Wound Repair Process Research Articles

Platelet rich plasma enhancement of skin regeneration in an ex vivo human experimental model

An original ex vivo wounded skin culture protocol using autologous Platelet Rich Plasma (PRP) and enriched Dulbecco’s Modified Eagle’s Medium demonstrated a favourable modulation of the epithelial cells and fibroblasts proliferation, a relevant antiinflammatory action and a favourable modulation of the re-organization of collagen and elastic fibres. The step by step regenerative effects of PRP on human skin wound repair and regeneration process was observed over a period of 10 days.

Poly (vinylpyrrolidone)‑iodine engineered poly (ε-caprolactone) nanofibers as potential wound dressing materials.

Facilitating the process of wound healing and effective treatment of wounds remains a serious challenge in healthcare. Wound dressing materials play a major role in the protection of wounds and in accelerating the natural healing process. In the present study, novel core/shell (c/s) nanofibrous mats of poly(vinyl pyrrolidone)‑iodine (PVPI) and polycaprolactone (PCL) were fabricated using a co-axial electrospinning process followed by their surface modification with poly-l-lysine. The developed nanofibrous mats were extensively characterized for their physicochemical properties using various analytical techniques. The core/shell structure of the PVP-I/PCL nanofibers was confirmed using TEM analysis. The PVP-I release studies showed an initial burst phase followed by a sustained release pattern of PVP-I over a period of 30days. The developed nanofibers exhibited higher BSA and fibrinogen adsorption as compared to pristine PCL. Cytotoxicity studies using MTT assay demonstrated that the PVP-I/PCL (c/s) nanofibers were cytocompatible at optimized PVP-I concentration (3wt%). The PCL-poly-l-lysine and PVP-I/PCL-poly-l-lysine nanofibers exhibited higher cell viability (24.2% and 21.4% higher at day 7) when compared to uncoated PCL and PVP-I/PCL nanofibers. The PVP-I/PCL nanofibers showed excellent antimicrobial activity against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. The inflammatory response of Mouse RAW 264.7 macrophage cells towards the nanofibers was studied using RT-PCR. It revealed that the pro-inflammatory cytokines (TNF-α and IL-1β) were significantly upregulated on PCL nanofibers, while their expression was comparatively lower on poly-l-lysine coated PCL or PVP-I/PCL(c/s) nanofibers. Overall, the study highlights the ability of poly-l-lysine coated PVP-I/PCL (c/s) nanofibers as potential wound dressing materials effectively facilitating the early stage wound healing and repair process by virtue of their selective modulation of inflammation, cell adhesion and antimicrobial properties.

Effect of exosomes derived from mir-126-modified mesenchymal stem cells on the repair process of spinal cord injury in rats.

To investigate the effect of the micro ribonucleic acid (miR)-126-modified mesenchymal stem cell (MSC)-derived exosomes (MSC-exos) on the repair process of spinal cord injury (SCI) in rats. MiR-126-modified MSCs were cultured, the exosomes were extracted, and a rat model of SCI was established. The Quantitative Polymerase Chain Reaction (qPCR) was carried out to detect the expression of miR-126 in the injured spinal cord, and the Western blotting (WB) was adopted to detect the expressions of the exosome-related molecules. Subsequently, the motor function recovery of rats was examined via the Basso, Beattie and Bresnahan (BBB) locomotor rating scale. The effects of miR-126 exosomes on the injury volume and NeuN retention following SCI were evaluated via immunohistochemistry. MSCs were able to package miR-126 into exosomes secreted. After SCI, the recovery of the hind limb function of rats was remarkably improved by miR-126-modified MSC-exos relative to the control group. Treatment with miR-126-modified MSC-exos remarkably decreased the injury volume, retained the neuronal cells, and triggered the axon regeneration following SCI. Besides, the expression of Ras homolog gene family member A (RhoA), identified as the downstream gene of miR-126, was downregulated in the group with miR-126-modified MSC-exos. Moreover, miR-126-modified MSC-exos activated the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. MiR-126-modified MSC-exos protect neurons of rats with SCI, stimulates axon regeneration, and improves the recovery of limb motor function after SCI.

