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Abstract/Syllabus:
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Irvine, Darrell, 20.462J Molecular Principles of Biomaterials, Spring 2006. (Massachusetts Institute of Technology: MIT OpenCourseWare), http://ocw.mit.edu (Accessed 10 Jul, 2010). License: Creative Commons BY-NC-SA
Molecular Principles of Biomaterials
Spring 2006
Synthetic molecules assemble into fibers that coax minerals into growing on top, a structure that mirrors bone. (Image by J. Hartgerink, Northwestern University; courtesy of the National Science Foundation.)
Course Highlights
This course features a complete set of assignments and exams with solutions.
Course Description
This course covers the analysis and design at a molecular scale of materials used in contact with biological systems, including biotechnology and biomedical engineering. Topics include molecular interactions between bio- and synthetic molecules and surfaces; design, synthesis, and processing approaches for materials that control cell functions; and application of state-of-the-art materials science to problems in tissue engineering, drug delivery, vaccines, and cell-guiding surfaces.
Syllabus
Overview
This course includes the analysis and design at a molecular scale of materials used in contact with biological systems, including biotechnology and biomedical engineering. Topics include molecular interactions between bio- and synthetic molecules and surfaces; design, synthesis, and processing approaches for materials that control cell functions; and application of state-of-the-art materials science to problems in tissue engineering, drug delivery, vaccines, and cell-guiding surfaces.
Course Focus
This course covers the fundamental concepts (physical chemistry, chemistry, and materials physics, and biology) behind the design at a molecular scale of synthetic materials with biological functions.
Evaluation
Grading criteria.
| ACTIVITIES |
PERCENTAGES |
| Homework (which may include Problem Sets, and Critical Evaluation of Recent Research Literature) |
30% |
| In-class Exam |
30% |
| Take-home Exam |
40% |
There is no final exam for the course.
Resources
20.462J does not have an assigned textbook; readings from selected texts and primary literature sources will be used throughout the course. Some of the useful text resources (in no particular order) include:
Ratner, B. D., A. S. Hoffman, F. J. Schoen, and J. E. Lemons. Biomaterials Science. Burlington, MA: Academic Press, 1996. ISBN: 9780125824613.
Fan, L. T., and S. K. Singh. Controlled Release: A Quantitative Treatment. Edited by H. -J. Cantow, et al. New York, NY: Springer-Verlag, 1989. ISBN: 9780387508238.
Flory, P. J. Principles of Polymer Chemistry. Ithaca, NY: Cornell University Press, 1953. ISBN: 9780801401343.
Dinh, S. M., J. D. DeNuzzio, and A. R. Comfort. Intelligent Materials for Controlled Release. New York, NY: American Chemical Society, 1999. ISBN: 9780841235953.
Yannas, I. V. Tissue and Organ Regeneration in Adults. New York, NY: Springer, 2001. ISBN: 9780387952147.
Lanza, R. P., R. Langer, and W. L. Chick. Principles of Tissue Engineering. Burlington, MA: Academic Press, 1997. ISBN: 9781570593420.
Mann, S. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry. New York, NY: Oxford University Press, 2002. ISBN: 9780198508823.
Mortimer, R. G. Physical Chemistry. Burlington, MA: Academic Press, 2000. ISBN: 9780125083454.
Saltzman, W. M. Drug Delivery: Engineering Principles for Drug Therapy. New York, NY: Oxford University Press, 2001. ISBN: 9780195085891.
Calendar
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Course calendar.
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LEC #
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TOPICS
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KEY DATES
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1
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Overview of Course, Orientation to Current Approaches and Types of Molecularly-designed Biomaterials
Biodegradable Polymeric Solids
Chemistry and Physical Chemistry of Hydrolysis
Links between Materials Structure and Hydrolysis Mechanisms
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2
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Biodegradable Polymeric Solids (cont.)
Factors Controlling Polymer Degradation Rates
Theory of Solid Polymer Erosion
Tailoring Degradable Polymer Structure and Composition
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Problem set 1 out
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3
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Controlled Release Devices
Types of Controlled Release Devices
Degradable Materials in Controlled Release Devices
Physical Chemistry Principles in Delivering Small Molecules vs. Proteins
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4
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Controlled Release Devices (cont.)
