Bioinspired 3D-printed scaffold embedding DDAB-nano ZnO/nanofibrous microspheres for regenerative diabetic wound healing

Metwally, Walaa M; El-Habashy, Salma E; El-Hosseiny, Lobna S; Essawy, Marwa M; Eltaher, Hoda M; El-Khordagui, Labiba; El-Khordagui, Labiba K

Abstract

There is a constant demand for novel materials/biomedical devices to accelerate the healing of hard-to-heal wounds. Herein, an innovative 3D-printed bioinspired construct was developed as an antibacterial/regenerative scaffold for diabetic wound healing. Hyaluronic/chitosan (HA/CS) ink was used to fabricate a bilayer scaffold comprising a dense plain hydrogel layer topping an antibacterial/regenerative nanofibrous layer obtained by incorporating the hydrogel with polylactic acid nanofibrous microspheres (MS). These were embedded with nano ZnO (ZNP) or didecyldimethylammonium bromide (DDAB)-treated ZNP (D-ZNP) to generate the antibacterial/healing nano/micro hybrid biomaterials, Z-MS@scaffold and DZ-MS@scaffold. Plain and composite scaffolds incorporating blank MS (blank MS@scaffold) or MS-free ZNP@scaffold and D-ZNP@scaffold were used for comparison. 3D printed bilayer constructs with customizable porosity were obtained as verified by SEM. The DZ-MS@scaffold exhibited the largest total pore area as well as the highest water-uptake capacity and in vitro antibacterial activity. Treatment of Staphylococcus aureus-infected full thickness diabetic wounds in rats indicated superiority of DZ-MS@scaffold as evidenced by multiple assessments. The scaffold afforded 95% wound-closure, infection suppression, effective regulation of healing-associated biomarkers as well as regeneration of skin structure in 14 d. On the other hand, healing of non-diabetic acute wounds was effectively accelerated by the simpler less porous Z-MS@scaffold. Information is provided for the first-time on the 3D printing of nanofibrous scaffolds using non-electrospun injectable bioactive nano/micro particulate constructs, an innovative ZNP-functionalized 3D-printed formulation and the distinct bioactivity of D-ZNP as a powerful antibacterial/wound healing promotor. In addition, findings underscored the crucial role of nanofibrous-MS carrier in enhancing the physicochemical, antibacterial, and wound regenerative properties of DDAB-nano ZnO. In conclusion, innovative 3D-printed DZ-MS@scaffold merging the MS-boosted multiple functionalities of ZNP and DDAB, the structural characteristics of nanofibrous MS in addition to those of the 3D-printed bilayer scaffold, provide a versatile bioactive material platform for diabetic wound healing and other biomedical applications.

Citation

Metwally, W. M., El-Habashy, S. E., El-Hosseiny, L. S., Essawy, M. M., Eltaher, H. M., El-Khordagui, L., & El-Khordagui, L. K. (2023). Bioinspired 3D-printed scaffold embedding DDAB-nano ZnO/nanofibrous microspheres for regenerative diabetic wound healing. Biofabrication, 16(1), Article 015001. https://doi.org/10.1088/1758-5090/acfd60

• Journal Article Type: Article
• Acceptance Date: Sep 26, 2023
• Online Publication Date: Oct 10, 2023
• Publication Date: Oct 10, 2023
• Deposit Date: Sep 29, 2023
• Publicly Available Date: Oct 18, 2023
• Journal: Biofabrication
• Print ISSN: 1758-5082
• Electronic ISSN: 1758-5090
• Publisher: IOP Publishing
• Peer Reviewed: Peer Reviewed
• Volume: 16
• Issue: 1
• Article Number: 015001
• DOI: https://doi.org/10.1088/1758-5090/acfd60
• Keywords: polylactic acid, infected-wound healing, customization, nanofibrous microspheres, bioinspired hydrogel scaffolds, multilevel porosity, hyaluronic acid-chitosan ink
• Public URL: https://nottingham-repository.worktribe.com/output/25389933
• Publisher URL: https://iopscience.iop.org/article/10.1088/1758-5090/acfd60
• Additional Information: Original content from this work may be used under the terms of the Creative Commons Attribution 4.0 license. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.