Dr. Raghavendra Raju gave a presentation on tissue engineering. He began by defining key terms like tissue engineering, regenerative medicine, bionics, biomimetic materials, and stem cell therapy. The basic principles of tissue engineering involve using artificial or inert scaffold materials combined with living cells to grow desired tissues. Mesenchymal stem cells from bone marrow are commonly used due to their ability to differentiate into bone and cartilage cells. Applications in orthopedics include treating bone defects, fractures that won't heal, cartilage damage, and tendon/meniscus injuries. Future advances in fields like molecular biology and tissue engineering may help manage anatomical changes from disease.

1. PRESENTER-Dr. RAGHAVENDRA RAJU

2. INTRODUCTION
 “TISSUE 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.

3.  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.

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

5. CLASSIC STATIC TRIANGLE OF
TISSUE ENGINEERING

6. MODERN DYNAMIC SPIRAL

7. SCAFFOLD –MATERIALS AND
SHAPE
Provide basic skeleton, shape and stability.
Two types–1.degradable.
2.non degradable.
Two techniques–selective laser melting.
computer aided design.
SCAFFOLDS SHOULD ALLOW CELL ADHESION IF
NECESSARY DISPLAY GROWTH FACTORS ON THEM.

8. Cells
 TWO MAIN APPROACHES –
 1.DIFFERENTIATED CELLS.(Poor proliferation and
large sample requirement)
2.STEM CELLS.

9. 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.

10. POTENCY OF STEM CELLS
 Totipotent 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 .

11. 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.

12. Adult stem cell
 Multipotent 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.

13. 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.

14. SIGNALS
 Required to exert a mitogenic or morphogenic effect.
 Usually used signals are growt factors
 Ex – 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.

15. BIOREACTERS
 They provide the required enviroment for growth of
engineered tissue.
 1.IN VITRO
 2.IN VIVO
 3.IN SILICO

16. IN VITRO BIOREACTER
 They 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.

17. IN VIVO/ ENDO CULTIVATION
BIOREACTER
 Patient 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 rejection
 2. enables the development of vascular system.
 Disadvantages –
 1. hard to control monitor tissue.

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

19. APPLICATIONS

20. THEME

21. STEM CELLS IN ORTHOPAEDICS
 MESENCHYMAL STEM CELL(MSC) ARE THE
CORNER STONE IN APPLICATION OF TISSUE
ENGINEERING IN ORTHOPAEDICS.
 ARE CALLED “ 21 CENTURY PENCILLIN”.

23.  Act as “construction manager” –
 Helps other cells to build things.
 Reduce inflammation.
 Angiogenesis.

24.  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.

25. USES
 CRITICAL BONE DFECTS.
 NON UNIONS.
 CARTILAGE DEFECTS , REPAIRS.
 TENDON REPAIRS.
 MENISCAL REPAIRS
 SPINAL CORD DEGENERATION
 INTERVERTEBRAL DEGENERATION
 MUSCULAR DYSTROPHIES

26.  SLE.
 MULTIPLE SCLEROSIS.
 IBD.
 INFLAMMATORY ARTHRITIS.

28. MSC IN BONE HEALING
 Enhance bone regeneration and union in critical bone
defects.
 Non union.
 Physeal regeneration.
 Improve bone quality in osteogenesis imperfecta.

30. TERIPATIDE(PARATHYROID
HORMONE) IN BONE HEALING

36. MSC IN CPT

37. Carrier sponge with MSC covering
the fracture site

39. MSC WITH SCAFFOLD IN GAP NON
UNION

40. ENDOCULTIVATION

42. MSC IN AVN OF FEMORAL HEAD

47. MSC IN ACL INJURIES

51. MENISCAL INJURIES

53. 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

54. PROTOCOL

55. ABRASION ARTHROPLASTY AND
MICRO FRACTURE

56. Autogenous Tissue Grafting
 Transfer normal articular cartilage into a damaged
area.
1: Preparation of recipient site
2: Harvest of the grafts
3,4: Preparation for the plug grafts
5: Insertion of the plugs
6: Completed mosaicplasty.

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

58. Autologous Chondrocyte
Implantation

60. Peterson autologous chondrocyte
implantation “sandwich”
technique
“Sandwich” technique of autogenous
chondrocyte implantation uses layers of
transplanted bone, periosteal flap,
chondrocytes, and periosteal flap

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

64.  Future developments in fields of molecular & cell
biology, developmental biology & tissue engineering,
will have significant impact on managing anatomic
changes due to disease process.
64

66. THANK YOU

67. REFERENCES
 MERCER TEXT BOOK OF ORTHOPAEDICS
 CHAPMAN TEXT BOOK OF ORTHOPAEDICS
 TISSUE ENGINEERING – LIPPINCOTT
 INTERNET
 TACHDIJIANS TEXT BOOK