Injectable Hydrogels: From Laboratory to Industrialization

Abstract

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.

Photocrosslinked gelatin hydrogel improves wound healing and skin flap survival by the sustained release of basic fibroblast growth factor

“…The cross-linking methods, based on chemical and physical linkages, are used to prepare hydrogels that are injectable 25 , 26 . These hydrogels exhibit relatively higher mechanical property and more suitable physicochemical properties ensuing greater durability over time due to stable covalent bonds 27 . However, these materials are inefficient owing to slow gelling, weak adhesion strength against wet tissue surface since their clinical applications are limited due to inflexibility or toxic degradation products 28 , 29 .…”

Bioactive Coatings on Titanium: A Review on Hydroxylation, Self-Assembled Monolayers (SAMs) and Surface Modification Strategies

“…In that way, the amount of active agent that is loaded and steadily released through the stable hydrogel network (from hours to months) is easily controlled and can be varied from specific low- to high-doses [ 143 ]. In addition, comparing them with multilayer coatings, hydrogel coatings could possess in general greater loadings and higher ability for high molecular weight biomolecules [ 144 ]. In Figure 9 , macroscopic and SEM photographs of an active coating of Ti6Al4V substrate based on hyaluronic acid hydrogel developed by i+Med S. Coop.…”

Current and Future Prospective of Injectable Hydrogels—Design Challenges and Limitations

“…They are prepared from natural and synthetic polymers through various mechanisms, such as physical and chemical crosslinking methods (discussed in 1.2 classification and synthesis) into different types with their respective advantages and disadvantages [ 7 ]. Some of the characteristics associated with IHs are shown in Figure 1 [ 9 ], whereas Figure 2 [ 10 ] shows the designated and fabricated IHs for photothermal antitumor therapy.…”

“…The fabrication of an injectable hydrogel from the lab to industrial process needs quality design approaches with critical quality attributes, as mentioned by [ 9 ]. Figure 4 summarizes all these parameters connected with the features of the starting material (active ingredients, biopolymers, solvents and components ratios) throughout the stages of the fabrication process (i.e., heating temperature, agitation speeds and reaction time), which are outlined in the Ishikawa model diagram to potentially modify these formulation steps.…”