Theory of Drug Release in Eroding Systems
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Problem set 1 due
Problem set 2 out
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5
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Case Studies in Complex Controlled Release
Pulsatile Release from Programmed Eroding Systems
Controlled Release Microchips
Combining Drug Delivery with Tissue Engineering
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Problem set 2 due
Problem set 3 out
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6
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Hydrogels as Biomaterials
Hydrogel Structure and Physical Chemistry
Methods of Polymerization
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7
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Hydrogels as Biomaterials (cont.)
Theory of Hydrogel Swelling
Physical Hydrogels
- Ionic and Hydrogen Bonding in Gels
- Association of Amphiphilic Block Copolymers
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Problem set 3 due
Problem set 4 out
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8
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Hydrogels as Biomaterials (cont.)
Polyelectrolyte Hydrogels
Coacervates
Polyelectrolyte Multi-layers
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9
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Hydrogels as Biomaterials (cont.)
Theory of Polyelectrolyte Gel Swelling
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Problem set 4 due
Problem set 5 out
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10
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Hydrogels as Biomaterials (cont.)
Applications of Hydrogels: Molecular Imprinting
Applications of Hydrogels: Glucose-sensitive Drug Delivery
Kinetics of Drug Diffusion Through Hydrogels
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11
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Engineering Biological Recognition of Biomaterials
Biological Recognition in Vivo
Protein-resistant and Cell-resistant Surfaces
Engineering Recognition of Biomaterials: Adhesion and Migration
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Problem set 5 due
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Exam 1
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12
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Engineering Biological Recognition of Biomaterials (cont.)
Enzymatic Recognition of Biomaterials
Cytokine Signaling from Biomaterials
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13
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Engineering Biological Recognition of Biomaterials (cont.)
Mimicking Cell-cell Contacts with Surfaces
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Problem set 6 out
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14
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Bioceramics and Biocomposites
Introduction to Biological Approaches to Biomineralization
Interfacial Biomineralization
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15
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Bioceramics and Biocomposites (cont.)
Biological Control of Mineralization within Vesicles
Biomimetic Syntheses: Microemulsion and Micellar Reactions Organic Templating of Inorganic Biomaterials: Natural and Synthetic Approaches
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Problem set 6 due
Problem set 7 out
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16
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Bioceramics and Biocomposites (cont.)
Theory of Controlled Nucleation
Bone Structure and Bone Biomimesis
Biocomposites in Device Applications and Drug Delivery
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17
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Molecular Devices
Molecular Switches via Proteins and 'Smart' Polymers
- Temperature, pH, and Light-sensitive Switches
Molecular Motors
- Kinesin-based Molecular Shuttles
- ATP Synthase-based Nano-rotors
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Problem set 7 due
Problem set 8 out
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18
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Nanoparticle and Microparticle Biomolecule Drug Carriers
Pro-drugs, Micelles, Liposomes, Polymerosomes, Nanoparticles, and Microparticles
Delivery of Drugs to Tissues via Systemic Circulation
Materials for Anti-Cancer Drug Delivery
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19
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Nanoparticle and Microparticle Biomolecule Drug Carriers (cont.)
Barriers to Systemic / Oral Delivery and Delivery of Molecules to Tissues
'Stealth' Particles
- Theory of Protein-resistant Particles
Experimental Function of Long-circulating Carriers and PEGylated Compounds
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Problem set 8 due
Take-home exam distributed
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Focus Topic: Integrating Biological Knowledge Into Biomaterials Design For Vaccines
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20
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Basic Biology of Vaccination and Viral Infections
Rudiments of Adaptive Immunity: The Basis of Vaccination
Viral Infections
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21
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Basic Biology of Vaccination and Viral Infections (cont.)
Vaccination Against Viruses: Parallels between Immunization and Infection
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22
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Drug Targeting and Intracellular Drug Delivery for Vaccines
Targeting Nano-carriers and Micro-carriers to Specific Cell Types
Chemistry of Antibodies for Targeting
Pathways of Intracellular Transport
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23
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Drug Targeting and Intracellular Drug Delivery for Vaccines (cont.)
