Dual Affinity Heparin-Based Hydrogels Achieve Pro-Regenerative Immunomodulation and Microvascular Remodeling.

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Ogle, Molly E; Krieger, Jack R; Tellier, Liane E; McFaline-Figueroa, Jennifer; Temenoff, Johnna S; Botchwey, Edward A

2018-04-09

The immune response to biomaterial implants critically regulates functional outcomes such as vascularization, transplant integration/survival, and fibrosis. To create "immunologically smart" materials, the host-material response may be engineered to optimize the recruitment of pro-regenerative leukocyte subsets which mature into corresponding wound-healing macrophages. We have recently identified a unique feature of pro-regenerative Ly6C low monocytes that is a higher expression of both the bioactive lipid receptor sphingosine-1-phosphate receptor 3 (S1PR3) and the stromal derived factor-1α (SDF-1α) receptor CXCR4. Therefore, we designed a bifunctional hydrogel to harnesses a mechanistic synergy between these signaling axes to enhance the recruitment of endogenous pro-regenerative monocytes. To overcome the challenge of codelivering two physiochemically distinct molecules-a large hydrophilic protein and hydrophobic small molecule-we engineered a dual affinity hydrogel that exploits the growth factor affinity of a heparin derivative (Hep -N ) and lipid chaperone activity of albumin. The sphingosine analog FTY720 and SDF-1α are successfully loaded and coreleased from the Hep -N -functionalized PEG-DA hydrogels while maintaining bioactivity. Placement of these hydrogels into a murine partial thickness skin wound demonstrates that corelease of FTY720 and SDF-1α yields superior recruitment of myeloid cells to the implant interface compared to either factor alone. Although in vivo delivery of FTY720 or SDF-1α individually promotes the enhanced recruitment of Ly-6C low anti-inflammatory monocytes, codelivery enhances the early accumulation and persistence of the differentiated wound healing CD206 + macrophages in the tissue surrounding the gel. Co-delivery similarly promoted the synergistic expansion of vasculature adjacent to the implant, a key step in tissue healing. Taken together, these findings suggest that the combination of chemotactic molecules may provide

Nature's Electric Potential: A Systematic Review of the Role of Bioelectricity in Wound Healing and Regenerative Processes in Animals, Humans, and Plants.

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Tyler, Sheena E B

2017-01-01

Natural endogenous voltage gradients not only predict and correlate with growth and development but also drive wound healing and regeneration processes. This review summarizes the existing literature for the nature, sources, and transmission of information-bearing bioelectric signals involved in controlling wound healing and regeneration in animals, humans, and plants. It emerges that some bioelectric characteristics occur ubiquitously in a range of animal and plant species. However, the limits of similarities are probed to give a realistic assessment of future areas to be explored. Major gaps remain in our knowledge of the mechanistic basis for these processes, on which regenerative therapies ultimately depend. In relation to this, it is concluded that the mapping of voltage patterns and the processes generating them is a promising future research focus, to probe three aspects: the role of wound/regeneration currents in relation to morphology; the role of endogenous flux changes in driving wound healing and regeneration; and the mapping of patterns in organisms of extreme longevity, in contrast with the aberrant voltage patterns underlying impaired healing, to inform interventions aimed at restoring them.

Summary of: Regenerative endodontics.

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Clark, Stephen J

2014-03-01

Significant advances in our understanding of the biological processes involved in tooth development and repair at the cellular and molecular levels have underpinned the newly emerging area of regenerative endodontics. Development of treatment protocols based on exploiting the natural wound healing properties of the dental pulp and applying tissue engineering principles has allowed reporting of case series showing preservation of tissue vitality and apexogenesis. To review current case series reporting regenerative endodontics. Current treatment approaches tend to stimulate more reparative than regenerative responses in respect of the new tissue generated, which often does not closely resemble the physiological structure of dentine-pulp. However, despite these biological limitations, such techniques appear to offer significant promise for improved treatment outcomes. Improved biological outcomes will likely emerge from the many experimental studies being reported and will further contribute to improvements in clinical treatment protocols.

Researches on regenerative medicine-current state

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WANG Zheng-guo

2012-11-01

Full Text Available 【Abstract】 Since 1980s, the rapid development of tissue engineering and stem cell research has pushed re-generative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD for the research on regenerative medicine. In order to push the translation of regenerative medicine forward—from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue—Regenerative Medi-cine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years. Key words: Regenerative medicine; Tissue engineering; Stem cells; Wound healing

Dental pulp stem cells: function, isolation and applications in regenerative medicine.

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Tatullo, Marco; Marrelli, Massimo; Shakesheff, Kevin M; White, Lisa J

2015-11-01

Dental pulp stem cells (DPSCs) are a promising source of cells for numerous and varied regenerative medicine applications. Their natural function in the production of odontoblasts to create reparative dentin support applications in dentistry in the regeneration of tooth structures. However, they are also being investigated for the repair of tissues outside of the tooth. The ease of isolation of DPSCs from discarded or removed teeth offers a promising source of autologous cells, and their similarities with bone marrow stromal cells (BMSCs) suggest applications in musculoskeletal regenerative medicine. DPSCs are derived from the neural crest and, therefore, have a different developmental origin to BMSCs. These differences from BMSCs in origin and phenotype are being exploited in neurological and other applications. This review briefly highlights the source and functions of DPSCs and then focuses on in vivo applications across the breadth of regenerative medicine. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Smart Dressings Based on Nanostructured Fibers Containing Natural Origin Antimicrobial, Anti-Inflammatory, and Regenerative Compounds

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Vanesa Andreu

2015-08-01

Full Text Available A fast and effective wound healing process would substantially decrease medical costs, wound care supplies, and hospitalization significantly improving the patients’ quality of life. The search for effective therapeutic approaches seems to be imperative in order to avoid the aggravation of chronic wounds. In spite of all the efforts that have been made during the recent years towards the development of artificial wound dressings, none of the currently available options combine all the requirements necessary for quick and optimal cutaneous regeneration. Therefore, technological advances in the area of temporary and permanent smart dressings for wound care are required. The development of nanoscience and nanotechnology can improve the materials and designs used in topical wound care in order to efficiently release antimicrobial, anti-inflammatory and regenerative compounds speeding up the endogenous healing process. Nanostructured dressings can overcome the limitations of the current coverings and, separately, natural origin components can also overcome the drawbacks of current antibiotics and antiseptics (mainly cytotoxicity, antibiotic resistance, and allergies. The combination of natural origin components with demonstrated antibiotic, regenerative, or anti-inflammatory properties together with nanostructured materials is a promising approach to fulfil all the requirements needed for the next generation of bioactive wound dressings. Microbially compromised wounds have been treated with different essential oils, honey, cationic peptides, aloe vera, plant extracts, and other natural origin occurring antimicrobial, anti-inflammatory, and regenerative components but the available evidence is limited and insufficient to be able to draw reliable conclusions and to extrapolate those findings to the clinical practice. The evidence and some promising preliminary results indicate that future comparative studies are justified but instead of talking about

The Hair Follicle: An Underutilized Source of Cells and Materials for Regenerative Medicine.

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Kiani, Mehrdad T; Higgins, Claire A; Almquist, Benjamin D

2018-04-09

The hair follicle is one of only two structures within the adult body that selectively degenerates and regenerates, making it an intriguing organ to study and use for regenerative medicine. Hair follicles have been shown to influence wound healing, angiogenesis, neurogenesis, and harbor distinct populations of stem cells; this has led to cells from the follicle being used in clinical trials for tendinosis and chronic ulcers. In addition, keratin produced by the follicle in the form of a hair fiber provides an abundant source of biomaterials for regenerative medicine. In this review, we provide an overview of the structure of a hair follicle, explain the role of the follicle in regulating the microenvironment of skin and the impact on wound healing, explore individual cell types of interest for regenerative medicine, and cover several applications of keratin-based biomaterials.

Stem Cells in Wound Healing: The Future of Regenerative Medicine? A Mini-Review.

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Duscher, Dominik; Barrera, Janos; Wong, Victor W; Maan, Zeshaan N; Whittam, Alexander J; Januszyk, Michael; Gurtner, Geoffrey C

2016-01-01

The increased risk of disease and decreased capacity to respond to tissue insult in the setting of aging results from complex changes in homeostatic mechanisms, including the regulation of oxidative stress and cellular heterogeneity. In aged skin, the healing capacity is markedly diminished resulting in a high risk for chronic wounds. Stem cell-based therapies have the potential to enhance cutaneous regeneration, largely through trophic and paracrine activity. Candidate cell populations for therapeutic application include adult mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells. Autologous cell-based approaches are ideal to minimize immune rejection but may be limited by the declining cellular function associated with aging. One strategy to overcome age-related impairments in various stem cell populations is to identify and enrich with functionally superior stem cell subsets via single cell transcriptomics. Another approach is to optimize cell delivery to the harsh environment of aged wounds via scaffold-based cell applications to enhance engraftment and paracrine activity of therapeutic stem cells. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for wound healing and discuss limitations for their clinical adoption. © 2015 S. Karger AG, Basel.

Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

Science.gov (United States)

Felder, Marcel; Sallin, Pauline; Barbe, Laurent; Haenni, Beat; Gazdhar, Amiq; Geiser, Thomas; Guenat, Olivier

2012-02-07

We present a microfluidic epithelial wound-healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow-focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system, a technique that is reported here for the first time. We demonstrate that alveolar epithelial cells cultured in a microfluidic environment preserve their phenotype before and after wounding. In addition, we report a wound-healing benefit induced by addition of HGF to the cell culture medium (19.2 vs. 13.5 μm h(-1) healing rate).

Cell-based regenerative strategies for treatment of diabetic skin wounds, a comparative study between human umbilical cord blood-mononuclear cells and calves' blood haemodialysate.

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Hala O El-Mesallamy

Full Text Available BACKGROUND: Diabetes-related foot problems are bound to increase. However, medical therapies for wound care are limited; therefore, the need for development of new treatment modalities to improve wound healing in diabetic patients is essential and constitutes an emerging field of investigation. METHODS: Animals were randomly divided into 8 groups (I-VIII (32 rats/group, all were streptozotocin (STZ-induced diabetics except groups III and VIII were non-diabetic controls. The study comprised two experiments; the first included 3 groups. Group I injected with mononuclear cells (MNCs derived from human umbilical cord blood (HUCB, group II a diabetic control group (PBS i.v. The second experiment included 5 groups, groups IV, V, and VI received topical HUCB-haemodialysate (HD, calves' blood HD, and solcoseryl, respectively. Group VII was the diabetic control group (topical saline. Standard circular wounds were created on the back of rats. A sample of each type of HD was analyzed using the high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS system. Wound area measurement and photography were carried out every 4 days. Plasma glucose, catalase (CAT, malondialdehyde (MDA, nitric oxide (NO and platelets count were assessed. Wound samples were excised for hydroxyproline (HP and histopathological study. RESULTS: Treatment with HUCB MNCs or HUCB-HD resulted in wound contraction, increased CAT, NO, platelets count, body weights, and HP content, and decreased MDA and glucose. CONCLUSION: Systemic administration of HUCB MNCs and topical application of the newly prepared HUCB-HD or calves' blood HD significantly accelerated the rate of diabetic wound healing and would open the possibility of their future use in regenerative medicine.

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

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Ayesha Bhatia

2016-01-01

Full Text Available Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

Science.gov (United States)

Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

2016-01-01

Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

Biomolecule delivery to engineer the cellular microenvironment for regenerative medicine.

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Bishop, Corey J; Kim, Jayoung; Green, Jordan J

2014-07-01

To realize the potential of regenerative medicine, controlling the delivery of biomolecules in the cellular microenvironment is important as these factors control cell fate. Controlled delivery for tissue engineering and regenerative medicine often requires bioengineered materials and cells capable of spatiotemporal modulation of biomolecule release and presentation. This review discusses biomolecule delivery from the outside of the cell inwards through the delivery of soluble and insoluble biomolecules as well as from the inside of the cell outwards through gene transfer. Ex vivo and in vivo therapeutic strategies are discussed, as well as combination delivery of biomolecules, scaffolds, and cells. Various applications in regenerative medicine are highlighted including bone tissue engineering and wound healing.

Burn Wound Healing and Treatment: Review and Advancements

Science.gov (United States)

2015-06-12

burns. BMJ. 2004;328:1427–9. 26. Kowalske KJ. Burn wound care. Phys Med Rehab Clin North Am. 2011;22:213–27. 27. Tan JQ, Zhang HH, Lei ZJ, Ren P, Deng C...resulting in keloid disease. Wound Repair Regen. 2010;18:139–53. 41. Claudinot S, Nicolas M, Oshima H, Rochat A, Barrandon Y. Long-term renewal of hair

Dynamic Reciprocity in the Wound Microenvironment

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Schultz, Gregory S.; Davidson, Jeffrey M.; Kirsner, Robert S.; Bornstein, Paul; Herman, Ira M.

2011-01-01

Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction amongst cells and their surrounding microenvironment. In the review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but cellular differentiation, migration, proliferation, and survival during tissue development, including e.g. embryogenesis, angiogenesis, as well as during pathologic processes including cancer diabetes, hypertension and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology, which may be understood within the DR framework. The implications of applying the principles of dynamic reciprocity to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. PMID:21362080

Microfluidic wound-healing assay to assess the regenerative effect of HGF on wounded alveolar epithelium.

OpenAIRE

Felder Marcel; Sallin Pauline; Barbe Laurent; Haenni Beat; Gazdhar Amiq; Geiser Thomas; Guenat Olivier

2012-01-01

We present a microfluidic epithelial wound healing assay that allows characterization of the effect of hepatocyte growth factor (HGF) on the regeneration of alveolar epithelium using a flow focusing technique to create a regular wound in the epithelial monolayer. The phenotype of the epithelial cell was characterized using immunostaining for tight junction (TJ) proteins and transmission electron micrographs (TEMs) of cells cultured in the microfluidic system a technique that is reported here ...

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier

Science.gov (United States)

Tan, Aaron; Chawla, Reema; Natasha, G; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R.; Seifalian, Alexander M.

2015-01-01

Summary The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. PMID:26422652

Regenerative medicine blueprint.

Science.gov (United States)

Terzic, Andre; Harper, C Michel; Gores, Gregory J; Pfenning, Michael A

2013-12-01

Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and surgical practice. Regenerative medicine is poised to provide innovative solutions in addressing major unmet needs for patients, ranging from congenital disease and trauma to degenerative conditions. Realization of the regenerative model of care predicates a stringent interdisciplinary paradigm that will drive validated science into standardized clinical options. Designed as a catalyst in advancing rigorous new knowledge on disease causes and cures into informed delivery of quality care, the Mayo Clinic regenerative medicine blueprint offers a patient-centered, team-based strategy that optimizes the discovery-translation-application roadmap for the express purpose of science-supported practice advancement.

A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes

OpenAIRE

Xiao, Jisheng; Chen, Siyu; Yi, Ji; Zhang, Hao; Ameer, Guillermo A.

2016-01-01

Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper io...

Wound Healing in Patients With Impaired Kidney Function.

Science.gov (United States)

Maroz, Natallia; Simman, Richard

2013-04-01

Renal impairment has long been known to affect wound healing. However, information on differences in the spectrum of wound healing depending on the type of renal insufficiency is limited. Acute kidney injury (AKI) may be observed with different wound types. On one hand, it follows acute traumatic conditions such as crush injury, burns, and post-surgical wounds, and on the other hand, it arises as simultaneous targeting of skin and kidneys by autoimmune-mediated vasculitis. Chronic kidney disease (CKD) and end-stage renal disease (ESRD) often occur in older people, who have limited physical mobility and predisposition for developing pressure-related wounds. The common risk factors for poor wound healing, generally observed in patients with CKD and ESRD, include poorly controlled diabetes mellitus, neuropathy, peripheral vascular disease, chronic venous insufficiency, and aging. ESRD patients have a unique spectrum of wounds related to impaired calcium-phosphorus metabolism, including calciphylaxis, in addition to having the risk factors presented by CKD patients. Overall, there is a wide range of uremic toxins: they may affect local mechanisms of wound healing and also adversely affect the functioning of multiple systems. In the present literature review, we discuss the association between different types of renal impairments and their effects on wound healing and examine this association from different aspects related to the management of wounds in renal impairment patients.

Current Concepts in Tissue Engineering: Skin and Wound.

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Tenenhaus, Mayer; Rennekampff, Hans-Oliver

2016-09-01

Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

Regenerative medicine primer.

