Supercritical Carbon Dioxide Transforms How Implantable Medical Devices Are Made Clean and Sterile

Every year, millions of patients receive implantable medical devices, from intraocular lenses and sutures to bone scaffolds and drug-eluting stents, and a growing share of these products are made from biocompatible polymers. Yet the manufacturing of polymer-based implants faces a stubborn problem: many of the solvents and harsh conditions used to clean, load, shape, and sterilize these materials can damage the very devices meant to improve or save lives. A comprehensive review published in the Annals of Biomedical Engineering by Zohra Laggoune, Yasmine Masmoudi, Valentine Pepe, and Elisabeth Badens of Aix-Marseille University, CNRS, and Centrale Med in Marseille argues that a single, remarkably versatile technology, supercritical carbon dioxide, could solve many of these problems across the entire production chain, from cleaning to sterilization.

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