Platelet lysate promotes the expansion of Tregulatory cells that favours in vitro wound healing by increasing keratinocyte migration and fibroblast production of extracellular matrix components.

Platelet lysate (PL) contains a cocktail of growth factors and cytokines that promote tissue repair and regeneration. In vitro studies have shown that PL may affect the reparative function of keratinocytes and fibroblasts, but little is known about the effect of PL on immune cells involved in wound healing. To analyse the effects of PL on Tcells involved in the wound repair process. The effect of PL on Tcell proliferation, activation, and cytokine production was measured by ELISA and cytofluorometry and regulatory function based on cytofluorometry and Foxp3 RNA expression. Using an in vitro model of wound healing, we investigated the effect of PL-treated Tcells on fibroblast proliferation and production of fibronectin and type-1 collagen as well as keratinocyte migration. PL induced Tlymphocyte proliferation and CD69 expression, and promoted a transient upregulation of IFN-γ and TNF-α. However, later on, PL enhanced the number of CD25+ Tcells releasing TGF-β and expressing Foxp3 RNA, which was accompanied by a suppression in the level of type 1 cytokines. In the in vitro model, supernatants of PL-treated Tcells positively affected the reparative capacity of human keratinocytes and induced fibroblast proliferation and production of fibronectin and type-1 collagen. These results indicate that PL temporally regulates Tcells during the healing process, enhancing protective cytokines in the early phase, followed by a prominent expansion of TGF-β+ Tregulatory cells that promote tissue regeneration and dampen the inflammatory response to prevent excessive tissue damage.

Inflammation as an orchestrator of cutaneous scar formation: a review of the literature.

Inflammation is a key phase in the cutaneous wound repair process. The activation of inflammatory cells is critical for preventing infection in contaminated wounds and results in the release of an array of mediators, some of which stimulate the activity of keratinocytes, endothelial cells, and fibroblasts to aid in the repair process. However, there is an abundance of data suggesting that the strength of the inflammatory response early in the healing process correlates directly with the amount of scar tissue that will eventually form. This review will summarize the literature related to inflammation and cutaneous scar formation, highlight recent discoveries, and discuss potential treatment modalities that target inflammation to minimize scarring.

Silver crosslinked injectable bFGF-eluting supramolecular hydrogels speed up infected wound healing.

Topical wound dressings with various silver compositions that exhibit effective bacterial inhibition properties are often used to treat infected wounds. However, a silver dressing with no bioactive functionality will typically delay subsequent wound repair processes. Therefore, development of a simple wound dressing containing silver and loaded with a bioactive drug is a very attractive solution. Herein, we developed a silver crosslinked injectable chitosan-silver hydrogel as a silver immobilization matrix, loaded with basic fibroblast growth factor (bFGF) as its cargo (namely, bFGF@CS-Ag) for treatment of both acute and infected wounds. The in vivo results showed that bFGF@CS-Ag significantly enhanced infectious wound regeneration compared to that of acute wounds. Further investigation demonstrated that the improved wound repair by bFGF@CS-Ag was ascribed to the effectiveness of bacterial inhibition, the promotion of granulation formation, collagen deposition, neovascularization and re-epithelization, and to the reduction of the inflammatory response through promotion of M2 macrophage polarization. These results proved that the immobilization of silver in the hydrogel not only reduced the side effects of silver on the bioactivity of bFGF but also allowed elution of bFGF in a controlled release manner. Thus, this novel system has promising therapeutic potential for topical treatment of wounds.

Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery.

Impaired wound healing and tissue regeneration have severe consequences on the patient's quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies.

Hypotonic, Acidic Oxidizing Solution Containing Hypochlorous Acid (HClO) as a Potential Treatment of Hailey-Hailey Disease.

