scholarly journals Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Da Yong Shin ◽  
Ji-Ung Park ◽  
Min-Ha Choi ◽  
Sukwha Kim ◽  
Hyoun-Ee Kim ◽  
...  

Abstract Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.

Author(s):  
Swathi Balaji ◽  
Abdul Q. Sheikh ◽  
Lee Morris ◽  
Foong Y. Lim ◽  
Timothy M. Crombleholme ◽  
...  

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.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hadeel A. Al-Rawaf ◽  
Sami A. Gabr ◽  
Ahmad H. Alghadir

Background. Circulating micro-RNAs are differentially expressed in various tissues and could be considered as potential regulatory biomarkers for T2DM and related complications, such as chronic wounds. Aim. In the current study, we investigated whether ginger extract enriched with [6]-gingerol-fractions either alone or in combination with vitamin D accelerates diabetic wound healing and explores underlying molecular changes in the expression of miRNA and their predicted role in diabetic wound healing. Methods. Diabetic wounded mice were treated with [6]-gingerol-fractions (GF) (25 mg/kg of body weight) either alone or in combination with vitamin D (100 ng/kg per day) for two weeks. Circulating miRNA profile, fibrogenesis markers, hydroxyproline (HPX), fibronectin (FN), and collagen deposition, diabetic control variables, FBS, HbA1c, C-peptide, and insulin, and wound closure rate and histomorphometric analyses were, respectively, measured at days 3, 6, 9, and 15 by RT–PCR and immunoassay analysis. Results. Treatment of diabetic wounds with GF and vitamin D showed significant improvement in wound healing as measured by higher expression levels of HPX, FN, collagen, accelerated wound closure, complete epithelialization, and scar formation in short periods (11-13 days, (P<0.01). On a molecular level, three circulating miRNAs, miR-155, miR-146a, and miR-15a, were identified in diabetic and nondiabetic skin wounds by PCR analysis. Lower expression in miR-155 levels and higher expression of miR-146a and miR-15a levels were observed in diabetic skin wounds following treatment with gingerols fractions and vitamin D for 15 days. The data showed that miRNAs, miR-146a, miR-155, and miR-15a, correlated positively with the expression levels of HPX, FN, and collagen and negatively with FBS, HbA1c, C-peptide, and insulin in diabetic wounds following treatment with GF and /or vitamin D, respectively. Conclusion. Treatment with gingerols fractions (GF) and vitamin D for two weeks significantly improves delayed diabetic wound healing. The data showed that vitamin D and gingerol activate vascularization, fibrin deposition (HPX, FN, and collagen), and myofibroblasts in such manner to synthesize new tissues and help in the scar formation. Accordingly, three miRNAs, miR-155, miR-146a, and miR-15, as molecular targets, were identified and significantly evaluated in wound healing process. It showed significant association with fibrin deposition, vascularization, and reepithelialization process following treatment with GF and vitamin D. It proposed having anti-inflammatory action and promoting new tissue formation via vascularization process during the wound healing. Therefore, it is very interesting to consider miRNAs as molecular targets for evaluating the efficiency of nondrug therapy in the regulation of wound healing process.


2021 ◽  
Vol 18 ◽  
Author(s):  
Saima Tufail ◽  
Muhammad Irfan Siddique ◽  
Muhammad Sarfraz ◽  
Muhammad Farhan Sohail ◽  
Muhammad Nabeel Shahid ◽  
...  

Introduction: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds. Aim: Aim of the present study is to fabricate nanofilm embedded with simvastatin loaded chitosan nanoparticles (CS-SIM-NPs) has been reported herein to explore the efficacy of SIM in diabetic wound healing. Methods: The NPs, prepared via ionic gelation, were 173nm ± 2.645 in size with a zeta potential -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats. Results: The results showed significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site. Conclusion: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.


2018 ◽  
pp. 116-124
Author(s):  
Damsir Eni Ungke

Diabetic injury is one form of chronic complications. Diabetes mellitus is an open wound on the skin surface that can be accompanied by local tissue death. Diabetes mellitus patients at risk of 29 times the occurrence of diabetic injuries. Diabetic injury is an open wound on the skin surface caused by the presence of macroangiopathy resulting in vascular insusifiensi and neuropati. Organs most often affected by diabetes mellitus complications include the leg blood vessels. Disorders of blood vessels that often occur in diabetes that is on the legs and feet. This study aims to determine the effectiveness of wound care using modern bandage (Metcofazin) on diabetic wound healing process at Emergency Hospital (IGD) Arifin Nu'mang Hospital of Sidrap Regency, and to know the effectiveness of wound care using conventional dressing (normal saline saline NaCl 0 , 9% and gauze bandage) to diabetic wound healing process at Emergency Injury Installation (IGD) Arifin Nu'mang Hospital of Sidrap Regency. The type of research used by the researcher is qualitative research with case study approach. This research has been conducted on 21 November until December 21, 2014 at the Emergency Installation (IGD) Arifin Nu'mang Hospital, Sidrap Regency. Samples used in this study are patients with diabetic injuries at Arifin Nu'mang Hospital Sidrap District with sampling technique by puposive sampling. The results of this study indicate that the treatment of luk a using a modern bandage (metcofazine) is more effective than wound care using conventional dressing (normal saline 0.9% NaCl saline and gauze dressing) on ​​diabetic wound healing process at Arifin Nu'mang Hospital Sidrap Hospital.


2019 ◽  
Vol 7 (6) ◽  
pp. 940-952 ◽  
Author(s):  
Weihan Xie ◽  
Xiaoling Fu ◽  
Fengling Tang ◽  
Yunfei Mo ◽  
Jun Cheng ◽  
...  

