Introduction to Biomaterials
- 1. Biomaterials A biomaterial is any material, that comprises whole or part of a living structure or a biomedical device which performs, increase, or replaces a function that has been lost through disease or injury. 1
- 2. Application of Biomaterials Tissue Engineering • Study of the growth of new connective tissues, or organs, from cells and a scaffold to produce a fully functional organ for implantation back into the donor host or by injecting / applying hydrogel. • Hydrogel=Self Healing Biomaterial Drug Delivery • Refers to approaches, formulations, technologies, and systems for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect. It is typically concerned with both quantity and duration of drug presence. 2
- 3. Tissue Engineering • Involve development of biological substitutes that restore, maintain, or improve function of tissue or whole organ. • Involving the combining of cells, scaffold, and bioactive agents to fabricate functional new tissue to replace damaged tissue. • Cells are often seeded in or onto biomaterials prior to transplantation. • These materials serve as temporary scaffolds and promote cell reorganization to a functional tissue. 3
- 4. Basic principle of Tissue engineering: Cells can be isolated (a) from the patient’s body, and expanded in a petridish in laboratory (b). Once we have enough number of cells, they can be seeded on a scaffold (c), and cultured in vitro in a bioreactor or incubator (d). When the construct is matured enough, then it can be implanted in the area of defect in patient’s body (e). Stem cells are biological cells found in all multicellular organisms, that can divide (through mitosis) and differentiate into diverse specialized cell types and can self- renew to produce more stem cells. 4
- 5. Scaffold • An artificial structure capable of supporting three- dimensional tissue formation. • Scaffold can be fabricated in the shape of the tissue we want to restore. 5
- 6. Scaffold • Examples of biomaterial used as scaffolds; 1. Collagen 2. Gelatin 3. Polyglycolic Acid (PGA) 4. Poly (L-Lactic Acid) (PLLA) 5. Poly (DL-Lactic-Co-Glycolic Acid) (PLGA) 6. Hydrogel (Smart Biomaterial) • Scaffold can be fabricated via various techiques; 1. 3-D Printing 2. Gas Foaming 3. Solvent Based Techniques 4. Electrospinning 6
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- 8. Scaffold To achieve the goal of tissue reconstruction, scaffolds must meet some specific requirements. A high porosity and an adequate pore size are necessary to facilitate cell seeding and diffusion throughout the whole structure of both cells and nutrients. Biodegradability is often an essential factor since scaffolds should preferably be absorbed by the surrounding tissues without the necessity of a surgical removal. The rate at which degradation occurs has to coincide as much as possible with the rate of tissue formation: this means that while cells are fabricating their own natural matrix structure around themselves, the scaffold is able to provide structural integrity within the body and eventually it will break down leaving the neotissue, newly formed tissue which will take over the mechanical load. 8
- 9. Scaffold Characteristics of scaffolds: 1) Biocompatibility Cells must adhere, function normally, and migrate onto the surface and eventually through the scaffold and begin to proliferate before laying down new matrix. After implantation, the scaffold or tissue engineered construct must elicit a negligible immune reaction in order to prevent it causing such a severe inflammatory response that it might reduce healing or cause rejection by the body. 9
- 10. Scaffold Characteristics of scaffolds: 2) Biodegradability • Scaffolds are not intended as permanent implants. The scaffold must therefore be biodegradable so as to allow cells to produce their own extracellular matrix. • The by-products of this degradation should also be non- toxic and able to exit the body without interference with other organs. 10
- 11. Scaffold Characteristics of scaffolds: 3) Mechanical properties Able to maintain the structure and function immediately after implantation and during remodeling of the implants . 4) Scaffold architecture Have an interconnected pore structure and high porosity to ensure cellular penetration and adequate diffusion of nutrients to cells within the construct and to the extra-cellular matrix formed by these cells. 11
- 12. Application : Scaffolds for Bone Tissue Natural bone matrix is a composite of biological ceramic (apatite) and biological polymer. Carbonated hydroxyapatite Ca10(PO4)6(OH)2 accounts for nearly two-thirds of the bone weight. The inorganic component provides compressive strength to the bone. Roughly one-third of the weight is from collagen fibers. Collagen fibers are tough and flexible , thus tolerate stretching, twisting and bending. For these reasons polymers, ceramics or their composites have been chosen as scaffold for bone repair. They can be synthetic or naturally occurring ones. Hydroxyapatite: A calcium phosphate mineral. Calcium phosphate is the name given to a family of minerals containing calcium ions (Ca2+) together with ortho-phosphates (PO4 3-), meta-phosphates (PO3 −) or pyrophosphates (P2O7 4-) 12
