Pathophysiology and Molecular Imaging of Diabetic Foot Infections

Rubitschung, Katie; Sherwood, Amber; Crisologo, Andrew P.; Bhavan, Kavita; Haley, Robert W.; Wukich, Dane K.; Castellino, Laila; Hwang, Helena; Fontaine, Javier La; Chhabra, Avneesh; Lavery, Lawrence A.; Öz, Orhan K.

doi:10.3390/ijms222111552

Cited by 33 publications

(34 citation statements)

References 166 publications

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“…Also, atrophy caused due to motor neuropathy leads to osteomyelitis. 34 All these changes damage the skin and lead to ulcers. Dryness of the skin occurs due to autonomic neuropathy in which sweat and oil gland activity is reduced.…”

Section: Aberrations In a Diabetic Wound Healing Processmentioning

confidence: 99%

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Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer

2022

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Diabetes mellitus is a chronic manifestation characterized by high levels of glucose in the blood resulting in several complications including diabetic wounds and ulcers, which predominantly require a longer duration of treatment and adversely affect the quality of life of the patients. Nanotechnology-based therapeutics (both intrinsic and extrinsic types) have emerged as a promising treatment in diabetic foot ulcer/chronic wounds owing to their unique characteristics and specific functional properties. In this review, we have focused on the significance of the use of lipids in the healing of diabetic ulcers, their interaction with the injured skin, and recent trends in lipid-based nanocarriers for the healing of diabetic wounds. Lipid nanocarriers are also being investigated for gene therapy in diabetic wound healing to encapsulate nucleic acids such as siRNA and miRNA, which could silence the expression of inflammatory cytokines overexpressed in chronic wounds. Additionally, these are also being explored for encapsulating proteins, peptides, growth factors, and other biological genetic material as therapeutic agents. Lipid-based nanocarriers encompassing a wide variety of carriers such as liposomes, niosomes, ethosomes, solid lipid nanoparticles, and lipidoid nanoparticles that are explored for the treatment of foot ulcers supplemented with relevant research studies have been discussed in the present review. Lipid-based nanodrug delivery systems have demonstrated promising wound healing potential, particularly in diabetic conditions due to the enhanced efficacy of the entrapped active molecules.

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Section: Aberrations In a Diabetic Wound Healing Processmentioning

confidence: 99%

“…Motor neuron innervation to the skeletal muscles of the leg gets distorted leading to loss of co-ordination in movements, deformity, and alterations in pressure points. Also, atrophy caused due to motor neuropathy leads to osteomyelitis . All these changes damage the skin and lead to ulcers.…”

Section: Aberrations In a Diabetic Wound Healing Processmentioning

confidence: 99%

Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer

2022

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“…The glucotoxic environment and its distal effectors impair and disrupt the flow of overlapping healing phases, leading to a stagnant wound, chronically arrested in an unproductive inflammatory phase [11,[53][54][55]. Diabetes predisposes to inflammation, which is more a condition than a transient reaction, while impairment in its resolution also perpetuates the inflammatory stage [56][57][58]. This model of chronic complex wound is therefore overloaded by a network of inflammatory cytokines, an uncontrolled production of local proteases, cytotoxic reactive oxygen and nitrogen species, and a polymicrobial biofilm [59].…”

Section: Overview Of Diabetic Foot Ulcers (Dfu)mentioning

confidence: 99%

“…This model of chronic complex wound is therefore overloaded by a network of inflammatory cytokines, an uncontrolled production of local proteases, cytotoxic reactive oxygen and nitrogen species, and a polymicrobial biofilm [59]. Mechanistically speaking, this phenotype seems to be driven by three major factors: precocious cellular senescence, proliferative arrest, and unscheduled apoptosis of granulation tissue-productive cells [5,57,[60][61][62][63][64].…”

Section: Overview Of Diabetic Foot Ulcers (Dfu)mentioning

confidence: 99%

A narrative review on Epidermal Growth Factor (EGF) intralesional infiltrations for diabetic complex wounds: The rational of an innovative delivery route

Berlanga‐Acosta¹,

Fernandez-Montequin²,

Santana-Milian³

et al. 2022

Vascul Dis Ther

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Diabetes mellitus remains as a pandemic disease, associated to progressive and irreversible complications including lower extremity ulcerations, derived from a predisposition to ischemia, neuropathy and an intrinsic wound healing failure. The molecular operators supporting wound chronicity remain elusive, but a local deficit of growth factors is invoked as a common cause for proliferative arrest, apoptosis, and cells senescence. The prodegradative environment of these lesions contributes to reduce growth factors availability and receptors' physiology. The introduction of growth factors in the clinical arena was precocious since critical pieces of chronicity pathophysiology had not been identified. The topical administration of these agents failed by the effect of local proteolysis, narrow bioavailability window, inadequate diffusion, and a harsh polymicrobial biofilm. To circumvent these pharmacodynamic limitations, we envisioned an intra-ulcer infiltrative delivery route for epidermal growth factor (EGF), based on the rationale derived from experimental evidences. The clinical development program with this procedure has comprised from a proofof-concept to post-marketing studies in poor-prognosis, ischemic, neuropathic, and neuroischemic wounds, involving more than 300 000 patients along 20 years. Pharmacovigilance studies demonstrated that infiltrated EGF is therapeutically effective and safe to circumvent the limitations of the classic topical administration. This pharmacological intervention has remained as an adjuvant therapy to conventional treatments and wound care protocols. Generation of EGF nanovesicles is envisioned as a promising future direction to trigger the re-epithelialization of stagnant, non-resurfaced diabetic wounds upon topical administration.

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“…As DFU inherently has a chronic course and requires long-term therapy, a proper diagnostic imaging test could be delayed in diabetic foot OM [ 13 ]. If treatment is initiated when a definite diagnosis of OM is made based on clinical symptoms, the infection may have progressed too far to receive on-time treatment [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Classification Model for Diabetic Foot, Necrotizing Fasciitis, and Osteomyelitis

Kim

Yoo

Lee

et al. 2022

Biology

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Diabetic foot ulcers (DFUs) and their life-threatening complications, such as necrotizing fasciitis (NF) and osteomyelitis (OM), increase the healthcare cost, morbidity and mortality in patients with diabetes mellitus. While the early recognition of these complications could improve the clinical outcome of diabetic patients, it is not straightforward to achieve in the usual clinical settings. In this study, we proposed a classification model for diabetic foot, NF and OM. To select features for the classification model, multidisciplinary teams were organized and data were collected based on a literature search and automatic platform. A dataset of 1581 patients (728 diabetic foot, 76 NF, and 777 OM) was divided into training and validation datasets at a ratio of 7:3 to be analyzed. The final prediction models based on training dataset exhibited areas under the receiver operating curve (AUC) of the 0.80 and 0.73 for NF model and OM model, respectively, in validation sets. In conclusion, our classification models for NF and OM showed remarkable discriminatory power and easy applicability in patients with DFU.

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Pathophysiology and Molecular Imaging of Diabetic Foot Infections

Cited by 33 publications

References 166 publications

Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer

Exploration of Lipid-Based Nanocarriers as Drug Delivery Systems in Diabetic Foot Ulcer

A narrative review on Epidermal Growth Factor (EGF) intralesional infiltrations for diabetic complex wounds: The rational of an innovative delivery route

Classification Model for Diabetic Foot, Necrotizing Fasciitis, and Osteomyelitis

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