Microgravity is not an exotic concept reserved only for astronauts; it is a working tool for a new generation of bioengineers and drug manufacturers. When a material or fluid is in a state of near-weightless freefall, common gravitational effects such as convection, sedimentation, and shear stresses caused by density differences are silenced. It is in such an environment, on the International Space Station (ISS), that a research team from the University of Connecticut (UConn) and biotech startup Eascra Biotech have demonstrated that Janus base nanomaterials (JBNs) can be produced in a significantly more uniform form than on Earth, which directly improves their therapeutic functionality in treating osteoarthritis and hard-to-penetrate solid tumors.

Why osteoarthritis is a pressing problem and why we need a new approach

Osteoarthritis is the most widespread form of arthritis and one of the leading causes of chronic pain and reduced mobility in adults. It affects tens of millions of people and often leads to complex, expensive surgical procedures, including joint replacement. Risk factors include age, excess body weight, previous joint injuries, and biomechanical stress. Standard therapies are predominantly symptomatic: they reduce pain and inflammation but do not regenerate worn cartilage or halt disease progression. This is why there is growing interest in regenerative and precisely targeted therapies that could intervene in the molecular pathways of cartilage degradation and stimulate the regeneration of the extracellular matrix without invasive surgery.

What JBNs are and how they self-assemble into functional nanostructures

Janus base nanomaterials (JBNs) are a special class of synthetic molecules inspired by DNA base pairs. Each molecule has two "faces" with carefully arranged hydrogen bond donors and acceptors. In an aqueous medium, these units first self-assemble into ring-shaped rosettes, and then stack "like plates" into hollow nanotubes or finely controlled nano-matrices. Such a geometry enables three key properties for medical application: (1) complete encapsulation of the therapeutic cargo (e.g., siRNA, mRNA, small molecules, protein drugs) for stability and controlled release; (2) precisely targeted penetration through dense biological barriers (cartilage, kidneys, the extracellular matrix of solid tumors); (3) a low immunological footprint, as the chemical motifs mimic nucleic bases and do not trigger a strong unwanted immune response.

On Earth, these nanostructures are typically obtained through gentle, aqueous self-assembly at room temperature, without extreme pressures or temperatures. But precisely because "nature builds" itself, any microscopic vortex or gradient caused by gravity can disrupt the uniformity of growth. Convection currents, sedimentation, and surface thermocapillary flows (Marangoni flows) create "hot spots" and dilutions in the solution, leading to aggregates, microvoids, and imperfect pores. The consequence is defects that compromise mechanical stability, reproducibility, and the ability to reliably carry a drug.

Microgravity as a "clean room" for self-assembly

In low Earth orbit, where the ISS circles the planet approximately 16 times a day at an altitude of about 400 kilometers, the effects of gravity are almost nullified. In such conditions, convection currents and particle sedimentation are silenced, and diffusion becomes the dominant mechanism of substance transport. For materials formed by self-assembly, this means a "calm" chemical environment: molecules have time to form thermodynamically favorable and more homogeneous arrangements, without local vortices and gradients that would "pull" them into the wrong phase or incorrect stacking order.

When the same chemical recipe and the same concentrations are transferred from an Earth-based reactor to a microgravity cassette, the difference is visible under an electron microscope and in measurements: more uniform tube diameters, more regular matrix layering, fewer defects, and more uniform porosity. And since geometry is key to the release and retention of the therapeutic cargo, an improvement in structure automatically translates into better therapeutic function.

What the UConn–Eascra team achieved in a series of space campaigns

As part of multiple spaceflights in 2024 and 2025, researchers optimized the protocols for the self-assembly of JBNs in microgravity. The results showed a significant leap in uniformity and structural regularity, with internal metrics of structure and porosity showing up to around 40% better ordering compared to the best batches made on Earth. The chemical formula remained the same; the key change was the elimination of gravity-driven flows during the critical phases of nucleation and maturation.

Due to these advancements, Eascra is developing an automated, closed system for the synthesis and maturation of JBNs in orbit. The goal is a process that, from dosing and controlled "mixing by diffusion," through the maturation time profile, to matrix hardening, works without human intervention, while recording all process parameters for quality analytics. The long-term vision includes transitioning from the ISS to future commercial platforms in low Earth orbit (LEO), with larger batches and more frequent sample rotations back to Earth for testing and validation.

How JBNs fit into the therapy of osteoarthritis

Cartilage is an avascular, dense tissue. This is why many injection therapies fail to deliver the drug to the deeper layers where chondrocytes live. Janus base nanoparticles are designed to "thread" through the collagen and proteoglycan network, carrying therapeutic molecules within their hollow core. In a realistically imagined treatment scenario, JBN particles encapsulating siRNA/mRNA would be delivered into the joint by injection; they would simultaneously suppress inflammatory pathways and catabolic enzymes and stimulate the expression of genes responsible for extracellular matrix synthesis.

For lesions that require mechanical support, a Janus base nano-matrix acts as a biodegradable scaffold: a micro-framework where chondrocytes can "anchor" and where proper biochemical signals for tissue regeneration can be maintained. The advantage is that such a matrix can be formulated to slowly release the therapeutic "cargo" and thus maintain the therapeutic effect over a longer period, reducing the number of repeated injections.