Science.gov (United States)

Terzic, Andre; Nelson, Timothy J

2013-07-01

The pandemic of chronic diseases, compounded by the scarcity of usable donor organs, mandates radical innovation to address the growing unmet needs of individuals and populations. Beyond life-extending measures that are often the last available option, regenerative strategies offer transformative solutions in treating degenerative conditions. By leveraging newfound knowledge of the intimate processes fundamental to organogenesis and healing, the emerging regenerative armamentarium aims to boost the aptitude of human tissues for self-renewal. Regenerative technologies strive to promote, augment, and reestablish native repair processes, restituting organ structure and function. Multimodal regenerative approaches incorporate transplant of healthy tissues into damaged environments, prompt the body to enact a regenerative response in damaged tissues, and use tissue engineering to manufacture new tissue. Stem cells and their products have a unique aptitude to form specialized tissues and promote repair signaling, providing active ingredients of regenerative regimens. Concomitantly, advances in materials science and biotechnology have unlocked additional prospects for growing tissue grafts and engineering organs. Translation of regenerative principles into practice is feasible and safe in the clinical setting. Regenerative medicine and surgery are, thus, poised to transit from proof-of-principle studies toward clinical validation and, ultimately, standardization, paving the way for next-generation individualized management algorithms. Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Nanotechnology and regenerative therapeutics in plastic surgery: The next frontier.

Science.gov (United States)

Tan, Aaron; Chawla, Reema; G, Natasha; Mahdibeiraghdar, Sara; Jeyaraj, Rebecca; Rajadas, Jayakumar; Hamblin, Michael R; Seifalian, Alexander M

2016-01-01

The rapid ascent of nanotechnology and regenerative therapeutics as applied to medicine and surgery has seen an exponential rise in the scale of research generated in this field. This is evidenced not only by the sheer volume of papers dedicated to nanotechnology but also in a large number of new journals dedicated to nanotechnology and regenerative therapeutics specifically to medicine and surgery. Aspects of nanotechnology that have already brought benefits to these areas include advanced drug delivery platforms, molecular imaging and materials engineering for surgical implants. Particular areas of interest include nerve regeneration, burns and wound care, artificial skin with nanoelectronic sensors and head and neck surgery. This study presents a review of nanotechnology and regenerative therapeutics, with focus on its applications and implications in plastic surgery. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. All rights reserved.

Injectable Polyurethane Composite Scaffolds Delay Wound Contraction and Support Cellular Infiltration and Remodeling in Rat Excisional Wounds

Science.gov (United States)

Adolph, Elizabeth J.; Hafeman, Andrea E.; Davidson, Jeffrey M.; Nanney, Lillian B.; Guelcher, Scott A.

2011-01-01

Injectable scaffolds present compelling opportunities for wound repair and regeneration due to their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound width and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable polyurethane biocomposite scaffold that enhances cutaneous wound healing in a rat model. PMID:22105887

Multiple functions of gingival and mucoperiosteal fibroblasts in oral wound healing and repair.

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Chiquet, Matthias; Katsaros, Christos; Kletsas, Dimitris

2015-06-01

Fibroblasts are cells of mesenchymal origin. They are responsible for the production of most extracellular matrix in connective tissues and are essential for wound healing and repair. In recent years, it has become clear that fibroblasts from different tissues have various distinct traits. Moreover, wounds in the oral cavity heal under very special environmental conditions compared with skin wounds. Here, we reviewed the current literature on the various interconnected functions of gingival and mucoperiosteal fibroblasts during the repair of oral wounds. The MEDLINE database was searched with the following terms: (gingival OR mucoperiosteal) AND fibroblast AND (wound healing OR repair). The data gathered were used to compare oral fibroblasts with fibroblasts from other tissues in terms of their regulation and function during wound healing. Specifically, we sought answers to the following questions: (i) what is the role of oral fibroblasts in the inflammatory response in acute wounds; (ii) how do growth factors control the function of oral fibroblasts during wound healing; (iii) how do oral fibroblasts produce, remodel and interact with extracellular matrix in healing wounds; (iv) how do oral fibroblasts respond to mechanical stress; and (v) how does aging affect the fetal-like responses and functions of oral fibroblasts? The current state of research indicates that oral fibroblasts possess unique characteristics and tightly controlled specific functions in wound healing and repair. This information is essential for developing new strategies to control the intraoral wound-healing processes of the individual patient. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Specific sizes of hyaluronan oligosaccharides stimulate fibroblast migration and excisional wound repair.

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Cornelia Tolg

Full Text Available The extracellular matrix polysaccharide hyaluronan (HA plays a key role in both fibrotic and regenerative tissue repair. Accumulation of high molecular weight HA is typical of regenerative repair, which is associated with minimal inflammation and fibrosis, while fragmentation of HA is typical of postnatal wounds, which heal in the presence of inflammation and transient fibrosis. It is generally considered that HA oligosaccharides and fragments of a wide size range support these processes of adult, fibrotic wound repair yet the consequences of sized HA fragments/oligosaccharides to each repair stage is not well characterized. Here, we compared the effects of native HA, HA oligosaccharide mixtures and individual sizes (4-10 mer oligosaccharides, 5 and, 40 kDa of HA oligosaccharides and fragments, on fibroblast migration in scratch wound assays and on excisional skin wound repair in vivo. We confirm that 4-10 mer mixtures significantly stimulated scratch wound repair and further report that only the 6 and 8 mer oligosaccharides in this mixture are responsible for this effect. The HA 6 mer promoted wound closure, accumulation of wound M1 and M2 macrophages and the M2 cytokine TGFβ1, but did not increase myofibroblast differentiation. The effect of 6 mer HA on wound closure required both RHAMM and CD44 expression. In contrast, The 40 kDa HA fragment inhibited wound closure, increased the number of wound macrophages but had no effect on TGFβ1 accumulation or subsequent fibrosis. These results show that specific sizes of HA polymer have unique effects on postnatal wound repair. The ability of 6 mer HA to promote wound closure and inflammation resolution without increased myofibroblast differentiation suggests that this HA oligosaccharide could be useful for treatment of delayed or inefficient wound repair where minimal fibrosis is advantageous.

Regulation of Regenerative Responses by Factors in the Extracellular Matrix during Axolotl (Ambystoma mexicanum) Limb Regeneration

OpenAIRE

Phan, Anne Quy

2014-01-01

Salamanders are unique among adult vertebrates in their ability to regenerate complex body structures after traumatic injury. Axolotl limb regeneration is a stepwise sequence of three requisite processes: (1) scarless wound healing to generate a regenerative wound epithelium, (2) blastema formation by migration, proliferation and dedifferentiation to create a mass of multipotent regeneration-competent progenitor cells, and (3) induction of pattern formation by interaction of cells with opposi...

Late sensory function after intraoperative capsaicin wound instillation

DEFF Research Database (Denmark)

Aasvang, E K; Hansen, J B; Kehlet, H

2010-01-01

is partly re-established after skin injection of capsaicin. However, no study has evaluated the long-term effects of wound instillation of purified capsaicin on sensory functions. METHODS: Patients included in a double-blind placebo-controlled randomized study of the analgesic effect of capsaicin after....... placebo group at the 1-week follow-up (Pfunction on the operated side between groups at the pre-operative, 1-week or 2 1/2 year post-operative follow-up (P>0.05). The sensory function......BACKGROUND: Intense capsaicin-induced C-fiber stimulation results in reversible lysis of the nerve soma, thereby making capsaicin wound instillation of potential interest for the treatment of post-operative pain. Clinical histological and short-term sensory studies suggest that the C-fiber function...

Wound Healing Activity of a New Formulation from Platelet Lysate

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Akram Jamshidzadeh

2016-03-01

Full Text Available Platelet-rich plasma (PRP is an attractive preparation in regenerative medicine due to its potential role in the healing process in different experimental models. This study was designed to investigate the wound healing activity of a new formulation of PRP. Different gel-based formulations of PRP were prepared. Open excision wounds were made on the back of male Sprague-Dawley rats, and PRP gel was administered topically once daily until the wounds healed completely (12 days. The results revealed that the tested PRP formulation significantly accelerated the wound healing process by increasing the wound contraction, tissue granulization, vascularization, and collagen regeneration. Interestingly, this study showed that there were no significant differences between the PRP and its gel-based formulation in all the above mentioned parameters. Although this investigation showed that PRP formulation had significant wound healing effects, the PRP gel-based formulation also had significant wound healing properties. This might indicate the wound healing properties of the PRP gel ingredients in the current investigation.

Regenerative rehabilitation: a new future?

Science.gov (United States)

Perez-Terzic, Carmen; Childers, Martin K

2014-11-01

Modern rehabilitation medicine is propelled by newfound knowledge aimed at offering solutions for an increasingly aging population afflicted by chronic debilitating conditions. Considered a core component of future health care, the rollout of regenerative medicine underscores a paradigm shift in patient management targeted at restoring physiologic function and restituting normative impact. Nascent regenerative technologies offer unprecedented prospects in achieving repair of degenerated, diseased, or damaged tissues. In this context, principles of regenerative science are increasingly integrated in rehabilitation practices as illustrated in the present Supplement. Encompassing a growing multidisciplinary domain, the emergent era of "regenerative rehabilitation" brings radical innovations at the forefront of healthcare blueprints.

