Current trends in wound healing processes.
Wound healing is a disturbing area of human biological process due to the inability of our tissues to regenerate competent after injury. In addition, any small interferance to the healing process could lead to significant complication that exacerbate the injury effect. The articles posted here are based on current studies that have been done on wound healing process.
Abstract: Currently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries. A depilatory cream (Nair™, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (AlgerbrushII). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal) or HPMC liquid (GenTeal) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist. Corneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls. This study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel.
Pub.: 23 May '18, Pinned: 25 May '18
Abstract: Adipose-derived stem cells (ADSCs) transplant has been reported to be a potential treatment for burn wounds. However, the effects of autogenicity and allogenicity of ADSCs on burn wound healing have not been investigated and the method for using ADSCs still needs to be established. This study compared the healing effects of autologous and allogenic ADSCs and determined an optimal method of using ADSCs to treat acute burn wounds. Experiments were performed in 20 male Wistar rats (weight, 176-250 g; age, 6-7 weeks). Two identical full-thickness burn wounds (radius, 4 mm) were created in each rat. ADSCs harvested from inguinal area and characterized by their high multipotency were injected into burn wounds in the original donor rats (autologous ADSCs group) or in other rats (allogenic ADSCs group). The injection site was either the wound center or the four corners 0.5 cm from the wound edge. The reduction of burn surface areas in the two experimental groups and in control group were evaluated with Image J software for 15 days post-wounding to determine the wound healing rates. Wound healing was significantly faster in the autologous ADSCs group compared to both the allogenic ADSCs group (p<0.05) and control group (p<0.05). Wound healing in the allogenic ADSC group did not significantly differ from that in control group. Notably, ADSC injections 0.5cm from the wound edge showed significantly improved healing compared to ADSCs injections in the wound center (p<0.05). This study demonstrated the therapeutic efficacy of ADSCs in treating acute burn wounds in rats. However, only autologous ADSCs improved healing in acute burn wounds; allogenic ADSCs did not. This study further determined a superior location of using ADSCs injections to treat burn wounds including the injection site. Future studies will replicate the experiment in a larger and long-term scale burn wounds in higher mammalian models to facilitate ADSCs therapy in burn wound clinical practice.
Pub.: 23 May '18, Pinned: 25 May '18
Abstract: Epidermal stem cells residing in the skin play an essential role in epidermal regeneration. When skin is injured, the stem cells are first activated to proliferate, and subsequently the progeny migrate and differentiate to regenerate the epidermis. Here, we demonstrate that the vitamin D receptor (VDR) is essential for these processes to occur. The requirement for VDR on epidermal stem cell function was revealed in conditional VDR knockout (cKO) mice, in which VDR was deleted from stem cells and progeny, and mice were maintained on a low calcium diet. First, self-renewal and niche formation of epidermal stem cells were impaired. Wound-induced activation of epidermal stem cells was blunted associated with a reduction of β-catenin signaling. Second, wound induced migration of stem cells and progeny was impaired as shown by lineage tracing and delayed migration of VDR silenced cells. Epidermal differentiation of progeny was impaired at the wounding site associated with reduced E-cadherin expression. Deletion of VDR also changed stem cell fate blunting hair development, increasing sebaceous glands, and altering expression and location of epidermal markers. These results suggest that VDR is required for self-renewal, migration and differentiation of epidermal stem cells and progeny during cutaneous wound healing. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Pub.: 23 May '18, Pinned: 25 May '18
Abstract: Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. Nude mice given total doses >15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. At highest dosage (15 Gy × 3), open wounds persisted on Day 15. However, wounds injected with cultured ASCs were nearly healed on Day 12, and those treated with injection of centrifuged fat or micronized connective tissue healed faster than untreated controls (p<0.05). There was no significance between treated groups. Irradiation damage and tissue devitalization were dose-dependent, though fractionated protocols helped to reduce. ASCs and other fat-derived products harboring ASCs successfully revitalized irradiated tissues and accelerated wound healing.
Pub.: 23 May '18, Pinned: 25 May '18
Abstract: Wound healing is a complex biological process with specific phases. Photobiomodulation (PBM) decreases the inflammatory infiltrate, stimulating fibroblast proliferation and angiogenesis, and therefore, is indicated for wound healing. Vitamin A is used to reverse the inhibitory effects on wound healing and accelerate the healthy granulation tissue. The study aimed to evaluate the effect of topical vitamin A and PBM (GaAlAs) in inflammatory phase of cutaneous wounds. Forty Wistar male rats were separated into four groups: (1) control (CG); (2) laser group (LG) GaAlAs, 670 nm, 30 mW, energy per point of 0.9 J, radiating by 1 point in 30 s; (3) vitamin A group (VitAG); and (4) laser group plus vitamin A (LG + VitAG). Wounds were surgically made by a punch biopsy with 10 mm of diameter on the back of the animals and all treatments were started according to the experiment. The treatments were administered for four consecutive days and biopsy was performed on day 4. We performed both H&E and immunohistochemistry analysis. The results were compared between groups by one-way analysis of variance ANOVA test with post hoc Tukey (p < 0.05). Inflammatory infiltrate increased significantly in LG compared to CG and VitAG (p < 0.05). Regarding angiogenesis, VEGF expression was increased significantly in LG and LG + VitAG groups, p < 0.01. The results indicate that proposed treatments were effective on the healing process improved by LG and LG + VitAG. We show that laser plus vitamin A enhances healing by reducing the wound area and may have potential application for clinical management of cutaneous wounds.
