Ramille Shah
Assistant Professor of Materials Science and Engineering and Department of Surgery, Feinberg School of Medicine
Education
Ph.D. Biomaterials, MIT, Cambridge, MA
B.S. Materials Science and Engineering (cum laude), Northwestern University, Evanston, IL
Research Interests
My group focuses on investigating new biomaterial strategies for the repair and regeneration of tissues damaged by disease or traumatic injury including musculoskeletal and liver tissues. There are 4 major projects in my research program so far: 1) 3D bioplotted scaffolds for tissue engineering, 2) Development and characterization of soy-based biomaterials, 3) Development and characterization of self-assembling collagen-hyaluronic acid membranes for augmenting tissue repair, and 4) Investigating the effects of low intensity, long duration ultrasound on cellular behavior in 3D scaffolding systems.
3D Bioplotted Scaffolds for Tissue Engineering. Control of 3D scaffold architecture such as porosity, pore size, pore shape, and pore interconnectivity can significantly impact scaffold mechanical and degradation properties, as well as cell behavior within the tissue engineering constructs. With the use of our 3D Bioplotter, we have the ability to create precise and reproducible 3D scaffolds layer-by-layer with 100% pore interconnectivity. Pore interconnectivity is extremely important for sufficient nutrient diffusion and to support cell migration and viability throughout the entire scaffold. We are developing methods to fabricate constructs with more complex shapes (i.e. for craniofacial reconstruction) and sophisticated internal structures (i.e. creating channels for blood vessel growth). Using this approach, we aim to further our understanding of the specific role of scaffold architecture on material properties and cellular response such as cell viability, proliferation, migration, differentiation, and biosynthesis to better engineer biocompatible and biodegradable constructs for the repair of tissue or replacement of organs. We are currently developing optimal procedures to be able to print scaffolds derived from a variety of synthetic and natural polymer systems with precise pore characteristics. We have already been able to print scaffolds from biodegradable synthetic polymers, and we are attempting to bioprint new biocompatible materials and composites such as protein-based composites (derived from collagen and soy) and poly(octanediol-co-citrate) (POC).
Soy-Based Biomaterials. My group is exploring the use of soy protein to create 3D biodegradable constructs with tunable porosity, scaffold architecture, mechanical properties, and degradation characteristics for tissue regeneration. The advantages of soy over other proteins such as collagen or silk that are commonly used to create tissue engineering scaffolds is that soy protein comes from an abundant plant-derived natural and renewable resource, and it has thermoplastic qualities that make it a more versatile protein to be able to process into materials with more tunable and stable mechanical properties (compared to collagen). Thus far we have successfully fabricated and characterized porous 3D soy protein scaffolds made via freeze-drying as well as soy protein nanofibrous scaffolds made via electrospinning. We have also demonstrated that these constructs can support mesenchymal stem cell adhesion, viability, and proliferation. In the next few years, we plan to be able to better control soy protein scaffold pore architecture through bioplotting, as well as develop these scaffolds for bone and cartilage regeneration. Furthermore, we plan to develop more fully an understanding of the biocompatibility of soy protein as a biomaterial implant through in depth immunological analysis using rodent animal models and comparing it to animal-derived collagen scaffolds.
Collagen-Hyaluronic Acid Membranes. Our group is developing new self-assembling membranes and composites that consist of collagen and hyaluronic acid (HA) as bioactive membrane coatings to enhance the repair of rotator cuff injuries. Through sequential application of solutions of collagen and HA, a membrane can be formed by the simple interfacial and electrostatic interaction between the positively-charged collagen and oppositely-charged HA. The use of collagen and HA is advantageous because both are major components of the natural extracellular matrix, providing inherent biocompatibility and bioactivity to the material. Thus far we have characterized the mechanical and microstructural properties of these membranes and composites with hydroxyapatite, as well as their ability to support cell viability/proliferation and steady protein release. I am planning in the next few years to test collagen-HA membrane biocompatibility, degradation, and potential for bone and tendon regeneration, as well as wound healing applications.
Investigating the Effects of Low Intensity Long Duration Ultrasound on Cellular Behavior within 3D Scaffolding Systems. Ultrasound has been used clinically over several decades for treating damaged ligaments/tendons, fractured bones and cartilage; accelerating wound healing; and improving the strength and elasticity of scar tissue. The use of ultrasound technologies has recently emerged as an alternative cell stimulation technique; however, only few have investigated its use in conjunction with 3D scaffolds to enhance tissue regeneration. Furthermore, there is a lack of fundamental understanding with regard to the interplay between scaffold properties (i.e. pore structure and mechanical properties) and ultrasound wave propagation through tissue engineering constructs, which can ultimately have a significant impact on the local cellular response. We are investigating the coupled and combinatorial effects of scaffold pore structure, mechanical properties, and long duration ultrasonic stimulation, along with the delivery of genes or growth factors, to control the proliferation, migration, and differentiation of human mesenchymal stem cells. We are also developing models to understand ultrasonic wave propagation throughout different bioprinted porous scaffolds that we can subsequently correlate to experimental cell behavior. The outcomes of this research will define trends in scaffold and ultrasound parameters that can lead to optimal tissue regeneration.
Significant Professional Service
- Orthopaedic Research Society
- International Cartilage Repair Society
- Association for Women in Science
- Society for Women Engineers
- American Society for Engineering Education Fellow (MIT), 2001-04
- Society for Biomaterials
- Tissue Engineering and Regenerative Medicine International Society
Selected Publications
- Chien, K.B., Makridakis, E., Shah, R.N., “Three Dimensional Printing of Soy Protein Scaffolds for Tissue Regeneration” Tissue Engineering Part C 2012 (in press).
- Lee, S.S., Huang, B.J, Kaltz, S.R., Sur, S., Newcomb, C.J., Stock, S.R., Shah, R.N., Stupp, S.I., “Bone Regeneration with Low Dose BMP-2 Amplified by Biomimetic Supramolecular Nanofibers within Collagen Scaffolds.” Biomaterials 2012 (in press).
- Chung, E.J., Jakus, A.E., Shah, R.N., “In Situ Forming Collagen-Hyaluronic Acid Membrane Structures: Mechanism of Self-Assembly and Applications in Regenerative Medicine” Acta Biomaterialia 2012 (in press).
- Chien, K.B., Shah, R.N., “Novel Soy Protein Scaffolds for Tissue Regeneration: Material Characterization and Interaction with Human Mesenchymal Stem Cells” Acta Biomaterialia 2012, 8(2), 694.
- 5. Murphy, M.B., Blashki, D., Buchanan, R.M., Fan, D., De Rosa, E., Shah, R.N., Stupp, S.I., Weiner, B.K., Simmons, P.J., Ferrari, M., Tasciotti, E., “Multi-Composite Bioactive Osteogenic Sponges Featuring Mesenchymal Stem Cells, Platelet-Rich Plasma, Nanoporous Silicon Enclosures, and Peptide Amphiphiles for Rapid Bone Regeneration” Journal of Functional Materials 2011, 2 (2), 39.
