(4t) Designing Protein-Based Biomaterials for Biomedical Applications

Nature has had millennia to perfect the world around us. Proteins in our body, for example, have incredible functions from elastin’s ability to reversibly expand and contract for decades to collagen’s superior mechanical strength. Proteins found in marine mussels anchor the mussels to surfaces in extremely turbulent underwater environments. How can we utilize these tools nature optimized to solve modern-day biomedical problems? In my graduate work, I used these protein-based inspirations from nature and designed novel biomaterials for biomedical applications.

Recombinant Protein-Based Surgical Lung Sealants: Supported by my NSF graduate research fellowship and my Leslie Bottorff fellowship for clinical translation, I designed surgical lung sealant formulations to prevent the dangerous occurrence of air leaks after a lung surgery. A surgical lung sealant needs to be both pliable to prevent lung tissue fibrosis and adhesive in a moist physiological environment – a tough criteria that no commercially available surgical sealant has met. I modify recombinant elastin-like polypeptides (ELPs) with a bioinspired mussel adhesive moiety, L-3,4-dihydroxyphenalalanine (DOPA). The ELP in my formulation confers elasticity suited to match the elasticity in lung tissues, whereas DOPA confers wet adhesion to the material. Formulations achieved burst pressures at least 19 times greater than the transpulmonary pressures the lungs withstand. The formulations were elastic had no long-term swelling that would damage the tissue or alter the adhesion properties. These results demonstrate the feasibility of the DOPA-modified ELP as an elastic surgical lung sealant.

In Vitro Protein-Based Tissue Models for Biologics Absorption: In collaboration with other researchers at Purdue University and Eli Lilly and Company, I designed in vitro tissue models to characterize large molecule drug diffusion and recovery for early stage biologics development. The models are based on collagen and hyaluronic acid, two major biopolymers that impact large molecule diffusion and recovery in tissues. I incorporated aldehyde- and hydrazide-modified HA that crosslinks when combined, called HAX, into a collagen network to form hybrid ColHAX hydrogels. Changing the concentrations of collagen and HAX greatly impacts the hydrogel microstructure, swelling capacity, stiffness, and diffusion/recovery profile. I condensed these findings into a statistical design of experiments model that can take in a desired tissue property, such as pore size or water content, and output the collagen and HAX concentrations needed to obtain the desired tissue property. Because the material properties of ColHAX hydrogels span a large space, these hybrid gels can be and are used to model tissues as diverse as soft subcutaneous tissue and stiff pancreatic ductal adenocarcinoma tumor tissue.

Together, surgical sealants and biologics development make up two facets in the biomedical industry that can benefit from nature-inspired protein-based biomaterials. My future research will continue to utilize bioinspired biomaterials for biomedical applications.

Teaching Interests

Teaching and mentoring students has been an invaluable component to my graduate education. I have teaching experience in both statistical modeling and a chemical engineering laboratory course. In these two lab-based courses, I helped undergraduate students work through challenging engineering problems where creativity and critical thinking skills are vital. In addition to teaching experience, I mentor undergraduate researchers learning how to do independent research with my lab. I encourage these students to intellectually contribute to our work and take ownership of the work they do. For example, both of my current undergraduate students rose to the level of co-authorship on recent publications. I also have lasting interests in curriculum development demonstrated in my work with Purdue’s Introduce a Girl to Engineering Day and MIT’s dynaMIT. My involvement over several years for both of these programs has focused on developing hands-on instruction for secondary education students. I also have an education concentration from my undergraduate studies that focused on curriculum design and learning theory.