Hydrogels have emerged as pivotal materials in the biomedical field, transitioning from scientific curiosities to commercially successful products, such as soft contact lenses, in the 1960s [1,2]. This transformation has catalyzed extensive research efforts, expanding the potential applications of hydrogels across a diverse range of biomedical domains that now stand as a formidable alternative to conventional materials like thermoplastics, ceramics, and metals. The primary reason for this significant paradigm originates in their inherent biocompatibility, indeed [3,4].

Unlike metals or ceramics, which can provoke inflammatory responses or fibrosis when implanted in the body, hydrogels are generally associated with minimal immunogenicity and toxicity [5]. Their water-rich nature allows them to form a soft, tissue-mimicking interface, such that it reduces the risk of irritation and inflammation at the site of application [6]. Furthermore, the ability to be engineered for in vivo degradation at controlled rates that align with healing or regenerative processes accounts for one of the most compelling attributes of hydrogels [7]. This feature eliminates the necessity for secondary interventions, such as surgical removal, which improves patient outcomes and reduces healthcare costs. Hydrogels further offer a high degree of functionalization, which can be achieved by altering polymer compositions, adjusting crosslinking densities, or incorporating nanomaterials [8]. Such versatility enables hydrogels to actively participate in and modulate various physico-mechanical and biological processes, making them not just passive materials but dynamic players in biomedical applications.

While hydrogels are highly effective in purposes requiring soft, flexible structures, their mechanical properties often fall short for applications involving load-bearing tissues, such as bone or cartilage [9]. The intrinsic swelling behavior of hydrogels can additionally prompt mechanical instability over time, which limits their applicability in certain biomedical contexts. To address these challenges, the development of hydrogel nanocomposites has gained traction over the last decades (Fig. 1a). This approach leverages the synergistic combination of the favorable properties of hydrogels with the enhanced mechanical strength and functionality imparted by nanoparticles [10]. Nanoparticles can also be tailored to interact specifically with biological molecules, facilitating the controlled and targeted delivery of medicines or other therapeutic agents. This level of control over drug release kinetics and targeting specificity represents a huge benefit over traditional hydrogel systems.

Even with substantial enhancements, the quest to develop a truly practical prototype for real-world applications of such functionalized hydrogels remains an area of intense research and curiosity [17]. The challenge lies primarily in fine-tuning these materials to balance their mechanical properties, biocompatibility, and functional versatility to meet the complex demands of biomedical environments. Conventional methods for developing hydrogel nanocomposites, namely solution blending, electrospinning, and in-situ polymerization, are devoid of customization and design flexibility [18]. These techniques typically involve processing hydrogel nanocomposites onto two-dimensional (2D) substrates, which inherently constrain their capacity to replicate the complex 3D structures of human organs. Overcoming this pitfall is, therefore, instrumental to unlocking the full potential of hydrogel nanocomposites for biomedical applications.

3D printing, a subfield of additive manufacturing, has burst with tremendous possibilities for developing personalized items, setting the stage for the climax of design and prototyping with high precision and control [19]. This technology sparks unparalleled freedom in creating complex geometries with much less resource consumption, making it an invaluable tool for applications ranging from custom scaffold architectures in tissue engineering to drug-loaded implants with spatially controlled drug distribution [20,21]. Captivated by such promises, a number of 3D printing techniques, including extrusion-based printing, stereolithography, and inkjet printing, have been successfully adapted for the fabrication of hydrogel nanocomposites [22,23]. Nevertheless, reports on additive manufacturing of these materials are scarce. In this effort, we aim to provide an overview of hydrogel nanocomposites integrated with 3D printing technology, discuss critical fundamentals involved in developing hydrogel nanocomposites for advanced biomedical applications, and highlight prominent advancements in the field. After visiting typical polymers and nanomaterials used in fabricating hydrogel nanocomposites, the trending biomedical functions of hydrogel nanocomposites, such as biocompatibility and tissue-like properties, are explored. For the first time, 3D printing techniques and vital printing parameters for adequate manufacturing of hydrogel nanocomposites are critically examined. We hope this review serves as a useful toolbox for further investigations, paving the way for state-of-the-art discoveries in health care and biomedical avenues.