Mechanisms of Intracellular Delivery
Mimicking Viral Entry Strategies
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24
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DNA Vaccines
Gene Therapy and DNA Immunization
Mechanisms of DNA Vaccines
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25
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DNA Vaccines (cont.)
Delivery Systems for DNA
Systemic vs. Local Delivery
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Take-home exam due
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Further Reading:
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Readings
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Course readings.
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LEC #
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TOPICS
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READINGS
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1
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Overview of Course, Orientation to Current Approaches and Types of Molecularly-designed Biomaterials
Biodegradable Polymeric Solids
Chemistry and Physical Chemistry of Hydrolysis
Links between Materials Structure and Hydrolysis Mechanisms
|
|
|
2
|
Biodegradable Polymeric Solids (cont.)
Factors Controlling Polymer Degradation Rates
Theory of Solid Polymer Erosion
Tailoring Degradable Polymer Structure and Composition
|
von Burkersroda, F., L. Schedl, and A. Gopferich. "Why Degradable Polymers Undergo Surface Erosion or Bulk Erosion." Biomaterials 23, no. 21 (November 2002): 4221-4231.
Supplementary Readings
Young, R. J., and P. A. Lovell, eds. "Structure." Chapter 4 in Introduction to Polymers. 2nd ed. Boca Raton, FL: CRC Press, 2000. 241-309. ISBN: 9780748757404.
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3
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Controlled Release Devices
Types of Controlled Release Devices
Degradable Materials in Controlled Release Devices
Physical Chemistry Principles in Delivering Small Molecules vs. Proteins
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Saltzman, W. Mark, and W. L. Olbricht. "Building Drug Delivery into Tissue Engineering." Nat Rev Drug Discov 1, no. 3 (March 2002): 177-186.
———. "Drug Administration and Drug Effectiveness." Chapter 2 in Drug Delivery: Engineering Principles for Drug Therapy (Topics in Chemical Engineering). New York, NY: Oxford University Press, 2001. ISBN: 9780195085891.
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4
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Controlled Release Devices (cont.)
Theory of Drug Release in Eroding Systems
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Charlier, A., B. Leclerc, and G. Couarraze. "Release of Mifepristone from Biodegradable Matrices: Experimental and Theoretical Evaluations." Int J Pharm 200, no. 1 (April 25, 2000): 115-20.
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5
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Case Studies in Complex Controlled Release
Pulsatile Release from Programmed Eroding Systems
Controlled Release Microchips
Combining Drug Delivery with Tissue Engineering
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Santini, J. T., Jr., A. C. Richards, R. Scheidt, M. J. Cima, and R. Langer. "Microchips as Controlled Drug-Delivery Devices." Angew Chem Int Ed Engl 39, no. 14 (July 17, 2000): 2396-2407.
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6
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Hydrogels as Biomaterials
Hydrogel Structure and Physical Chemistry
Methods of Polymerization
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Peppas, N. A., Y. Huang, M. Torres-Lugo, J. H. Ward, and J. Zhang. "Physicochemical Foundations and Structural Design of Hydrogels in Medicine and Biology." Annu Rev Biomed Eng 2 (2000): 9-29.
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7
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Hydrogels as Biomaterials (cont.)
Theory of Hydrogel Swelling
Physical Hydrogels
- Ionic and Hydrogen Bonding in Gels
- Association of Amphiphilic Block Copolymers
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Flory, Paul J. Principles of Polymer Chemistry. Ithaca, NY: Cornell University Press, 1953, pp. 464-469 and pp. 576-581. ISBN: 9780801401343.
Supplementary Readings
———. Principles of Polymer Chemistry. Ithaca, NY: Cornell University Press, 1953, pp. 495-507. ISBN: 9780801401343.
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8
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Hydrogels as Biomaterials (cont.)
Polyelectrolyte Hydrogels
Coacervates
Polyelectrolyte Multi-layers
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Ron, E. S., and L. E. Bromberg. "Temperature-responsive Gels and Thermogelling Polymer Matrices for Protein and Peptide Delivery." Adv Drug Deliv Rev 31 no. 3 (May 4, 1998): 197-221.
Chandler, D. "Interfaces and the Driving Force of Hydrophobic Assembly." Nature 437, no. 7059 (September 29, 2005): 640-647.