Hailey–Hailey disease (HHD) is a rare, chronic and recurrent blistering disorder, characterized by erosions occurring primarily in intertriginous regions and histologically by suprabasal acantholysis. Mutation of the Golgi Ca2+-ATPase ATP2C1 has been identified as having a causative role in Hailey–Hailey disease. HHD-derived keratinocytes have increased oxidative-stress that is associated with impaired proliferation and differentiation. Additionally, HHD is characterized by skin lesions that do not heal and by recurrent skin infections, indicating that HHD keratinocytes might not respond well to challenges such as wounding or infection. Hypochlorous acid has been demonstrated in vitro and in vivo to possess properties that rescue both oxidative stress and altered wound repair process. Thus, we investigated the potential effects of a stabilized form of hypochlorous acid (APR-TD012) in an in vitro model of HHD. We found that treatment of ATP2C1-defective keratinocytes with APR-TD012 contributed to upregulation of Nrf2 (nuclear factor (erythroid-derived 2)-like 2). Additionally, APR TD012-treatment restored the defective proliferative capability of siATP2C1-treated keratinocytes. We also found that the APR-TD012 treatment might support wound healing process, due to its ability to modulate the expression of wound healing associated cytokines. These observations suggested that the APR-TD012 might be a potential therapeutic agent for HHD-lesions.

The Role of Immune Cells and Cytokines in Intestinal Wound Healing.

Intestinal wound healing is a complicated process that not only involves epithelial cells but also immune cells. In this brief review, we will focus on discussing the contribution and regulation of four major immune cell types (neutrophils, macrophages, regulatory T cells, and innate lymphoid cells) and four cytokines (interleukin-10, tumor necrosis factor alpha, interleukin-6, and interleukin-22) to the wound repair process in the gut. Better understanding of these immune factors will be important for developing novel targeted therapy.

Activation of STING signaling accelerates skin wound healing

BackgroundThe process of repair after skin injury is precisely regulated by a variety of mediators such as cytokines and chemokines. Recent reports demonstrated that cytoplasmic DNA-sensor cyclic GMP-AMP synthase (cGAS) activates the stimulator of interferon genes (STING) via production of cyclic GMP-AMP (cGAMP) and subsequently induces inflammatory cytokines, including type I interferon (IFN). ObjectiveWe examined whether activation of the STING pathway by cGAMP affects the process of skin wound repair. MethodsThe skin wound repair model was established using wild-type (WT) mice. Two full-thickness skin biopsies were taken from the right and left subscapular regions. One site was treated with ointment containing cGAMP, and the other was treated with a control ointment. Changes in wound size over time were calculated using photography. ResultsTreatment with cGAMP significantly accelerated skin wound healing up to day 6. Biochemical analyses showed that topical treatment with cGAMP on wound sites promoted STING signaling pathway and enhanced the expression of IFN-β, CXCL10 and CCL2 in the wound sites treated with cGAMP markedly compared with the control. The scratch assay also revealed that cGAMP treatment accelerated wound closure in mouse embryonic fibroblasts. The acceleration of skin wound repair by cGAMP in WT mouse was impaired by administration of anti-IFNR antibody and anti-CXCR3 antibody respectively. ConclusionThese results revealed that topical treatment with cGAMP accelerates skin wound healing by inducing type I IFN and CXCL10/CXCR3. Topical administration of cGAMP might contribute to new effective treatments for accelerating skin wound healing.

The Evolution of Animal Models in Wound Healing Research: 1993-2017.

