Secondly, the complexities of industrial production processes could hamper the ability to meet the demand of patients. The small volume laboratory batches are generally reproducible, but consistency, encompassing both physico-chemical and biological properties must be also ensured when moving to larger scale manufacturing process. However, we recognize that as the number of components increases, achieving a high level of control becomes extremely challenging, raising the risk of reproducibility issues across different batches. In addition to the possibility to scale the synthesis and formulation of the individual single components and combine them, it is also crucial to do so in accordance with the current Good Manufacturing Practices (GMP). This involves addressing challenges such as the variability of naturallyderived polymers, unreacted reagents and residual solvents in the final formulation. There are also concerns regarding impact of manufacturing conditions on the stability of the different components and the effectiveness of achieving sterility without compromising the structural and functional properties of the hybrid hydrogel. The implementation of Quality by Design (QbD) principles and a risk-based approach early in the development process can significantly reduce the odds of major problems occurring at later stages, facilitating smoother time-tomarket. The selection of the materials (polymers, NPs) is guided by the essential criteria such as biocompatibility, safety, and degradation without the generation of toxic byproducts. Beyond each individual component, that must not induce immune reactions and/or prolonged inflammatory response, it is the safety profile of the final formulation that must be assessed. This evaluation should be conducted on relevant biological conditions that mimic the complex in vivo environment faced after administration. For example, we have observed that swelling/degradation studies are predominantly performed in static conditions, yet, depending on the application, the hybrid hydrogels may be exposed to a continuous flow of liquid, which could affect degradation and/or drug release. What about the effect of motion, especially for hydrogels injected into the intraarticular cavity? In the context of bone healing materials, does the tested load correspond to human physiology?