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- 15. Mechanism • Cross-linking of polymer strains are essential in the self-healing propery of second generation biomaterial 15
- 16. Hydrogel (Self Healing Biomaterial) • Water swollen polymeric structures cross-linked together. – Cross-links produced through: • Chemical reaction to form covalent bonds • Entanglement of polymers • Hydrogen bonding and van der Walls forces 16
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- 19. Hydrogel response to environmental stimuli • Hydrogels as 3D cross-linked hydrophilic polymer networks are capable of swelling or de-swelling reversibly in water and retaining large volume of liquid in swollen state. Hydrogels can be designed with controllable responses as to shrink or expand with changes in external environmental conditions. 19
- 20. Important Properties • Swelling – Solute diffusion – Surface properties and mobility – Optical properties – Mechanical properties 20
- 21. Important Properties • pH sensitive hydrogels – pH responsive hydrogels contain acidic or basic pendent groups – In appropriate media these groups ionize forming charges on the gel • Increases swelling forces due to localization of charges on the pendent group • Mesh size can change significantly with little change in pH 21
- 22. Important Properties • Temperature sensitive hydrogels – Exhibit lower critical solution temperatures (LCST), temperature at which at which a polymer is soluble • Above this temperature the hydrogel is hydrophobic and does not significantly swell in water. 22
- 23. Mechanism 23
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- 25. Uses of Hydrogel • Biomaterial, coatings for medical devices, contact lenses – Biologically compatible • Drug delivery – Degradable, swelling properties • Many other biological applications – Develop human tissues • Food – Jell-o 25
- 26. • Schematic illustration of the most common tissue engineering approaches. 26 Applications Hydrogel – based scaffold : Ability to tailor their mechanical characteristics to mimic those of natural tissues.
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- 28. Drug Delivery for Healing Wounds • A dry hydrogel contains a water soluble drug • Anti-Fibrinolytic drugs (Aprotinin , Epsilon ‐ Aminocaproic Acid and Aminomethylbenzoic Acid ) promote blood clotting by preventing blood clots from breaking down. • Drug is immobile in the hydrogel matrix and begins to diffuse out when the hydrogel begins to swell with water. • Stop blood loss in seriously injured patients and, as a result, save lives. 28
- 29. Hydrogel Scaffold With Self-Forming Fibers Highly Effective for Burn Wounds • Nanogel, that’s excellent at promoting the healing of second and third degree burns. • The material is made out of peptide hydrogels that works like a scaffold within which cells can grow. • When water is added to this scaffold, the peptides naturally group together into fibers, trapping the water inside. This allows the material to be both porous, while retaining moisture that helps promote cellular growth. • The researchers compared the material against commonly used silicone dressings and found it to be significantly more effective at wound healing. There haven’t been human studies done yet, but the findings are certainly promising. 29
- 30. method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals 30
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- 32. Methods : 1) Controllable released method • delivery of compounds (e.g., drugs, proteins, fertilizers, nutrients, and other biologically active agents) at an effective level in response to time and stimuli (e.g., pH, temperature, enzymes, UV light, magnetic fields, osmosis) 32
- 33. Fig. 1 Drug levels in the plasma released from traditional release system, a combination of multiple oral capsules or injection dosing (blue dashed curve), and controlled release system (red continuous curve) 33
- 34. Ion-Exchange Controlled Release System 34
- 35. Advantages 35
- 36. 2) Sustained-Release Formulation • release the drug the time interval of release is same every time 36
- 37. Advantages • improved patient compliance due to less frequent drug administration • reduction of fluctuation in steady-state drug levels • maximum utilization of the drug • increased safety margin of potent drug, • reduction in healthcare costs through improved therapy • shorter treatment period. 37
- 38. 3) Pulsatile-Release Formulation • Release of finite amount of drug at distinct time intervals that are programmed into the drug product 38
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- 41. Advantages 41
- 42. 4) Delayed-Release Formulation • delay release of the medication until the tablet has passed through the stomach to prevent the drug from being destroyed or inactivated by gastric juices or where it may irritate the gastric mucosa 42
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- 47. Active Targeting • facilitates the active uptake of nanoparticles by the tumor cells themselves 47
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