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.

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.

Titanium (Ti) and its alloys have been demonstrated over the last decades to play an important role as inert materials in the field of orthopedic and dental implants. Nevertheless, with the widespread use of Ti, implant-associated rejection issues have arisen. To overcome these problems, antibacterial properties, fast and adequate osseointegration and long-term stability are essential features. Indeed, surface modification is currently presented as a versatile strategy for developing Ti coatings with all these challenging requirements and achieve a successful performance of the implant. Numerous approaches have been investigated to obtain stable and well-organized Ti coatings that promote the tailoring of surface chemical functionalization regardless of the geometry and shape of the implant. However, among all the approaches available in the literature to functionalize the Ti surface, a promising strategy is the combination of surface pre-activation treatments typically followed by the development of intermediate anchoring layers (self-assembled monolayers, SAMs) that serve as the supporting linkage of a final active layer. Therefore, this paper aims to review the latest approaches in the biomedical area to obtain bioactive coatings onto Ti surfaces with a special focus on (i) the most employed methods for Ti surface hydroxylation, (ii) SAMs-mediated active coatings development, and (iii) the latest advances in active agent immobilization and polymeric coatings for controlled release on Ti surfaces.

Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels’ physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in ¹H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against Staphylococcus aureus by significantly decreasing the pro-inflammatory cytokine levels.

Traditional wound dressings have not been able to satisfy the needs of the regenerative medicine biomedical area. With the aim of improving tissue regeneration, nanofiber-based wound dressings fabricated by electrospinning (ES) processes have emerged as a powerful approach. Nowadays, nanofiber-based bioactive dressings are mainly developed with a combination of natural and synthetic polymers, such as polycaprolactone (PCL) and chitosan (CHI). Accordingly, herein, PCL/CHI nanofibers have been developed with varying PCL:CHI weight ratios (9:1, 8:2 and 7:3) or CHI viscosities (20, 100 and 600 mPa·s) using a novel alternating current ES (ACES) process. Such nanofibers were thoroughly characterized by determining physicochemical and nanomechanical properties, along with wettability, absorption capacity and hydrolytic plus enzymatic stability. Furthermore, PCL/CHI nanofiber biological safety was validated in terms of cytocompatibility and hemocompatibility (hemolysis < 2%), in addition to a notable antibacterial performance (bacterial reductions of 99.90% for S. aureus and 99.91% for P. aeruginosa). Lastly, the enhanced wound healing activity of PCL/CHI nanofibers was confirmed thanks to their ability to remarkably promote cell proliferation, which make them ideal candidates for long-term applications such as wound dressings.

A significant number of people worldwide suffers from knee osteoarthritis (KOA), a chronic and painful disease that is linked to aging, traumatological events and sports medicine. Clinical research indicates that KOA exhibit an altered synovial fluid (SF) with lower endogenous hyaluronic acid (HA) concentration and viscoelastic properties. Nowadays, viscosupplementation by intra-articular HA injections is the most common treatment to restore endogenous HA performance in osteoarthritic SF. In this work, TrHCROSS®, Durolane®, Regenflex®Bio-plus and Monovisc® commercial crosslinked HA viscosupplements were compared in vitro against enzymatic degradation. As key research point, TrHCROSS® demonstrated a considerably increased enzymatic stability compared to the rest of examined viscosupplements, which highlights TrHCROSS® prolonged residence time in joint space reducing more durably and effectively osteoarthritic knee pain. Subsequently, an in-depth physicochemical characterization was realized to support efficacy and stability results of viscosupplements. All in all, TrHCROSS®, developed by SARE® technology, was found to be more successful in treating more durably and effectively KOA based on the remarkable outcomes of conducted trials, which were appropriate findings for the current research investigation.