ORTHOPAEDIC TISSUE ENGINEERING

ORTHOPAEDIC TISSUE ENGINEERINGPRESENTER-Dr. RAGHAVENDRA RAJU

INTRODUCTIONTISSUE ENGINEERING term was originally coined to denote the construction in the lab of a device containing viable cells and biololgical mediators in a synthetic or biological matrix that could be implanted into patients to facilitate regeneration of particular tissue. Synonyms regenerative medicine, bionics , biomimetic materials , stem cell theraphy.

Regenerative medicine- regeneration of damaged or missing tissues in human body.Bionics- combination of artificial electronic mechanisms and living tissues to work together as one unit.Biomimetic materials mimic living tissue surfaces.

BASIC PRINCIPLEINVOVLES THE USE OF ARTIFICIAL OR INERT SCAFFOLD MATERIALS AND LIVING CELLS WITH THE GOAL OF GROWING A DESIRED TISSUE WITH ITS CHARACTERISTIC BIOLOGICAL FUNCTION.

CLASSIC STATIC TRIANGLE OF TISSUE ENGINEERING

MODERN DYNAMIC SPIRAL

SCAFFOLD MATERIALS AND SHAPEProvide basic skeleton, shape and stability.Two types1.degradable. 2.non degradable.Two techniquesselective laser melting. computer aided design.

SCAFFOLDS SHOULD ALLOW CELL ADHESION IFNECESSARY DISPLAY GROWTH FACTORS ON THEM.

Cells TWO MAIN APPROACHES

1.DIFFERENTIATED CELLS.(Poor proliferation and large sample requirement)

2.STEM CELLS.

STEM CELLS

1. EMBRYONIC STEM CELLS- embryonic and fetal development.2. ADULT STEM CELLS- growth, tissue maintaince, regeneration of compromised tissues.Stem cells has the ability to differentiate into a more specialized cell , it depends on its potency.

POTENCY OF STEM CELLSTotipotent stem cells can form an entire organism-fertilized oocyte.Pluripotent stem cells can form the all the three germ layers- inner mass of blastocyst.Multipotent stem cells ability to form multiple cell types- adult mesenchymal cells .Oligopotent stem cells can form two or more lineages- neural stem cells.Unipotent stem cells form only one lineage spermatogonial stem cells .

Embryonic stem cells Quick proliferation capacity. Can differentiate into any cell type.Best choice for orthopaedic surgery in regeneration of bone and cartilage.Drawback ethical concern.

Adult stem cellMultipotent cells available for tissue engineering.Can be taken from various sites like mucosa , bone marrow, skeletal muscle , cornea, dental pulp etc.From bone marrow , adult mesenchymal cells are easily harvested to produce cells like osteblasts or chondrocytes.

INDUCED PLURIPOTENT CELLS A NOVEL THIRD GROUP OF PLURIPOTENT CELLS PRODUCED BY TISSUE ENGINEERING TECHNIQUE.Re program the adult stem cells backwards into embryonic stem cells .Methods transfection ,integration of transcription factors.Draw backs chance of malignancy.

SIGNALSRequired to exert a mitogenic or morphogenic effect.Usually used signals are growt factorsEx PDGF, IGF, VEGF, BMP.BMP is particularly important in inducing differentiation of mesenchymal precursor cells in to osteoblasts and have been succesfully used in humans.

BIOREACTERSThey provide the required enviroment for growth of engineered tissue.

1.IN VITRO2.IN VIVO3.IN SILICO

IN VITRO BIOREACTERThey condition the tissue engineering constructs before subsequent implantation in the recepient.They attempt to stimulate conditions of in vivo.Advantages- 1.better control over culture. 2.ease of checking quality of engineered tissue.Disadvantages- 1. risk of infection , rejection 2.limitation in size of tissue to be engineered.

IN VIVO/ ENDO CULTIVATION BIOREACTERPatient serves as his / her own bioreacter where by the required tissue is cultivated in his / her own body on indiviualized matrix.Advantages 1. decreases the risk of immunological rejection2. enables the development of vascular system.Disadvantages 1. hard to control monitor tissue.

IN SILICO BIOREACTERTissue growth process are stimulated by computers which act as virtual bioreacters.They optimize positioning of cells , timming and manner of stimulation.Awaiting final evaluation.

TISSUE ENGINEERING IN ORTHOPEADICS APPLICATIONS

THEME

STEM CELLS IN ORTHOPAEDICSMESENCHYMAL STEM CELL(MSC) ARE THE CORNER STONE IN APPLICATION OF TISSUE ENGINEERING IN ORTHOPAEDICS. ARE CALLED 21 CENTURY PENCILLIN.

Act as construction manager Helps other cells to build things.Reduce inflammation.Angiogenesis.

MSC can be found in 1.Bone marrow( best for orthopaedic uses).2.adipose tissue. 3.blood.4.joint(rarely).6o ml of BM aspirate yields 70- 90 thousand of msc.THERAPEUTIC LEVEL 10^7 10^9 CELLS.

USESCRITICAL BONE DFECTS.NON UNIONS.CARTILAGE DEFECTS , REPAIRS.TENDON REPAIRS.MENISCAL REPAIRS SPINAL CORD DEGENERATIONINTERVERTEBRAL DEGENERATIONMUSCULAR DYSTROPHIES

SLE.MULTIPLE SCLEROSIS.IBD.INFLAMMATORY ARTHRITIS.

BONE HEALING

MSC IN BONE HEALINGEnhance bone regeneration and union in critical bone defects.Non union.Physeal regeneration.Improve bone quality in osteogenesis imperfecta.

TERIPATIDE(PARATHYROID HORMONE) IN BONE HEALING

MSC IN CPT

Carrier sponge with MSC covering the fracture site

MSC WITH SCAFFOLD IN GAP NON UNION

ENDOCULTIVATION

AVN OF FEMORAL HEAD

MSC IN AVN OF FEMORAL HEAD

MSC IN ACL INJURIES

MENISCAL INJURIES

STEM CELLS IN CARTILAGE DEFECTS

FOUR BASIC TECHNIQUES(A) STIMULATION OF INTRINSIC HEALING POTENTIAL(B) ALTERATION OF LOADS (C) TRANSFER OF AUTOGENOUS TISSUE AND CELLS(D) TRANSFER OF ALLOGRAFT TISSUE

PROTOCOL

ABRASION ARTHROPLASTY AND MICRO FRACTURE

Autogenous Tissue GraftingTransfer normal articular cartilage into a damaged area.

1: Preparation of recipient site2: Harvest of the grafts3,4: Preparation for the plug grafts5: Insertion of the plugs6: Completed mosaicplasty.

Osteochondral autografts can be transplanted into damaged areas (2 cm to 3.5cms) from areas of less weight bearing on the femoral condyle.

Autologous Chondrocyte Implantation

Peterson autologous chondrocyte implantation sandwich technique

Sandwich technique of autogenous chondrocyte implantation uses layers of transplanted bone, periosteal flap, chondrocytes, and periosteal flap

A disadvantage of autologous chondrocyte implantation is the prolonged postoperative rehabilitation that requires strict compliance of the patient with weight bearing and activity restrictions.

Future developments in fields of molecular & cell biology, developmental biology & tissue engineering, will have significant impact on managing anatomic changes due to disease process.

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THANK YOU

REFERENCES MERCER TEXT BOOK OF ORTHOPAEDICSCHAPMAN TEXT BOOK OF ORTHOPAEDICSTISSUE ENGINEERING LIPPINCOTTINTERNETTACHDIJIANS TEXT BOOK