The pharmacology of regenerative medicine.

Science.gov (United States)

Christ, George J; Saul, Justin M; Furth, Mark E; Andersson, Karl-Erik

2013-07-01

Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.

The application of an enamel matrix protein derivative (Emdogain) in regenerative periodontal therapy: a review.

NARCIS (Netherlands)

Sculean, A.; Schwarz, F.; Becker, J.; Brecx, M.

2007-01-01

Regenerative periodontal therapy aims at reconstitution of the lost periodontal structures such as new formation of root cementum, periodontal ligament and alveolar bone. Findings from basic research indicate that enamel matrix protein derivative (EMD) has a key role in periodontal wound healing.

Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

Directory of Open Access Journals (Sweden)

Flavia Bruna

2016-01-01

Full Text Available Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adult’s BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adult’s BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

Electrospun polymeric dressings functionalized with antimicrobial peptides and collagen type I for enhanced wound healing

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Felgueiras, H. P.; Amorim, M. T. P.

2017-10-01

Modern wound dressings combine medical textiles with active compounds that stimulate wound healing while protecting against infection. Electrospun wound dressings have been extensively studied and the electrospinning technique recognized as an efficient approach for the production of nanoscale fibrous mats. The unique diverse function and architecture of antimicrobial peptides (AMPs) has attracted considerable attention as a tool for the design of new anti-infective drugs. Functionalizing electrospun wound dressings with these AMPs is nowadays being researched. In the present work, we explore these new systems by highlighting the most important characteristics of electropsun wound dressings, revealing the importance of AMPs to wound healing, and the methods available to functionalize the electrospun mats with these molecules. The combined therapeutic potential of collagen type I and these AMP functionalized dressings will be highlighted as well; the significance of these new strategies for the future of wound healing will be clarified.

Yorkie regulates epidermal wound healing in Drosophila larvae independently of cell proliferation and apoptosis.

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Tsai, Chang-Ru; Anderson, Aimee E; Burra, Sirisha; Jo, Juyeon; Galko, Michael J

2017-07-01

Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis. Using a GFP-tagged Yki transgene we show that Yki transiently translocates to some epidermal nuclei upon wounding. Genetic analysis strongly suggests that Yki interacts with the known wound healing pathway, Jun N-terminal kinase (JNK), but not with Platelet Derived Growth Factor/Vascular-Endothelial Growth Factor receptor (Pvr). Yki likely acts downstream of or parallel to JNK signaling and does not appear to regulate either proliferation or apoptosis in the larval epidermis during wound repair. Analysis of actin structures after wounding suggests that Yki and Sd promote wound closure through actin regulation. In sum, we found that Yki regulates an epithelial tissue repair process independently of its previously documented roles in balancing proliferation and apoptosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Regenerative potential and healing dynamics of the periodontium: a critical-size supra-alveolar periodontal defect study.

Science.gov (United States)

Polimeni, Giuseppe; Susin, Cristiano; Wikesjö, Ulf M E

2009-03-01

The nature and characteristics of the newly formed periodontium obtained following regenerative procedures remain a matter of controversy. The objective of this study was to evaluate the regenerative potential of the periodontal attachment and healing dynamics as observed from the spatial distribution of newly formed cementum, periodontal ligament (PDL) and alveolar bone following optimal circumstances for wound healing/regeneration in a discriminating animal model. Critical-size, 6-mm, supra-alveolar, periodontal defects were surgically created in six young adult Beagle dogs. Space-providing ePTFE devices with 300-microm laser-drilled pores were implanted to support wound stability and space provision in one jaw quadrant/animal. Treatments were alternated between left and right jaw quadrants in subsequent animals. The gingival flaps were advanced to submerge the defect sites for primary intention healing. Histometric analysis followed an 8-week healing interval. Healing was uneventful in all animals. The histometric analysis showed that cementum regeneration (2.99 +/- 0.22 mm) was significantly greater than PDL (2.54 +/- 0.18 mm, p=0.03) and bone regeneration (2.46 +/- 0.26 mm, p=0.03). The wound area showed significant positive non-linear effect on cementum (log beta=1.25, palveolar bone virtually regenerate in parallel under optimal circumstances for periodontal wound healing/regeneration. Moreover, space provision positively influences the extent of periodontal regeneration.

Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

Directory of Open Access Journals (Sweden)

Elster Eric A

2010-05-01

Full Text Available Abstract Background Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality. Methods In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult. Results Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38% had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%. Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1, and MIP-2α (CXCL2. Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators. Conclusion These findings suggest that the

Regenerative Rehabilitation – a New Future?

Science.gov (United States)

Perez-Terzic, Carmen; Childers, Martin K.

2014-01-01

Modern rehabilitation medicine is propelled by newfound knowledge aimed at offering solutions for an increasingly aging population afflicted by chronic debilitating conditions. Considered a core component of future healthcare, the roll-out of regenerative medicine underscores a paradigm shift in patient management targeted at restoring physiologic function and restituting normative impact. Nascent regenerative technologies offer unprecedented prospects in achieving repair of degenerated, diseased or damaged tissues. In this context, principles of regenerative science are increasingly integrated in rehabilitation practices as illustrated in the present Supplement. Encompassing a growing multidisciplinary domain, the emergent era of “regenerative rehabilitation” brings radical innovations at the forefront of healthcare blueprints. PMID:25310603

Modern collagen wound dressings: function and purpose.

Science.gov (United States)

Fleck, Cynthia Ann; Simman, Richard

2010-09-01

Collagen, which is produced by fibroblasts, is the most abundant protein in the human body. A natural structural protein, collagen is involved in all 3 phases of the wound-healing cascade. It stimulates cellular migration and contributes to new tissue development. Because of their chemotactic properties on wound fibroblasts, collagen dressings encourage the deposition and organization of newly formed collagen, creating an environment that fosters healing. Collagen-based biomaterials stimulate and recruit specific cells, such as macrophages and fibroblasts, along the healing cascade to enhance and influence wound healing. These biomaterials can provide moisture or absorption, depending on the delivery system. Collagen dressings are easy to apply and remove and are conformable. Collagen dressings are usually formulated with bovine, avian, or porcine collagen. Oxidized regenerated cellulose, a plant-based material, has been combined with collagen to produce a dressing capable of binding to and protecting growth factors by binding and inactivating matrix metalloproteinases in the wound environment. The increased understanding of the biochemical processes involved in chronic wound healing allows the design of wound care products aimed at correcting imbalances in the wound microenvironment. Traditional advanced wound care products tend to address the wound's macroenvironment, including moist wound environment control, fluid management, and controlled transpiration of wound fluids. The newer class of biomaterials and wound-healing agents, such as collagen and growth factors, targets specific defects in the chronic wound environment. In vitro laboratory data point to the possibility that these agents benefit the wound healing process at a biochemical level. Considerable evidence has indicated that collagen-based dressings may be capable of stimulating healing by manipulating wound biochemistry.

Early induction of NRF2 antioxidant pathway by RHBDF2 mediates rapid cutaneous wound healing.

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Hosur, Vishnu; Burzenski, Lisa M; Stearns, Timothy M; Farley, Michelle L; Sundberg, John P; Wiles, Michael V; Shultz, Leonard D

2017-04-01

Rhomboid family protein RHBDF2, an upstream regulator of the epidermal growth factor (EGF) receptor signaling, has been implicated in cutaneous wound healing. However, the underlying molecular mechanisms are still emerging. In humans, a gain-of-function mutation in the RHBDF2 gene accelerates cutaneous wound healing in an EGFR-dependent manner. Likewise, a gain-of-function mutation in the mouse Rhbdf2 gene (Rhbdf2 cub/cub ) shows a regenerative phenotype (rapid ear-hole closure) resulting from constitutive activation of the EGFR pathway. Because the RHBDF2-regulated EGFR pathway is relevant to cutaneous wound healing in humans, we used Rhbdf2 cub/cub mice to investigate the biological networks and pathways leading to accelerated ear-hole closure, with the goal of identifying therapeutic targets potentially effective in promoting wound healing in humans. Comparative transcriptome analysis of ear pinna tissue from Rhbdf2 cub/cub and Rhbdf2 +/+ mice at 0h, 15min, 2h, and 24h post-wounding revealed an early induction of the nuclear factor E2-related factor 2 (NRF2)-mediated anti-oxidative pathway (0h and 15min), followed by the integrin-receptor aggregation pathway (2h) as early-stage events immediately and shortly after wounding in Rhbdf2 cub/cub mice. Additionally, we observed genes enriched for the Fc fragment of the IgG receptor IIIa (FCGR3A)-mediated phagocytosis pathway 24h post-wounding. Although cutaneous wound repair in healthy individuals is generally non-problematic, it can be severely impaired due to aging, diabetes, and chronic inflammation. This study suggests that activation of the NRF2-antioxidant pathway by rhomboid protein RHBDF2 might be beneficial in treating chronic non-healing wounds. Copyright © 2017 Elsevier Inc. All rights reserved.

