The application of hydrogels in orthopedics has long bedeviled chemists because of a lack of mechanical capacity. But what if you could develop an injectable hydrogel with properties that provide robust shock-absorbing properties in the joint? 

The Need for Innovation 

Osteoarthritis is a rapidly growing disease that hundreds of millions of people around the world suffer from. It diminishes mobility, leads to constant pain, and can trigger mental health problems. Treatment straddles short-lived symptom management and invasive surgical intervention. This “treatment gap” is what we set to bridge with innovative hydrogel technology—crosslinked polymer networks with high water content. 

Hydrogels offer tunable mechanics: their elasticity, for instance, can be adjusted by crosslink density, polymer composition, water content, and other factors. They are also permeable and biocompatible. In theory, all this makes them an ideal fit for orthopedic applications. And indeed, hydrogels such as hyaluronic acid are widely used as intra-articular injections to restore lubrication. Yet, the available treatments provide only transient relief and do not address the mechanical causes of the disease. Bulk hydrogels are too soft and fragile to function in the dynamic, high-load environment of the knee, lacking the structural integrity needed to withstand repeated compression and shear forces. As a result, they cannot provide true load-bearing support in joints.

To overcome these deficits, we developed a hydrogel-based load-bearing scaffold for meniscal regeneration, engineered to replicate the native tissue’s mechanical profile and support cellular integration. However, the approach was too invasive, requiring implantation, specialized surgeon training, and patient-specific customization, which limited its clinical feasibility. 

Moving on from this idea, we transformed the platform into a hydrogel microparticle system. Delivered via an injection, the microparticles disperse within the synovial cavity and mix with the synovial fluid, where they create a cushioning effect that unloads stress from the articular cartilage. This evolution—from a permanent implant scaffold to an “injectable implant” that reconstructs its mechanical function within the joint—highlights the unique chemistry underlying the technology. By combining minimally invasive delivery with load-bearing performance, this hydrogel could introduce a new approach for joint-preserving therapies in osteoarthritis.

In Search of the Right Material

When setting out in search of a hydrogel that could become our injectable implant, we were looking for the attributes for intra-articular application mentioned previously. The formulation developed uses natural polysaccharides and amino acid derivatives, chosen for their low immunogenicity, degradability, and compatibility with regulatory frameworks. One of its defining features is to provide structural integrity while allowing the network to adapt to the highly variable mechanical environment of the knee. The hydrogel responds to cyclic loading, dissipates stress, and maintains its functionality under shear—mimicking the adaptive behavior of biological tissues such as cartilage and synovium. 

One essential material property required of the hydrogel was shear-thinning behavior, whereby its viscosity decreases in response to applied shear stress, to allow smooth delivery through 19- to 23-gauge needles, with rapid recovery of its structure once in place. Other crucial advantages are that the hydrogel exhibits a gradual breakdown at a predictable rate and extended retention, with residence times of several months in vivo—far exceeding the clearance profile of hyaluronic acid. Its viscoelastic properties are tuned to mirror the damping behavior of synovial fluid and soft cartilage, ensuring effective lubrication, impact absorption, and mechanical integration. 

Supporting Joint Function

It wasn’t only a matter of finding the right formulation; we also had to think about the architecture of the hydrogel. Bulk hydrogels often fail in vivo due to rapid clearance and mechanical breakdown. To address these limitations, we developed the material as hydrogel microparticles (HMPs): small, discrete hydrogel building blocks that can flow and pack together—a format specifically designed for dynamic, load-bearing environments like the knee. 

Each microparticle functions as an individual mechanical unit that is both compressible and resilient, able to absorb and dissipate forces generated during joint movement. The microparticles may help protect tissue surfaces, slow degeneration, and contribute to pain reduction in load-bearing joints. Dispersed uniformly throughout the synovial space, the HMPs behave like an internal cushion that moves with the joint, supporting not just lubrication, but also mechanical modulation of the diseased environment.

The hydrogel also has a high surface-area-to-volume ratio, supporting interaction with synovial membranes, while its adaptive load distribution can respond to movement and redistributing shear.