Precise penetration into solid tumors: application in oncology

Solid tumors—for example, pancreatic cancer or triple-negative breast cancer—have a dense stroma, elevated interstitial pressure, and uneven vascularization, which makes drug delivery extremely difficult. JBNs offer a double advantage: (1) they can be functionalized with ligands that target specific receptors on tumor cells or stromal elements, which increases selectivity; (2) their hollow architecture allows for the complete encapsulation of cytostatics, targeted inhibitors, or nucleic acids, reducing the exposure of healthy tissues and side effects. Since JBNs chemically mimic DNA motifs, they do not elicit a strong unwanted immune response and can retain the drug in the tumor longer than classic carriers.

What microgravity changes at the level of fluid physics

In terrestrial conditions, production solutions are constantly "plagued" by convection (due to temperature and density differences), sedimentation (settling of particles due to gravity), and Marangoni flows (flows along an interface boundary caused by surface tension gradients). These processes create non-uniform microenvironments where nano-rosettes and nanotubes grow at different rates and in the wrong places. In microgravity, these effects are dramatically reduced; diffusion becomes the main transport mechanism, and all molecules "see" similar conditions. This leads to more uniform nucleation, slower but more regular growth, and, ultimately, a more stable nano-architecture with fewer defects.

From demonstration to industrial production

The first space-based batches of JBNs were designed as a proof of feasibility and a direct comparison with batches made on Earth. But as measurable differences in structure and function were repeatedly observed, the focus shifted to scaling. Eascra is developing automated cassettes and controllers that can serially conduct synthesis and maturation in orbit with minimal crew involvement. Such robotization reduces the cost per batch and opens the door to larger quantities, which is a prerequisite for preclinical and, in the long term, clinical programs.

In parallel, logistics chains are being established: more frequent supply flights to the ISS, faster return of samples to Earth, and migration towards commercial platforms in low Earth orbit (LEO). As the LEO industry matures, flight costs are dropping, and the iterative cycle of "formulate–produce–test–repeat" is becoming feasible even for agile biotech teams.

The safety and regulatory horizon

The path to the patient leads through preclinical and clinical trials and compliance with good manufacturing practice (GMP) standards. JBNs have an important advantage: the basic chemistry takes place in mild, aqueous conditions, without organic solvents and high temperatures. This facilitates proving purity and reduces the risks of contamination. Automated, closed, single-use reactors further simplify sterility control and traceability of process parameters—which is crucial for regulatory approval.

Broader market and potential: beyond joints, towards other dense tissues

If the advantages of uniformity and functionality are confirmed in further validations, the platform could open doors to therapies for indications where drug delivery has so far been a bottleneck: kidney diseases (due to dense basement membranes), fibrotic diseases of the lungs and liver, and tumors with a particularly rich extracellular matrix. Another operational gain: JBNs can maintain the bioactivity of the cargo at room temperature, which reduces dependence on the "cold chain" and potentially expands the availability of precision therapy beyond the largest clinical centers.

Context of time: where the project is today

As of today's date, October 03, 2025, the team has multiple space campaigns and constant protocol iteration behind them. The spring cargo flight missions to the ISS in 2025 included additional experiments aimed at further increasing uniformity and fully automated reaction management. An analysis of the stability of space-produced batches is underway—how long they retain their mechanical properties and therapeutic efficacy during storage—as well as comparisons with the latest batches produced on Earth. The team is also testing parameters that could be translated into hybrid processes: starting self-assembly in space and finishing "maturation" under controlled conditions on Earth, to reduce costs and cycle time.

Why LEO is the right address for this kind of production

LEO is not "deep space"; it is an infrastructure about 400 km from Earth that can be reached in hours, and samples can be returned to the laboratory within days. Such a rhythm allows for rapid iterations, and the growth of commercial platforms expands capacity and pushes down costs. For processes that require quiet conditions without gravitational interference—like the self-assembly of JBNs—LEO is an industrial niche that has an immediate benefit on Earth: better batches, more uniform properties, more predictable drug release, and, potentially, better treatment outcomes.

A look ahead: from osteoarthritis to personalized oncology

The JBN platform is inherently modular. The same "channels" and "matrices" can carry different therapeutic packages tailored to the genomics of a tumor or the molecular profile of a degenerative disease in an individual patient. In combination with diagnostics that monitor inflammatory pathways in real-time from blood or synovial fluid, the possibility opens up for phased, precise dosing instead of single "shock" therapies. It is precisely this smoothness of the process in microgravity—fewer defects and greater reproducibility—that becomes the translator of science into a stable medical product.

For readers and researchers from Croatia and the region, the message is practical: space manufacturing is no longer fiction. Through partnerships and industrial collaborations, it is possible to design processes that exploit microgravity for uniform materials that are difficult to reproducibly produce on Earth, and then apply them in therapies with high unmet needs. Guidelines, calls, and technical guides are regularly published on the websites of the ISS National Lab, in the papers of UConn's nanomedicine laboratory, and on the pages of Eascra Biotech, which can serve as a starting point for one's own project ideas and international consortia.