Leveraging Biomaterial Systems to Address Traumatic Brain Injurys Dr. Sarah Stabenfeldt September 12th, 2025 -- A. James Clark Hall @ UMD
Dr. Stabenfeldt’s presentation focused on her research of traumatic brain injuries. Despite the prevalence of various types of traumatic brain injury, there are limited treatment options currently available, making research into traumatic brain injury remedies extremely valuable. Most of these limited treatments focus on alleviating secondary symptoms like intracranial pressure and edema, as opposed to controlling and treating the initial bodily reaction. Dr. Stabenfeldt researches this reaction and engineers nanoparticles as treatment. The experimental design consisted of male and female mice placed inside a contraption that induces targeted and consistent brain injuries. From there, the physical and immune response is tracked and analyzed. Physically, neural death, axonal dysfunction, and hypertension were the primary injuries to the brain. Chemically, female mice displayed heightened immune responses with extreme swelling. A critical component of this research involves understanding how biological sex and hormones influence injury susceptibility and recovery outcomes. Dr. Stabenfeldt’s work highlights that while male mice typically exhibit a biphasic blood-brain barrier (BBB) disruption that opens and quickly reseals, female mice demonstrate a sustained window of permeability that remains open for at least 24 hours post-injury. This difference is linked to distinct hormonal responses to trauma: following injury, males tend to suppress testosterone—which is associated with increased BBB permeability—while females may experience a promotion of testosterone levels alongside the presence of estrogen and progesterone. These hormonal fluctuations dictate the "therapeutic window," creating a scenario where a drug administered a day after injury might successfully reach the brain in a female subject but fail to cross the resealed barrier in a male. To overcome the formidable difficulty of crossing the BBB, which strictly limits the transport of therapeutics into the central nervous system, Dr. Stabenfeldt employs advanced nanoparticle designs. Her laboratory utilizes phage display technology to identify "nanobodies"—single-chain antibody fragments—that function like "Velcro," allowing nanoparticles to actively target and latch onto specific injury markers such as fibrin. The physical design of these carriers is also crucial; studies using PEGylated nanoparticles revealed that smaller particles are capable of penetrating deeper into the injured brain tissue, whereas larger particles remain restricted to the surface. This engineering approach has led to innovations such as "platelet-like particles" (PLPs), which are hydrogel-based systems designed to mimic natural platelets and target clotting specifically at the site of injury.
Dr. Stabenfeldt’s points were convincing because the numbers show just how big the gap in TBI care really is. Globally, TBI affects 50 to 60 million people a year and costs around $400 billion, yet we still don't have treatments that target the underlying damage (Maas et al. 1004). The statistics on sex differences were extremely surprising. Even though men are hospitalized more often for TBI, women frequently end up with worse, longer-lasting symptoms (Bharadwaj et al. 2155). Dr. Stabenfeldt’s research backed this up, showing that 24 hours after an injury, the blood-brain barrier in females is nearly 2.5 times leakier than males (Bharadwaj et al. 2160). This proves that a "one-size-fits-all" approach doesn't work because the biology is completely different at that time point. Her team showed that small nanoparticles can actually get deep into the damaged brain tissue, while larger ones get stuck on the surface. These specific statistics make a strong case that we need treatments designed for the specific timing and biology of the patient. A major reason previous treatments have failed is that researchers fell into a logical trap. For decades, scientists relied on the "conventional wisdom" that they should only use male animals in experiments because female hormones made things too complicated. This is a logical fallacy known as a Hasty Generalization, where it is assumed that results from males apply to everyone. Dr. Stabenfeldt’s work shows why this is not in humanity’s best interest. She found that the barrier protecting the brain behaves completely differently in females, staying open for 24 hours after an injury, while in males it closes much faster (Bharadwaj et al. 2160). Because researchers historically only looked at males, they completely missed this opportunity to treat women effectively, and understand how pharmaceuticals and therapeutics should be adjusted to different types of people.
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