Lessons Learned 

The development of this new hydrogel for orthopedic applications involved a series of critical refinements to translate an initially promising concept into a formulation suitable for clinical use. Achieving the balance among injectability, intra-articular retention, and manufacturing reproducibility required multiple rounds of optimization, each informed by empirical feedback and performance evaluation.

The need for compatibility with fine-gauge needles necessitated careful adjustment of particle size, formulation rheology, and structural integrity. 

Another important insight emerged during testing under dynamic, physiologic conditions. Materials that demonstrated favorable retention profiles in static models did not always maintain the same behavior in actively articulating joints. This underscored the need for robust control over particle size and material consistency to support both functional efficacy and future scale-up.

Overall, each stage of development contributed to a progressively more robust and application-ready platform. These experiences highlighted the value of integrating practical deployment considerations—such as delivery mechanics and joint biomechanics—into the early stages of material design.

Importantly, hydrogels should be regarded not just as passive carriers, but as active mechanical components. Their stiffness, swelling kinetics, and viscoelastic properties influence both therapeutic efficacy and biomechanical integration, and should be integral to their design. Platforms that support modular tuning—of degradation kinetics, drug release profiles, and mechanical properties—enable broader applicability across clinical indications. Early and continuous engagement with clinicians ensures design decisions align with real-world surgical workflows, injection techniques, and patient-specific needs. This is increasingly important as the field moves toward multifunctional therapies that integrate mechanical support, controlled biological signaling, and minimally invasive delivery into unified treatment strategies.

A Mechanically Informed Future 

Osteoarthritis remains one of the most pressing and complex challenges in musculoskeletal health. It is not merely a disease of aging cartilage—it is a multifactorial, progressive condition shaped by chronic inflammation, tissue breakdown, and, increasingly recognized, mechanical dysfunction. Traditional approaches have largely focused on alleviating symptoms through pharmacological or surgical means, without addressing the mechanical environment that drives disease progression. But the next generation of therapies must go further. Effective treatment requires tools that engage with the joint as a dynamic system, integrating structural, biological, and biomechanical insights.

Hydrogels—long valued for their biocompatibility and versatility—are now being reimagined as active participants in joint therapy. No longer confined to passive roles as drug carriers or space fillers, they can now be engineered to adapt to motion, modulate stress, and support tissue recovery. The shift from bulk gels to injectable HMPs represents a leap forward. By distributing mechanical load, absorbing impact forces, and conforming to joint movement, HMPs offer a novel way to influence disease from within—without altering anatomy or relying on external fixation.

Our hydrogel technology was developed with this vision in mind: a mechanically responsive, minimally invasive material system that could be delivered in the clinic, tailored to the joint environment. The ability to bridge early- to mid-stage osteoarthritis with a treatment that is both scalable and responsive to the biomechanics of the joint opens the door to true disease modification, rather than temporary relief. 

By reducing mechanical stress on cartilage and synovium, promoting joint homeostasis, and extending intra-articular residence time, HMPs offer a compelling alternative to both traditional visco-supplements and surgical interventions. 

This marks a pivotal moment. The convergence of material innovation, biomechanics, and translational design enables a new category of therapies—ones that not only address symptoms but also structural and functional causes. Success requires more than chemistry; it demands a multidisciplinary approach rooted in the realities of joint biology and motion.

In this evolving landscape, hydrogel microparticles exemplify how science and engineering can work together to reshape the future of joint health. Not just to treat osteoarthritis—but to fundamentally change how we intervene, preserve, and restore the function of one of the body’s most essential, and most burdened, systems.

Jorg Schelfhout is the founder and chief scientific officer of Allegro Biotech, a Belgium-based company dedicated to developing next-generation injectable hydrogel platforms for orthopedic and regenerative medicine. His work at Allegro focuses on translating lab-scale formulations into scalable, regulatory-ready products designed for intra-articular use. Dr. Schelfhout holds a Ph.D. in biomedical engineering from Ghent University, where his research focused on the development of injectable hydrogels for soft tissue engineering.