Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal–Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice

Abstract

The employment of metal–organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer–Emmett–Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N2 isotherms was found to be 1868, 1392, 1706, and 1179 m2/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu2+ and Zn2+ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.

Carbomer Hydrogel Composed of Cu2O and Hematoporphyrin Monomethyl Ether Promotes the Healing of Infected Wounds

“…Compared with carrying Cu 2+ ions, Cu 2 O nanoparticles could provide a long-term copper ions release that conducts a sustaining antibacterial ability. 19 Owing to the fact that skin defect should be controlled at the very beginning, this research would not explore the time of antibiotic capacity. Meanwhile, the oxidation of Cu 2 O can protect HMME from inactivation and loss of antibacterial activity.…”

Exogeneous metal ions as therapeutic agents in cardiovascular disease and their delivery strategies

“…For peripheral vascular diseases of diabetes, Cu 2+ , Ag + , etc. can prevent the occurrence of local secondary infection in the form of wound dressings [ 111 , 112 ]. After further research and improvement, the above mechanisms may be utilized for the treatment of CVDs.…”

Enhancing antibacterial properties by regulating valence configurations of copper: a focus on Cu-carboxyl chelates

“…For example, copper metal–organic framework nanoparticles, stabilized with folic acid, exhibit enhanced wound-healing properties in diabetes. 8 A copper/carbon hybrid nanoenzyme showed high catalytic activity based on the copper states of Cu(0) and Cu( ii ) for antibacterial therapy. 9 Hydrothermally crystallized copper-doped mesoporous silica microspheres also allow the coexistence of Cu( i ) and Cu( ii ).…”