Immediate and long-term biocompatibility, including biodegradability and/or bioelimination must remain the guiding principle. However, natural polymers often suffer from low traceability and significant batch variability, while synthetic ones, although more controllable may be excessively stable in biological conditions. Hence, research focused on synthesizing polymers with functions that precisely control their degradation should be prioritized. Additionally, the concern of ethical and sustainable sourcing of natural polymers, would argue in favor of the use of the synthetic ones. However, reaction conditions for synthetic polymers must be adapted, rethought, or newly developed to minimize the environmental impact of these innovative biomedical approaches. Efforts should focus on greener chemistry, reducing energy consumption, limiting the use of toxic organic solvents, and minimizing harmful waste, for which improved management practices are essential. Implementing microfluidic-based strategies could enable a more precise utilization of materials, thereby reducing waste and associated costs. This advance would make hybrid hydrogels more affordable and contribute to minimize the environmental footprint of companies involved in their development.