Significance: Wound healing is a complex and dynamic series of events influenced by a variety of intrinsic and extrinsic factors. Problematic wounds, particularly chronic wounds and pathologic scars, remain clinically significant burdens. Modeling physiologic and aberrant wound repair processes using in vitro or in vivo models have contributed to Advances in Wound Care (AWC); however, the fidelity of each model used, particularly with respect to its species-specific limitations, must be taken into account for extrapolation to human patients. Twenty-five years of wound healing models published in Wound Repair and Regeneration (1993-2017) and AWC (2012-2017) were collected and analyzed to determine trends in species utilization and models used. Recent Advances: In 25 years, 1,521 original research articles utilizing one or more wound models were published (total of 1,665 models). Although 20 different species were used over the course of 25 years, 5 species were most commonly utilized: human, mouse, rat, pig, and rabbit. In vivo modeling was used most frequently, followed by in vitro, ex vivo, and in silico modeling of wound healing processes. Critical Issues: A comparison of articles from 1993 to 1997 and 2013 to 2017 periods showed notable differences in model and species usage. Experiments utilizing mouse and human models increased, while the usage of pig models remained constant, rabbit and rat models declined in the more recent time period examined compared to the time period two decades before. Future Directions: This analysis shows notable changes in types of models and species used over time which may be attributed to new knowledge, techniques, technology, and/or reagents. Explorations into mechanisms of limb regeneration and wound healing of noncutaneous tissues have also contributed to a shift in modeling over time. Changes within the journals (i.e., page expansion and increased rejection rates), research funding, and model expense may also influence the observed shifts.

Mineralocorticoid Receptor Signaling Contributes to Normal Muscle Repair After Acute Injury.

Acute skeletal muscle injury is followed by a temporal response of immune cells, fibroblasts, and muscle progenitor cells within the muscle microenvironment to restore function. These same cell types are repeatedly activated in muscular dystrophy from chronic muscle injury, but eventually, the regenerative portion of the cycle is disrupted and fibrosis replaces degenerated muscle fibers. Mineralocorticoid receptor (MR) antagonist drugs have been demonstrated to increase skeletal muscle function, decrease fibrosis, and directly improve membrane integrity in muscular dystrophy mice, and therefore are being tested clinically. Conditional knockout of MR from muscle fibers in muscular dystrophy mice also improves skeletal muscle function and decreases fibrosis. The mechanism of efficacy likely results from blocking MR signaling by its endogenous agonist aldosterone, being produced at high local levels in regions of muscle damage by infiltrating myeloid cells. Since chronic and acute injuries share the same cellular processes to regenerate muscle, and MR antagonists are clinically used for a wide variety of conditions, it is crucial to define the role of MR signaling in normal muscle repair after injury. In this study, we performed acute injuries using barium chloride injections into tibialis anterior muscles both in myofiber MR conditional knockout mice on a wild-type background (MRcko) and in MR antagonist-treated wild-type mice. Steps of the muscle regeneration response were analyzed at 1, 4, 7, or 14 days after injury. Presence of the aldosterone synthase enzyme was also assessed during the injury repair process. We show for the first time aldosterone synthase localization in infiltrating immune cells of normal skeletal muscle after acute injury. MRcko mice had an increased muscle area infiltrated by aldosterone synthase positive myeloid cells compared to control injured animals. Both MRcko and MR antagonist treatment stabilized damaged myofibers and increased collagen infiltration or compaction at 4 days post-injury. MR antagonist treatment also led to reduced myofiber size at 7 and 14 days post-injury. These data support that MR signaling contributes to the normal muscle repair process following acute injury. MR antagonist treatment delays muscle fiber growth, so temporary discontinuation of these drugs after a severe muscle injury could be considered.

T Lymphocytes Attenuate Dermal Scarring by Regulating Inflammation, Neovascularization, and Extracellular Matrix Remodeling.

Objective: While tissue injury and repair are known to involve adaptive immunity, the profile of lymphocytes involved and their contribution to dermal scarring remain unclear. We hypothesized that restoration of T cell deficiency attenuates dermal scarring.Approach: We assessed the temporal–spatial distribution of T lymphocytes and their subtypes during the physiological dermal wound repair process in mice. Also, we compared the scarring outcomes between wild-type (WT) and severe combined immunodeficient (SCID) mice, which are lymphocyte deficient. Complementary gain-of-function experiments were performed by adoptively transferring lymphocyte subsets to validate their contribution to tissue repair in wounded SCID mice.Results: CD4+ T lymphocytes were present within dermal wounds of WT mice beginning on day 1 and remained through day 30. Wounds of SCID mice exhibited accelerated closure, increased inflammation, limited neovascularization, and exacerbated scarring compared with WT mice. Conversely, transfer of either mixed B and T lymphocytes or CD4+ lymphocytes alone into SCID mice resulted in moderated healing with less inflammation, collagen deposition, and scarring than control SCID wounds. In contrast, transfer of other lymphocyte subsets, including helper T lymphocytes (CD3+CD4+CD25−), CD8+ T cells and B cells, or regulatory T lymphocytes (CD4+CD25+CD127low), did not reduce scar.Innovation: The finding that lymphocytes delay wound healing but reduce scar is novel and provides new insights into how dermal scarring is regulated.Conclusion: Our data support a suppressive role for CD4+ T cells against inflammation and collagen deposition, with protective effects in early-stage dermal wound healing. These data implicate adaptive immunity in the regulation of scarring phenotypes.