LXA4 actions direct fibroblast function and wound closure

International Nuclear Information System (INIS)

Herrera, Bruno S.; Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice; Leung, Kai P.; Van Dyke, Thomas E.

2015-01-01

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A 4 (LXA 4 ), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA 4 on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA 4 receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA 4 receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA 4 slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA 4 tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA 4 in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF-β1 up-regulates LXA 4 receptor (ALX

In-vitro- and in-vivo-studies on the application of an innovative wound healing system for burn patients on the basis of a spray-transplantation of primary isolated skin cells and an active wound dressing made of hollow fiber capillaries

OpenAIRE

Plettig, Jörn

2016-01-01

The treatment of acute burns, especially for patients with 2b degree wounds, is not resolved satisfactorily. The thesis evaluates an innovative therapeutic concept based on a primary skin cell isolation from fetal or adult tissue, an autologous spray-transplantation and a temporary wound supply via an active wound dressing based on hollow fiber capillaries. The aim is to increase the yield of regenerative basal keratinocyte precursor cells through a gentle isolation technique and to distribut...

Wound healing potential of adipose tissue stem cell extract.

Science.gov (United States)

Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

2017-03-25

Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

Wilms Tumor 1b defines a wound-specific sheath cell subpopulation associated with notochord repair

Science.gov (United States)

Lopez-Baez, Juan Carlos; Zeng, Zhiqiang; Brunsdon, Hannah; Salzano, Angela; Brombin, Alessandro; Wyatt, Cameron; Rybski, Witold; Huitema, Leonie F A; Dale, Rodney M; Kawakami, Koichi; Englert, Christoph; Chandra, Tamir; Schulte-Merker, Stefan

2018-01-01

Regenerative therapy for degenerative spine disorders requires the identification of cells that can slow down and possibly reverse degenerative processes. Here, we identify an unanticipated wound-specific notochord sheath cell subpopulation that expresses Wilms Tumor (WT) 1b following injury in zebrafish. We show that localized damage leads to Wt1b expression in sheath cells, and that wt1b+cells migrate into the wound to form a stopper-like structure, likely to maintain structural integrity. Wt1b+sheath cells are distinct in expressing cartilage and vacuolar genes, and in repressing a Wt1b-p53 transcriptional programme. At the wound, wt1b+and entpd5+ cells constitute separate, tightly-associated subpopulations. Surprisingly, wt1b expression at the site of injury is maintained even into adult stages in developing vertebrae, which form in an untypical manner via a cartilage intermediate. Given that notochord cells are retained in adult intervertebral discs, the identification of novel subpopulations may have important implications for regenerative spine disorder treatments. PMID:29405914

Attenuated Innate Immunity in Embryonic Stem Cells and Its Implications in Developmental Biology and Regenerative Medicine.

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Guo, Yan-Lin; Carmichael, Gordon G; Wang, Ruoxing; Hong, Xiaoxiao; Acharya, Dhiraj; Huang, Faqing; Bai, Fengwei

2015-11-01

Embryonic stem cells (ESCs) represent a promising cell source for regenerative medicine. Intensive research over the past 2 decades has led to the feasibility of using ESC-differentiated cells (ESC-DCs) in regenerative medicine. However, increasing evidence indicates that ESC-DCs generated by current differentiation methods may not have equivalent cellular functions to their in vivo counterparts. Recent studies have revealed that both human and mouse ESCs as well as some types of ESC-DCs lack or have attenuated innate immune responses to a wide range of infectious agents. These findings raise important concerns for their therapeutic applications since ESC-DCs, when implanted to a wound site of a patient, where they would likely be exposed to pathogens and inflammatory cytokines. Understanding whether an attenuated immune response is beneficial or harmful to the interaction between host and grafted cells becomes an important issue for ESC-based therapy. A substantial amount of recent evidence has demonstrated that the lack of innate antiviral responses is a common feature to ESCs and other types of pluripotent cells. This has led to the hypothesis that mammals may have adapted different antiviral mechanisms at different stages of organismal development. The underdeveloped innate immunity represents a unique and uncharacterized property of ESCs that may have important implications in developmental biology, immunology, and in regenerative medicine. © 2015 AlphaMed Press.

Tissue Engineering in Regenerative Dental Therapy

Directory of Open Access Journals (Sweden)

Hiral Jhaveri-Desai

2011-01-01

Full Text Available Tissue engineering is amongst the latest exciting technologies having impacted the field of dentistry. Initially considered as a futuristic approach, tissue engineering is now being successfully applied in regenerative surgery. This article reviews the important determinants of tissue engineering and how they contribute to the improvement of wound healing and surgical outcomes in the oral region. Furthermore, we shall address the clinical applications of engineering involving oral and maxillofacial surgical and periodontal procedures along with other concepts that are still in experimental phase of development. This knowledge will aid the surgical and engineering researchers to comprehend the collaboration between these fields leading to extounding dental applications and to ever-continuing man-made miracles in the field of human science.

LXA{sub 4} actions direct fibroblast function and wound closure

Energy Technology Data Exchange (ETDEWEB)

Herrera, Bruno S. [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Kantarci, Alpdogan; Zarrough, Ahmed; Hasturk, Hatice [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States); Leung, Kai P., E-mail: kai.p.leung.civ@mail.mil [Microbiology Branch, US Army Dental and Trauma Research Detachment, Institute of Surgical Research, JBSA Fort Sam Houston, TX (United States); Van Dyke, Thomas E., E-mail: tvandyke@forsyth.org [Department of Applied Oral Sciences, Center for Periodontology, The Forsyth Institute, Cambridge, MA (United States)

2015-09-04

Timely resolution of inflammation is crucial for normal wound healing. Resolution of inflammation is an active biological process regulated by specialized lipid mediators including the lipoxins and resolvins. Failure of resolution activity has a major negative impact on wound healing in chronic inflammatory diseases that is manifest as excess fibrosis and scarring. Lipoxins, including Lipoxin A{sub 4} (LXA{sub 4}), have known anti-fibrotic and anti-scarring properties. The goal of this study was to elucidate the impact of LXA{sub 4} on fibroblast function. Mouse fibroblasts (3T3 Mus musculus Swiss) were cultured for 72 h in the presence of TGF-β1, to induce fibroblast activation. The impact of exogenous TGF-β1 (1 ng/mL) on LXA{sub 4} receptor expression (ALX/FPR2) was determined by flow cytometry. Fibroblast proliferation was measured by bromodeoxyuridine (BrdU) labeling and migration in a “scratch” assay wound model. Expression of α-smooth muscle actin (α-SMA), and collagen types I and III were measured by Western blot. We observed that TGF-β1 up-regulates LXA{sub 4} receptor expression, enhances fibroblast proliferation, migration and scratch wound closure. α-SMA levels and Collagen type I and III deposition were also enhanced. LXA{sub 4} slowed fibroblast migration and scratch wound closure at early time points (24 h), but wound closure was equal to TGF-β1 alone at 48 and 72 h. LXA{sub 4} tended to slow fibroblast proliferation at both concentrations, but had no impact on α-SMA or collagen production by TGF-β1 stimulated fibroblasts. The generalizability of the actions of resolution molecules was examined in experiments repeated with resolvin D2 (RvD2) as the agonist. The activity of RvD2 mimicked the actions of LXA{sub 4} in all assays, through an as yet unidentified receptor. The results suggest that mediators of resolution of inflammation enhance wound healing and limit fibrosis in part by modulating fibroblast function. - Highlights: • TGF

Computational Approach to Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

Science.gov (United States)

2014-01-01

Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5: 953–964. 61. Koh , T. J., and L. A. DiPietro. 2011. Inflammation and wound healing: the role...of the macrophage. Expert Rev. Mol. Med. 13: e23. 62. Mirza, R., L. A. DiPietro, and T. J. Koh . 2009. Selective and specific macrophage ablation is... Raman spectroscopic mapping. Wound Repair Regen. 18: 409–416. 66. Forsberg, J. A., E. A. Elster, R. C. Andersen, E. Nylen, T. S. Brown, M. W. Rose, A

