The transfer of some innovative technologies from the laboratory to industrial scale is many times not taken into account in the design and development of some functional materials such as hydrogels to be applied in the biomedical field. There is a lack of knowledge in the scientific field where many aspects of scaling to an industrial process are ignored, and products cannot reach the market. Injectable hydrogels are a good example that we have used in our research to show the different steps needed to follow to get a product in the market based on them. From synthesis and process validation to characterization techniques used and assays performed to ensure the safety and efficacy of the product, following regulation, several well-defined protocols must be adopted. Therefore, this paper summarized all these aspects due to the lack of knowledge that exists about the industrialization of injectable products with the great importance that it entails, and it is intended to serve as a guide on this area to non-initiated scientists. More concretely, in this work, the characteristics and requirements for the development of injectable hydrogels from the laboratory to industrial scale is presented in terms of (i) synthesis techniques employed to obtain injectable hydrogels with tunable desired properties, (ii) the most common characterization techniques to characterize hydrogels, and (iii) the necessary safety and efficacy assays and protocols to industrialize and commercialize injectable hydrogels from the regulatory point of view. Finally, this review also mentioned and explained a real example of the development of a natural hyaluronic acid hydrogel that reached the market as an injectable product.

Stable hyaluronic acid nanogels were obtained following the water-in-oil microemulsion method by covalent crosslinking with three biocompatible crosslinking agents: Divinyl sulfone, 1,4-butanediol diglycidyl ether (BDDE), and poly(ethylene glycol) bis(amine). All nanoparticles showed a pH-sensitive swelling behavior, according to the pKa value of hyaluronic acid, as a consequence of the ionization of the carboxylic moieties, as it was corroborated by zeta potential measurements. QELS studies were carried out to study the influence of the chemical structure of the crosslinking agents on the particle size of the obtained nanogels. In addition, the effect of the molecular weight of the biopolymer and the degree of crosslinking on the nanogels dimensions was also evaluated for BDDE crosslinked nanoparticles, which showed the highest pH-responsive response.

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