The Role of Matrix Metalloproteinases in Diabetic Wound Healing in relation to Photobiomodulation

The integration of several cellular responses initiates the process of wound healing. Matrix Metalloproteinases (MMPs) play an integral role in wound healing. Their main function is degradation, by removal of damaged extracellular matrix (ECM) during the inflammatory phase, breakdown of the capillary basement membrane for angiogenesis and cell migration during the proliferation phase, and contraction and remodelling of tissue in the remodelling phase. For effective healing to occur, all wounds require a certain amount of these enzymes, which on the contrary could be very damaging at high concentrations causing excessive degradation and impaired wound healing. The imbalance in MMPs may increase the chronicity of a wound, a familiar problem seen in diabetic patients. The association of diabetes with impaired wound healing and other vascular complications is a serious public health issue. These may eventually lead to chronic foot ulcers and amputation. Low intensity laser irradiation (LILI) or photobiomodulation (PBM) is known to stimulate several wound healing processes; however, its role in matrix proteins and diabetic wound healing has not been fully investigated. This review focuses on the role of MMPs in diabetic wound healing and their interaction in PBM.

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Therapeutic Role of Nitric Oxide in Diabetic Wound Healing: A Systematic Review

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i33b31798 ◽

2021 ◽

pp. 68-80

Author(s):

Mayur Meghashyam Chavhan ◽

Ranjit Vinayak Gadhave ◽

Yogita Sachin Ozarde ◽

Ganesh Bhaurao Choudhari

Keyword(s):

Nitric Oxide ◽

Wound Healing ◽

Bacterial Infections ◽

The Body ◽

Low Level Laser Therapy ◽

Diabetic Patients ◽

Diabetic Wound ◽

Impaired Wound Healing ◽

Diabetic Wound Healing

Post injury, healing of wound is essential for recovery of uprightness of the body, which is one of the complex, continuous and unanticipated chains of events in case of diabetic patients. Nitric oxide represents a potential wound therapeutic agent due to its ability to regulate inflammation and eradicate bacterial infections. Impaired wound healing is a prominent diabetic complication which may lead to amputations also. In addition to modern medicines we can use nitric oxide therapy prominently for diabetic wound healing. Prominent and proven role of nitric oxide as well as conventional materials (like metformin and hydrogen sulphide, whey proteins, acidified nitrile etc), therapies (like low level laser therapy, hyperbaric oxygen therapy etc) and techniques (like in vivo implants with biosensors) can be taken into consideration. Many plant extracts showed promising results for wound healing activity by increasing nitric oxide levels. Use of modern technologies such as implant with biosensor and technique like sonic head hog gene are available for diabetic wound healing using Nitric oxide. In this review, an attempt has been made to compile comprehensive updated information of role of nitric oxide in diabetic wound healing, which may be exploited by focusing more on development of effective strategies to treat diabetes-associated wound.

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Angiogenic Nanoscaffold Accelerates Diabetic Wound Healing and Improves Wound Tissue Strength in db/db Mice

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206874 ◽

2009 ◽

Cited By ~ 1

Author(s):

Swathi Balaji ◽

Abdul Q. Sheikh ◽

Lee Morris ◽

Foong Y. Lim ◽

Timothy M. Crombleholme ◽

...

Keyword(s):

Wound Healing ◽

Healing Process ◽

Wound Healing Process ◽

Diabetic Patients ◽

Diabetic Wound ◽

Normal Wound Healing ◽

Inflammatory Phase ◽

Diabetic Wound Healing ◽

Ecm Degradation ◽

Chronic Ulcers

Chronic ulcers are a leading cause of morbidity in diabetic patients. Diabetes is associated with major changes in the wound microenvironment and disruption of normal wound healing process, characterized by a prolonged inflammatory phase with elevated levels of wound proteases and increased degradation of extracellular matrix (ECM) components [1]. This impedes wound healing due to a lack of provisional matrix, impaired recruitment and survival of endothelial (EC) and endothelial precursor (EPC) cells, and insufficient neovascularization, resulting in delayed healing. Therefore, strategies focused on restoring the diabetic wound microenvironment by decreasing ECM degradation and promoting neovascularization are promising for development of new therapies to treat chronic diabetic ulcers.

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Dimethyl fumarate accelerates wound healing under diabetic conditions

Journal of Molecular Endocrinology ◽

10.1530/jme-18-0102 ◽

2018 ◽

Vol 61 (4) ◽

pp. 163-172 ◽

Cited By ~ 4

Author(s):

Ying Li ◽

Fuzhe Ma ◽

Huimin Li ◽

Yuguo Song ◽

Huan Zhang ◽

...

Keyword(s):

Wound Healing ◽

Oxidative Damage ◽

Critical Role ◽

Dimethyl Fumarate ◽

Related Factor ◽

Diabetic Wound ◽

Diabetic Mice ◽

Impaired Wound Healing ◽

Diabetic Wound Healing

Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) – a master of cellular antioxidants scavenging excessive DM-induced free radicals – in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation and accelerated wound closure in diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG) or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) – inducible in DM – in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing.