A review of the regenerative endodontic treatment procedure

Directory of Open Access Journals (Sweden)

Bin-Na Lee,

2015-08-01

Full Text Available Traditionally, apexification has been used to treat immature permanent teeth that have lost pulp vitality. This technique promotes the formation of an apical barrier to close the open apex so that the filling materials can be confined to the root canal. Because tissue regeneration cannot be achieved with apexification, a new technique called regenerative endodontic treatment was presented recently to treat immature permanent teeth. Regenerative endodontic treatment is a treatment procedure designed to replace damaged pulp tissue with viable tissue which restores the normal function of the pulp-dentin structure. After regenerative endodontic treatment, continued root development and hard tissue deposition on the dentinal wall can occur under ideal circumstances. However, it is difficult to predict the result of regenerative endodontic treatment. Therefore, the purpose of this study was to summarize multiple factors effects on the result of regenerative endodontic treatment in order to achieve more predictable results. In this study, we investigated the features of regenerative endodontic treatment in comparison with those of other pulp treatment procedures and analyzed the factors that have an effect on regenerative endodontic treatment.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

Science.gov (United States)

Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

2017-10-01

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Wound healing potential of adipose tissue stem cell extract

International Nuclear Information System (INIS)

Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

2017-01-01

Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. - Highlights: • Topical application of ATSC-Ex results in faster wound closure than normal wound in vivo. • ATSC-Ex enhances dermal fibroblast proliferation, migration and extracellular matrix production. • This study suggests that ATSC-Ex is an effective source to augment wound healing.

Mast Cells Regulate Wound Healing in Diabetes.

Science.gov (United States)

Tellechea, Ana; Leal, Ermelindo C; Kafanas, Antonios; Auster, Michael E; Kuchibhotla, Sarada; Ostrovsky, Yana; Tecilazich, Francesco; Baltzis, Dimitrios; Zheng, Yongjun; Carvalho, Eugénia; Zabolotny, Janice M; Weng, Zuyi; Petra, Anastasia; Patel, Arti; Panagiotidou, Smaro; Pradhan-Nabzdyk, Leena; Theoharides, Theoharis C; Veves, Aristidis

2016-07-01

Diabetic foot ulceration is a severe complication of diabetes that lacks effective treatment. Mast cells (MCs) contribute to wound healing, but their role in diabetes skin complications is poorly understood. Here we show that the number of degranulated MCs is increased in unwounded forearm and foot skin of patients with diabetes and in unwounded dorsal skin of diabetic mice (P diabetic mice. Pretreatment with the MC degranulation inhibitor disodium cromoglycate rescues diabetes-associated wound-healing impairment in mice and shifts macrophages to the regenerative M2 phenotype (P diabetic mice deficient in MCs have delayed wound healing compared with their wild-type (WT) controls, implying that some MC mediator is needed for proper healing. MCs are a major source of vascular endothelial growth factor (VEGF) in mouse skin, but the level of VEGF is reduced in diabetic mouse skin, and its release from human MCs is reduced in hyperglycemic conditions. Topical treatment with the MC trigger substance P does not affect wound healing in MC-deficient mice, but improves it in WT mice. In conclusion, the presence of nondegranulated MCs in unwounded skin is required for proper wound healing, and therapies inhibiting MC degranulation could improve wound healing in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

New strategies in clinical care of skin wound healing.

Science.gov (United States)

Günter, C I; Machens, H-G

2012-01-01

The prevalence of chronic wounds is closely correlated to the aging population and so-called civilizational diseases. Therefore, they are causing morbidity and mortality of millions of patients worldwide, with an unbroken upward trend. As a consequence, chronic wounds induce enormous and rapidly growing costs for our health care systems and society in general. Thus, medically effective and cost-efficient treatment methods are urgently needed. Methods of 'regenerative medicine' might offer innovative scientific solutions, including the use of stem cells, growth factors and new bioactive materials. These tools are experimentally well described but clinically poorly performed. The main reasons for this are both legislative and economic. This review describes state-of-the-art techniques, up-to-date research projects, innovative preclinical and clinical approaches in wound care, and activities to translate these innovative techniques into clinical routine. Copyright © 2012 S. Karger AG, Basel.

Electrofabrication of functional materials: Chloramine-based antimicrobial film for infectious wound treatment.

Science.gov (United States)

Qu, Xue; Liu, Huan; Zhang, Chuchu; Lei, Yu; Lei, Miao; Xu, Miao; Jin, Dawei; Li, Peng; Yin, Meng; Payne, Gregory F; Liu, Changsheng

2018-06-01

Electrical signals can be imposed with exquisite spatiotemporal control and provide exciting opportunities to create structure and confer function. Here, we report the use of electrical signals to program the fabrication of a chloramine wound dressing with high antimicrobial activity. This method involves two electrofabrication steps: (i) a cathodic electrodeposition of an aminopolysaccharide chitosan triggered by a localized region of high pH; and (ii) an anodic chlorination of the deposited film in the presence of chloride. This electrofabrication process is completed within several minutes and the chlorinated chitosan can be peeled from the electrode to yield a free-standing film. The presence of active NCl species in this electrofabricated film was confirmed with chlorination occurring first on the amine groups and then on the amide groups when large anodic charges were used. Electrofabrication is quantitatively controllable as the cathodic input controls film growth during deposition and the anodic input controls film chlorination. In vitro studies demonstrate that the chlorinated chitosan film has antimicrobial activities that depend on the chlorination degree. In vivo studies with a MRSA infected wound healing model indicate that the chlorinated chitosan film inhibited bacterial growth, induced less inflammation, developed reorganized epithelial and dermis structures, and thus promoted wound healing compared to a bare wound or wound treated with unmodified chitosan. These results demonstrate the fabrication of advanced functional materials (i.e., antimicrobial wound dressings) using controllable electrical signals to both organize structure through non-covalent interactions (i.e., induce chitosan's reversible self-assembly) and to initiate function-conferring covalent modifications (i.e., generate chloramine bonds). Potentially, electrofabrication may provide a simple, low cost and sustainable alternative for materials fabrication. We believe this work is

Optimal thermoeconomic performance of an irreversible regenerative ferromagnetic Ericsson refrigeration cycle

International Nuclear Information System (INIS)

Xu, Zhichao; Guo, Juncheng; Lin, Guoxing; Chen, Jincan

2016-01-01

On the basis of the Langevin theory of classical statistical mechanics, the magnetization, entropy, and iso-field heat capacity of ferromagnetic materials are analyzed and their mathematical expressions are derived. An irreversible regenerative Ericsson refrigeration cycle by using a ferromagnetic material as the working substance is established, in which finite heat capacity rates of low and high temperature reservoirs, non-perfect regenerative heat of the refrigeration cycle, additional regenerative heat loss, etc. are taken into account. Based on the regenerative refrigeration cycle model, a thermoeconomic function is introduced as one objective function and optimized with respect to the temperatures of the working substance in the two iso-thermal processes. By means of numerical calculation, the effects of the effective factor of the heat exchangers in high/low temperature reservoir sides, efficiency of the regenerator, heat capacity rate of the low temperature reservoir, and applied magnetic field on the optimal thermoeconomic function as well as the corresponding cooling rate and coefficient of performance are revealed. The results obtained in this paper can provide some theoretical guidance for the optimal design of actual regenerative magnetic refrigerator cycle. - Highlights: • Thermodynamic performance of ferromagnetic material is analyzed. • An irreversible regenerative ferromagnetic Ericsson refrigeration cycle is set up. • The thermoeconomic objective function is introduced and optimized. • Impacts of the thermoeconomic and other parameters are discussed.

Effect of laser irradiation for healing of the skin-muscle wounds of animals

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Lapina, Victoria A.; Veremei, Eduard I.; Pancovets, Evgeniy A.

2000-05-01

The purpose of our investigation was to study the medical effect of low-intensity laser influence on healing of skin- muscle wounds of agricultural animals. We used the laser radiation of low intensity for cub's therapy: to sucking-pigs after herniotomy and castration, to cattle cubs after skin- muscle wounds. The animals were kept under clinical observation up to their recovery. The recuperation dynamic was observed by changing of blood quotients, leukograms, sizes of inflammatory edema, general behavior of animals. The positive dynamic of blood quotients of the experimental animal groups was really higher than that in control. The analysis of wound healing after laser influence shows that wound surface of experimental group was to a great extent smaller in comparison with control group of animals. So, these facts testify about anti-inflammatory action of laser radiation, which hastens regenerative and rehabilitative processes. Analysis of the obtained experimental data has revealed the positive influence of laser irradiation on the dynamics of wound adhesion of agricultural animals.