Colony size and depth affect wound repair in a branching coral

Coral colonies regularly suffer tissue damage from natural and anthropogenic sources. The resultant wounds can decrease colony fitness and act as sources of infection or algal overgrowth. By systematically breaking branches on 54 Pocillopora meandrina colonies and following in situ tissue regeneration (April–August 2017), variation in the wound recovery process was investigated within colonies, among colonies, and across four sites on O‘ahu, Hawai‘i. Ninety-five percent of all wounds healed, with an average healing time of 42 days. Average healing time was not different between initial and subsequent wounds. The relative importance of intrinsic factors, extrinsic factors, and disturbance history for the wound repair process was examined. Previous colony stressors, i.e., percent live coral tissue and bleaching history, were not correlated with wound healing time. These results indicate that wound repair is a priority for P. meandrina. Colony size and depth were significantly correlated with wound healing time: larger colonies healed 14 days faster than smaller colonies, and deeper colonies healed 25 days slower than shallower colonies. These findings support the hypothesis that larger colonies have more energy available for tissue regeneration. The observation of longer healing times for deeper colonies is likely driven by extrinsic factors that vary with depth, including temperature, wave energy, and irradiance. Overall, we show that wound healing in P. meandrina is physiologically resilient to previous stressors, but is affected by both colony size and depth. Understanding drivers of variation in regenerative processes for corals is critical for predicting coral population recovery after disturbances.

The effect of hyaluronic acid on the skin healing in rats

Purpose: The objective of this study was to examine the effect of topical hyaluronic acid (HA) treatment on wound healing in rats. Methods: Wistar rats were randomly selected and allocated into 2 groups, with six rats each, all of them submitted to skin lesions (open wound with 5mm diameter). Group 1 – rats treated with topical 0,9% saline application in skin wounds. Group 2 – rats treated with topical hyaluronic acid 0,4% on skin wounds once a day for 7 days. After anesthesia on the 7th postoperative day, a biopsy of the skin dorsal wound area was performed for histopathological examination. A classification system based on the degree of reepithelization, granulation tissue formation and collagen organization were used to relate the morphological differences in wound healing. Results: Rats from control group treated with saline solution, on day 7, presented a general impairment of healing process, marked by an incomplete reepithelization (score 2,67 ± 0,4), a persistent exudation, fibrin, reduced accumulation of granulation tissue (score 2,2 ± 0,5) and a slight collagen deposition (score 2,43 ± 0,5), compared with the HA group. On the other side, morphological differences were visible on the evolution of wound repair process in rats treated with HA with a significant reduction in fibrinous exudation, epidermal lining reconstitution by complete reepithelization (score 3,8 ± 0,6), an increased accumulation of granulation tissue at wound edge and bed (score 3,7 ± 1,1), moderate collagen deposition (3,8 ± 0,7). The respective differences between the groups were significant (p<0,05). Conclusions: Based on these findings, we may conclude that HA treatment contributes to improve healing of open wounds.

Eccentric exercise results in a prolonged increase in interleukin-6 and tumor necrosis factor-α levels in rat skeletal muscle.

