**9. Conclusions**

**Table 2.** Algorithm used to estimate the economical impact of antibacterial coating technologies.

192 Hydrogels

**Table 3.** In this simulation, assuming an average cost of primary joint replacement of € 8000 per patient, an average cost of DAC® of € 1170 per case (i.e., two packages per patient), an expected reduction of postsurgical infections by using the coating of 90% and an average cost of PJI treatment of € 50,000 [6, 74], it can be calculated that DAC® is in economical balance if used in a population of patients with an expected periprosthetic infection rate, without the coating, of 2.6%.

Biofilm- and implant-related infections represent a dramatic and increasing burden worldwide. Available data show that hyaluronic acid has a proven *in vitro* antiadhesive/antibiofilm effect against some of the most common pathogens, and HA has been used safely, alone or in combination with other polymers, with satisfactory results in different conditions associated with biofilm-related chronic infections. Clinical data in various applications, including dentistry, urology, wound management, dermatology and orthopedics, paved the way to the possible use of HA as a protective coating barrier of implants.

The chemical derivatization of hyaluronic acid with polylactic acid allows the formation of graft copolymers, which, when contacted with an aqueous medium, can be used to produce hydrogels, like the recently CE-marked DAC®, with appropriate characteristics for easy preparation and application at the time of surgery. Resulting medicated hydrogel is transparent, easily spreadable over a surface, like a titanium prosthesis, and has a specifically designed duration; moreover, it has proven, peculiar, antiadhesive and antibiofilm capabilities. If required, it may also be easily loaded, at surgery, with antibacterial agents that will be released over the following hours or few days in effective high local concentrations. In fact, as a passive protective barrier, DAC® hydrogel has some limits. Among others, the antiadhesive/antibiofilm effect is limited and may vary, depending on the type of the microorganism, the bacterial load, the local environment, etc.; moreover, HA protection may be neutralized by the possible ability of some bacteria to produce hyaluronidase, an enzyme that catalyzes the degradation of hyaluronic acid [52], while collagen and hyaluronan may even become possible ligands for microbial attachment in particular situations, or the coating can be covered by other host's proteins to which bacteria may anchor [72, 73]. To overcome some of these limits, possible loading of the hyaluronic-based hydrogel with antibiotics is technically feasible and has been found safe in various preclinical and clinical settings, being a possible option for clinicians.

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In fact, both *in vitro* and *in vivo* studies did confirm the safety and efficacy of the hydrogel coating with and without loaded antibacterials.

Clinical results also clearly point out the efficacy of the DAC® coating to significantly reduce early postsurgical infection after joint replacement or internal osteosynthesis, without any detectable local side effect both concerning wound and bone healing. Moreover, no changes in organ-specific serum markers or systemic unwanted effects were noted. The high biocompatibility of its basic constituents and the short time (less than 3 days) needed for a complete hydrogel resorption make the possible occurrence of longer term side effects quite unlikely.

Finally, economical consideration points out the high cost-to-benefit ratio of the large-scale use of DAC® coating, especially in a population with at least one risk factor for infection.

The versatility of the device and its safety profile may open the way to application in other surgical fields that share similar infection risk as orthopedics and trauma.