Influence of acidic pH on keratinocyte function and re-epithelialisation of human in vitro wounds.

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Lönnqvist, Susanna; Emanuelsson, Peter; Kratz, Gunnar

2015-01-01

Chronic wounds are one of the greatest challenges for the healthcare system. Today, a plethora of dressings are used in the treatment of these wounds, each with specific influence on the wound environment. Due to differences in the permeability of the dressings the use will result in differences in the pH balance in the wound bed. However, little is known about how changes in the pH in the wound environment affect the different phases of the healing process. The aim of the present study was to investigate the effects of acidic pH on the regeneration phase by studying keratinocyte function in vitro and re-epithelialisation in an in vitro model of human skin. In vitro assays showed reduced viability and migration rates in human keratinocytes when pH was lowered. Real time PCR revealed differential expression of genes related to wound healing and environmental impairment. Tissue culture showed no re-epithelialisation of wounds subjected to pH 5.0 and moderate re-epithelialisation at pH 6.0, compared to controls at pH 7.4. The results indicate that lowering pH down to pH 5.0 in wounds is counterproductive in aspect of keratinocyte function which is crucial for successful wound healing.

Current overview on challenges in regenerative endodontics

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Bansal, Ramta; Jain, Aditya; Mittal, Sunandan

2015-01-01

Introduction: Regenerative endodontics provides hope of converting the non-vital tooth into vital once again. It focuses on substituting traumatized and pathological pulp with functional pulp tissue. Current regenerative procedures successfully produce root development but still fail to re-establish real pulp tissue and give unpredictable results. There are several drawbacks that need to be addressed to improve the quality and efficiency of the treatment. Aim: The aim of this review article is to discuss major priorities that ought to be dealt before applications of regenerative endodontics flourish the clinical practice. Materials and Methods: A web-based research on MEDLINE was done using filter terms Review, published in the last 10 years and Dental journals. Keywords used for research were “regenerative endodontics,” “dental stem cells,” “growth factor regeneration,” “scaffolds,” and “challenges in regeneration.” This review article screened about 150 articles and then the relevant information was compiled. Results: Inspite of the impressive growth in regenerative endodontic field, there are certain loopholes in the existing treatment protocols that might sometimes result in undesired and unpredictable outcomes. Conclusion: Considerable research and development efforts are required to improve and update existing regenerative endodontic strategies to make it an effective, safe, and biological mode to save teeth. PMID:25657518

Regenerative Medicine Build-Out

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Pfenning, Michael A.; Gores, Gregory J.; Harper, C. Michel

2015-01-01

Summary Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Significance Regenerative medicine is at the

Regenerative Medicine Build-Out.

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Terzic, Andre; Pfenning, Michael A; Gores, Gregory J; Harper, C Michel

2015-12-01

Regenerative technologies strive to boost innate repair processes and restitute normative impact. Deployment of regenerative principles into practice is poised to usher in a new era in health care, driving radical innovation in patient management to address the needs of an aging population challenged by escalating chronic diseases. There is urgency to design, execute, and validate viable paradigms for translating and implementing the science of regenerative medicine into tangible health benefits that provide value to stakeholders. A regenerative medicine model of care would entail scalable production and standardized application of clinical grade biotherapies supported by comprehensive supply chain capabilities that integrate sourcing and manufacturing with care delivery. Mayo Clinic has rolled out a blueprint for discovery, translation, and application of regenerative medicine therapies for accelerated adoption into the standard of care. To establish regenerative medical and surgical service lines, the Mayo Clinic model incorporates patient access, enabling platforms and delivery. Access is coordinated through a designated portal, the Regenerative Medicine Consult Service, serving to facilitate patient/provider education, procurement of biomaterials, referral to specialty services, and/or regenerative interventions, often in clinical trials. Platforms include the Regenerative Medicine Biotrust and Good Manufacturing Practice facilities for manufacture of clinical grade products for cell-based, acellular, and/or biomaterial applications. Care delivery leverages dedicated interventional suites for provision of regenerative services. Performance is tracked using a scorecard system to inform decision making. The Mayo Clinic roadmap exemplifies an integrated organization in the discovery, development, and delivery of regenerative medicine within a growing community of practice at the core of modern health care. Regenerative medicine is at the vanguard of health care

Natural and synthetic polymers for wounds and burns dressing.

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Mogoşanu, George Dan; Grumezescu, Alexandru Mihai

2014-03-25

In the last years, health care professionals faced with an increasing number of patients suffering from wounds and burns difficult to treat and heal. During the wound healing process, the dressing protects the injury and contributes to the recovery of dermal and epidermal tissues. Because their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body, some natural polymers such as polysaccharides (alginates, chitin, chitosan, heparin, chondroitin), proteoglycans and proteins (collagen, gelatin, fibrin, keratin, silk fibroin, eggshell membrane) are extensively used in wounds and burns management. Obtained by electrospinning technique, some synthetic polymers like biomimetic extracellular matrix micro/nanoscale fibers based on polyglycolic acid, polylactic acid, polyacrylic acid, poly-ɛ-caprolactone, polyvinylpyrrolidone, polyvinyl alcohol, polyethylene glycol, exhibit in vivo and in vitro wound healing properties and enhance re-epithelialization. They provide an optimal microenvironment for cell proliferation, migration and differentiation, due to their biocompatibility, biodegradability, peculiar structure and good mechanical properties. Thus, synthetic polymers are used also in regenerative medicine for cartilage, bone, vascular, nerve and ligament repair and restoration. Biocompatible with fibroblasts and keratinocytes, tissue engineered skin is indicated for regeneration and remodeling of human epidermis and wound healing improving the treatment of severe skin defects or partial-thickness burn injuries. Copyright © 2013 Elsevier B.V. All rights reserved.

Mechanical cues in orofacial tissue engineering and regenerative medicine.

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Brouwer, Katrien M; Lundvig, Ditte M S; Middelkoop, Esther; Wagener, Frank A D T G; Von den Hoff, Johannes W

2015-01-01

Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues. © 2015 by the Wound Healing Society.

INFLUENCE OF LOCAL RONKOLEIKIN TREATMENT UPON CLINICAL COURSE OF PURULENT WOUNDS AND FUNCTIONAL ACTIVITY OF WOUND PHAGOCYTES IN PATIENTS WITH ODONTOGENIC PHLEGMONAE

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I. I. Dolgushin

2009-01-01

Full Text Available Abstract. The aim of the work was to evaluate clinical features of purulent wounds trend and functional activity of local wound phagocytes in the patients with odontogenic phlegmones in the course of local treatment with Ronkoleukin. A randomized clinical study was performed which included sixty-five patients with odontogenic phlegmones. Their age ranged from 18 to 74 years old. The group was divided in two parts, i.e., patients of a comparison group (n = 33 receiving a conventional combined drug therapy, and the persons from study group (n = 32 who were subject to local immunotherapy with Ronkoleukin, applied along with conventional therapy. It was established that the local therapy with Ronkoleikin exerts distinct positive effects, i.e., increase in wound-located lymphocytes and macrophages, acceleration of phasic dynamics of inflammatory events, augmentation of an lysosomal luminescence index (2.3-fold, enhancement of phagocytosis intensity in wound neutrophiles and macrophages (1.9-2-fold, strengthening the reserve abilities of wound neutrophils (1.3-fold. These effects create favorable conditions for elimination of pathogen and optimal healing of purulent wounds in the patients with odontogenic phlegmones.

The Double-Edged Sword: Conserved Functions of Extracellular Hsp90 in Wound Healing and Cancer

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Hance, Michael W.; Nolan, Krystal D.; Isaacs, Jennifer S., E-mail: isaacsj@musc.edu [Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC 29412 (United States)

2014-05-06

Heat shock proteins (Hsps) represent a diverse group of chaperones that play a vital role in the protection of cells against numerous environmental stresses. Although our understanding of chaperone biology has deepened over the last decade, the “atypical” extracellular functions of Hsps have remained somewhat enigmatic and comparatively understudied. The heat shock protein 90 (Hsp90) chaperone is a prototypic model for an Hsp family member exhibiting a duality of intracellular and extracellular functions. Intracellular Hsp90 is best known as a master regulator of protein folding. Cancers are particularly adept at exploiting this function of Hsp90, providing the impetus for the robust clinical development of small molecule Hsp90 inhibitors. However, in addition to its maintenance of protein homeostasis, Hsp90 has also been identified as an extracellular protein. Although early reports ascribed immunoregulatory functions to extracellular Hsp90 (eHsp90), recent studies have illuminated expanded functions for eHsp90 in wound healing and cancer. While the intended physiological role of eHsp90 remains enigmatic, its evolutionarily conserved functions in wound healing are easily co-opted during malignancy, a pathology sharing many properties of wounded tissue. This review will highlight the emerging functions of eHsp90 and shed light on its seemingly dichotomous roles as a benevolent facilitator of wound healing and as a sinister effector of tumor progression.

