Biomedical Engineering Reference
In-Depth Information
18
Improving Blood Compatibility
of Biomaterials Using a Novel
Antithrombin-Heparin
Covalent Complex
Leslie Roy Berry and Anthony Kam Chuen Chan
CONTENTS
18.1 Introduction .........................................................................................................................
535
18.2 Antithrombin.......................................................................................................................
538
18.2.1 Chemical Structure of Antithrombin .....................................................................
538
18.2.2 Functional Biochemistry of Antithrombin ............................................................
539
18.3 Heparin................................................................................................................................
541
18.3.1 Chemical Structure of Heparin ..............................................................................
541
18.3.2 Functional Biochemistry of Heparin .....................................................................
542
18.4 Overview of Covalent Antithrombin-Heparin Complexes.................................................
544
18.4.1 Limitations of Current Heparins ............................................................................
544
18.4.2 Potential Advantages of Covalent Antithrombin-Heparin Complexes .................
545
18.5 Development of Covalent Antithrombin-Heparin Complexes ...........................................
547
18.5.1 Concepts for Covalent Antithrombin-Heparin Synthesis......................................
547
18.5.2 Chemical Structures and
In Vitro
Activities ..........................................................
548
18.5.3 Effects
In Vivo
........................................................................................................
553
18.6 Surface Coating with Covalent Antithrombin-Heparin Complexes ..................................
556
18.6.1 Chemistry and
In Vitro
Characterization...............................................................
556
18.6.2
In Vivo
Performance ..............................................................................................
558
18.7 Future Directions.................................................................................................................
560
References ......................................................................................................................................
560
18.1 INTRODUCTION
Use of biomaterials in clinical diagnosis and treatment is an increasingly prevalent application of
chemical polymers.
1,2
Indeed, catheters,
3
stents,
4
heart valves,
5
bypass circuits,
6
dialysis devices,
7
and other devices constructed from biochemical polymers have enabled major advances in medical
care. One persistent problem associated with the biomaterials involves biocompatibility of the poly-
mer surfaces with blood. In particular, thrombotic complications induced by interactions between
the biomaterials and the vascular system remain an obstacle to their functional utility.
8
This is a
vexing issue especially in the pediatric population requiring catheters for blood sampling or treat-
ment. Studies have clearly established that central venous catheters cause up to 90% of thromboses
occurring in neonates
9
and approximately 60% of thromboses observed in children.
10
Clot forma-
tion in and around catheter lines not only prevents treatment from being received by the pediatric
535
