**6. DAC® hydrogel** *in vivo* **activity**

**5.4. DAC® hydrogel coating ability**

188 Hydrogels

For any device candidate to act as a coating of orthopedic and trauma biomaterials, mechanical adherence to the implant surface plays a key role. In particular, DAC® hydrogel has been designed to be spread manually at the time of surgery and to not interfere with the usual surgical techniques of press-fit insertion of an implant. The ability of DAC® hydrogel to completely cover even sand-blasted titanium surface and resist scraping has been confirmed by

that may be locally released, contributing to eliminate all remaining planktonic bacteria.

**Figure 4.** Rationale for intra-operative mixing of DAC® hydrogel coating with antibacterial agents. Schematic representation of different scenarios. (a) Noncoated implants may get colonized by biofilm-forming bacteria (yellow circles) and infection will develop. (b) Antiadhesive coating may reduce/prevent bacterial adhesion, while the immune system (orange circles and red stars) and the systemically administered antibiotics (blue star) kill planktonic microorganisms. (c) However, if bacterial load is large enough, or if immune response and local antibiotic levels are inadequate, surviving bacteria may eventually colonize the implant, once the coating has been hydrolyzed or covered by host's proteins. (d) To prevent this, the antibacterial hydrogel may be loaded, at the time of surgery, with antibiotic agents (blue stars)

Safety and efficacy of the DAC® hydrogel have been investigated in several animal studies.

Concerning efficacy, in an acute model of highly contaminated implant-related infection in the rabbit, Giavaresi and coworkers [55] found that a vancomycin-loaded DAC® coating was associated with local bacterial load reduction ranging from 72 to 99%, compared to uncoated controls.

In another large investigation in the rabbit model, Boot et al. [56] showed, at longer follow-up and without systemic antibiotic prophylaxis, the ability of vancomycin-loaded DAC®-coated implants to significantly resist infection, compared to uncoated controls. Both studies did also reveal the absence of local or systemic side effects. In line with this observation, a more recent paper, focused on the impact on bone healing and implant osteointegration, reported no detrimental effects of vancomycin-loaded DAC® or of DAC® alone [57].

Another study on a rat model of acutely infected osteosynthesis did provide evidence that vancomycin-loaded DAC®-coated plates and screws not only are associated with a significant reduction of infection but also protect from the occurrence of septic nonunion, compared to uncoated implants [58]. This study is the very first demonstration that bone healing in a contaminated fracture can be improved by using an osteosynthesis coated with a fast-resorbable, antibiotic-loaded hydrogel.

> 18.1 ± 4.5 months (range 12–30), 253 patients were available for evaluation. On average, 5.7 mL (range: 1–10 mL) of DAC® hydrogel was needed to coat the implant. Gentamicin and vancomycin were the most used antibiotics, at concentration of, respectively, 4% or 2%. Six surgical site infections (4.6%) were observed in the control group compared to none in the treated group (P < 0.02). No local or systemic side effects related to DAC® hydrogel coating were observed and no detectable interference with bone healing was reported [61, 62] (cf. **Table 1**). Preliminary results of the possible use of the DAC® hydrogel coating in one-stage exchange of infected prosthesis did also recently show the efficacy and safety of the device in this challenging application [63]. Further studies are currently under way concerning joint replace-

> **Table 1.** Summary of the main results of the published clinical multicenter trials on DAC® hydrogel coating in orthopedics

Romanò et al. [58] 380 14.5 ± 5.5 0.6 6 0.003 None Malizos et al. [60] 256 18.1 ± 4.5 0 4.6 <0.02 None

**DAC-treated SSI rate (%)**

Hyaluronic-Based Antibacterial Hydrogel Coating for Implantable Biomaterials in Orthopedics…

**Controls SSI rate (%)**

**P Side** 

http://dx.doi.org/10.5772/intechopen.73203

**effects**

191

Periprosthetic joint infections (PJI) are associated with increased costs for public health systems, mainly due to additional surgeries, prolonged hospitalization, increased length of rehabilitation and increased use of antibiotics [64]. Moreover, PJIs are associated with an increase in morbidity and mortality [65]. Unless novel, effective measures are taken to reduce the incidence of surgical site infections (SSIs), these complications will become an accruing burden to

Cost-effectiveness of antibacterial coatings of joint prostheses can be calculated, comparing their direct and indirect hospital costs with those of unprotected implants, taking into consideration the expected surgical site infection rate and using a decision-analytic modeling

**Table 2** reports an algorithm used to calculate the overall economic impact of DAC® hydrogel coating. The following variables are included for calculation: average cost and number of primary joint replacements; average cost of the antibacterial coating per patient; incidence of PJI and expected reduction of infection rate with the use of the coating; average cost of PJI

Various scenarios can be simulated with the reported algorithm, depending on the relative

Considering the undiscounted price of DAC® hydrogel at our institution of € 585.00 per package and two packages of DAC® as the standard use per patient, it can be calculated that, if the

approach, as previously described by Diaz-Ledezma et al. [68] and Kapadia et al. [69].

ment in bone tumors, spine surgery, exposed fractures and dentistry.

**Follow-up (months)**

the health care system in the next two decades [66, 67].

treatment and expected number of cases.

value given to each variable.

**8. Economic impact**

**Reference Number of** 

SSI, surgical site infection.

and trauma.

**patients**
