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.

Wound Dressing Hydrogel of Enteromorpha prolifera Polysaccharide–Polyacrylamide Composite: A Facile Transformation of Marine Blooming into Biomedical Material

“…The migration rate of L929 cells cultured with hEGF-loaded PEP-PAM hydrogel reached 17.8 ± 6.6% at 24 h and 25.6 ± 4.4% at 72 h, whereas those values for the control were 3.6 ± 1.3% at 24 h and 7.8 ± 2.2% at 72 h, respectively (Figure A). It can be seen that the hEGF-loaded hydrogel promoted cell proliferation and cell migration, and these results are consistent with a previous report …”

Copper-Epigallocatechin Gallate Enhances Therapeutic Effects of 3D-Printed Dermal Scaffolds in Mitigating Diabetic Wound Scarring

“…As shown in Figure K, the E/C hydrogel exhibited a rapid release of Cu 2+ in the first 24 h, reaching 51.67 ± 4.77% at 24 h. The release rate of Cu 2+ tended to be stable from the second day until the release rate reached 81.6 ± 4.17% after 5 days. The results showed that the E/C hydrogel had a good sustained-release effect on Cu 2+ and were consistent with previous studies of Cu-loaded hydrogels. , Continuous release of non-cytotoxic levels of copper ions can provide longer-lasting stimulation to surrounding cells …”

Metal–Organic Frameworks Incorporated Polycaprolactone Film for Enhanced Corrosion Resistance and Biocompatibility of Mg Alloy

“…The crystallinity of the MOF powders was characterized using XRD. As presented in Figure 2a, except in terms of intensity, the as-prepared MOF-FA exhibited almost the same diffraction peaks as did HKUST-1, being located at 11.6°, 9.5°, and 13.4°, matching well with previously reported images of HKUST-1 29,30 and suggesting that the modification of FA did not change the crystal structure of HKUST-1. The peak intensity weakened after the modification of the FA, and the corresponding full width at half-maximum decreased significantly, indicating a decreased crystal size, which is in agreement with the observation made by TEM (Figure 1b).…”