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A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

ABSTRACT: Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein we set out to assess whether copper metal organic framework nanoparticles (HKUST-1 NPs) embedded within an antioxidant thermoresponsive citrate-based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST-1 and poly-(polyethyleneglycol citrate-co-N-isopropylacrylamide) (PPCN) were synthesized and characterized. HKUST-1 NP stability in a protein solution with and without embedding them in PPCN hydrogel was determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes were measured. Wound closure rates and wound blood perfusion were assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST-1 NP disintegrated in protein solution while HKUST-1 NPs embedded in PPCN (H-HKUST-1) were protected from degradation and copper ions were slowly released. Cytotoxicity and apoptosis due to copper ion release were significantly reduced while dermal cell migration in vitro and wound closure rates in vivo were significantly enhanced. In vivo, H-HKUST-1 induced angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion-releasing H-HKUST-1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.

SUBMITTER: Xiao J

PROVIDER: S-EPMC5513192 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

Xiao Jisheng J Chen Siyu S Yi Ji J Zhang Hao H Ameer Guillermo A GA

Advanced functional materials 20161123 1

Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions ...[more]

PMID: 28729818

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Project description:Pesticides are agrochemical compounds used to kill pests (insects, rodents, fungi, or unwanted plants), which are key to meet the world food demand. Regrettably, some important issues associated with their widespread/extensive use (contamination, bioaccumulation, and development of pest resistances) demand a reduction in the amount of pesticide applied in crop protection. Among the novel technologies used to combat the deterioration of our environment, metal-organic frameworks (MOFs) have emerged as innovative and promising materials in agroindustry since they possess several features (high porosity, functionalizable cavities, ecofriendly composition, etc.) that make them excellent candidates for the controlled release of pesticides. Moving toward a sustainable development, in this work, we originally describe the use of pesticides as building blocks for the MOF construction, leading to a new type of agricultural applied MOFs (or AgroMOFs). Particularly, we have prepared a novel 2D-MOF (namely, GR-MOF-7) based on the herbicide glufosinate and the widely used antibacterial and fungicide Cu2+. GR-MOF-7 crystallizes attaining a monoclinic P21/c space group, and the asymmetric unit is composed of one independent Cu2+ ion and one molecule of the Glu2- ligand. Considering the significant antibacterial activity of Cu-based compounds in agriculture, the potential combined bactericidal and herbicidal effect of GR-MOF-7 was investigated. GR-MOF-7 shows an important antibacterial activity against Staphylococcus aureus and Escherichia coli (involved in agricultural animal infections), improving the results obtained with its individual or even physical mixed precursors [glufosinate and Cu(NO3)2]. It is also an effective pesticide against germination and plant growth of the weed Raphanus sativus, an invasive species in berries and vines crops, demonstrating that the construction of MOFs based on herbicide and antibacterial/antifungal units is a promising strategy to achieve multifunctional agrochemicals. To the best of our knowledge, this first report on the synthesis of an MOF based on agrochemicals (what we have named AgroMOF) opens new ways on the safe and efficient MOF application in agriculture.

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A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

Publications

A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

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