Nitric oxide-releasing biomaterials for promoting wound healing in impaired diabetic wounds: State of the art and recent trends

Ahmed, Rashid; Augustine, Robin; Chaudhry, Maryam; Akhtar, Usman A.; Zahid, Alap Ali; Tariq, Muhammad; Falahati, Mojtaba; Ahmad, Irfan; Hasan, Anwarul

doi:10.1016/j.biopha.2022.112707

Cited by 53 publications

(36 citation statements)

References 197 publications

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“…One reason for the difficulty in healing diabetic wounds is the persistent inflammatory cell infiltration and chronic inflammation due to the high glycaemic environment and microangiopathy in the wounds [ 39 , 40 ]. The presence of bacteria and infection undoubtedly exacerbates inflammatory tropism, ultimately creating a dysfunctional immune response and promoting long-term survival of bacteria in diabetic wounds [ 41 , 42 ]. Therefore, the first task in promoting trauma recovery is to expose the exogenous stimulation of the trabecular microenvironment by pathogenic bacteria, which is an essential step in reversing the chronic inflammation of the wound and transforming it into a new phase of pro-repair immunity.…”

Section: Resultsmentioning

confidence: 99%

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation

et al. 2022

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Background The complicated hyperglycaemic and chronic inflammation of diabetic wounds in orthopaedic surgery leads to dysregulated immune cell function and potential infection risk. Immune interventions in diabetic wounds face a possible contradiction between simultaneous establishment of the pro-inflammatory microenvironment in response to potential bacterial invasion and the anti-inflammatory microenvironment required for tissue repair. To study this contradiction and accelerate diabetic-wound healing, we developed a photocurable methacryloxylated silk fibroin hydrogel (Sil-MA) system, co-encapsulated with metformin-loaded mesoporous silica microspheres (MET@MSNs) and silver nanoparticles (Ag NPs). Results The hydrogel system (M@M–Ag–Sil-MA) enhanced diabetic-wound healing via spatiotemporal immunomodulation. Sil-MA imparts a hydrogel system with rapid in situ Ultra-Violet-photocurable capability and allows preliminary controlled release of Ag NPs, which can inhibit bacterial aggregation and create a stable, sterile microenvironment. The results confirmed the involvement of Met in the immunomodulatory effects following spatiotemporal dual-controlled release via the mesoporous silica and Sil-MA. Hysteresis-released from Met shifts the M1 phenotype of macrophages in regions of diabetic trauma to an anti-inflammatory M2 phenotype. Simultaneously, the M@M–Ag–Sil-MA system inhibited the formation of neutrophil extracellular traps (NETs) and decreased the release of neutrophil elastase, myeloperoxidase, and NETs-induced pro-inflammatory factors. As a result of modulating the immune microenvironmental, the M@M–Ag–Sil-MA system promoted fibroblast migration and endothelial cell angiogenesis in vivo, with verification of enhanced diabetic-wound healing accompanied with the spatiotemporal immunoregulation of macrophages and NETs in a diabetic mouse model. Conclusions Our findings demonstrated that the M@M–Ag–Sil-MA hydrogel system resolved the immune contradiction in diabetic wounds through spatiotemporal immunomodulation of macrophages and NETs, suggesting its potential as a promising engineered nano-dressing for the treatment of diabetic wounds in orthopaedic surgery. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation

et al. 2022

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“…Products ( i.e. , patches/ matrices) that release NO are used to treat diabetic wounds by different mechanisms like enhancement of angiogenic activity, endothelial cell proliferation, conferring antimicrobial substances, and promoting cell migration to the injured site[ 174 ]. Only a few clinical studies have reported the beneficial effects of NO-releasing devices, and several products are in the clinical trial.…”

Section: Recent Approaches In Clinical Trialsmentioning

confidence: 99%

“…Flavonoids an important class of phytoconstituents, exerted anti-inflammatory and antioxidant effect, and also enhances angiogenesis and re-epithelialization. Preclinical trials found the effectiveness of isoliquiritin, isoflavonoid, naringenin, dihydromyricetin, dihydroquercetin, quercetin, hesperidin, kaempferol, proanthocyanidins, icariin, puerarin, rutin, genistein, luteolin, rutoside, silymarin, daidzein, genistein, and epigallocatechin gallate to cure wound[ 174 ]. Flavonoids positively regulate MMP-2, MMP-8, MMP-9, MMP-13, Ras/Raf/ MEK/ERK, PI3K/Akt, and NO pathways.…”

