BMM 305 Biomaterials. Biological Recognition. Dr. Ersin Emre Oren

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1 BMM 305 Biomaterials Dr. Ersin Emre Oren Department of Biomedical Engineering Department of Materials Science & Nanotechnology Engineering TOBB University of Economics and Technology Ankara - TURKEY Bionanodesign Laboratory eeoren@etu.edu.tr

2 3 main classes of synthetic biomaterials used today are Metals & Alloys Ceramics A titanium hip prosthesis with a ceramic head and polyethylene acetabular cup Polymers

3 Biomaterials implies biology + materials. A central premise of the biomaterials field has been The surface dictates the biological reaction Biology uses surfaces and interfaces All in vivo biomaterials directly exploit surfaces

4 When a synthetic material is placed in a biological environment a series of reactions is initiated almost instantaneously: Water molecules (and H + and OH ), being the lowest molecular weight species, should reach the biomaterial surface first (in milliseconds). and sets the stage for the biological reactions to follow. Proteins, dissolved in serum arrive next at the surface by diffusion convection (in some cases) Once at the surface, proteins can adsorb, desorb, exchange with other proteins, denature, Increase/decrease their biological activity The Imaging Technology Group Beckman Institute for Advanced Sci. & Tech. This complex landscape, comprised of many proteins, becomes the environment to which cells will respond (and cells do indeed respond to proteins).

5 When biomaterials are implanted into animals or humans, protein adsorption onto the foreign surface occurs within seconds of implantation. This rapid protein adsorption means that cells arriving at the biomaterial surface probably interact with the adsorbed protein layer rather than interacting directly with the material itself. Thus, the initial protein adsorption onto a biomaterial surface plays a key role in how the body responds to an implanted biomaterial. The body s first response to any injury is inflammation, and much study has been done on the influence of protein adsorption on the inflammatory response. Biomaterials and medical devices are interfaced against tissues, so understanding tissues, their organization, and their properties is important. Extracellular matrix is the extracellular part of multicellular structure (e.g., organisms, tissues, biofilms) that typically provides structural and biochemical support to the surrounding cells.

6 ADSORBED PROTEINS ON BIOMATERIALS Biomaterials vs donor tissues or organs not attacked by the immune system attacked by the immune system, This fundamental difference arises from the presence of immunologically recognizable biologic motifs on donor tissue, and their absence on synthetic materials. Nonetheless, there are other types of biological responses to implanted biomaterials that often weaken their usefulness, including the clotting of blood and the foreign-body reaction. The basis is the adsorption of adhesion proteins to the surface of the biomaterials that are recognized by the integrin receptors present on most cells. Integrins are transmembrane receptors that mediate the attachment between a cell and its surroundings, such as other cells or the extracellular matrix (ECM)

7 ADSORBED PROTEINS ON BIOMATERIALS Adhesion Proteins are proteins, preadsorption of which onto a solid substrate greatly increases surface adhesiveness to many kinds of cells. Fibroblast A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, and plays a critical role in wound healing. fibronectin preadsorption greatly increases the adhesion of fibroblasts albumin preadsorption prevents the adhesion of fibroblasts Fibronectin 1 non-wettable polystyrene surface wettable polystyrene surface

8 Major mechanisms affecting biological activity of adsorbed proteins: Affinity of the adhesion protein for a surface, affecting how much of the proteins is present on a particular surface; Molecular potency, defined as the degree to which the adsorbed adhesion protein expresses its biological activity Changes in Biological properties of adsorbed proteins Molecular Structure Site Availability Molecular potency Surface properties are generally grouped into 3 categories: Geometric Chemical Electrical

9 Ordered Self-Assembly of proteins [GBP-1 on Au(111)] Au(111) 500 nm 100 nm

10 MHGKTQATSGTIQS MHGKTQATSGTIQS MHGKTQATSGTIQS

11 In solution no surface In solution on surface

12 C ( t) 1 expkobst C K 1 eq Irving Langmuir ( ) The Nobel Prize in Chemistry 1932 was awarded to Irving Langmuir "for his discoveries and investigations in surface chemistry".

13 d d ka1c kd kac kac kd dt dt u d ab dt 1 du b dt u u a b du bu dt d dt k C k C k du dt du bdt u d b dt a b a a d d 1 du dt b dt ln u bt c u exp bt c exp exp a b d expbt u c bt k C k k C d exp k C k t a d a a d k C k C k d exp k C k t a a d a d kc a d k C k k C k a d a d k C k k C k exp k C k t (0) kc a d exp 0 0 a d a d a d (0) 0 d k C a kc a 1 exp kac kd t k C k a d C ( t) 1 expkac kd t k C d k a

14 Nobel Prize in Chemistry (1932) C ( t) 1 expkac kd t k C d k a 1 Keq C ( t) 1 expkobst C K 1 eq k obs Irving Langmuir ( ) () t t

15 Properties of Materials Next Lecture: We will continue with the BIOLOGICAL RECOGNITION topic!