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9
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Hydrogels as Biomaterials (cont.)
Theory of Polyelectrolyte Gel Swelling
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De, S. K., N. R. Aluru, B. Johnson, W. C. Crone, D. J. Beebe, and J. Moore. "Equilibrium Swelling and Kinetics of pH-responsive Hydrogels: Models, Experiments, and Simulations." Journal of Microelectromechanical Systems 11, no. 5 (October 2002): 544-555.
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10
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Hydrogels as Biomaterials (cont.)
Applications of Hydrogels: Molecular Imprinting
Applications of Hydrogels: Glucose-sensitive Drug Delivery
Kinetics of Drug Diffusion through Hydrogels
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Supplementary Readings
Lustig, Steven R., and Nikolaos A. Peppas. "Solute Diffusion in Swollen Membranes. IX. Scaling Laws for Solute Diffusion in Gels." Journal of Applied Polymer Science 36, no. 4 (August 5, 1988): 735-747.
Canal, T., and N. A. Peppas. "Correlation between Mesh Size and Equilibrium Degree of Swelling of Polymeric Networks." J Biomed Mater Res 23, no. 10 (October 1989): 1183-1193.
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11
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Engineering Biological Recognition of Biomaterials
Biological Recognition in Vivo
Protein-resistant and Cell-resistant Surfaces
Engineering Recognition of Biomaterials: Adhesion and Migration
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Hirano, Y., and D. J. Mooney. "Peptide and Protein Presenting Materials for Tissue Engineering." Advanced Materials 16, no. 1, (January 2004): 17-25.
Discher, D. E., P. Janmey, and Y. L. Wang. "Tissue Cells Feel and Respond to the Stiffness of their Substrate." Science 310, no. 5751 (November 18, 2005): 1139-1143.
Supplementary Readings
Lodish, Harvey, Arnold Berk, Lawrence Zipursky, Paul Matsudaira, David Baltimore, and James Darnell, eds. "The Extracellular Matrix." In Molecular Biology of the Cell. 4th ed. New York, NY: W.H. Freeman, October 1999, pp. 1124-1150. ISBN: 9780716737063.
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Exam 1
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12
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Engineering Biological Recognition of Biomaterials (cont.)
Enzymatic Recognition of Biomaterials
Cytokine Signaling from Biomaterials
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Schense, J. C., J. Bloch, P. Aebischer, and J. A. Hubbell. "Enzymatic Incorporation of Bioactive Peptides into Fibrin Matrices Enhances Neurite Extension." Nat Biotechnol 18, no. 4 (April 2000): 415-419.
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13
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Engineering Biological Recognition of Biomaterials (cont.)
Mimicking Cell-cell Contacts with Surfaces
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|
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14
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Bioceramics and Biocomposites
Introduction to Biological Approaches to Biomineralization
Interfacial Biomineralization
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Mann, Stephen. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry. New York, NY: Oxford University Press, 2002, chapter 3, pp. 24-37. ISBN: 9780198508823.
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15
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Bioceramics and Biocomposites (cont.)
Biological Control of Mineralization within Vesicles
Biomimetic Syntheses: Microemulsion and Micellar Reactions Organic Templating of Inorganic Biomaterials: Natural and Synthetic Approaches
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Mann, Stephen. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry. New York, NY: Oxford University Press, 2002, chapter 6, pp. 89-102. ISBN: 9780198508823.
Supplementary Readings
Allen, Samuel M., and Edwin L. Thomas. The Structure of Materials (MIT Series in Materials Science and Engineering). New York, NY: Wiley, 1999, pp. 135-138. ISBN: 9780471000822.
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16
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Bioceramics and Biocomposites (cont.)
Theory of Controlled Nucleation
Bone Structure and Bone Biomimesis
Biocomposites in Device Applications and Drug Delivery
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Vogel, Viola. "Reverse Engineering: Learning from Proteins How to Enhance the Performance of Synthetic Nanosystems." MRS Bulletin 27, no. 12 (December 2002): 972-978.