Pub.: 22 May '18, Pinned: 25 May '18
Abstract: The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20–45% of PF was released in the first 7 h and 70–90% released within 48 h. The rheological properties of the ointment remained stable throughout storage at 25 ± 2°C/60% RH. Animal studies showed treatments of burn wounds during the inflammatory stage of wound healing with PF ointments at different drug concentrations had no adverse effects on reepithelization. Moreover, 6.5% PF ointment (F3) reduced the expression of pro-inflammatory cytokines IL-12p70 and TNFα. This study suggests that hydrocarbon base ointment could be a promising dosage form for topical delivery of PF in treatment of deep partial-thickness burns.
Pub.: 11 May '18, Pinned: 25 May '18
Abstract: is a spice with various pharmacological properties. Crocin, picrocrocin, and safranal are the main compositions of saffron that have recently been considered in the therapy of many diseases. High-performance liquid chromatography analysis revealed presence of these compounds in our saffron extract. This study was carried out to evaluate the effect of saffron on burn wound healing at an model. Saffron was topically applied on burn wounds in rats; the percentage of wound closure, wound contraction, and the levels of main cytokines and growth factors were measured. The saffron extract was also applied to evaluate the proliferation and migration of human dermal fibroblast (HDF) cells using scratch assay and resulted in active proliferation and migration of the HDF cells in a dose-dependent manner. A clear enhanced healing was observed in the saffron-treated wounds compared to the silver sulfadiazine and negative control groups. Decreased expression of interleukin-1 and transforming growth factor-1 (TGF-1) during the inflammatory phase demonstrated the role of saffron in promoting wound healing. In addition, enhanced TGF-1 expression during the proliferative phase and basic fibroblast growth factor during the remodeling phase represented regenerative and anti-scarring role of saffron, respectively. Our histological and biochemical findings also confirmed that saffron significantly stimulated burn wound healing by modulating healing phases. Therefore, saffron can be an optimal option in promoting skin repair and regeneration. Application of this herbal medicinal drug should be encouraged because of its availability and negligible side effects. Georg Thieme Verlag KG Stuttgart · New York.
Pub.: 24 May '18, Pinned: 25 May '18
Abstract: In this study, we report the development of a hyaluronic acid (HA)-based composite hydrogel containing calcium fluoride (CaF2) with good biocompatibility and antibacterial properties for multifunctional wound dressing applications. CaF2 was newly selected for incorporation within HA because it can release both Ca2+ and F– ions, which are well-known ions for affecting cell proliferation and inhibiting bacterial growth, respectively. In particular, an in situ precipitation process enables easy control over the released amount of F– ions by simply adjusting the precursor solutions (calcium chloride (CaCl2) and ammonium fluoride (NH4F)) used for the CaF2 precipitation. CaF2 particles were uniformly embedded within a HA-based pure hydrogel using an in situ precipitation process. Through variation of the CaCl2 and NH4F concentrations used in the precipitation as well as the precipitation time, composite hydrogels with different ion-release profiles were obtained. By controlling the precipitation time, especially for 10 min and after 30 min, large differences in the ion-release profiles as a function of CaF2 concentration were observed. A shorter precipitation time resulted in faster release of fluoride, whereas for the 30 min and 1 h samples, sustained ion release was achieved. Colony tests and live/dead assays using Escherichia coli and Staphylococcus aureus revealed a lower density of bacteria on the CaF2 composite hydrogels than on the pure hydrogel for both strains. In addition, improved cellular responses such as cell attachment and proliferation were also observed for the CaF2 composite hydrogels compared to those for the pure hydrogel. Furthermore, the composite hydrogels exhibited excellent wound healing efficiency, as evidenced by an in vitro cell migration assay. Finally, monitoring of the wound closure changes using a full-thickness wound in a rat model revealed the accelerated wound healing capability of the CaF2 composite hydrogels compared with that of the pure hydrogel. Based on our findings, these CaF2 composite hydrogels show great potential for application as advanced hydrogel wound dressings with antibacterial properties and accelerated wound-healing capabilities.
Pub.: 12 May '18, Pinned: 25 May '18
Abstract: A large proportion of patients develop poor amputation stump healing. We hypothesize that Laser-Assisted Fluorescent Angiography (LAFA) can predict inadequate tissue perfusion and healing. Over an 8-month period we reviewed all patients who underwent lower extremity amputation and LAFA. We evaluated intra-operative LAFA global and segmental stump perfusion, and post-operative modified Bates-Jensen (mBJS) wound healing scores. In 15 patients, amputation stumps with lower global perfusion demonstrated higher mBJS (P = 0.01). Lower suture-line perfusion also correlated with more eschar formation (P < 0.001). Diabetic patients had higher mBJS (P = 0.009), lower stump perfusion (P = 0.02), and increased eschar volume (P < 0.001). LAFA is a useful adjunct for intra-operative stump perfusion assessment and can predict areas of poor stump healing and eschar formation. Diabetic patients seem to be at higher risk of stump eschar formation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Pub.: 24 May '18, Pinned: 25 May '18