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.
Hyaluronic acid (HA) hydrogels display a wide variety of biomedical applications ranging from tissue engineering to drug vehiculization and controlled release. To date, most of the commercially available hyaluronic acid hydrogel formulations are produced under conditions that are not compatible with physiological ones. This review compiles the currently used approaches for the development of hyaluronic acid hydrogels under physiological/mild conditions. These methods include dynamic covalent processes such as boronic ester and Schiff-base formation and click chemistry mediated reactions such as thiol chemistry processes, azide-alkyne, or Diels Alder cycloaddition. Thermoreversible gelation of HA hydrogels at physiological temperature is also discussed. Finally, the most outstanding biomedical applications are indicated for each of the HA hydrogel generation approaches.
Biomedical devices have become essential in the health care. Every day, an enormous number of these devices are used or implanted in humans. In this context, the bacterial contamination that could be developed in implanted devices is critical since it is estimated that infections kill more people than other medical causes. Commonly, these infections are treated with antibiotics, but the biofilm formation on implant surfaces could significantly reduce the effectiveness of these antibiotics since bacteria inside the biofilm is protected from the drug. In some cases, a complete removal of the implant is necessary in order to overcome the infection. In this context, antibacterial coatings are considered an excellent strategy to avoid biofilm formation and, therefore, mitigate the derived complications. In this review, the main biomaterials used in biomedical devices, the mechanism of biofilm formation, and the main strategies for the development of antibacterial coatings, are reviewed. Finally, the main polymer-based strategies to develop antibacterial coatings are summarized, with the aim of these coatings being to avoid the bacteria proliferation by controlling the antibacterial mechanisms involved and enhancing long-term stability.
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.
Colloidal nanosized folate‐conjugated hydrogels for targeted chemotherapy were prepared via a versatile and efficient postsynthetic modification pathway starting from P(NPA‐co‐NIPAM). The modifications included the introduction of 4‐methylpyridine as pH‐sensitive pendant groups and the conjugation of folic acid to the microgel network. The microgels showed a specific swelling at pH < 6 (endosomes) as judged by DLS studies varying the external pH. The relative composition of the microgels shows a clear influence on the pH volume transition shifting. The potential of the microgels for anticancer drug release at pH = 5.0 was confirmed. Therefore, they are a promising targeting carrier for improved anticancer chemotherapy.
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