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are well-known cytokines with pro-inflammatory capabilities, and have been shown to be involved in adaptation to exercise as multifaceted myokines. However, the precise role of IL-6 and TNF-α during exercise-induced skeletal muscle injury and subsequent repair processes is not fully understood. In this study, IL-6 and TNF-α were examined in soleus muscles at the gene and protein levels using in situ hybridization and immunohistochemical staining, respectively, and serum levels of IL-6 and TNF-α were determined before and after a 90-min downhill running session in rats. There were no changes in serum levels of IL-6 and TNF-α after exercise, but IL-6 and TNF-α mRNA increased and maintained high expression in muscles for 1-2weeks after exercise. IL-6 and TNF-a mRNAs were identified in both the cytoplasm and the nuclei of myocytes, as well as in invading inflammatory cells. IL-6 and TNF-α protein mainly distributed in cytoplasm unevenly and had a prolonged expression until 2weeks after eccentric exercise. Our results demonstrate that there is increased IL-6 and TNF-α expression in skeletal muscle that is induced by eccentric exercise and that the high expression of IL-6 and TNF-α in the long-term phase after eccentric exercise may be more involved in the subsequent recovery of damaged muscle.

Remote Postischemic Conditioning Promotes Stroke Recovery by Shifting Circulating Monocytes to CCR2+ Proinflammatory Subset.

Brain injury from stroke is typically considered an event exclusive to the CNS, but injury progression and repair processes are profoundly influenced by peripheral immunity. Stroke stimulates an acute inflammatory response that results in a massive infiltration of peripheral immune cells into the ischemic area. While these cells contribute to the development of brain injury, their recruitment has been considered as a key step for tissue repair. The paradoxical role of inflammatory monocytes in stroke raises the possibility that the manipulation of peripheral immune cells before infiltration into the brain could influence stroke outcome. One such manipulation is remote ischemic limb conditioning (RLC), which triggers an endogenous tolerance mechanism. We observed that mice subjected to poststroke RLC shifted circulating monocytes to a CCR2+ proinflammatory monocyte subset and had reduced acute brain injury, swelling, and improved motor/gait function in chronic stroke. The RLC benefits were observed regardless of injury severity, with a greater shift to a CCR2+ subset in severe stroke. Adoptive transfer of CCR2-deficient monocytes abolished RLC-mediated protection. The study demonstrates the importance of RLC-induced shift of monocytes to a CCR2+ proinflammatory subset in attenuating acute injury and promoting functional recovery in chronic stroke. The defined immune-mediated mechanism underlying RLC benefits allows for an evidence-based framework for the development of immune-based therapeutic strategies for stroke patients.SIGNIFICANCE STATEMENT Stroke is the leading cause of physical disability worldwide but has few treatment options for patients. Because remote ischemic limb conditioning (RLC) elicits endogenous tolerance in neither an organ- nor a tissue-specific manner, the immune system has been considered a mediator for an RLC-related benefit. Application of RLC after stroke increased a proinflammatory CCR2+ monocyte subset in the blood and the brain. RLC reduced acute stroke injury and promoted motor/gait function during the recovery phase. The RLC benefits were absent in mice that received CCR2-deficient monocytes. This preclinical study shows the importance of CCR2+ proinflammatory monocytes in RLC benefits in stroke and provides a therapeutic RLC platform as a novel immune strategy to improve outcomes in stroke patients.

Development of MicroRNA-146a-Enriched Stem Cell Secretome for Wound-Healing Applications.

Secretome-based therapies have the potential to become the next generation of viable therapeutic wound repair treatments. However, precise strategies aimed to refine and control the secretome composition are necessary to enhance its therapeutic efficacy and facilitate clinical translation. In this study, we aim to accomplish this by transfecting human adipose-derived stem cells (hASCs) with microRNA-146a, which is a potent regulator of angiogenesis and inflammation. The secretome composition obtained from the transfected hASCs (secretome146a) was characterized and compared to nontransfected hASCs secretome to evaluate changes in angiogenic and anti-inflammatory growth factor, cytokine, and miRNA content. In vitro proliferation, migration, and tubular morphogenesis assays using human umbilical vein endothelial cells (HUVECs) were completed to monitor the proangiogenic efficacy of the secretome146a. Finally, the anti-inflammatory efficacy of the secretome146a was assessed using HUVECs that were activated to an inflammatory state by IL-1β. The resulting HUVEC gene expression and protein activity of key inflammatory mediators were evaluated before and after secretome treatment. Overall, the secretome146a contained a greater array and concentration of therapeutic paracrine molecules, which translated into a superior angiogenic and anti-inflammatory efficacy. Therefore, this represents a promising strategy to produce therapeutic secretome for the promotion of wound repair processes.

