Inflammation and neuropeptides: the connection in diabetic wound healing

Abnormal wound healing is a major complication of both type 1 and type 2 diabetes, with nonhealing foot ulcerations leading in the worst cases to lower-limb amputation. Wound healing requires the integration of complex cellular and molecular events in successive phases of inflammation, cell proliferation, cell migration, angiogenesis and re-epithelialisation. A link between wound healing and the nervous system is clinically apparent as peripheral neuropathy is reported in 30–50% of diabetic patients and is the most common and sensitive predictor of foot ulceration. Indeed, a bidirectional connection between the nervous and the immune systems and its role in wound repair has emerged as one of the focal features of the wound-healing dogma. This review provides a broad overview of the mediators of this connection, which include neuropeptides and cytokines released from nerve fibres, immune cells and cutaneous cells. In-depth understanding of the signalling pathways in the neuroimmune axis in diabetic wound healing is vital to the development of successful wound-healing therapies.

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Healing Effects of Photobiomodulation on Diabetic Wounds

Applied Sciences ◽

10.3390/app9235114 ◽

2019 ◽

Vol 9 (23) ◽

pp. 5114

Author(s):

Nicolette Houreld

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Chronic Wounds ◽

Diabetic Patients ◽

Diabetic Wound ◽

Recurrence Rates ◽

Speed Up ◽

Diabetic Wound Healing ◽

Underlying Mechanisms ◽

Diabetic Wounds

Diabetic patients frequently develop chronic ulcers of the lower extremities, which are a frequent cause for hospitalization and amputation, placing strain on patients, their families, and healthcare systems. Present therapies remain a challenge, with high recurrence rates. Photobiomodulation (PBM), which is the non-invasive application of light at specific wavelengths, has been shown to speed up healing of chronic wounds, including diabetic foot ulcers (DFUs). PBM produces photophysical and photochemical changes within cells without eliciting thermal damage. It has been shown to promote tissue regeneration and speed up wound repair by reducing inflammation and oxidative stress, accelerating cell migration and proliferation, and promoting extracellular matrix production and release of essential growth factors. The shortage of rigorous, well-designed clinical trials makes it challenging to assess the scientific impact of PBM on DFUs, and lack of understanding of the underlying mechanisms also hinders the conventional use of this therapy. This review gives a glimpse into diabetic wound healing and PBM, and the effects of PBM on diabetic wound healing.

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Plasma Exosomes Loaded pH-Responsive Carboxymethylcellulose Hydrogel Promotes Wound Repair by Activating the Vascular Endothelial Growth Factor Signaling Pathway in Type 1 Diabetic Mice

Journal of Biomedical Nanotechnology ◽

10.1166/jbn.2021.3165 ◽

2021 ◽

Vol 17 (10) ◽

pp. 2021-2033

Author(s):

Lijuan Huang ◽

Yijie Shi ◽

Mengdie Li ◽

Tao Wang ◽

Liang Zhao

Keyword(s):

Vascular Endothelial Growth Factor ◽

Wound Healing ◽

Growth Factor ◽

Wound Repair ◽

Vascular Endothelial ◽

Diabetic Wound ◽

Ph Responsive ◽

Diabetic Wound Healing ◽

Endothelial Growth Factor

Chronic wound healing plagues thousands of diabetic patients and brings social and economic burdens. Plasma exosomes (P-Exos), regarded as nanosized therapeutic agents, have shown therapeutic efficacy in promoting diabetic wound healing. The present work prepared the P-Exos-loaded pH-responsive carboxymethylcellulose (P-Exos-loaded CMC) hydrogel to investigate its ability to accelerate diabetic wound healing and to explore its underlying mechanisms. The results showed that the P-Exos-loaded CMC hydrogel was an effective therapeutic agent for accelerating diabetic wound repair. It promoted the local wound healing process in diabetic type 1 mice and enhanced angiogenesis and re-epithelialization via activating angiogenesis-related pathways mediated by vascular endothelial growth factor (VEGF).

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Co-Transplantation of Skin-Derived Precursors and Collagen Sponge Facilitates Diabetic Wound Healing by Promoting Local Vascular Regeneration

Cellular Physiology and Biochemistry ◽

10.1159/000438537 ◽

2015 ◽

Vol 37 (5) ◽

pp. 1725-1737 ◽

Cited By ~ 15

Author(s):

Tingyu Ke ◽

Mei Yang ◽

Duo Mao ◽

Meifeng Zhu ◽

Yongzhe Che ◽

...

