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Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing

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Abstract

Deep full-thickness burn wounds are prone to multi-drug resistant (MDR) infections following injury, which extends the healing time. Thus, providing a bioactive hydrogel dressing with prolonged antimicrobial activity and reduced dressing changes is quite desirable for accelerating burn wound healing and preventing scarring. To achieve this, we developed an injectable hydrogel based on silk sericin (SS), poly(vinyl alcohol) (PVA), and PVA microspheres (MSs) containing vancomycin (VA), gentamicin (GEN), or their association (VG) for the healing of infected burn wounds. The microspheres were prepared by inverse emulsion crosslinking, while the hydrogels were prepared by freeze-thawing cycles. Antibacterial studies showed that gentamicin acts synergistically with vancomycin by increasing the bacterial killing rate and enhancing the biofilm inhibition and eradication effects on methicillin-resistant Staphylococcus aureus more than on Pseudomonas aeruginosa and Escherichia coli. Findings from FESEM images showed that the microspheres were sphere-shaped with a smooth surface and their average diameter ranging from 26.22 to 32.42 μm suitable for parenteral drug delivery. The prepared hydrogel containing 10% of microspheres was more elastic than viscous, with lower tan delta values (< 1) suited for deeper injection with homogeneous tissue integration. The incorporation of VG-PVAMS in the PVA/SS hydrogel led to zero-order release kinetics and efficient antimicrobial effects. Moreover, the in vivo study using a rat full-thickness burn model showed that the VG-PVAMS@PVA/SS hydrogel displays a better therapeutic effect than drug-free PVAMS@PVA/SS hydrogel and Tegaderm™ film dressing by inducing early vascularization and collagen deposition, leading to early re-epithelialization and burn wound closure.

Graphical abstract

ToC. Development of vancomycin/gentamicin-PVA microsphere@PVA/SS hydrogel with sustained drug release, excellent mechanical, and biological properties for burn wound healing.

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Acknowledgements

The authors sincerely thank the Analysis and Test Center at Huazhong University of Science and Technology for the related characterizations of various samples.

Funding

This work was financially supported by the National Natural Science Foundation of China (51973076); BRICS STI Framework Programme 3rd call 2019, the National Key Research and Development Program of China (2018YFE0123700); and the Fundamental Research Funds for the Central Universities (2020kfyXJJS035).

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Authors and Affiliations

  1. Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China

    Bianza Moise Bakadia, Biaou Oscar Ode Boni, Ruizhu Zheng, Zhijun Shi, Lallepak Lamboni & Guang Yang

  2. Institut Superieur des Techniques Medicales de Lubumbashi, Lubumbashi, Democratic Republic of the Congo

    Bianza Moise Bakadia

  3. Department of Plastic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China

    Aimei Zhong

  4. State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, China

    Xiahong Li

  5. Department of Environmental Sciences, School of Agriculture and Environmental Sciences, University of South Africa, P.O. Box 392, Florida, Johannesburg, 1710, South Africa

    Abeer Ahmed Qaed Ahmed

  6. Département Des Sciences de La Vie Et de La Terre, Faculté Des Sciences Et Techniques, Université de Kara, Kara, Togo

    Tiatou Souho

  7. Laboratoire de Biologie Moléculaire Et Virologie, Institut National d’Hygiène-Togo, 26 Rue Nangbéto, Quartier Administratif, PO Box 1396, Lomé, Togo

    Lallepak Lamboni

  8. College of Life Science and Technology, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan City, 430074, China

    Dingwen Shi

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  1. Bianza Moise Bakadia
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Bianza Moise Bakadia and Aimei Zhong contributed equally to this work.

Highlights

• Poly(vinyl alcohol) (PVA)/silk sericin (SS) hydrogels loaded with vancomycin–gentamicin/PVA microspheres were synthesized.

• Vancomycin and gentamicin exhibited a synergistic antibacterial effect in loaded hydrogels.

• The biological properties of the hydrogels improved obviously with microsphere loading.

• The microsphere hydrogel exhibited sustained drug release, antibacterial activity, and excellent cytocompatibility.

• The microsphere hydrogel system accelerates full-thickness burn wound healing.

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Bakadia, B.M., Zhong, A., Li, X. et al. Biodegradable and injectable poly(vinyl alcohol) microspheres in silk sericin-based hydrogel for the controlled release of antimicrobials: application to deep full-thickness burn wound healing. Adv Compos Hybrid Mater 5, 2847–2872 (2022). https://doi.org/10.1007/s42114-022-00467-6

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