Supercritical carbon dioxide, often abbreviated scCO2, is carbon dioxide held above its critical temperature of about 31 degrees Celsius and its critical pressure of roughly 74 bar. In this state, the gas and liquid phases merge into a single fluid with an unusual combination of properties: it diffuses into materials like a gas but dissolves substances like a liquid. Crucially, its solvent power can be tuned simply by adjusting pressure and temperature, and at the end of any process the fluid simply evaporates, leaving behind a dry, residue-free product. Because carbon dioxide is non-toxic, non-flammable, inexpensive, and generally recognized as safe, it has long attracted attention as a green solvent in industries ranging from decaffeination of coffee to dry cleaning of textiles.

The review’s central message is that scCO2 is not just a niche laboratory curiosity but a technology that can be applied at nearly every stage of implant manufacturing. The first stage is cleaning. Polymer devices fabricated by molding, extrusion, or additive manufacturing can carry residues of organic solvents such as chloroform or tetrahydrofuran, which are toxic and strictly regulated by bodies like the European Medicines Agency. Conventional drying and vacuum treatments struggle to remove these residues from deep within polymer matrices, but scCO2, with its high diffusivity and tunable solvency, can extract them efficiently. Studies cited in the review show that carbon dioxide extraction removed residual chloroform from biodegradable polymers and eliminated solvents from PLGA microspheres, producing products that meet stringent regulatory limits on residual solvents.

Cleaning with supercritical fluids also addresses a subtler challenge: the intricate geometry of modern implants. Devices such as angioplasty catheters and microfabricated components contain narrow channels and microholes that liquid cleaning agents cannot reliably penetrate. Pulse cleaning with supercritical carbon dioxide, in which pressure is cycled to drive the fluid in and out of confined spaces, has been demonstrated for deep microholes and is now used industrially. The review notes that companies in the medical device sector have already adopted supercritical cleaning lines, and pharmaceutical contract manufacturers operate GMP-certified supercritical units, evidence that the technology has moved beyond the pilot scale.

The second major application is impregnation, the loading of drugs or bioactive compounds into polymer implants. Traditional methods involve soaking devices in solvent solutions, which can leave toxic residues and offer limited control over how much drug is loaded and where it ends up. Supercritical impregnation works differently: the drug is dissolved in scCO2, which swells and plasticizes the polymer, allowing the active compound to diffuse deep into the matrix. When pressure is released, the carbon dioxide escapes and the drug remains trapped inside. Because scCO2 is a weak solvent for most polar drugs, small amounts of co-solvents such as ethanol can be added to boost loading, and these co-solvents are far less problematic than the chlorinated solvents used in conventional approaches.

The Marseille group and collaborators have applied this technique to a striking range of devices. Foldable intraocular lenses made of hydrophobic acrylic polymers have been loaded with antibiotics and anti-inflammatory drugs such as gatifloxacin, with in situ spectroscopic monitoring of carbon dioxide sorption and polymer swelling used to control and optimize the process. Contact lenses have been impregnated with antifungal and antibacterial agents for the treatment of keratitis. Bioresorbable suture threads have been loaded with drugs in a proof-of-concept study explicitly aimed at industrial scale-up, and biodegradable ureteral stents have been made to elute ketoprofen to reduce patient discomfort. Wound dressings, electrospun polyurethane fibers, and chitosan sponges have all been successfully impregnated with therapeutic agents ranging from natural extracts to hormones.

The third application is foaming, which is central to tissue engineering. Porous scaffolds provide a three-dimensional template for cells to colonize and regenerate tissue, but conventional methods for creating porosity, such as solvent casting with particulate leaching or freeze-drying, often leave toxic residues or produce poorly connected pore networks. In supercritical foaming, carbon dioxide is dissolved into the polymer under pressure and then rapidly depressurized, causing the gas to nucleate into countless bubbles that expand into pores. The process is solvent-free, operates at relatively low temperatures compatible with biodegradable polyesters, and yields scaffolds with interconnected porosity. Researchers have produced foams of polylactic acid, polycaprolactone, and their composites with hydroxyapatite for bone regeneration, and combined foaming and impregnation in a single step to create drug-loaded porous patches and scaffolds in one continuous operation.

