Having attended a basic course on biomaterials (suggested, not mandatory).

This course provides basics of biology necessary for understanding the biomaterials  and biofluids concepts; it can be followed by non-biological background students. 

This course can be followed without having a fluid dynamics background.

Slides are provided in advance to each class.

Interactive teaching, including class discussions.

1. Biocompatibility & Hemocompatibility: Materials versus Biomaterials. Fundamental concepts to understand the proper design of biomaterials and control host response by body fluid interaction. Definitions of biomaterials and biocompatibility; Factors impacting biocompatibility; Cells; Blood cells; Inflammation (acute and chronic); Foreign body reaction; Fibrotic encapsulation. The immune system; Innate immunity and adaptive immunity; Cell-mediated immunity and humoral immunity; Antibodies (immunoglobulins and antigens); T and B lymphocytes; Failure of immune system (hypersensitivity, allergy, autoimmunity and immunodeficiency); Systemic toxicity and hypersensitivity to implanted biomaterials (dose, exposure time, synergistic effects, metal ions and haptens);  Carcinogenesis associated to implanted biomaterials; Wound healing. Hemocompatibility: Vroman effect, protein deposition cascade, from protein adsorbtion to thrombus, surface induced thrombosis, influence of surfaces, coagulation proteins and platelets. Fibrinogen, fibrin and fibrinolysis. Protein immobilization on surfaces. Blood cell types; Inflammation (acute and chronic), fibrotic encapsulation, the role of macrophages. ISO 10993-1, Biological Evaluation of Medical Devices. Medical versus non-medical devices.
2. Body fluids & transport phenomena: Fluid definition (Newtonian, non-Newtonian, pseudoplastics, others) and key properties (viscosity, density, capillary action, surface tension). Definitions and types of biofluids. Human body composition, body fluid classifications. Biofluid compartments; Intracellular and extracellular fluids; Urines; Blood and plasma; Oral fluids (chemical composition, REDOX potential, pH, temperature variations and buffer system in saliva); Gastro-intestinal fluids (pH variation, buffering systems, microbiota); Other body fluids (e.g. lymphatic; cerebro-spinal, synovial; menstrual, sweat, tears, etc.). Circulating fluids and basic principles of fluid dynamics. Human circulatory system (Hagen-Poiseuille equation, pressure loss, blood viscosity versus shear rate; large vases, Fåhræus Lindqvist effect, capillary exchange); hematocrit and blood viscosity; plasma composition; erythrocytes and oxygen transport; thrombocytes and hemostasis. Diffusion. Fluids changing composition with time, stimuli and age. Hematomas, granulomas; infections. Gaseous fluids: breathing and transpiration. Selectively permeable membrane. Some history of body fluids; urine as an ultrafiltrated waste fluid useful to assess medical conditions. transport processes (osmosis, osmotic pressure, membrane permeability, flow rate, concentration); transport across biological membranes (facilitated diffusion passive transport or active transport); hypertonic, hypotonic and isotonic solutions; colloids; plasma as a colloidal solution; oncotic pressure; hydrostatic pressure; Starling equation for transport through capillaries; glomerulus and renal filtration.
3. In vitro biofluids: Simulating body fluids: Artificial solutions (artificial saliva, Ringer solution, artifial urines). Cell cultures: historic hints and applications; cell types (primary, transformed, cell lines); culture media composition; culture flasks an 3D cellular models. Mass transport phenomena in biological tissues affecting biomaterials and cells: convection, diffusion, diffusion distance, hypoxia, limiting factors to cell survival. Theoretical modeling to explore the relationships among cell density, diffusion distance, and cell viability within a graft. 
4. Polymer biodegradation & surface coatings. Biodegradable polymers: General concepts of: biodegradation, bioresorption and bioabsorption; Natural biopolymers: Proteins (collagen, gelatin, collagen peptides); Synthetic polymers: Aliphatic polyesters (PLA, PGA, PLGA) and Polyanhydrides; Degradation mechanisms: Degradation and erosion, Bulk and surface degradation, hydrolysis and enzymatic attacks; Factors affecting degradation; Case studies. Surface and interface definition, interfacial properties, fouling, surface tension and free energy; Young’s equation of the contact angle; Wenzel and Cassie-Baxter models; superhydrophobicity; capillary effect; Lotus effect and applications in antifouling/antimicrobial surfaces; biofilm formation; quantification of protein adsorption. Degradation mechanisms (class demo on in vitro biodegradation of biopolymers in different media, effect of pH, enzymes, weight loss.
5. Drug Delivery Systems (DDS): Drug Delivery Systems (DDS): Introduction (definition of DD, traditional DDS). Principles, origins, evolution and advantages of Controlled Drug Delivery Systems (CDDS): History of CDDS, classification of CDDS, categorizing of DDS by size: Macroscale DDS (“zero order” constant delivery rate DDS); Macroscale and microscale DDS (site-specific, sustained delivery rate DDS); Nanoscale DDS (targeted DDS). Implanted macroscale DDS: Non-degradable and biodegradable systems. Microscale DDS: Injected Microparticle depots (microspheres) and release mechanisms, phase-separating depot systems. Nanoscale DDS (targeted DDS): Passive and active targeting, different targeting nanocarriers, nanofibers. Case studies.
6. (Bio)material/biofluid interactions: Blood-biomaterials interactions. Kidney filtration biomembrane (fenestrations, slits, solute size and charge, filtration area, extraction ratio, filtration rates); kidney failures and uremic toxins (size, protein-bound solutes); the artificial kidney (historic notes and apparata); membranes (Hildebrand solubility parameter, concentrated versus dilute polymer solutions, lacquers, casting membranes, phase inversion technique, ternary diagram, pore formation); membrane classification according to pore size (reverse osmosis, nano-, ultra-, micro-filtration); hemodialysis membrane separation characteristics (skin, pores and stroma); hemodialyzer structures; hemo-dialysis/filtration/diafiltration (diffusion and convection); membrane materials (cellulose and synthetic, biocompatibility); hollow fibers (wall thickness, hydrophilic/phobic, polarization concentration, sieving, fouling, pressure drop); fluoropolymers (PTFE, ePTFE, PDF); biotextiles; vascular grafts; endovascular prostheses. Biofluid absorption: case study products: baby diaper, female pads. Material composition according to fluid type (urine or menses). Absorbency: Jurin’s law for capillary tubes; Washburn equation for porous materials; pee modeling (Richards equation); patents on materials with superabsorbent (SAP) properties; HIPE foam; osmotic behavior of SAP; SAP principle of function, production (radical polymerization of acrylic acid based components), swelling, surface gradients. Smart biomaterials for targeted DDS: pH-responsive (anionic and cationic) hydrogels for targeted drug delivery in the gastrointestinal tract (gellan gum and chitosan). 
7. Metals & corrosion in body fluids: Human environment: element composition, chlorine ion concentration and pH variation in pathology (hematoma, wounds). Oral versus interstitial fluids. Basic principles of metals and corrosion in the human body. Stainless steels; Cobalt and Titatium alloys. Corrosion and opacification of dental materials (galvanic pain, cariogenesis and allergy, acid-producing and sulfate-reducing oral micro-organisms). Tooth restorations (amalgams, fixed partial denture, removable partial denture, pergengival implants). Current pathways in metallic restorations of teeth. 
8. Bioreactors, microfluidics & organs-on-chip:Bioreactors (spinner flasks, flow perfusion bioreactors, cell-expansion bioreactors), bioreactor-induced mechanical stimulation (shear stress). Examples of bioreactors developed at Otolab and fluid dynamics studies. Microfluidics and organs-on-a-chip. Introduction to microfluidics. Challenges and opportunities. Basics of microfluidics physics. Viscosity and implications on microfluidic devices. Special phenomena associated with the micro-scale: laminar flow (Reynolds Number), diffusion and mixing, capillary phenomena, surface energy. Wettability. Hydrophilic and hydrophobic surfaces. Organs-on-a-chip. Definitions. Challenges and opportunities. Bioinspired vs. biomimetic approaches. Description of specific case studies: lungs, kidney, heart, brain.
9. Body fluid diagnostics using materials: Plasma-materials interaction: protein electrophoresis (principle of function, and polyacrylamide membrane properties); ELISA assay: colorimetric reaction; direct/indirect competitive reaction; basic steps; example: pregnancy test; clinical applications; spectrophotometer/fluorimeter principle of function. Laboratory experience. 