Keyword(s):

Wound Healing ◽

Wound Repair ◽

Expression Patterns ◽

Collagen Sponge ◽

Health Concern ◽

Diabetic Wound ◽

Paracrine Signalling ◽

Vascular Regeneration ◽

Diabetic Wound Healing

Background/Aims: Impaired diabetes wound healing can often lead to serious complications and remains a major health concern due to the lack of effective therapeutic approaches. Compromised angiogenesis, disrupted growth factor and cytokine activity are all attributable to diabetic wound healing impairment. The skin-derived precursors (SKPs) have been shown to differentiate into vascular and nerve cells, both of which are crucial components for wound repair. Given their easy accessibility and multipotency, the SKPs were proposed as an ideal therapeutic candidate for diabetic wound healing. Since the efficacy of cell therapy is limited by poor cell survival, collagen sponge was employed for better SKPs delivery. Methods: SKPs were isolated and transplanted directly to the wound areas of diabetic mice in the absence and presence of collagen sponge. The effects of SKPs and/or collagen sponge on diabetic wound healing were examined histologically as well as immunostaining of isolectin and α-SMA. Mechanisms via which the SKPs facilitate wound healing were then investigated by transplanting SKPs that have been pre-labelled with a fluorescence dye, Dil. Expression patterns of Dil and an SKP marker, nestin, was also examined. Results and Conclusion: Accelerated wound healing and enhanced local capillary regeneration could be observed 14 days after skin ablation from both SKPs and collagen sponge co-transplanted and collagen sponge only groups. Subsequent analyses further revealed superior pro-angiogenic effects from the SKP and collagen sponge co-delivered group, which are mainly attributable to in vivo transdifferentation and paracrine signalling of the SKPs.

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Stem Cell Therapy for T1 D and T2 D Diabetic patients

International Journal of Scientific and Engineering Research ◽

10.14299/ijser.2020.10.10 ◽

2020 ◽

Vol 11 (10) ◽

pp. 23-25

Author(s):

Nandakumar Ravichandran

Keyword(s):

Diabetic Retinopathy ◽

Beta Cells ◽

Chronic Condition ◽

Major Complication ◽

Limb Ischemia ◽

Diabetic Patients ◽

Insulin Production ◽

Working Age

Diabetes is a chronic condition that causes several diseases. Type 1 and Type 2 dependent diabetes are shown more concern in today’s world. Type1 dependent patients suffers from inability of the Beta cells to produce insulin whereas Type 2 dependent patients suffers from insufficient insulin production. Diabetic Retinopathy, Nephropathy, Critical Limb Ischemia and impaired glucose tolerance are some of the major risk factors of Diabetes. Diabetic Retinopathy is a major complication of Diabetes causing blindness in working age adults. This article discusses some research methods involved in the generation of Beta cells carried out by certain authors, hypothesis and future works in this field.

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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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Identification of Specific miRNAs in Neutrophils of Type 2 Diabetic Mice: Overexpression ofmiRNA-129-2-3pAccelerates Diabetic Wound Healing

Diabetes ◽

10.2337/db18-0313 ◽

2018 ◽

Vol 68 (3) ◽

pp. 617-630 ◽

Cited By ~ 11

Author(s):

Takahiro Umehara ◽

Ryoichi Mori ◽

Kimberly A. Mace ◽

Takehiko Murase ◽

Yuki Abe ◽

...

Keyword(s):

Wound Healing ◽

Diabetic Wound ◽

Diabetic Mice ◽

Diabetic Wound Healing ◽

Type 2 Diabetic

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

Journal of Diabetes Research ◽

10.1155/2016/2897656 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 51

Author(s):

Sandra Matabi Ayuk ◽

Heidi Abrahamse ◽

Nicolette Nadene Houreld

Keyword(s):

Wound Healing ◽

Matrix Metalloproteinases ◽

Vascular Complications ◽

Diabetic Patients ◽

Main Function ◽

Diabetic Wound ◽

Impaired Wound Healing ◽

Inflammatory Phase ◽

Diabetic Wound Healing

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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Strain-Programmable Patch for Diabetic Wound Healing

10.1101/2021.06.07.447423 ◽

2021 ◽

Author(s):

Georgios Theocharidis ◽

Hyunwoo Yuk ◽

Heejung Roh ◽

Liu Wang ◽

Ikram Mezghani ◽

...

Keyword(s):

Wound Healing ◽

Chronic Wounds ◽

Ex Vivo ◽

Numerical Models ◽

Diabetic Patients ◽

Diabetic Wound ◽

Memory Mechanism ◽

Culture Models ◽

Diabetic Wound Healing

Chronic wounds with impaired healing capability such as diabetic foot ulcers (DFU) are devastating complications in diabetic patients, inflicting rapidly growing clinical and economic burdens in aging societies. Despite recent advances in therapeutic approaches, limited benefits of the existing solutions highlight the critical need for novel therapeutic solutions for diabetic wound healing. Here we propose a strain-programmable patch capable of rapid robust adhesion on and programmable mechanical contraction of wet wounded tissues over days to offer a new therapeutic platform for diabetic wounds. The strain-programmable patch, consisting of a dried bioadhesive layer and a pre-stretched elastomer backing, implements a hydration-based shape-memory mechanism to achieve both uniaxial and biaxial contractions and stress remodeling of wet wounds in a programmable manner. We develop theoretical and numerical models to rationally guide the strain-programming and mechanical modulation of wounds. In vivo rodent and ex vivo human skin culture models validate the programmability and efficacy of the proposed platform and identify mechanisms of action for accelerated diabetic wound healing.

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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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