Preparation and characterization of a hydrogel containing anti-VEGF (bevacizumab) liposomes to prevent bone tissue repair at injured growth plates.

By





ACKNOWLEDGEMENT

I, (Name) wish to proclaim that all contents of this work / memory stand in my own work without any support, and this thesis / dissertation has been no research on the academic and professional in the past. It also signifies my own views and does not closely relate to the university.

Signature: _______________________________

Date: __________________________

DECLARATION

I, (Your name), would like to declare that all contents included in this study stand for my individual work without any aid, and this proposal has not been submitted for any examination at academic as well as professional level, previously. It is also represents my very own views and not essentially those that are associated with other university.

Signed __________________ Date _________________

Table of Contents

ACKNOWLEDGEMENTI

DECLARATIONII

CHAPTER 1: LITERATURE REVIEW1

INTRODUCTION1

1.1.1 Growth Plate Injuries and Bone Growth Defects1

1.1.2 Potential Role of Local Angiogenesis in the Bony Repair2

1.1.3 Local and Sustained Delivery of Anti-VEGF Therapy3

1.1.4 Bone formation4

1.1.5 Cartilage Response to Mechanical Injury5

1.2.1 DEFINITION OF TERMS7

1.2.2 Hydrogel7

1.2.3 Injectable Hydrogels7

1.2.4 Anti-VEGF (bevacizumab)8

1.2.5 Liposomes8

1.2.6 Angiogenesis9

1.3.1 POST NATAL BONE FORMATION9

1.3.2 Bone repair and Angiogenesis10

1.3.3 Angiogenesis during adult life11

1.3.4 Angiogenic stimulators12

1.4.1 PRELIMINARY STUDY ON VEGF12

1.4.2 VEGF gene13

1.4.3 VEGF receptors13

1.4.4 VEGF in malignancy14

1.5.1 ANTI-VEGF NEUTRALIZING ANTIBODY14

1.5.2 PDGF + FGF215

1.6.1 THE USE OF CHITOSAN IN CARTILAGE REPAIR17

1.6.2 Chitosan17

1.6.3 Properties of Chitosan18

1.6.4 Chitosan and Therapeutic Inflammation18

1.6.5 Chitosan characteristics19

1.6.6 Biological properties - that are desirable for cartilage repair system20

1.6.7 Chitosan - thermosensitve system21

1.6.8 Preparation of chitosan by chemical methods22

1.6.9 Chitosan - thermosensitve system22

1.7 Summary23

REFERENCES25

CHAPTER 1: LITERATURE REVIEW

INTRODUCTION

Over few decades, the tissue engineering techniques for the regeneration of the bone has been elevated considerably. The bones are considered to be an essential organ in the vertebrates, which support, move and protect a variety of organs that produces the white and the red blood cells and they also store minerals. World wide, every year there is millions of bone fracturing occurring (Praemer & Furner, 1992, p. 85). After the spinal arthrogenesis, skeletal trauma, trabecular void following oeteoporotic insufficiency features severe loss of bones occurs. Even there are several infections such as surgical resections and osteomyelitis due to cyst involvement and metastatic tumour after which the bone loss occurs. Therefore for the reconstructive surgery the repair of bone defects is a highly tedious challenge.

1.1.1 Growth Plate Injuries and Bone Growth Defects

Growth plates are mainly situated at the end of all long bones that are accountable for the lengthening of a child's skeleton via a tightly regulated process called endochondral ossification (Tortora &Grabowski, 2000). Due to its cartilaginous nature, the growth plate is the slightest rigid and rigid district of the long bone in vertebrates and is involved in approximately 20% of childhood fracture. Injury to the growth plate can be problematic due to its limited self-repair ability (Iannotti ,1990, pp. 1).

In vertebrates, bone is the principal calcified tissue and is a multifaceted organ responsible for protection, hearing, fat storage, pH regulation, structural support, mineral storage, and metabolism. Although often considered static, bone is a dynamic organ, ...