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17
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Molecular Devices
Molecular Switches via Proteins and 'Smart' Polymers
- Temperature, pH, and Light-sensitive Switches
Molecular motors
- Kinesin-based Molecular Shuttles
- ATP Synthase-based Nano-rotors
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Hammer, Daniel A., and Dennis E. Discher. "Synthetic Cells-Self-Assembling Polymer Membranes and Bioadhesive Colloids." Annual Review of Materials Research 31 (August 2001): 387-404.
Allen T. M., and P. R Cullis. "Drug Delivery Systems: Entering the Mainstream." Science 303, no. 5665 (March 19, 2004): 1818-1822.
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18
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Nanoparticle and Microparticle Biomolecule Drug Carriers
Pro-drugs, Micelles, Liposomes, Polymerosomes, Nanoparticles, and Microparticles
Delivery of Drugs to Tissues via Systemic Circulation
Materials for Anti-cancer Drug Delivery
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Stolnik, S., L. Illum, and S. S. Davis. "Long Circulating Microparticulate Drug Carriers." Advanced Drug Delivery Reviews 16, no. 2 (September 1995): 195-214 (20).
Supplementary Readings
Halperin, A. "Polymer Brushes that Resist Adsorption of Model Proteins: Design Parameters." Langmuir 15, no. 7 (1999): 2525-2533.
Efremova, Nadezhda V., Bruce Bondurant, David F. O'Brien, and Deborah E. Leckband. "Measurements of Interbilayer Forces and Protein Adsorption on Uncharged Lipid Bilayers Displaying Poly(ethylene glycol) Chains." Biochemistry 39 no. 12 (2000): 3441-3451.
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19
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Nanoparticle and Microparticle Biomolecule Drug Carriers (cont.)
Barriers to Systemic / Oral Delivery and Delivery of Molecules to Tissues
'Stealth' Particles
- Theory of Protein-resistant Particles
Experimental Function of Long-circulating Carriers and PEGylated Compounds
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Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit. "The Immunology of Vaccination." In Vaccines. Philadelphia, PA: Saunders, 2003, pp. 28-39. ISBN: 9780721696881.
Abbas, Abul K., Andrew H. Lichtman, and Jordan S. Pober. "General Properties of Immune Responses." In Cellular and Molecular Immunology. 4th ed. Philadelphia, PA: W.B. Saunders Company, 2000. pp. 3-16. ISBN: 07216823323.
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Focus Topic: Integrating Biological Knowledge Into Biomaterials Design For Vaccines
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20
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Basic Biology of Vaccination and Viral Infections
Rudiments of Adaptive Immunity: The Basis of Vaccination
Viral Infections
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Raychaudhuri, S., and K. L. Rock. "Fully Mobilizing Host Defense: Building Better Vaccines." Nat Biotechnol 16, no. 11 (November 1998): 1025-1031.
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21
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Basic Biology of Vaccination and Viral Infections (cont.)
Vaccination Against Viruses: Parallels between Immunization and Infection
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Wang, C., Q. Ge, D. Ting, D. Nguyen, H. R. Shen, J. Chen, H. N. Eisen, J. Heller, R. Langer, and D. Putnam. "Molecularly Engineered Poly (ortho ester) Microspheres for Enhanced Delivery of DNA Vaccines." Nat Mater 3, no. 3 (March 2004): 190-196. (Epub: February 15, 2004).
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22
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Drug Targeting and Intracellular Drug Delivery for Vaccines
Targeting Nano-carriers and Micro-carriers to Specific Cell Types
Chemistry of Antibodies for Targeting
Pathways of Intracellular Transport
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Pack, D. W., A. S. Hoffman, S. Pun, and P. S. Stayton. "Design and Development of Polymers for Gene Delivery." Nat Rev Drug Discov 4, no. 7 (July 2005): 581-593.
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23
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Drug Targeting and Intracellular Drug Delivery for Vaccines (cont.)
Mechanisms of Intracellular Delivery
Mimicking Viral Entry Strategies
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Carter, P. "Improving the Efficacy of Antibody-based Cancer Therapies." Nat Rev Cancer 1, no. 2 (November 2001): 118-129.
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24
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DNA Vaccines
Gene Therapy and DNA Immunization
Mechanisms of DNA Vaccines
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25
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DNA Vaccines (cont.)
Delivery Systems for DNA
Systemic vs. Local Delivery
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