Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

Henshaw, Frances R; Boughton, Philip; Lo, Lisa; McLennan, Susan V.; Twigg, Stephen M.

doi:10.1155/2015/236238

Cited by 48 publications

(29 citation statements)

References 42 publications

(63 reference statements)

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“…Neutrophils and macrophage infiltrations are important in the acute inflammatory phase of wound healing as these cells remove debris and kill bacteria through phagocytosis [21,22]. Moreover, this cascade is important to prepare the wound bed for subsequent recruitment and proliferation of cells; however, excessive inflammatory response will impair tissue granulation processes such as angiogenesis [17,23].…”

Section: Discussionmentioning

confidence: 99%

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Effect of Thymoquinone on Wound Healing in Alloxan-Induced Diabetic Rats

Yusmin

Ahmad

2017

Asian J Pharm Clin Res

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Objective: Nigella sativa and its active constituent thymoquinone (TQ) have been extensively documented for its pharmacological values, but its application in wound healing in particular in a diabetic wound healing model is less documented. Methods:In our study, alloxan-induced diabetic rats were used as a chronic delayed wound model and topical administration of TQ 10% w/v were used to assess the role and function of TQ in wound healing through wound contraction and histological analysis.Results: Although statistically insignificant, we found out that TQ accelerated wound healing in post-wounding day 3 (inflammatory phase), whereas aggressively decelerating wound healing in post-wounding day 7 (proliferation phase). In addition, our histological analyses of wound granulation tissues at post-wounding day 14 substantiate our claim by showing that TQ treatment had delayed wound healing progression of the diabetic rats. Conclusions:Our study shows that TQ accelerates wound healing during the inflammatory phase; however, decelerate rapidly during the proliferation phase. We speculate the acceleration of wound healing during the inflammatory phase was due to its well-documented antioxidant, anti-inflammatory, and antimicrobial properties while its deceleration of wound healing during the proliferation phase was due to its well-documented antiangiogenic effect.

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Section: Discussionmentioning

confidence: 99%

“…Hyperglycemia induces pathological changes in endothelial function resulting to abnormal angiogenesis [33]. The local metabolic environment is impaired by diabetes manifesting macro-and microvascular dysfunction that contributes to delayed wound healing [23].…”

Section: Discussionmentioning

confidence: 99%

Effect of Thymoquinone on Wound Healing in Alloxan-Induced Diabetic Rats

Yusmin

Ahmad

2017

Asian J Pharm Clin Res

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“…93 The potential application of growth factors to aid wound healing in diabetic foot ulcers is an area of growing therapeutic interest. 94 Becaplermin is a recombinant plateletderived growth factor available as an ointment and has shown some benefit for foot ulcers. 95 Granulocyte colonystimulating factor has been reported to improve resolution of infection in a pilot study of this condition.…”

Section: Wound Dressingsmentioning

confidence: 99%

Preventing and treating foot complications associated with diabetes mellitus

2015

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Diabetes mellitus is associated with a series of macrovascular and microvascular changes that can manifest as a wide range of complications. Foot ulcerations affect ∼2-4% of patients with diabetes mellitus. Risk factors for foot lesions include peripheral and autonomic neuropathy, vascular disease and previous foot ulceration, as well as other microvascular complications, such as retinopathy and end-stage renal disease. Ulceration is the result of a combination of components that together lead to tissue breakdown. The most frequently occurring causal pathways to the development of foot ulcers include peripheral neuropathy and vascular disease, foot deformity or trauma. Peripheral vascular disease is often not diagnosed in patients with diabetes mellitus until tissue loss is evident, usually in the form of a nonhealing ulcer. Identification of patients with diabetes mellitus who are at high risk of ulceration is important and can be achieved via annual foot screening with subsequent multidisciplinary foot-care interventions. Understanding the factors that place patients with diabetes mellitus at high risk of ulceration, together with an appreciation of the links between different aspects of the disease process, is essential to the prevention and management of diabetic foot complications.

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“…There does appear some hope that new therapies directed to molecular defects (eg, addition of stem cells) can impact on hard-to-heal DFUs. Treatments such as the inclusion of growth factors (eg, platelet-derived growth factors) 69 and the use of neutraceuticals added either topically or to wound dressings 70 may also have some utility in the treatment of hard-to-heal DFUs.…”

Section: Patient Factors -Physical Defective Healing and Chronic Inflmentioning

confidence: 99%

Hard-to-heal diabetes-related foot ulcers: current challenges and future prospects

Nubé¹,

Frank²,

White³

et al. 2016

CWCMR

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Diabetes-related foot ulceration is a frequent cause for hospital admission and the leading cause of nontraumatic lower limb amputation, placing a high burden on the health system, patient, and their families. Considerable advances in treatments and the establishment of specialized services and teams have improved healing rates and reduced unnecessary amputations. However, amputation rates remain high in some areas, with unacceptable variations within countries yet to be resolved. Specific risk factors including infection, ischemia, ulcer size, depth, and duration as well as probing to bone (or osteomyelitis), location of ulcer, sensory loss, deformity (and high plantar pressure), advanced age, number of ulcers present, and renal disease are associated with poor outcome and delayed healing. To assist in prediction of difficult-to-heal ulcers, more than 13 classification systems have been developed. Ulcer depth (or size), infection, and ischemia are the most common risk factors identified. High-quality treatment protocols and guidelines exist to facilitate best practice in the standard of care. Under these conditions, 66%-77% of foot ulcers will heal. The remaining proportion represents a group unlikely to heal and who will live with a non-healing wound or undergo amputation. The authors have applied their experience of managing patients in this discussion of why some ulcers are harder to heal. The article explores the effects of patient non-adherence to treatment, comorbid mental illness, a failure of research to be translated into the everyday practice of many clinicians, and the impact of delayed access to specialized treatment. These factors when combined with the main published risk factors of size, infection, ischemia and pressure are perceived as critical barriers to healing.

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Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

Cited by 48 publications

References 42 publications

Effect of Thymoquinone on Wound Healing in Alloxan-Induced Diabetic Rats

Effect of Thymoquinone on Wound Healing in Alloxan-Induced Diabetic Rats

Preventing and treating foot complications associated with diabetes mellitus

Hard-to-heal diabetes-related foot ulcers: current challenges and future prospects

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