Underpinning all of these applications is a body of physical chemistry that the review examines in detail. Carbon dioxide sorption into polymers lowers the glass transition temperature and, in semicrystalline polymers, can depress the melting point, effects that are exploited in foaming but must be controlled to avoid unwanted deformation during cleaning or impregnation. Techniques such as in situ ATR-FTIR spectroscopy, high-pressure differential scanning calorimetry, and quartz crystal microbalance measurements allow researchers to follow swelling, sorption, and thermal transitions in real time. Solubility data for drugs in scCO2, modeled with density-based correlations and increasingly with machine learning approaches, guide the selection of process conditions. This chemical engineering perspective, the authors emphasize, is what turns promising laboratory results into robust, reproducible industrial processes.

The final and perhaps most consequential application is sterilization. Conventional methods each carry drawbacks for polymer implants: gamma and electron-beam irradiation can degrade polymer chains and alter mechanical properties, ethylene oxide leaves toxic residues and raises environmental and worker-safety concerns, and steam autoclaving requires temperatures that destroy many biodegradable materials. Supercritical carbon dioxide sterilization works at near-ambient temperatures. The mechanism is multifactorial: the pressurized fluid penetrates cells and spores, rapid depressurization can rupture membranes, and carbon dioxide acidifies intracellular environments. Additives such as hydrogen peroxide, water, or ethanol dramatically enhance spore kill rates, allowing the process to achieve the sterility assurance levels required by international standards such as ISO 14937.

Evidence for clinical relevance is accumulating. Decellularized heart valves sterilized with supercritical carbon dioxide retained their biomechanical properties, and a study of anterior cruciate ligament reconstruction using scCO2-sterilized allografts reported favorable clinical outcomes. Sensitive biomaterials including collagen-based products, polysaccharide membranes, and hydrogels have been sterilized at low temperature without loss of structure or bioactivity. The technology has even been applied to inactivate SARS-CoV-2 on personal protective equipment. Regulatory momentum is building: the U.S. Food and Drug Administration has run innovation challenges to identify new sterilization methods, partly driven by concerns over ethylene oxide emissions, and a commercial supercritical sterilization system has received NIH funding for further development. The review concludes that while challenges remain, particularly in validating processes across diverse device geometries and scaling high-pressure equipment, supercritical carbon dioxide stands out as a sustainable, gentle, and remarkably flexible platform that could one day serve as a standard across the whole life cycle of polymer implants, from the first wash to the final sterile pouch.

Subject of Research: Use of supercritical carbon dioxide in the cleaning, impregnation, foaming, and sterilization of implantable polymer-based medical devices

Article Title: Implantable Polymer-Based Medical Devices Go Supercritical: From Cleaning to Sterilization

Article References: Laggoune, Z., Masmoudi, Y., Pepe, V., & Badens, E. (2026). Implantable Polymer-Based Medical Devices Go Supercritical: From Cleaning to Sterilization. Annals of Biomedical Engineering. https://doi.org/10.1007/s10439-026-04392-3

Image Credits: AI Generated

DOI: 10.1007/s10439-026-04392-3

Keywords: supercritical carbon dioxide, implantable medical devices, biomedical polymers, sterilization, drug impregnation, foaming, tissue engineering scaffolds, green solvents, residual solvent removal, intraocular lenses, biodegradable polymers, chemical engineering

Traditional lithium-ion batteries, though powerful, have been ill-suited for integration with biological tissues due to their rigid structures and potential biocompatibility issues. The imperative to create an energy source that can flex, bend, and move harmoniously with tissue calls for a fundamentally different approach, one that embarks on both the materials and design frontiers. Here, the researchers introduce a microscale battery scaffolded on soft, flexible substrates while maintaining exceptional electrochemical performance, thereby addressing the dual demands of mechanical compliance and energy density.

Central to this new battery is an intricate architecture that employs novel polymeric matrices infused with lithium-ion conducting compounds. This synthesis enables the battery to achieve mechanical softness akin to biological tissue, measured by low Young’s modulus values far below that of conventional rigid cells. The resulting device can deform repeatedly under physiological strains without compromising ionic conductivity or triggering catastrophic failure modes. This remarkable mechanical resilience is a testament to the interdisciplinary synergy of materials science, electrochemistry, and bioengineering.

Power efficiency, however, is only part of the equation. The team meticulously optimized the electrolyte compositions to ensure stability over extended cycling, minimizing degradation processes that plague microscale lithium batteries. By leveraging cutting-edge nanostructured electrode materials, the battery sustains a robust charge capacity while mitigating dendrite formation—a notorious issue that can short-circuit lithium-ion systems. This meticulous balance between performance and safety is crucial for long-term in vivo application, where maintenance or replacement of implants poses significant risks.

