Lecture Summaries

The summaries below provide an overview of what was covered in each session of this course. Detailed lecture notes are not available for this course.

1 Introduction to the Course We will go over the syllabus, including expectations and goals of the class, an overview of the course, and an introduction to the first two papers. We will also discuss strategies for reading primary scientific papers.
2 Mechanobiology of Materials The mechanical properties and stiffness of a material have a direct effect on cell function and stem cell lineage. We will discuss two papers that demonstrate creative approaches to preparing material substrates that allow one to determine the effect of substrate mechanical properties on cell behavior. The first paper uses a simple hydrogel substrate that can be tuned to different stiffnesses and thereby control differentiation of stem cells toward a specific lineage. The second uses a patterned substrate of micron-sized posts that have variable deformability, creating surfaces of varying stiffness and resulting in changes in cell behavior.
3 Controlling Cell Morphology Substrate geometry plays a major role in the biophysical regulation of cell function. Micro-patterning techniques have allowed scientists to study the effects of surface topography on numerous cell types. We will discuss two examples of how surface shape influences cell proliferation and differentiation. The first paper demonstrates how vascular endothelial cell shape governs whether individual cells grow or die, independent of cell adhesion factors. The second paper demonstrates how cell shape, independent of soluble factors, has a strong influence on the differentiation of human mesenchymal stem cells (MSCs) from bone marrow.
4 Altering Gene Expression Advances in the field of nanoparticle carriers for small interfering RNA have demonstrated enormous potential in modifying gene expression. This approach might enable disease to be treated at a genetic level. Here we will read two examples of papers that have developed carriers for siRNAs, demonstrating functional silencing in animal models. The first paper demonstrates the use of a broad library-based approach to find ultra-high efficiency siRNA carriers, and demonstrates therapeutic efficacy in a non-human primate model. The second paper discuses the use of a nanoparticle carrier to deliver siRNA, which laid the groundwork for the first evidence of an siRNA therapy success in human clinical trials.
5 Biomimetic Signaling Integrins are transmembrane cell receptors that play an important role in helping cells attach to their local microenvironment. Studies of integrin binding to extracellular matrix (ECM) proteins led to the discovery of small signaling domains composed of specific amino acid residues within long-chain ECM proteins. These oligopeptides were found to elicit similar cell responses as the long-chain proteins. We will discuss two papers in which "biomimetic" sequences have been used to modify the surface of biomaterials. In the first paper, hydrogels functionalized with cell adhesion peptides are used to control the attachment and morphology of marrow stromal cells. The second paper uses self-assembling nanofibers displaying cell adhesion ligands to study effects of cell adhesion, spreading, and migration.
6 Targeting with Nanoparticles Nanoparticles have demonstrated the potential to serve as targeting therapies for disease. One method to ensure that a payload enclosed in a nanoparticle reaches its target is to functionalize the particle surface with targeting groups. This is most often done using antibodies, but here we will examine some creative non-antibody strategies for nanoparticle targeting. The first uses aptamers, oligonucleotide sequences with binding specificity for prostate cancer cells, to deliver encapsulated chemotherapy to tumors. The second uses chlorotoxin, a toxin derived from scorpion venom, to target particles to brain tumors across the blood-brain barrier.
7 Materials for Vaccination Non-biological materials have been developed to address challenges in the efficacy of current vaccine and immunotherapy technologies. The thought is that these materials can more specifically target the delivery of antigens to antigen presenting cells (i.e. dendritic cells), to in turn, induce T-cell immunity. Here we discuss two papers describing biomaterial vehicles for targeted antigen delivery. The first paper discusses the effect of nanoparticles diameter on cell targeting. In the second paper, adjuvant- and antigen- loaded nanoparticles are used to target dendritic cells.
8 Engineering Vascular Structure In this next series of classes, we will draw on our knowledge of biophysical and biochemical cues to discuss ways in which researchers design higher ordered tissue structures. In this class, we will discuss tissue engineered vascular structures. The first paper uses synthetic polymer meshes to culture smooth muscle cells under pulsatile media flow conditions in a bioreactor. The second paper describes a fully biological tissue engineering technology to fabricate small-diameter tubular vascular grafts via rapid prototyping techniques.
9 Field Trip A behind the scenes look at some of the biomaterials science research focused on the cell-material interface in the laboratory of Bob Langer.
10 Cell-like Materials Materials that circulate through the body disguised as cells could have applications for many new therapies. Here we discuss two approaches that have been used to create artificial red blood cells, either by controlling mechanical properties or controlling surface characteristics. In the first paper, materials are made into the size, shape, and stiffness of red blood cells to achieve long-term circulation. In the second paper, a polymeric material is coated with the membrane of a red blood cell, which facilitates improved circulation of the particles.
11 Repairing the Nervous System Because of a lack of regenerative capacity, restoring function to the damaged central nervous system is a challenging task. Materials can participate in this process by delivering soluble or matrix cues that promote the growth of new neurons across an injured segment of spinal cord. We will discuss such methods in this class. From the first paper, we will examine the implantation of a scaffold into a spinal cord injury site that releases a soluble factor known to promote the growth of neurons. From the second paper, we will read about an injectable gel that delivers immobilized cues to growing neurons and helps to promote improved motor function following spinal cord injury.
12 Final Class

Oral Presentations

After the oral presentations, we will discuss the course in general, including an overview of what we have learned about engineering cell-instructive biomaterials.