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International Journal of Bioprinting                        3DP hydrogels to combat antibiotic-resistant bacteria





















































            Figure 8. In vitro activity of the 3D-printed GelMA-Rif-NPs, GelMA-Van-NPs, and GelMA-Rif-Van-NPs with bacterial attachment (a–d) and planktonic
            bacterial (e–h) growth in the medium of S. aureus RN4220, S. aureus Rif , S. aureus Van , and S. aureus AMC 201. Each group was analyzed in six replicates
                                                         R
                                                                   R
            and the data are expressed in LogCFU. Note: * indicates a P-value of 0.01–0.05, ** indicates a P-value of 0.001–0.01. (i) Representative SEM images of each
            hydrogel inoculated with each bacterial strain at 1,000× magnification.
            hydrogels showed three single nucleotide polymorphisms   joint infections. PMMA cement loaded with antibiotics
            (SNPs) in the rpoB fragment that corresponded to three   are the most common biomaterials used in clinics and
            amino acid substitutions, namely S463R (AGC→AGA),   can effectively provide local antimicrobial activity at the
            D471G (GAC→GGC), and R484H (CGT→CAT) (Table 3).    surgical site. However, only a limited number of antibiotics
            No mutations were found in the S. aureus RN4220 cultured   can be incorporated in PMMA due to its polymerization
            with GelMA-C-NPs hydrogel nor in the S. aureus AMC   at high temperatures. Moreover, their long-term antibiotic
            201 isolates cultured from GelMA-C-NPs or GelMA-Rif-  release at sub-therapeutic concentration can induce
            NPs. Although S. aureus AMC 201 cultured from GelMA-  the development of antimicrobial resistance. Using
            Rif-NPs hydrogel had a high MIC for Rif (>128 µg/mL), no   biomaterials like hydrogels can solve both problems,
            mutations were found in the sequenced amplicon of rpoB,   as thermo-labile antibiotics can be incorporated and
            indicating another mechanism of resistance.        some hydrogels are biodegradable. The degradation of
                                                               the polymeric matrix should prevent the release of sub-
            4. Discussion                                      therapeutic antibiotic concentration . Previous studies
                                                                                             [44]
            Antibiotic-loaded devices are commonly used for local   have shown  the effective incorporation of  antibiotics
            delivery in orthopedics to prevent or treat bone and   in  hydrogels  such  as an  injectable  gentamicin-loaded

            Volume 9 Issue 3 (2023)                         74                         https://doi.org/10.18063/ijb.683
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