scholarly journals Strain-Programmable Patch for Diabetic Wound Healing

2021 ◽  
Author(s):  
Georgios Theocharidis ◽  
Hyunwoo Yuk ◽  
Heejung Roh ◽  
Liu Wang ◽  
Ikram Mezghani ◽  
...  

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.

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ursula Hopfner ◽  
Matthias M. Aitzetmueller ◽  
Philipp Neßbach ◽  
Michael S. Hu ◽  
Hans-Guenther Machens ◽  
...  

Introduction. Although chronic wounds are a major personal and economic burden, treatment options are still limited. Among those options, adipose-derived stromal cell- (ASC-) based therapies rank as a promising approach but are restricted by the harsh wound environment. Here we use a commercially available fibrin glue to provide a deliverable niche for ASCs in chronic wounds. Material and Methods. To investigate the in vitro effect of fibrin glue, cultivation experiments were performed and key cytokines for regeneration were quantified. By using an established murine chronic diabetic wound-healing model, we evaluated the influence of fibrin glue spray seeding on cell survival (In Vivo Imaging System, IVIS), wound healing (wound closure kinetics), and neovascularization of healed wounds (CD31 immunohistochemistry). Results. Fibrin glue seeding leads to a significantly enhanced secretion of key cytokines (SDF-1, bFGF, and MMP-2) of human ASCs in vitro. IVIS imaging showed a significantly prolonged murine ASC survival in diabetic wounds and significantly accelerated complete wound closure in the fibrin glue seeded group. CD31 immunohistochemistry revealed significantly more neovascularization in healed wounds treated with ASCs spray seeded in fibrin glue vs. ASC injected into the wound bed. Conclusion. Although several vehicles have shown to successfully act as cell carrier systems in preclinical trials, regulatory issues have prohibited clinical usage for chronic wounds. By demonstrating the ability of fibrin glue to act as a carrier vehicle for ASCs, while simultaneously enhancing cellular regenerative function and viability, this study is a proponent of clinical translation for ASC-based therapies.


2019 ◽  
Vol 9 (23) ◽  
pp. 5114
Author(s):  
Nicolette Houreld

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.


2021 ◽  
Author(s):  
Biyun Lan ◽  
Liming Zhang ◽  
Liqun Yang ◽  
Junfeng Wu ◽  
Na Li ◽  
...  

Abstract Excessive expression of matrix metalloproteinase 9 (MMP-9) impedes healing of diabetic chronic wounds, thus wound dressing that could effectively inhibit the expression of MMP-9 offers significant clinical translation for diabetic wound healing. Herein, a hybrid hydrogel dressing was developed for localized and sustained delivery of MMP-9 siRNA (siMMP-9). siMMP-9 was complexed with Gly-TETA (GT), the GT/siMMP9 complex was then loaded into a thermosensitive hydrogel based on Pluronic F-127 (PF) and methylcellulose (MC). In vitro, this hybrid hydrogel dressing exhibited negligible cytotoxicity, prolonged the release of GT/siMMP-9 for up to 7 days, and significantly reduced MMP-9 expression. In vivo assessment in diabetic rats demonstrated that hydrogel provided localized and sustained delivery via the thermosensitive controlled release of entrapped GT/siMMP-9 into wound tissues for 7 days, resulting in dramatic MMP-9 silencing which significantly improved diabetic wound closure. This hybrid hydrogel dressing exhibited excellent biocompatibility, with no observed systemic toxicity in rats. Taken together, the hybrid hydrogel dressing may constitute an effective and biocompatible means of enhancing diabetic wound healing through effective silencing of the MMP-9 gene, and this hydrogel delivery system also offers a platform for in vivo delivery of siRNA for the treatment of other diseases.


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.


2015 ◽  
Vol 37 (5) ◽  
pp. 1725-1737 ◽  
Author(s):  
Tingyu Ke ◽  
Mei Yang ◽  
Duo Mao ◽  
Meifeng Zhu ◽  
Yongzhe Che ◽  
...  

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.


Author(s):  
Nina Dasari ◽  
Austin Jiang ◽  
Anna Skochdopole ◽  
Jayer Chung ◽  
Edward Reece ◽  
...  

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.


2021 ◽  
Vol 12 (6) ◽  
pp. 7621-7632

Diabetes Mellitus is the most prevalent metabolic disorder that is increasing at an alarming rate worldwide. The unregulated glucose level leads to various types of health disorders, and one of the major diabetic complications is delayed wound healing. Due to the more side effects of synthetic drugs, there is a need to explore plants and their phytochemicals for medicinal purposes. It was found that Quercetin, a flavonoid, increases the rate of diabetic wound healing by enhancing the expression of SIRT1. This demands more insight towards Quercetin and its similar compounds, as it is hypothesized that similar compounds may have similar biological properties. Thus similarity searching was done to identify the most similar compounds of Quercetin, and then the molecular docking of the screened compounds was performed using AutoDock Vina. The unique ligands were docked into the active site of SIRT1 protein (PDB ID: 4ZZJ). The binding free energy of the interacting ligand with the protein was estimated. Six compounds were identified which possess the maximum structural similarity with Quercetin, and upon docking, it was found that gossypetin and herbacetin have similar binding modes and binding energy as that of Quercetin (-7.5 kcal/mol). Therefore, the hypothesis has been validated by in silico analysis. Our study identified two phytochemicals, Gossypetin, and Herbacetin which can prove beneficial for improving diabetic wound healing but needs to be validated further by in vitro and in vivo studies.


2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Nicolette N. Houreld

Impaired wound healing is a common complication associated with diabetes with complex pathophysiological underlying mechanisms and often necessitates amputation. With the advancement in laser technology, irradiation of these wounds with low-intensity laser irradiation (LILI) or phototherapy, has shown a vast improvement in wound healing. At the correct laser parameters, LILI has shown to increase migration, viability, and proliferation of diabetic cellsin vitro; there is a stimulatory effect on the mitochondria with a resulting increase in adenosine triphosphate (ATP). In addition, LILI also has an anti-inflammatory and protective effect on these cells. In light of the ever present threat of diabetic foot ulcers, infection, and amputation, new improved therapies and the fortification of wound healing research deserves better prioritization. In this review we look at the complications associated with diabetic wound healing and the effect of laser irradiation bothin vitroandin vivoin diabetic wound healing.


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