Many pathophysiologic conditions can interrupt the normal wound healing process and lead to chronic wounds due to the arrest of macrophages in their inflammatory phenotype.


2020 ◽  
Vol 133 (19) ◽  
pp. jcs235838
Author(s):  
Peilang Yang ◽  
Xiqiao Wang ◽  
Di Wang ◽  
Yan Shi ◽  
Meng Zhang ◽  
...  

ABSTRACTBesides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-degrading enzyme led to insufficient insulin levels in diabetic skin during wound healing, which ultimately reduced the recovery rate of diabetic wounds. We confirmed that topical insulin application could reverse the impaired inflammation reaction in the diabetic wound environment and promote healing of diabetic wounds. Our study revealed that insulin promoted apoptosis of neutrophils and subsequently triggered polarization of macrophages. Both in vivo and in vitro studies verified that insulin re-established phagocytosis function and promoted the process of phagocytosis-induced apoptosis in neutrophils. Furthermore, we found that insulin treatment also promoted efferocytosis of the apoptosed neutrophils by macrophages, and thus induced macrophages to change their polarization state from M1 to M2. In conclusion, our studies proved that the exogenous application of insulin could improve diabetic wound healing via the restoration of the inflammatory response.


2021 ◽  
Author(s):  
Ya Guan ◽  
Hong Niu ◽  
Zhongting Liu ◽  
Yu Dang ◽  
Jie Shen ◽  
...  

Non-healing diabetic wound is one of the most common complications for diabetic patients. Chronic hypoxia is among the prominent factors that delay the wound healing process. Therefore, sustained oxygenation to alleviate hypoxia is hypothesized to promote diabetic wound healing. Yet it cannot be achieved by current clinical approaches including hyperbaric oxygen therapy. Herein, we developed a sustained oxygenation system consisting of oxygen-release microspheres and a reactive oxygen species (ROS)-scavenging hydrogel. The hydrogel was used to capture the ROS that is elevated in the diabetic wounds, and that may be generated due to oxygen release. The sustainedly released oxygen augmented survival and migration of keratinocytes and dermal fibroblasts; promoted angiogenic growth factor expression, and angiogenesis in the diabetic wounds; and decreased M1 macrophage density. These effects led to a significant increase of wound closure rate. These findings reveal that sustained oxygenation alone without using drugs is capable of healing diabetic wounds.


2019 ◽  
Vol 17 (1) ◽  
pp. 72
Author(s):  
Cut Raihanah ◽  
Nurul Mahyani ◽  
Kintoko Kintoko

Diabetic wound healing is delayed by many factors, including high TNF-α expression and low TGF-β expression which can affect the formation of new epithelial tissue and collagen as the main goal of the wound healing process. One of the diabetic wound healing agent is biosurfactant dialkyl alginate where so far its use in cream form for diabetic wound has never been reported. This study aimed to determine TNF-α, TGF-β, reepithelization and the collagenization of biosurfactant dialkyl alginate cream in diabetic biopsy wounds in STZ-induced rat. Biosurfactant dialkyl alginate was made in cream form and applied to biopsy wounds on the backs of rat twice a day for 9 days. Observation of TNF-α and TGF-β expression were performed by immunohistochemical staining, while epithelial and collagen with staining HE and Mallory. The results showed that the biosurfactant dialkyl alginate cream had an activity to decrease TNF-α expression, increase TGF-β expression and reepithelization but did not have any significant activity on collagenization. These results suggest that the biosurfactant dialkyl alginate cream can accelerate the healing of diabetic wound.


2020 ◽  
Vol 10 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Ran Wei ◽  
Shijun Nie ◽  
Jing Ma ◽  
Changmei Feng ◽  
Hongyu Kuang

Diabetic wound ulcers and unhealed ulcerations have caused in severe difficulties of diabetic patients all around the world. The anti-microbial peptides (AMP) and nanomaterials have been demonstrated beneficial in diabetic wound healing studies. Diabetic wound healing process can be delayed significantly due to the infection issues. Hence in this report, biologically synthesized cerium oxide (CeO2) nanoparticles incorporated with reduced graphene oxide (RGO) and AMP for effective and rapid diabetic wound healing have been reported. At first, reduced graphene oxide was prepared from graphene oxide to prepare CeO2/RGO nanocomposites. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites were accordingly prepared to study the diabetic wound healing process. Rats, the wound healing models with the wound size of about 1.5 cm2 were tested with the as-prepared samples. Further, the prepared samples were tested in a wound healing model of rate with the wound of size 1.5 cm2. Almost complete recovery of wounds i.e., 100% closure of wound area was observed after 2 weeks of treatment by the prepared samples. Biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites enhances rapid keratinocytes proliferation by short time thereby it proves the enhanced ability of the prepared samples to act as a wound healing in-vivo drugs. HE and MTC staining protocols to illustrate histological observations elucidates the keratinocytes creation by biocompatible AMP (IP-1) functionalized CeO2/RGO nanocomposites.


2021 ◽  
Author(s):  
Arisa Kita ◽  
Yuki Saito ◽  
Miura Norihiro ◽  
Maki Miyajima ◽  
Takatoshi Yotsuyanagi ◽  
...  

Abstract Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes physiological wound process; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. In this study, we demonstrate that the number of p15INK4B + senescent PDGFR-α + mesenchymal cells in adipose tissue transiently increases in early phases of wound healing in non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in wound healing impairment and an alteration in the cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results give novel insight into how regulation of senescence in adipose tissue contributes to the wound healing process and provide the basis for the development of therapeutic approaches for wound healing impairment in diabetes.


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