We are seeing a quiet but consequential revival of an old dream: medicines and engineered fluids that can carry or release oxygen where the body needs it most. In labs and early clinical studies, researchers are testing several families of approaches that promise to change how medics treat battlefield hemorrhage, ischemic injury, and blunt trauma. These are not simple bandages or smarter tourniquets. They are biochemical interventions that alter how oxygen travels in blood or how tissues extract it, and they raise both operational promise and hard safety questions.
One path back into the clinic is hemoglobin-based oxygen carriers. These are engineered hemoglobin molecules or hemoglobin conjugates designed to function outside of red blood cells and deliver oxygen to tissues when blood is unavailable or impractical to use. After decades of starts and stops, regulators and researchers are trying to learn from past failures by mapping the biochemical behaviors that drove toxicity in earlier products. The U.S. Food and Drug Administration has compiled comparative biochemical profiles of previously tested HBOCs to help explain why some formulations caused oxidative injury, hypertension, and other complications, and to steer safer designs going forward.
A concrete example currently in human testing is a PEGylated, carboxyhemoglobin product known as PP-007 or SANGUINATE. It is a modified bovine hemoglobin engineered to carry carbon monoxide bound to heme while acting as an oxygen transfer agent. Prolong Pharmaceuticals has advanced this candidate through multiple trials and reported Phase 1 work and early clinical presentations focused on acute ischemic stroke. The company has described a safety profile that enabled further development and received regulatory attention including Fast Track designation for stroke, signaling that the FDA sees potential benefit in urgent ischemic indications. These developments highlight how engineered hemoglobin formulations are being reexamined for targeted clinical use.
Perfluorocarbon emulsions are a parallel technical family. PFCs dissolve large amounts of oxygen and can transport it physically rather than chemically. They have been tested for decades under names like Perftoran and others, and recent reviews and animal studies from 2023 and 2024 show renewed interest, particularly for organ perfusion and neuroprotection models. A growing body of preclinical work suggests PFCs can improve microvascular oxygen delivery in experimental brain injury and organ perfusion settings, even while the clinical translation challenge remains real.
Not every strategy relies on handing oxygen to tissues in a new carrier. Some small molecules modify hemoglobin itself to make it give up oxygen more readily in hypoxic tissue. Efaproxiral, an allosteric hemoglobin modifier, is a well known research example that increases oxygen unloading and has been used in experimental oncology and preclinical models to boost tissue oxygen tension during radiation therapy. Laboratory work and earlier clinical studies document measurable increases in tissue oxygen partial pressures after dosing, which supports the principle that pharmacologic modulation of hemoglobin can change oxygen delivery dynamics.
Why does any of this matter for resilience and for military medicine? The benefits are obvious on paper. Forward medics could carry compact oxygen therapeutics that do not require blood typing or cold chain logistics. Donor shortages, austere environments, and mass casualty events make universal, shelf-stable oxygen carriers appealing. For trauma in the field, a safe oxygen therapeutic could extend the time window for evacuation or reduce immediate mortality from hemorrhagic shock. In organ preservation and surgical contexts, artificial oxygen carriers might extend organ viability and ease transport bottlenecks. These operational advantages are why both private biotechs and academic labs have re-engaged with the problem.
But the history of oxygen therapeutics is a cautionary tale. Past HBOCs and PFC products performed well in early efficacy experiments but then manifested vasoactive or oxidative side effects in larger trials. Mechanistic work indicates that free hemoglobin outside red blood cells undergoes redox chemistry and can generate reactive intermediates that harm endothelium, trigger inflammation, and raise blood pressure. That is the core safety challenge that modern programs are trying to solve through chemical modification, PEGylation, and more precise biophysical profiling. The regulatory mood is now more forensic than permissive: the field must show not only oxygen delivery but also a mitigated toxicity profile.
There are three near-term research realities to watch. First, the most credible candidates are moving through careful, indication-specific trials, typically for acute ischemia rather than broad transfusion replacement. Second, transfusion replacement remains a high bar. Regulators will expect convincing evidence that a product is at least as safe as current standards, and historically HBOCs have struggled with that. Third, translational work now emphasizes situational uses like machine perfusion of organs or adjuncts in stroke where the benefit risk calculus is more favorable and the intervention window is narrow. Recent studies in organ perfusion and stroke models showcase that strategic, narrow indications could be the path to real-world use.
Beyond the bench and clinic there are ethical and operational questions that demand attention. If a product can alter oxygen delivery, could it be repurposed for performance enhancement by nonmedical actors? How should military medical doctrine integrate a therapy that may temporarily alter physiology but carry downstream risks? Who decides when a medic in a forward position deploys an experimental oxygen therapeutic when the patient is also exposed to blast, toxins, or prolonged evacuation timelines? The dual use nature of respiration-modifying biotech is obvious and requires rules of engagement, robust consent frameworks for clinical research, and transparent oversight.
If policymakers and funders want resilience outcomes, the most useful investments are not simply more animal efficacy screens. They are studies that link chemical structure to predictable safety signals, standardized assays for oxidative potential, and independent, precompetitive data sharing about mechanisms that drove earlier failures. Regulators have already started assembling side by side comparisons that point the way. The pragmatic approach is to fund indication-focused trials, de-risk the toxicology profile early, and build deployment concepts that pair novel oxygen therapeutics with concrete protocols for use in austere settings.
The laboratory work now being reported is promising in that it returns the field to first principles: can we move oxygen without breaking the body in the process. The answer is not yet yes at scale, but the advances in molecular engineering and a clearer regulatory playbook mean that over the next several years we may see oxygen therapeutics that are safe enough for specific, high-value uses. For strategists and medics thinking about resilience, the responsible stance is to follow the science, demand transparent safety data, and prepare doctrine and logistics for a future where a vial or infusion could buy an extra hour for wounded service members or a damaged organ. That extra hour could be decisive, but only if the interventions are both effective and safe.