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<p>Chronic wounds in the skin require new hydrogel formulations that can heal regenerating damaged tissue and release therapeutic molecules that benefit healing and higher swelling capacities. In a previous study, synthetic molybdenum complexes based on molybdenum (Mo), terephthalic acid (BDC), and bis(2-hydroxyethyl) terephthalate (BHET) demonstrated that they stimulate fibroblast in vitro viability, representing potential candidates to be applied as fillers in collagen hydrogels for tissue engineering. Continuing this work, new composite hydrogels based on collagen and these molybdenum complexes varied their mass concentration (1 or 4&#xa0;mg). The objective was to enhance collagen’s rheological and antimicrobial properties without altering biocompatibility. These materials were characterized using physicochemical techniques, including wide angle x-ray scattering (WAXS), scanning electron microscope (SEM), attenuated total reflection Fourier-transform infrared (ATR-FTIR), thermogravimetric analysis (TGA), rheology, and crosslinking assessed by ninhydrin assay. In addition, the in vitro biocompatibility of dermis porcine fibroblast and human monocytes was tested growing on the hydrogels. The hydrogels do not present cytotoxic effects on the cells tested and show good safety in topical applications because they are biocompatible materials with antibacterial properties. Coenzyme Q-10 can control chronic inflammation, helping tissue healing. Thus, Q-10 was encapsulated in situ in the hydrogel synthesis, and their release kinetic profiles were obtained. It was found that a significant amount of Mo-complexes (4&#xa0;mg) in the collagen matrix generated the best biological and physicochemical properties. Indeed, the hydrogel with 4&#xa0;mg of the molybdenum complex BHET-Mo (CBH4) shows a 100% release of Q10 with a sustainable behavior, large storage (G’ = 240&#xa0;kPa), and loss modulus (G’’ = 70&#xa0;kPa) and swelling capacity (41 739%). In comparison, the hydrogel with 4&#xa0;mg of the molybdenum complex BDC-Mo (CBD4) should be considered for skin regeneration since it dramatically stimulates the metabolic activity of fibroblasts (186%) and monocytes (240%) with a relative antimicrobial activity against E. Coli of 100% compared with ampicillin (positive control).</p> Graphical abstract <p>Collagen-Mo-complexes hydrogels with outstanding results for in vitro biocompatibility (CBD4) and drug release (CBH4).</p> <p></p>

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In vitro biocompatibility and drug release of collagen-mo-complexes hydrogels for tissue engineering

  • 期刊论文

  • 发表日期：

    2025年2月11日

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  • Denis A. Cabrera-Munguia,
  • Cesar E. Castañeda-Calzoncit,
  • Jesús A. Claudio-Rizo,
  • Martin Caldera-Villalobos,
  • M. Ileana León-Campos,
  • Lucia F. Cano-Salazar

摘要

Chronic wounds in the skin require new hydrogel formulations that can heal regenerating damaged tissue and release therapeutic molecules that benefit healing and higher swelling capacities. In a previous study, synthetic molybdenum complexes based on molybdenum (Mo), terephthalic acid (BDC), and bis(2-hydroxyethyl) terephthalate (BHET) demonstrated that they stimulate fibroblast in vitro viability, representing potential candidates to be applied as fillers in collagen hydrogels for tissue engineering. Continuing this work, new composite hydrogels based on collagen and these molybdenum complexes varied their mass concentration (1 or 4 mg). The objective was to enhance collagen’s rheological and antimicrobial properties without altering biocompatibility. These materials were characterized using physicochemical techniques, including wide angle x-ray scattering (WAXS), scanning electron microscope (SEM), attenuated total reflection Fourier-transform infrared (ATR-FTIR), thermogravimetric analysis (TGA), rheology, and crosslinking assessed by ninhydrin assay. In addition, the in vitro biocompatibility of dermis porcine fibroblast and human monocytes was tested growing on the hydrogels. The hydrogels do not present cytotoxic effects on the cells tested and show good safety in topical applications because they are biocompatible materials with antibacterial properties. Coenzyme Q-10 can control chronic inflammation, helping tissue healing. Thus, Q-10 was encapsulated in situ in the hydrogel synthesis, and their release kinetic profiles were obtained. It was found that a significant amount of Mo-complexes (4 mg) in the collagen matrix generated the best biological and physicochemical properties. Indeed, the hydrogel with 4 mg of the molybdenum complex BHET-Mo (CBH4) shows a 100% release of Q10 with a sustainable behavior, large storage (G’ = 240 kPa), and loss modulus (G’’ = 70 kPa) and swelling capacity (41 739%). In comparison, the hydrogel with 4 mg of the molybdenum complex BDC-Mo (CBD4) should be considered for skin regeneration since it dramatically stimulates the metabolic activity of fibroblasts (186%) and monocytes (240%) with a relative antimicrobial activity against E. Coli of 100% compared with ampicillin (positive control).

Graphical abstract

Collagen-Mo-complexes hydrogels with outstanding results for in vitro biocompatibility (CBD4) and drug release (CBH4).