Construction of heparin-based hydrogel incorporated with Cu5.4O ultrasmall nanozymes for wound healing and inflammation inhibition

Abstract

Excessive production of inflammatory chemokines and reactive oxygen species (ROS) can cause a feedback cycle of inflammation response that has a negative effect on cutaneous wound healing. The use of wound-dressing materials that simultaneously absorb chemokines and scavenge ROS constitutes a novel ‘weeding and uprooting’ treatment strategy for inflammatory conditions. In the present study, a composite hydrogel comprising an amine-functionalized star-shaped polyethylene glycol (starPEG) and heparin for chemokine sequestration as well as Cu 5.4 O ultrasmall nanozymes for ROS scavenging (Cu 5.4 O@Hep-PEG) was developed. The material effectively adsorbs the inflammatory chemokines monocyte chemoattractant protein-1 and interleukin-8, decreasing the migratory activity of macrophages and neutrophils. Furthermore, it scavenges the ROS in wound fluids to mitigate oxidative stress, and the sustained release of Cu 5.4 O promotes angiogenesis. In acute wounds and impaired-healing wounds (diabetic wounds), Cu 5.4 O@Hep-PEG hydrogels outperform the standard-of-care product Promogram® in terms of inflammation reduction, increased epidermis regeneration, vascularization, and wound closure.

Reactive-oxygen-species-scavenging nanomaterials for resolving inflammation

“… Materials Working mechanisms Indications Ref. CeO 2 NPs SOD- and CAT-mimetic nanozyme activities Colitis; acute liver injury; stroke therapy; Alzheimer's disease; monocrotaline-induced pulmonary arterial hypertension; diabetic ulcer wounds; Parkinson's disease; rheumatoid arthritis [ 36 , 41 , 45 , [119] , [120] , [121] , [122] , [123] ] Pt NPs POD-, CAT-, and SOD-like nanozyme activities Chronic inflammatory diseases; vascular diseases; cerebral cavernous malformation disease; hepatic ischemia/reperfusion injury [ 50 , [124] , [125] , [126] ] Cu-based NPs POD-, CAT-, SOD-, and glutathione-like enzyme activities Parkinson's disease; kidney and liver injury; inflamed wounds; enteritis and wound healing; caries [ 15 , 56 , 57 , 127 , 128 ] PB NPs POD-, CAT-, and SOD-like multienzyme activities High glucose contents, and oxygen glucose deprivation and reperfusion; acute pancreatitis; dextran sulfate sodium-induced colitis; brain diseases; inflammatory bowel disease [ 16 , [59] , [60] , [61] , [62] ] SOD-containing NPs SOD enzyme activity Brain ischemia–reperfusion injury; colitis; testicular oxidative stress; myocardial ischemia–reperfusion injury; neuroprotective [ 63 , 65 , [129] , [130] , [131] ...…”

“…At the same time, Cu 5.4 O USNPs, as a nanozyme, scavenged ROS to reduce oxidative stress and promoting angiogenesis. Thus, the inflammation feedback cycle was completely broken via capturing pro-inflammatory factors and scavenging ROS concurrently [ 56 ].

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Construction of pH‐Dependent Nanozymes with Oxygen Vacancies as the High‐Efficient Reactive Oxygen Species Scavenger for Oral‐Administrated Anti‐Inflammatory Therapy

“…Also the nanozyme could pass through the digestive tract and target the inflamed site to exert anti-inflammation effect by the size-mediated and charge-mediated mechanisms. It has been previously reported that the CeO 2 [29] and copper nanoparticles (NPs) [30,31] with high efficacy could alleviate diseases at low dosage, helping for the further clinical applications. In comparison with these reported ROS-scavenging nanomaterial, such as CeO 2 and copper NPs, the nanozyme NiCo 2 O 4 @PVP exhibited inherent superiority, especially in vivo application.…”

“…In comparison with these reported ROS-scavenging nanomaterial, such as CeO 2 and copper NPs, the nanozyme NiCo 2 O 4 @PVP exhibited inherent superiority, especially in vivo application. NiCo 2 O 4 @PVP possessed outstanding stability even treating with acidic conditions (pH = 1.2) for 12 h. The excellent properties of acid resistance of the nanozyme NiCo 2 O 4 @PVP enabled it to be used not only in body surface, like copper NPs, [30] but also in vivo, especially in the digest tract. This ensured the wide application scope of the nanozyme NiCo 2 O 4 @PVP.…”

Application of Electrospun Nanofiber Membrane in the Treatment of Diabetic Wounds

“…Complications of diabetic vascular disease lead to lack of necessary oxygen and nutrients for wound healing, which makes angiogenesis difficult and hinders the transition of wound healing from the inflammation stage to the proliferation stage [42][43][44][45]. In the later inflammation stage of normal wounds, macrophages change from pro-inflammatory M1 macrophages to repair-promoting M2 macrophages, which accelerates the process of inflammation.…”