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Vitamin D ameliorates impaired wound healing in streptozotocin-induced diabetic mice by suppressing NF-κB-mediated inflammatory genes

Bioscience Reports ◽

10.1042/bsr20171294 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 18

Author(s):

YiFeng Yuan ◽

Sushant K. Das ◽

MaoQuan Li

Keyword(s):

Vitamin D ◽

Wound Healing ◽

Inflammatory Responses ◽

Vitamin D Supplementation ◽

Diabetic Wound ◽

Diabetic Mice ◽

Impaired Wound Healing ◽

Diabetic Wound Healing ◽

Diabetic Wounds

Diabetic wounds are characterized by delayed wound healing due to persistent inflammation and excessive production of reactive oxygen species. Vitamin D, which is well acknowledged to enhance intestinal calcium absorption and increase in plasma calcium level, has recently been shown to display beneficial effects in various vascular diseases by promoting angiogenesis and inhibiting inflammatory responses. However, the role of Vitamin D in diabetic wound healing is still unclear. In the present study, we investigated the role of Vitamin D in cutaneous wound healing in streptozotocin (STZ)-induced diabetic mice. Four weeks after injection of STZ, a full thickness excisional wound was created with a 6-mm diameter sterile biopsy punch on the dorsum of the mice. Vitamin D was given consecutively for 14 days by intraperitoneal injection. Vitamin D supplementation significantly accelerated wound healing in diabetic mice and improved the healing quality as assessed by measuring the wound closure rate and histomorphometric analyses. By monitoring the level of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL) 6 (IL-6), IL-1β) in the wounds, reduced inflammatory response was found in VD treatment group. Furthermore, nuclear factor κB (NF-κB) pathway was found to be involved in the process of diabetic wound healing by assessing the relative proteins in diabetic wounds. Vitamin D supplementation obviously suppressed NF-κB pathway activation. These results demonstrated that Vitamin D improves impaired wound healing in STZ-induced diabetic mice through suppressing NF-κB-mediated inflammatory gene expression.

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Camel whey protein enhances diabetic wound healing in a streptozotocin-induced diabetic mouse model: the critical role of β-Defensin-1, -2 and -3

Lipids in Health and Disease ◽

10.1186/1476-511x-12-46 ◽

2013 ◽

Vol 12 (1) ◽

Cited By ~ 42

Author(s):

Gamal Badr

Keyword(s):

Wound Healing ◽

Mouse Model ◽

Whey Protein ◽

Critical Role ◽

Diabetic Mouse ◽

Diabetic Wound ◽

Diabetic Wound Healing

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Updates in Diabetic Wound Healing, Inflammation, and Scarring

Seminars in Plastic Surgery ◽

10.1055/s-0041-1731460 ◽

2021 ◽

Author(s):

Nina Dasari ◽

Austin Jiang ◽

Anna Skochdopole ◽

Jayer Chung ◽

Edward Reece ◽

...

Keyword(s):

Wound Healing ◽

Disease Process ◽

Wound Dehiscence ◽

Diabetic Patients ◽

Wound Infections ◽

Diabetic Wound ◽

Complex Process ◽

Diabetic Wound Healing ◽

Almost All ◽

Diabetic Wounds

AbstractDiabetic patients can sustain wounds either as a sequelae of their disease process or postoperatively. Wound healing is a complex process that proceeds through phases of inflammation, proliferation, and remodeling. Diabetes results in several pathological changes that impair almost all of these healing processes. Diabetic wounds are often characterized by excessive inflammation and reduced angiogenesis. Due to these changes, diabetic patients are at a higher risk for postoperative wound healing complications. There is significant evidence in the literature that diabetic patients are at a higher risk for increased wound infections, wound dehiscence, and pathological scarring. Factors such as nutritional status and glycemic control also significantly influence diabetic wound outcomes. There are a variety of treatments available for addressing diabetic wounds.

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Beyond hematopoietic targets: the role of erythropoietin in diabetic wound healing

Biomarkers in Medicine ◽

10.2217/bmm.11.30 ◽

2011 ◽

Vol 5 (3) ◽

pp. 365-367

Author(s):

Saher Hamed

Keyword(s):

Wound Healing ◽

Diabetic Wound ◽

Diabetic Wound Healing

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Abnormal Cell Responses and Role of TNF-αin Impaired Diabetic Wound Healing

BioMed Research International ◽

10.1155/2013/754802 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9 ◽

Cited By ~ 53

Author(s):

Fanxing Xu ◽

Chenying Zhang ◽

Dana T. Graves

Keyword(s):

Wound Healing ◽

Macrophage Polarization ◽

Diabetic Wound ◽

Major Health Problem ◽

Abnormal Cell ◽

Fibroblast Migration ◽

Cell Responses ◽

Impaired Healing ◽

Diabetic Wound Healing

Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF-αalso contributes to impaired healing. In this paper, we discuss the abnormal cell responses in diabetic wound healing and the contribution of TNF-α.

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