Brunmaier, Laura

• Ph.D., Biomedical Engineering, South Dakota School of Mines & Technology

• B.S., Applied Biological Sciences, South Dakota School of Mines & Technology

Engineering a Basement Membrane-Inspired Protein Therapy to Restore Endothelial Integrity and Prevent Thrombosis.

Endothelial damage disrupts vascular homeostasis, leading to thrombosis, inflammation, and impaired vascular function. Current therapeutic approaches, such as anticoagulants and anti-inflammatory drugs, fail to actively restore endothelial cell (EC) integrity or prevent recurrent injury. To address this critical gap, we propose the development of a basement membrane inspired protein therapy (BMIPT) composed of laminin, nidogen-2, and perlecan, crosslinked with a biosafe crosslinker, to promote EC regeneration and barrier restoration. This project focuses on developing the BMIPT formulation to enhance surface attachment and bioactivity while assessing its effectiveness in facilitating EC adhesion, migration, and function. We will systematically evaluate protein coating efficiency using ELISA and immunofluorescence staining, ensuring BMPS retention on cellularized and non-cellularized surfaces. To confirm that BMIPT EC regeneration, we will conduct scratch assays to measure EC migration, followed by immunofluorescence imaging and RNA-sequencing analysis to verify the maintenance of the EC phenotype, and the formation of tight junctions. The expected outcome of this research is a protein-based therapeutic that accelerates repair ECs, reduces thrombotic risk, and improves vascular stability. Successful completion of this work will provide proof-of-concept data for BMIPT as a potential clinical intervention in vascular grafts, stent coatings, and regenerative therapies.

Optimization and Distribution of a Chemically-Defined Media System with Protocol-Driven Weaning of ECs from FBS.

Recent regulatory shifts and scientific momentum is shifting toward human-relevant in vitro platforms, supported by initiatives like the FDA Modernization Act 2.0 and NIH Tox21. This shift underscores the urgent need for standardized, human-relevant tools that improve the predictive power of early-phase testing. A key barrier to this translation is the widespread use of fetal bovine serum (FBS) which contributes to batch variability and disease transmission. The development of a chemically-defined media (CDM) for EC culture is essential for advancing in vitro models, improving translational research, and mitigating the risks associated with FBS. A key challenge in transitioning to serum-free culture conditions is ensuring that EC maintain their native phenotype, function, and a viable proliferation rate for experimentation. In this project, we focus on optimizing the CDM and adaptation method that is tailored for ECs. Following optimization, we will utilize immunofluorescence staining and RNA-sequencing analysis to verify that the conditions do not induce unwanted loss of phenotype. Scalability for distribution will be evaluated by determining stability, consistency, and sterility. The expected outcome of this research is optimization and verification of EC function through RNA-seq and fluorescence imaging, and the development of protocols for shipping materials and determining post-shipment viability.

Development of Human Microphysiological Vascular Platform to Investigate the Deleterious Effects of Radiation.

The development of vascular microphysiological systems (MPS) has revolutionized in vitro modeling, providing biomimetic platforms to study EC behavior under controlled conditions. MPSs provide a platform to enable precise investigation of angiogenic processes, including EC sprouting and vessel stabilization, elements that are critical for understanding vascular development, disease progression, and therapeutic responses. This project focuses on engineering a MPS of angiogenesis to examine cytokine significance and dose-dependent responses on EC sprouting and vessel stabilization. Using computer-aided design, 3D digital light processing printing, and casting methods, we will fabricate specialized microfluidic devices capable of sustaining the growth of cells. ECs will be seeded within the device and exposed to controlled gradients of cytokines, such as vascular endothelial growth factor and fibroblast growth factor, to quantify the effects of the cytokine on sprouting dynamics, vessel branching, and barrier integrity. To systematically assess angiogenic responses, we will employ immunofluorescence imaging and RNA-sequencing to evaluate EC proliferation and lumen formation. The expected outcomes of this project include the development of a stable, in vitro vascular bed to be used to investigate the effects of ionizing radiation.

Clinical Immersion and Innovation: From Idea to Proof-of-Concept.

This project is a student led, students actively observe real-world medical workflows, document procedural challenges, inefficiencies, and unmet clinical needs, and participate in guided discussions with physicians and engineering mentors to define specific problems and potential solution pathways. The identified problems must be justified through identifying the relevant gap, proposing a solution, and defining the impact of the innovation. The project then transitions to an iterative design phase where participants develop prototypes of medical devices or process improvements using tools such as CAD modeling, 3D printing, etc. Benchtop testing and validation follow, assessing prototype functionality, safety, usability, and performance through simulated scenarios and engineering metrics. The expected outcome is a functional proof-of-concept prototype that directly addresses the identified clinical need, demonstrating technical feasibility and potential patient impact.