Section: Medicinal Plants and Phytoconstituents In Diabetic Woundmentioning

confidence: 99%

Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets

Chakraborty¹,

Borah²,

Dutta³

et al. 2022

WJD

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Diabetes mellitus is a chronic metabolic disorder resulting in an increased blood glucose level and prolonged hyperglycemia, causes long term health conse-quences. Chronic wound is frequently occurring in diabetes patients due to compromised wound healing capability. Management of wounds in diabetic patients remains a clinical challenge despite many advancements in the field of science and technology. Increasing evidence indicates that alteration of the biochemical milieu resulting from alteration in inflammatory cytokines and matrix metalloproteinase, decrease in fibroblast and keratinocyte functioning, neuropathy, altered leukocyte functioning, infection, etc. , plays a significant role in impaired wound healing in diabetic people. Apart from the current pharmacotherapy, different other approaches like the use of conventional drugs, antidiabetic medication, antibiotics, debridement, offloading, platelet-rich plasma, growth factor, oxygen therapy, negative pressure wound therapy, low-level laser, extracorporeal shock wave bioengineered substitute can be considered in the management of diabetic wounds. Drugs/therapeutic strategy that induce angiogenesis and collagen synthesis, inhibition of MMPs, reduction of oxidative stress, controlling hyperglycemia, increase growth factors, regulate inflammatory cytokines, cause NO induction, induce fibroblast and keratinocyte proliferation, control microbial infections are considered important in controlling diabetic wound. Further, medicinal plants and/or phytoconstituents also offer a viable alternative in the treatment of diabetic wound. The focus of the present review is to highlight the molecular and cellular mechanisms, and discuss the drug targets and treatment strategies involved in the diabetic wound.

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“…Since NO is important for wound healing and shows antibacterial efficacy in many studies, different types of NO donors such as RSNOs (S-nitrosocysteine, S-nitrosoalbumin S-nitrosoglutathione), N-diazeniumdiolates (NONOates), metal nitrosyls, and others were used [ 91 , 92 ]. There are many reports that state exogenous NO donors represent a promising method to promote wound healing by enhancing cell proliferation, collagen deposition, and angiogenic activities improving granulation tissue formation [ 93 ].…”

Section: Modulation Of Dermal Nod Content and Possible Effectsmentioning

confidence: 99%

Enhancement of Nitric Oxide Bioavailability by Modulation of Cutaneous Nitric Oxide Stores

Suschek

Feibel

Kohout³

et al. 2022

Biomedicines

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The generation of nitric oxide (NO) in the skin plays a critical role in wound healing and the response to several stimuli, such as UV exposure, heat, infection, and inflammation. Furthermore, in the human body, NO is involved in vascular homeostasis and the regulation of blood pressure. Physiologically, a family of enzymes termed nitric oxide synthases (NOS) generates NO. In addition, there are many methods of non-enzymatic/NOS-independent NO generation, e.g., the reduction of NO derivates (NODs) such as nitrite, nitrate, and nitrosylated proteins under certain conditions. The skin is the largest and heaviest human organ and contains a comparatively high concentration of these NODs; therefore, it represents a promising target for many therapeutic strategies for NO-dependent pathological conditions. In this review, we give an overview of how the cutaneous NOD stores can be targeted and modulated, leading to a further accumulation of NO-related compounds and/or the local and systemic release of bioactive NO, and eventually, NO-related physiological effects with a potential therapeutical use for diseases such as hypertension, disturbed microcirculation, impaired wound healing, and skin infections.

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Nitric oxide-releasing biomaterials for promoting wound healing in impaired diabetic wounds: State of the art and recent trends

Cited by 53 publications

References 197 publications

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation

An injectable photo-cross-linking silk hydrogel system augments diabetic wound healing in orthopaedic surgery through spatiotemporal immunomodulation

Evolving spectrum of diabetic wound: Mechanistic insights and therapeutic targets

Enhancement of Nitric Oxide Bioavailability by Modulation of Cutaneous Nitric Oxide Stores

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