• Notes taken in class
• Slides give from the teacher after each class
• Articles shared.

Contact the teacher for the didactical material and course information.

• The exam is made up of one ongoing written assignment and one final oral test. If a student does not provide assignments during the course, he/she will have to provide it anyway before/at the oral exam.
• The written assignment consist of gruop homework on specific case studies with written report or slide presentation.
• The written test will be passed if the student demonstrate in-depth knowledge, capability of summarizing, representing and discussing the findings.
• The oral test consists of an interview between the candidate and the lecturer on a topic of the program. The student could be requested to also solve written problems/exercises in front of the lecturer. 
• The oral test will be passed if the student has demonstrated sufficient in-dept knowledge, has reached sufficient skills and behaviors on the selected topic.

http://matnano.ing.unipi.it/en/

This course of Biofluids and Materials Interactiom is designed to provide a general understanding of the multidisciplinary field of biofluids, intended as body fluids and body-simulating fluids, and to give a key focus on their interaction with biomaterials. Specifically, it aims at developing in the attendants all the necessary skills as well as the fundamental theoretical and technical competences with the ultimate goal to have graduated students who can successfully interface with the multidisciplinary scenario of biomaterials-related products and technologies, both in industrial (e.g., pharma) and research environments. Some current and innovative applications of biomaterials placed in a biofluidic environment will be evaluated to highlight the connections existing between material properties, function, biological responses and clinical applications. Due to the multidisciplinary nature of this topic, both teamwork and self-learning will be stimulated.