20.462J | Spring 2006 | Graduate

Molecular Principles of Biomaterials



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


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.


Controlled Release Devices

Types of Controlled Release Devices

Degradable Materials in Controlled Release Devices

Physical Chemistry Principles in Delivering Small Molecules vs. Proteins

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.


Controlled Release Devices (cont.)

Theory of Drug Release in Eroding Systems

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.

Case Studies in Complex Controlled Release

Pulsatile Release from Programmed Eroding Systems

Controlled Release Microchips

Combining Drug Delivery with Tissue Engineering

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.

Hydrogels as Biomaterials

Hydrogel Structure and Physical Chemistry

Methods of Polymerization

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.

Hydrogels as Biomaterials (cont.)

Theory of Hydrogel Swelling

Physical Hydrogels

  • Ionic and Hydrogen Bonding in Gels
  • Association of Amphiphilic Block Copolymers

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.


Hydrogels as Biomaterials (cont.)

Polyelectrolyte Hydrogels


Polyelectrolyte Multi-layers

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.


Hydrogels as Biomaterials (cont.)

Theory of Polyelectrolyte Gel Swelling

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.

Hydrogels as Biomaterials (cont.)

Applications of Hydrogels: Molecular Imprinting

Applications of Hydrogels: Glucose-sensitive Drug Delivery

Kinetics of Drug Diffusion through Hydrogels

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.


Engineering Biological Recognition of Biomaterials

Biological Recognition in Vivo

Protein-resistant and Cell-resistant Surfaces

Engineering Recognition of Biomaterials: Adhesion and Migration

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.

  Exam 1  

Engineering Biological Recognition of Biomaterials (cont.)

Enzymatic Recognition of Biomaterials

Cytokine Signaling from Biomaterials

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.

Engineering Biological Recognition of Biomaterials (cont.)

Mimicking Cell-cell Contacts with Surfaces


Bioceramics and Biocomposites

Introduction to Biological Approaches to Biomineralization

Interfacial Biomineralization

Mann, Stephen. Biomineralization: Principles and Concepts in Bioinorganic Materials Chemistry. New York, NY: Oxford University Press, 2002, chapter 3, pp. 24-37. ISBN: 9780198508823.

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

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.


Bioceramics and Biocomposites (cont.)

Theory of Controlled Nucleation

Bone Structure and Bone Biomimesis

Biocomposites in Device Applications and Drug Delivery

Vogel, Viola. “Reverse Engineering: Learning from Proteins How to Enhance the Performance of Synthetic Nanosystems.” MRS Bulletin 27, no. 12 (December 2002): 972-978.

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

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.


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

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.


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

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.

Focus Topic: Integrating Biological Knowledge Into Biomaterials Design For Vaccines

Basic Biology of Vaccination and Viral Infections

Rudiments of Adaptive Immunity: The Basis of Vaccination

Viral Infections

Raychaudhuri, S., and K. L. Rock. “Fully Mobilizing Host Defense: Building Better Vaccines.” Nat Biotechnol 16, no. 11 (November 1998): 1025-1031.

Basic Biology of Vaccination and Viral Infections (cont.)

Vaccination Against Viruses: Parallels between Immunization and Infection

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).

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

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.

Drug Targeting and Intracellular Drug Delivery for Vaccines (cont.)

Mechanisms of Intracellular Delivery

Mimicking Viral Entry Strategies

Carter, P. “Improving the Efficacy of Antibody-based Cancer Therapies.” Nat Rev Cancer 1, no. 2 (November 2001): 118-129.

DNA Vaccines

Gene Therapy and DNA Immunization

Mechanisms of DNA Vaccines


DNA Vaccines (cont.)

Delivery Systems for DNA

Systemic vs. Local Delivery


Course Info

As Taught In
Spring 2006
Learning Resource Types
Problem Sets with Solutions
Exams with Solutions
Lecture Notes