Biomaterials Research Victor Breedveld
Dr. Breedveldʼs complex fluids group studies the microstructure and mechanical properties of a range of biological materials. Examples include proteins in drug formulations, biopolymers as thickeners in food and cosmetic products, and hydrogel‑forming block copolypeptides for tissue engineering and drug delivery applications. For all these materials, it is very important to estab‑ lish the relation between the structure of individ‑ ual molecules, their assembly into larger structures and the macroscopic mechanical properties (viscosity and gel strength) of the resulting materials. Novel microrheological techniques developed in the Breedveld group play a critical role in these studies. Microrheology can be applied to very small sample volumes (microliters), which makes the method feasible for high‑throughput screening of many different samples; for example, for the optimization of new protein‑based drug formulations. These solutions typically contain many addi‑ tives to stabilize the drug formulation during manufacturing and storage, but the impact of additives on protein structure and functionality is often unknown. Sys‑ tematic testing of the impact of each component is prohibitively expensive, and experimental proteins are often only available in very small quantities. Dr. Breed‑ veldʼs group is investigating the use of high‑throughput microrheology as a screening tool for these drug formulations. In another project, his group has been studying the formation of hydro‑ gels from synthetic block copolypeptides. The inherent biocompatibility of polypeptides makes them excellent candidates for tissue engineering and drug delivery. In collaboration with Prof. Deming at UC, Los Angeles, systematic stud‑ ies have been performed to reveal the relation between molecular architecture and gel properties. A particular focus of the research in the Breedveld group has been to investigate the response of these materials to changes in pH and ionic strength, mimicking in vivo conditions during potential applications.
Mark Prausnitz
Dr. Prausnitz uses biomaterials science to develop novel drug delivery systems. Topics include self‑ administered microneedle patches for influenza vaccination, bioadhesive microdiscs for treatment of glaucoma, and laser‑activated carbon nanopar‑ ticles for improved gene therapy. Flu vaccines are usually given by clinical person‑ nel using a hypodermic needle. The Prausnitz lab, in collaboration with Dr. Richard Compans at the Emory Vaccine Center, is working to develop patches containing dozens of micron‑scale nee‑ dles coated with vaccine that can be self‑applied to the skin. Challenges in bioma‑ terials include the design of microneedles with sufficient mechanical strength, low cost, and biocompatibility as well as the formulation of coatings that adhere strongly to microneedles, dissolve rapidly in skin, and provide stability to vaccines during storage. Treatment of glaucoma is challenging because patients do not take their re‑ quired multiple daily eye drops. The Prausnitz lab is collaborating with Dr. Henry Edelhauser at Emoryʼs Department of Ophthalmology to develop drug‑loaded mi‑ croparticles with increased residence time on the eye to reduce the dosing fre‑ quency. Biomaterials challenges include design of polymer particles that encap‑ sulate and release drugs at controlled rates, adhere to the eyeʼs mucous surface, and have a disk shape that minimizes removal by convective flow of tear fluid. Gene therapy has been plagued by the need for a safe and effective gene delivery method. In collaboration with Drs. Thom Orlando and Mostafa El‑Sayed in Georgia Techʼs School of Chemistry and Biochemistry, the Prausnitz lab has ob‑ served that exposure of carbon nanoparticles to near‑infrared laser light stimu‑ lates the carbon‑steam reaction of C(s) + H2O(l) → CO(g) + H2(g). The resulting large volume expansion generates a shock wave that temporarily permeabilizes cells to entry of DNA. Biomaterials challenges emphasize design of nanoparticles that op‑ timize gene delivery.
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Carson Meredith
Dr. Meredithʼs research in biomaterials involves two major thrusts: (1) using combinatorial and high‑throughput approaches to rapidly screen cell interactions with new polymers for biomedical de‑ vices and (2) developing novel polymer‑metal nanoparticle composites for imaging applications. These two project areas fit nicely into his groupʼs overall research efforts in advanced interfacial ma‑ terials. The key to biomaterials development is en‑ gineering the interface between the material (often a polymer) and the biological system (cells & proteins). Dr. Meredith has pioneered techniques for rapid‑screening of these complex interactions. Using combinatorial methods, libraries containing thou‑ sands of distinct polymers can be cultured with cells in a single experiment. For example, this method enabled discovery of a novel way to blend existing FDA‑ap‑ proved polymers to create unique control over bone and cardiovascular smooth‑ muscle cells. The key is controlling the surface micro‑ and nanostructures, to which mammalian cells are very sensitive. Certain sizes and shapes of surface mi‑ crostructures interfere with the cellsʼ ability to communicate with one another. This interference is used constructively by Dr. Meredith to adjust growth rate and other cell functions. This control “knob” is important in developing regenerative medical devices, such as those that could be used to treat arteries damaged by cardiovascular disease. Graduate students Pedro Zapata, Jing Su (BME), Gracy Wingkono, and Charlene Rincon contributed to these advances. The Meredith group has also developed new ways to package and deliver imaging contrast agents – used to enhance or enable images of tissues in MRIs, X‑ rays, and optical cameras. Working with collaborators Jeff and Valerie Sitterle of GTRI, ChBE undergrad Lance Rodeman, and ChBE graduate student Jung Hyun Lee, the team recently filed an invention disclosure on a new process for embed‑ ding highly light‑scattering nanoparticles into polymer microbeads that can be safely used in diagnostic procedures.
Lakeshia Taite
Dr. Taiteʼs research interests focus on the devel‑ opment of bioactive materials that can be used to guide tissue growth and deliver drugs to spe‑ cific cells and tissues. From the initial characteri‑ zation of these materials and their encourage‑ ment of biological responses, she can assess the ability of these materials in building effective tools for biomedical applications and can ex‑ plore using more advanced techniques in chemical synthesis to tailor the activity of these biofunctional materials. A major focus in Dr. Taiteʼs research group is the application of biological principles and engineering to develop substitutes that restore, maintain, or im‑ prove the function of human tissues or organs. Research projects use novel materials that mimic the natural cellular environment, and focus on promoting cell adhesion, controlling synthesis of matrix proteins, and regulating cell growth. Current projects are centered on materials that can serve as cardiovas‑ cular substitutes for patients in need of bypass grafts and matrices that support the growth of cancer cells for the study of tumor progression and metastasis. Dr. Taiteʼs group is also involved in the development of novel drug deliv‑ ery systems for cardiovascular applications and cancer therapies. Nitric oxide (NO) has several biological functions that make it a therapeutic candidate for a wide range of disease states. Studies are currently underway to target novel NO donors to sites of disease as both a therapeutic and a tool to further study the effects of NO on cells and tissues. Research in the Taite lab spans several fields with the common goal of producing biocompatible materials having broad clinical relevance. As such, the laboratory is interdisciplinary, with interests in chemical and biological en‑ gineering, cell and molecular biology, and polymer chemistry.