Smart nano-in-microparticles to tackle bacterial infections in skin tissue engineering

Chronic wounds (resulting from underlying disease, metabolic disorders, infections, trauma, and even tumours) pose significant health problems. In this work, microparticles, based on polysaccharides (maltodextrin or dextran) and amino acids, and doped with antibacterial nanoparticles (CuO or ZnO NPs) are designed. Smart nano-in-microparticles with a hierarchical 3D structure are developed. The ultimate goal aims at an innovative platform to achieve skin repair and to manage skin colonization by avoiding infection that could delay and even impair the healing process.

Highlights

  • Smart microparticles doped with metal oxide nanoparticles (nano-in-microparticles) have been manufactured using spray-dried.
  • Smart nano-in-microparticles with a hierarchical 3D structure have been developed.
  • The systems are able to safely and effectively enhance wound healing in preclinical murine model.
  • The systems inhibit bacterial proliferation.

The microparticles are prepared by spray-drying and cross-linked by heating, to obtain insoluble scaffolds able to facilitate cell proliferation in the wound bed. The nano-in-microparticles are characterized using a multidisciplinary approach: chemico–physical properties (SEM, SEM-EDX, size distribution, swelling and degradation properties, structural characterization – FTIR, XRPD, SAXS – mechanical properties, surface zeta potential) and preclinical properties (in vitro biocompatibility and whole-blood clotting properties, release studies and antimicrobial properties, and in vivo safety and efficacy on murine burn/excisional wound model) were assessed. The hierarchical 3D nano-in microparticles demonstrate to promote skin tissue repair in a preclinical study, indicating that this platform deserves particular attention and further investigation will promote the prototypes translation to clinics.

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Materials

MD (Glucidex 2, molecular mass: 8589 g/mol [20], degree of polymerization: 52.9, dextrose equivalent value: 2, Roquette, Giusto Faravelli, Milan, Italy) and DX (from Leuconostoc mesenteroides Mr ∼200,000, Sigma-Aldrich, Milan, Italy) were used as polysaccharides (Fig. S1). Gly, Cys and Thr (Sigma-Aldrich, Milan, Italy) were used as amino acids. Citric acid (CA, Sigma-Aldrich, Milan, Italy) was used as cross-linking agent. ZnO (Zinc oxide, dispersion nanoparticles, <100 nm particle size (TEM), ≤40 nm avg. part. Size, 20 wt % in H2O, Sigma-Aldrich, Milan, Italy) and CuO NPs (Copper (II) oxide nanopowder, <50 nm particle size, Sigma-Aldrich, Milan, Italy) were used as inorganics.

Marco Ruggeri, Barbara Vigani, Cinzia Boselli, Antonia Icaro Cornaglia, Daniele Colombo, Rita Sànchez-Espejo, Elena Del Favero, Narcisa Mandras, Janira Roana, Lorenza Cavallo, Laura Cantù, Cesar Viseras, Silvia Rossi, Giuseppina Sandri, Smart nano-in-microparticles to tackle bacterial infections in skin tissue engineering, Materials Today Bio, 2022, 100418, ISSN 2590-0064,
https://doi.org/10.1016/j.mtbio.2022.100418.

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