<p>Implant-associated infections remain a major challenge in bone regeneration, often compromising the long-term success of hydroxyapatite-based biomaterials. A new sulfonated quinoxaline aldehyde, 2-ethoxy-4-formylphenyl 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonate (B6), was synthesized and covalently grafted onto chitosan via Schiff base condensation to yield derivatives with controlled degrees of substitution (d1–d4). Which were subsequently incorporated into hydroxyapatite to form composite systems (dH0–dH4). Structural characterization using Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) confirmed successful Schiff base formation, while thermogravimetric analysis (TGA) indicated enhanced thermal stability. Scanning electron microscopy with energy-dispersive X-ray analysis (SEM–EDX) and Brunauer–Emmett–Teller (BET) analyses revealed homogeneous hydroxyapatite dispersion and a mesoporous architecture (44.8 m<sup>2</sup> g<sup>− 1</sup>, ~ 20&#xa0;nm pores) for the optimized composite. Among the investigated formulations, dH2 exhibited the most balanced physicochemical and biological performance. The dH2 composite exhibited pronounced antimicrobial activity, achieving biofilm inhibition of 89.65% against <i>Bacillus cereus</i> and 86.65% against <i>Staphylococcus aureus</i>, with MIC values lower than those of reference antibiotics under the tested conditions. Cytotoxicity assessment using Vero and MG-63 cells demonstrated excellent biocompatibility, with &gt; 99% cell viability at ≤ 125&#xa0;µg/mL and IC<sub>50</sub> values of 344.99 and 156.62&#xa0;µg/mL, respectively. These findings indicate that the developed chitosan–quinoxaline Schiff base hydroxyapatite composite represents a multifunctional, infection-resistant platform suitable for bone regeneration applications.</p>

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Chitosan-quinoxaline Schiff base hydroxyapatite composite with antimicrobial properties for bone regeneration

  • Abdelrahman Barakat,
  • Gameel A. M. Ehagali,
  • Shahira H. EL-Moslamy,
  • Moustafa S. Abusaif,
  • Medhat E. Owda,
  • Yousry A. Ammar,
  • Mohamed B. Ghazy

摘要

Implant-associated infections remain a major challenge in bone regeneration, often compromising the long-term success of hydroxyapatite-based biomaterials. A new sulfonated quinoxaline aldehyde, 2-ethoxy-4-formylphenyl 2,3-dioxo-1,2,3,4-tetrahydroquinoxaline-6-sulfonate (B6), was synthesized and covalently grafted onto chitosan via Schiff base condensation to yield derivatives with controlled degrees of substitution (d1–d4). Which were subsequently incorporated into hydroxyapatite to form composite systems (dH0–dH4). Structural characterization using Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) confirmed successful Schiff base formation, while thermogravimetric analysis (TGA) indicated enhanced thermal stability. Scanning electron microscopy with energy-dispersive X-ray analysis (SEM–EDX) and Brunauer–Emmett–Teller (BET) analyses revealed homogeneous hydroxyapatite dispersion and a mesoporous architecture (44.8 m2 g− 1, ~ 20 nm pores) for the optimized composite. Among the investigated formulations, dH2 exhibited the most balanced physicochemical and biological performance. The dH2 composite exhibited pronounced antimicrobial activity, achieving biofilm inhibition of 89.65% against Bacillus cereus and 86.65% against Staphylococcus aureus, with MIC values lower than those of reference antibiotics under the tested conditions. Cytotoxicity assessment using Vero and MG-63 cells demonstrated excellent biocompatibility, with > 99% cell viability at ≤ 125 µg/mL and IC50 values of 344.99 and 156.62 µg/mL, respectively. These findings indicate that the developed chitosan–quinoxaline Schiff base hydroxyapatite composite represents a multifunctional, infection-resistant platform suitable for bone regeneration applications.