature=related

Engineering Tissue

Corneal Tissue Engineering

Blood vessel tissue engineering

Liver tissue engineering

Cartilage tissue engineering

Bone tissue engineering

Key Factors involving tissue engineering

Cell Culture( stem cell, osteoblast,

chondrocyte, hepatocyte

Signaling Molecules (Growth

Factors, proteins

Scaffold( ceramics

collagen, polymers)

Tissue/Organ regeneration

Interactive traids of responsive cells

Supportive matrix

Bioactive molecules promoting

differentiation and regeneration

Application of tissue engineering

3D culture

TransplantationCellular and tissue bases productAlternative to animal test

Developing procedures used in cartilage tissue engineering

1st generation 2nd generation 3rd generation

Principle approach

Autologous cell transplant

Performed tissue flaps 3D construct

In vivo regeneration and guided tissue repair

Important

component Periosteal flaps( 修補組織 骨骼 )

Delivery substances and scaffold( 體內重新建構 )

Growth factors and biomaterials( 體內再生 )

Cartilage Tissue Engineering

I. Autologous chondrocyte

1. Isolation of tissue sample from patients

2. Tissue regeneration by precursor cells

or embryonic stem cells

articular cartilage repair, nasal septal

cartilage scaffolds for cartilage for

tissue repair

ECM ( Extra cellular Matrix)

ECM interaction directly influence cell signaling via

cell adhesion molecules such as integrin and

cadhedrin, fibronectin, collagen, laminin….

Extracellular Matrix in relation to epithelium endothelium and connective tissue

Epithelial cell

Basement membrane

Endothelial lining the capillary

Connective tissue with interatitial matrix

Fibroblast

http://inano.au.dk/organization/research-groups/nanobiointerfaces/research/steering-stem-cell-differentiation/

Steering Stem Cell Differentiation

Differentiation of stem cells induced by binding to extracellular matrix components (e.g. proteins such as fibronectin, collagen and laminin)components

II. Scaffold for tissue construction

1. Act as shape and guidance template for

in vitro and in vivo tissue development

2. Permit 3D immobilization and maintain

differentiation

materials: hyaluronic acid, collagen, alginate,

chutosan, synthetic biodegradable poly( -

hydroxy ester) polyacetic acid,( PLIA), polyglycolic

acid( PGA), PLGA……

Chondrocyte or Mesenchyma stem cell

Polymer fiberEmbedding medium

( hydrogel)

Biosynthetic scaffolds

Collagen scafold

Tissue scafold +Cellsand

Growth factors

In vivo transplant

http://www.youtube.com/watch?v=0QJh0yc2mAI&feature=related

Engineering Organs from Scratch

Tissue in cardiovascular structure

Advantages:

1. Avoid repeat operation

2. No rejection by the patients immune system

3. Cells behave like endothelial cells may have low

thrombus formation and low infection

i.e. valves, blood vessels, vascular patches

Basic steps in tissue engineering of a cardiac valve

Bone marrow cells harvest

Valve scaffold

Cell- scaffold construct

http://bme.dentistry.dal.ca:16080/bme/mlee/PorcineValve.jpg

Approaches to create a vascular graft

Cross linking

Exogenous chemicals

Mechanical stimulations

Cells + tubular scaffold Endothelial lining In vivo implantation

Smooth muscle cells progenitor cells collagen gel/elastin fibrin

Extra cellular matrix

Biodegradable polymers

Autulogous EC Circulating EPC Allogenic EC Embryonic stem cell

Non-thromgenicity Immune response Remodeling

American Journal of Transplantation 2004; 4 (Suppl. 6): 36–42

http://www.synthecon.com/Graphics/pga_lg.jpg

http://www.fibercellsystems.com/images/cross-section.jpg

http://channel.nationalgeographic.com/series/explorer/4828/Photos/3671755be79cd210VgnVCM1000000100007fRCRD#tab-Videos/09347_00

How to Build a Beating Heart

http://channel.nationalgeographic.com/series/explorer/4828/Photos/3671755be79cd210VgnVCM1000000100007fRCRD#tab-Videos/10008_00

http://channel.nationalgeographic.com/series/explorer/4828/Photos/3671755be79cd210VgnVCM1000000100007fRCRD#tab-Videos/09346_00

Artificial skinskin substitute

Adhere to the substrate,

Durable and sufficiently elastic

Tolerate some deformation

Allow evaporative water loss

Provide a microbial barrier

Promote homeostasis

Easy to use

Readily available immediately after injury, and elicit a Regeneration-like response from the wound bed without evoking an inflammatory, foreign-body, or non- self immunologic reaction.

Annu. Rev. Med. 2000. 51:231–244

Artificial skin

Artificial skin

Therapy using Artificial skin

MSC (Mesenchyma Stem Cells)

Proliferate in cultures

Differentiate into multiple mesenchyma lineage

ie. correction of genetic disorder of ,

i.e bone cartilage

Cell seeding on cotton gauze framed collagen substratum

Formation of multilayer mesenchyma cells

Physical detachment

3D culture

Preparation of 3-D mesenchyma cells

Seeding of mesenchyma cells

confluent mesenchyma cells

Seeding of epithelial cells

Coculture of epithelial and mesenchyma cells

Detachment of epithelial cells –attached

mesenchyma cell sheet

Formation of hetero-spheroid

Preparation of 3-D mesenchyma cells

Osteoblast

Arise from mesenchyma cells( MSC)

MSC may be differentiate into osteoblast in vitro

Cultured osteoblast may form extracellular

matrix in culture

Bone marrow derived osteoblast

Cultured bone

T. Uemura et al. / Biomaterials 24 (2003) 2277–2286

Transplantation of cultured bone cells

Bone marrow derived osteoblast

Cultured bone

Transplantation of cultured bone cells

T. Uemura et al. / Biomaterials 24 (2003) 2277–2286

T. Uemura et al. / Biomaterials 24 (2003) 2277–2286

T. Uemura et al. / Biomaterials 24 (2003) 2277–2286

http://www.jove.com/details.php?id=2691

Elastomeric PGS Scaffolds in Arterial Tissue Engineering

http://www.youtube.com/watch?v=ofiLcTs7_Ys&feature=related

Tissue Engineering -- Building Body Parts