This document discusses various biomaterial fabrication techniques. It begins with an introduction to biomaterials and their uses. It then describes common materials used as biomaterials and the evolution of biomaterials. Several scaffold fabrication techniques are outlined, including solvent casting, melt molding, gas foaming, freeze drying, and fiber bonding. Limitations of these techniques are noted. Rapid prototyping and nanofabrication techniques that allow for more control and precision are also summarized.

1. ARJUN G NAMBOODIRI Polymer processing Laboratory 4/6/10 BIOMATERIAL FABRICATION TECHNIQUES

3. INTRODUCTION “ Non viable material used in medical devices intended to interact with biological systems” (Williams 1987) A biomaterial is "any substance (other than drugs) or combination of substances synthetic or natural in origin, which can be used for any period of time, as a whole or as a part of a system which treats, augments, or replaces any tissue, organ, or function of the body". BIOMATERIAL ONE MUST HAVE EITHER VAST KNOWLEDGE OR DIFFERENT COLLABORATORS WITH DIFFERENT SPECIALITIES INORDER TO DEVELOP BIOMATERIALS IN MEDICINE AND DENTISTRY

4. USE OF BIOMATERIALS REPLACEMENT OF DISEASED OR DAMAGED PARTS ASSIST IN HEALING IMPROVE FUNCTION CORRECT FUNCTIONAL ABNORMALITIES AID TO DIAGONISE AID TO TREATMENT CORRECT COSMETIC PROBLEMS

6. Evolution of Biomaterials Structural Functional Tissue Engineering Constructs (Scaffolds) Soft Tissue Replacements First generation Second Generation Third Generation

9. Advantage - Highly porous scaffold with porosity up to 93% and an average pore diameters up to 500 u m can be prepared using this technique. Disadvantage - A disadvantage of this method is that it can only be used to produce thin wafers or membranes up to 3mm thick.

11. In the work done by Thompson et al in 1995 they used the COMPRESSION MOULDING PRINCIPLE where a TEFLON MOULD was used with PLGA and gelatin micro spheres of specific diameter, and then heating the mould above the glass-transition temperature of PLGA while applying pressure to the mixture (This treatment causes the PLGA particles to bond together. Once the mould is removed, the gelatin component is leached out by immersing in water and the scaffold is then dried.

14. FREEZE DRYING The pore size can be controlled by the freezing rate and pH; a fast freezing rate produces smaller pores. Freeze-drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to the gas phase. Yannas et al., 1980 Collagen scaffolds have been made by freezing a dispersion or solution of collagen and then freeze drying . Dagalakis et al., 1980; Doillon et al., 1986

16. FIBER BONDING PGA fibers are immersed in PLLA solution.

18. RAPID PROTOTYPING TECHNIQUE 3D Solid modeling Data preparation Part Building Redesign Pass Reject A family of fabrication processes developed to make engineering prototypes in minimum lead time based on a CAD model of the item

19. BENEFITS: 1) Reduced lead times to produce prototype components. 2) Improved ability to visualize the part geometry due to its physical existence. 3) Earlier detection and reduction of design errors. 4) Increased capability to compute manufacturing properties of components and assemblies.

21. Technology invented at MIT by Bredt et al (1998) 1. Layer of powder spread on platform 2. Ink-jet printer head deposits drops of binder* on part cross-section 3. Binder dissolves and joins adjacent powder particles 4. Table lowered by layer thickness 5. New layer of powder deposited above previous layer 6. Repeat steps 2-4 till part is built 7. Shake powder to get part *Materials used: starch, plaster-ceramic powder Three Dimensional Printing (3DP)

23. 3D printed testpart with interconnecting channels. (a) Whole structure. (b) Detail view of the interconnecting channel structure with diameter of about 500 μ m. HA scaffolds seeded with MC3T3-E1 cells Binder (Schelofix)

24. STEREOLITHOGRAPHY 1. Raw material: photocurable monomer by a laser beam 2. Part constructed in layers of thickness 3. Supporting platform  in container at depth . UV laser solidifies part cross- section 4. Platform lowered by 5. Part cross-section computed at current height 6. Repeat Steps 4, 5 7. Removed completed part, 8. Break off supporting structures 9. Cure the part in oven. Polymerization occurs by the exposure of liquid resin to laser. He-Cd Laser UV beam Rotating mirror High-speed stepper motors Focusing system Liquid resin Part Platform Elevation control Support structures He-Ne Laser Sensor system for resin depth

26. Porous polylactide constructs Light microscopy images showing the spreading of mouse pre-osteoblasts after 1 d of culturing on PDLLA network

29. (a) STL design file of porous scaffold. (b) PCL scaffold fabricated by SLS. cortical shell and areas of trabeculated structures within the marrow space

32. PCL scaffold with a lay-down pattern fabricated by FDM HA–PCL scaffolds have a fine apatite coating 3-dimensional distribution of cells within the scaffolds. PCL HA-PCL

37. TOWARDS NANOTECHNLOGY !!!

40. NANO FABRICATION TECHNIQUES ELECTROSPINNING SELF ASSEMBLY

42. SAPNS repair for the animal brain. ( a ) Molecular model of the RADA16-I molecular building block. ( b ) Molecular model of numerous RADA16-I molecules undergo self assembly to form well ordered nanofibers with the hydrophobic alanine sandwich inside and hydrophilic residues on the outside. ( c ) The SAPNS is examined by using scanning electron microscopy. (Scale bar, 500 nm.)

43. When the electrical force at the surface of a polymer solution or polymer melt overcomes the surface tension, a charged jets is ejected. ELECTROSPINNING FIRST DESCRIPTION Electrospinning was in 1902 when J. F. Cooley filed a United States patent entitled ‘Apparatus for electrically dispersing fibres’ Electro-spinning uses an electrical charge to form a mat of fine fibers.

44. Poly styrene fibers Polyvinyl pyrolidone fibers

46. In summary, biomaterials fabricated by traditional techniques are inadequate for the growth of thick cross-sections of tissue due to the diffusion constraints posed by foam structures . Rapid prototyping fabrication systems provide a solution to this problem by creating scaffolds with controlled internal microarchitecture , which should increase the mass transport of oxygen and nutrients deep into the structure. Yet with all these technique available we do not have any guidelines to which type of technique is best for which kind of polymers The development of new nanotechnology Techniques to develop better and more promising biomaterials is on the go CONCLUSION

47. 1. The Design of Scaffolds for Use in Tissue Engineering. Part II. Rapid Prototyping Techniques, TISSUE ENGINEERING Volume 8, Number 1, 2002. 2. Processing and Fabrication of Advanced Materials VIII by K. A. Khor, T. S. Srivatsan M. Wang, W. Zhou, F. Boey on 1999 3. Biomaterials and bioengineering handbook, Donald L Wiss,2003. 4. Three-dimensional tissue fabrication, Valerie Liu Tsang, Sangeeta N. Bhatia, Advanced Drug Delivery Reviews 56 (2004) 1635– 1647 REFERENCES

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