The applications envisioned for this technology are transformative, particularly in the domain of tissue stimulation therapies. Whether it be neural implants designed to modulate brain activity in neurological disorders or cardiac pacemakers requiring highly adaptive power sources, the battery’s gentle mechanical profile and microscale footprint offer unprecedented versatility. By integrating seamlessly with soft tissues, devices powered by such batteries could reduce inflammatory responses and improve patient comfort, marking a paradigm shift in implantable medical devices.

Importantly, the fabrication process of this microscale battery incorporates scalable techniques compatible with contemporary manufacturing protocols. Using advanced lithographic patterning and solution-based deposition techniques, the researchers demonstrate not only device uniformity but also the potential for mass production. This manufacturability ensures that the leap from laboratory prototypes to clinical applications is more feasible, bridging a critical translational gap that often hinders biomedical technologies.

Beyond its immediate application, the battery embodies broader implications for the emerging field of soft robotics and wearable electronics. Devices that intimately conform to human skin or internal organs require power sources that move and flex unhindered. The soft lithium-ion battery’s tailored mechanical and electrochemical properties offer a blueprint for future energy storage solutions that can integrate into dynamic biointerfaces, supporting a wide array of digital health technologies.

Further enhancing its biointegration potential, the battery components are engineered with biocompatible materials designed to mitigate cytotoxicity. This careful material selection and surface functionalization reduce adverse immune reactions and enable prolonged implantation durations. Preliminary biocompatibility assessments suggest favorable outcomes, positioning the battery as a candidate not only for temporary therapeutic use but also for chronic implant scenarios.

The researchers validate their system through rigorous in vitro and ex vivo testing, highlighting its performance under physiologically relevant conditions. The battery consistently delivers stable power output during cyclic mechanical deformation, simulating the movements encountered within living tissues. Such reliability under stress underscores the device’s readiness for transition to preclinical animal studies, where dynamic biological environments will pose even more complex challenges.

At the heart of the device lies a synergistic integration of solid-state electrolytes and soft electrode composites, a design that departs from conventional liquid electrolyte batteries. This architecture bolsters safety by minimizing risks of leakage and flammability—critical considerations for implantable systems. Moreover, the microscale dimensions align well with emerging minimally invasive surgical techniques, allowing the battery to be embedded without significant disruption to host tissues.

Researchers note that while the current prototype excels in energy density and mechanical conformity, ongoing work aims to extend its operational lifespan and charge retention capabilities. Iterative improvements in electrode material synthesis and electrolyte optimization are underway, aiming to tune the battery to the specific power profiles demanded by various biomedical devices. The adaptability of the platform technology suggests a flexible roadmap for customization across multiple therapeutic modalities.

Strategically, this development aligns with the broader trajectory towards smart implants capable of responsive, real-time bioelectronic therapies. Energy autonomy, facilitated by durable and compliant batteries, is essential for such devices to function untethered over extended periods. The march toward closed-loop bioelectronic systems—where sensing, stimulation, and adaptation occur seamlessly—depends fundamentally on such advances in energy storage technology.

The implications for patient care are profound. Empowered by reliable microscale batteries, implantable devices can become less intrusive and more effective, advancing precision medicine paradigms. Patients could experience improved mobility and comfort, with devices capable of delivering complex stimulation protocols tailored in situ. The integration of this technology into neural prosthetics, for example, holds promise for restoring function in patients suffering from paralysis or neurodegenerative diseases.

From an innovation standpoint, the work embodies the collaborative fusion of disciplines—drawing on advanced material synthesis, electrochemistry, mechanical engineering, and biomedical science. This cross-pollination exemplifies the future of medical device engineering, where holistic approaches can solve long-standing challenges in powering bio-integrated electronics. As this technology matures, it is expected to inspire a wave of novel device designs leveraging soft, high-performance batteries.

In conclusion, the microscale soft lithium-ion battery represents a significant stride towards fully implantable, minimally invasive medical devices capable of sophisticated tissue stimulation. It addresses key challenges of mechanical compatibility, energy delivery, safety, and manufacturability, carving a new path for energy storage solutions in bioelectronics. The research not only marks a milestone in battery innovation but also heralds a future where seamless integration between electronics and living tissue becomes the norm rather than the exception.

Subject of Research: A microscale soft lithium-ion battery designed for powering tissue stimulation devices with high mechanical compliance and electrochemical stability.

Article Title: A microscale soft lithium-ion battery for tissue stimulation.

Article References:
Zhang, Y., Sun, T., Yang, X. et al. A microscale soft lithium-ion battery for tissue stimulation. Nat Chem Eng 1, 691–701 (2024). https://doi.org/10.1038/s44286-024-00136-z

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s44286-024-00136-z