A novel microcurrent dressing for wound healing in a rat skin defect model

BackgroundThe exogenous application of low-intensity electric stimulation (ES) may mimic a natural endogenous bioelectric current and accelerate the repair process of skin wounds. This study designed a novel microcurrent dressing (MCD) and evaluated its potential effects on wound healing in a rat skin defect model.MethodsFirst, wireless ES was integrated into a medical cotton cushion to fabricate the MCD, and its electrical property was examined by using a universal power meter. Then, animal experiments were conducted to evaluate the MCD’s effect. Forty-five rats were randomized into control (Con) group, Vaseline gauze (VG) group and MCD group. A full-thickness round skin incision 1.5 cm in diameter was made on the back of each animal. Apart from routine disinfection, the Con rats were untreated, whereas the other two groups were treated with VG or MCD. On days 3, 7 and 14 post injury, the wound areas were observed and measured using image analysis software following photography, and the skin samples were harvested from wound tissue. Then, histopathological morphology was observed routinely by hematoxylin and eosin (HE) staining; tumor necrosis factor α (TNF-α) and interleukin (IL)-1β expression were detected by Western blotting. Vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) expression were detected with immunohistochemistry.ResultsThe MCD generated a sf electric potential greater than 0.95 V. Animal experiments showed that the wound-healing rate in the MCD group was significantly increased compared with the Con and VG groups (P < 0.05 or P < 0.01). Histopathological observation revealed an alleviated inflammatory response, induced vascular proliferation and accelerated epithelization in the MCD group. Moreover, samples from the MCD group expressed reduced TNF-α and IL-1β levels and increased VEGF and EGF levels compared with those of the other two groups (P < 0.05 or P < 0.01). However, no significant difference was noted between the Con and VG groups at each time point.ConclusionsThe MCD generates a stable and lasting ES and significantly promotes wound healing by reducing inflammation duration and increasing growth factors expression. Thus, MCD may act as a promising biomaterial device for skin wound healing.

The link between advanced glycation end products and apoptosis in delayed wound healing.

Advanced glycation end products (AGEs) are naturally occurring molecules that start to accumulate from embryonic developmental stages and form as part of normal ageing. When reducing sugars interact with and modify proteins or lipids, AGE production occurs. AGE formation accelerates in chronic hyperglycemic conditions, and high AGE levels have been associated with the pathogenesis of various diseases. In addition, enhanced levels of AGEs have been linked to delayed wound healing as seen in patients with diabetes mellitus. Research has provided numerous ways in which a high AGE concentration results in impaired wound healing, including oxidative stress, structural and functional changes to proteins important in wound repair, an enhanced inflammatory response by activation of transcription factors, and possible exaggerated apoptosis of cells necessary to the wound repair process. Apoptosis is a naturally occurring cell death process that is significant for normal tissue functioning and plays an important role in wound repair by preventing a prolonged inflammatory response and excessive scar formation. Abnormal apoptosis affects wound healing, resulting in slow healing wounds. This review will summarize the role of AGEs in wound healing, focusing on the mechanisms by which AGEs lead to apoptosis in various cell types. The review provides the way forward for medical research and molecular studies as it focuses on the mechanisms by which AGEs induce apoptosis in various cell types, including fibroblasts, osteoblasts, neuronal cells, and endothelial cells. Reviewing the mechanisms of AGE-linked apoptosis is important in understanding the impact of high AGE levels in delayed wound healing in diabetic patients due to abnormal apoptosis of cells necessary to the wound healing process.