Platelet-Rich Fibrin and Soft Tissue Wound Healing: A Systematic Review.

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Miron, Richard J; Fujioka-Kobayashi, Masako; Bishara, Mark; Zhang, Yufeng; Hernandez, Maria; Choukroun, Joseph

2017-02-01

The growing multidisciplinary field of tissue engineering aims at predictably regenerating, enhancing, or replacing damaged or missing tissues for a variety of conditions caused by trauma, disease, and old age. One area of research that has gained tremendous awareness in recent years is that of platelet-rich fibrin (PRF), which has been utilized across a wide variety of medical fields for the regeneration of soft tissues. This systematic review gathered all the currently available in vitro, in vivo, and clinical literature utilizing PRF for soft tissue regeneration, augmentation, and/or wound healing. In total, 164 publications met the original search criteria, with a total of 48 publications meeting inclusion criteria (kappa score = 94%). These studies were divided into 7 in vitro, 11 in vivo, and 31 clinical studies. In summary, 6 out of 7 (85.7%) and 11 out of 11 (100%) of the in vitro and in vivo studies, respectively, demonstrated a statistically significant advantage for combining PRF to their regenerative therapies. Out of the remaining 31 clinical studies, a total of 8 reported the effects of PRF in a randomized clinical trial, with 5 additional studies (13 total) reporting appropriate controls. In those clinical studies, 9 out of the 13 studies (69.2%) demonstrated a statistically relevant positive outcome for the primary endpoints measured. In total, 18 studies (58% of clinical studies) reported positive wound-healing events associated with the use of PRF, despite using controls. Furthermore, 27 of the 31 clinical studies (87%) supported the use of PRF for soft tissue regeneration and wound healing for a variety of procedures in medicine and dentistry. In conclusion, the results from the present systematic review highlight the positive effects of PRF on wound healing after regenerative therapy for the management of various soft tissue defects found in medicine and dentistry.

Regenerative Rehabilitation: Combining Stem Cell Therapies and Activity-Dependent Stimulation.

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Moritz, Chet T; Ambrosio, Fabrisia

2017-07-01

The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery. The potential clinical benefits of regenerative rehabilitation will likely become a critical aspect in the standard of care for many neurological and musculoskeletal disorders.

Stem cells and chronic wound healing: state of the art

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Leavitt T

2016-03-01

Full Text Available Tripp Leavitt, Michael S Hu, Clement D Marshall, Leandra A Barnes, Michael T Longaker, H Peter Lorenz Hagey Laboratory for Pediatric Regenerative Medicine, Division of Plastic Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA Abstract: Currently available treatments for chronic wounds are inadequate. A clearly effective therapy does not exist, and treatment is often supportive. This is largely because the cellular and molecular processes underlying failure of wound repair are still poorly understood. With an increase in comorbidities, such as diabetes and vascular disease, as well as an aging population, the incidence of these intractable wounds is expected to rise. As such, chronic wounds, which are already costly, are rapidly growing as a tremendous burden to the health-care system. Stem cells have garnered much interest as a therapy for chronic wounds due to their inherent ability to differentiate into multiple lineages and promote regeneration. Herein, we discuss the types of stem cells used for chronic wound therapy, as well as the proposed means by which they do so. In particular, we highlight mesenchymal stem cells (including adipose-derived stem cells, endothelial progenitor cells, and induced pluripotent stem cells. We include the results of recent in vitro and in vivo studies in both animal models and human clinical trials. Finally, we discuss the current studies to improve stem cell therapies and the limitations of stem cell-based therapeutics. Stem cells promise improved therapies for healing chronic wounds, but further studies that are well-designed with standardized protocols are necessary for fruition. Keywords: stem cells, chronic wounds, cell therapy, wound healing

Bioinspired porous membranes containing polymer nanoparticles for wound healing.

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Ferreira, Ana M; Mattu, Clara; Ranzato, Elia; Ciardelli, Gianluca

2014-12-01

Skin damages covering a surface larger than 4 cm(2) require a regenerative strategy based on the use of appropriate wound dressing supports to facilitate the rapid tissue replacement and efficient self-healing of the lost or damaged tissue. In the present work, A novel biomimetic approach is proposed for the design of a therapeutic porous construct made of poly(L-lactic acid) (PLLA) fabricated by thermally induced phase separation (TIPS). Biomimicry of ECM was achieved by immobilization of type I collagen through a two-step plasma treatment for wound healing. Anti-inflammatory (indomethacin)-containing polymeric nanoparticles (nps) were loaded within the porous membranes in order to minimize undesired cell response caused by post-operative inflammation. The biological response to the scaffold was analyzed by using human keratinocytes cell cultures. In this work, a promising biomimetic construct for wound healing and soft tissue regeneration with drug-release properties was fabricated since it shows (i) proper porosity, pore size, and mechanical properties, (ii) biomimicry of ECM, and (iii) therapeutic potential. © 2014 Wiley Periodicals, Inc.

Influence of hydrophilic polymers on functional properties and wound healing efficacy of hydrocolloid based wound dressings.

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Jin, Sung Giu; Yousaf, Abid Mehmood; Kim, Kyeong Soo; Kim, Dong Wuk; Kim, Dong Shik; Kim, Jin Ki; Yong, Chul Soon; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

2016-03-30

The purpose of this study was to investigate the influence of different hydrophilic polymers on the swelling, bioadhesion and mechanical strength of hydrocolloid wound dressings (HCDs) in order to provide an appropriate composition for a hydrocolloid wound dressing system. In this study, the HCDs were prepared with styrene-isoprene-styrene copolymer (SIS) and polyisobutylene (PIB) as the base using a hot melting method. Additionally, numerous SIS/PIB-based HCDs were prepared with six hydrophilic polymers, and their wound dressing properties were assessed. Finally, the wound healing efficacy of the selected formulations was compared to a commercial wound dressing. The swelling ratio, bioadhesive force and mechanical strengths of HCDs were increased in the order of sodium alginate>sodium CMC=poloxamer=HPMC>PVA=PVP, sodium alginate>sodium CMC=poloxamer>PVA>HPMC=PVP and sodium alginate≥PVA>PVP=HPMC=sodium CMC>poloxamer, respectively. Among the hydrophilic polymers tested, sodium alginate most enhanced the swelling capacity, bioadhesive force and mechanical strengths. Thus, the hydrophilic polymers played great role in the swelling, bioadhesion and mechanical strength of SIS/PIB-based HCDs. The HCD formulation composed of PIB, SIS, liquid paraffin and sodium alginate at the weight ratio of 20/25/12/43 gave better wound dressing properties and more excellent wound healing efficacy than the commercial wound dressing. Therefore, the novel HCD formulation could be a promising hydrocolloid system for wound dressings. Copyright © 2016 Elsevier B.V. All rights reserved.

Preventive and Regenerative Foam Rolling are Equally Effective in Reducing Fatigue-Related Impairments of Muscle Function following Exercise

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Johannes Fleckenstein, Jan Wilke, Lutz Vogt, Winfried Banzer

2017-12-01

Full Text Available Objectives of the study were to compare the effects of a single bout of preventive or regenerative foam rolling (FR on exercise-induced neuromuscular exhaustion. Single-centre randomised-controlled study was designed. Forty-five healthy adults (22 female; 25±2 yrs were allocated to three groups: 1 FR of the lower limb muscles prior to induction of fatigue, 2 FR after induction of fatigue, 3 no-treatment control. Neuromuscular exhaustion was provoked using a standardized and validated functional agility short-term fatigue protocol. Main outcome measure was the maximal isometric voluntary force of the knee extensors (MIVF. Secondary outcomes included pain and reactive strength (RSI. Preventive (-16% and regenerative FR (-12% resulted in a decreased loss in MIVF compared to control (-21%; p 0.8, p < 0.1. Differences over time (p < 0.001 between groups regarding pain and RSI did not turn out to be clinically meaningful. A single bout of foam rolling reduces neuromuscular exhaustion with reference to maximal force production. Regenerative rather than preventive foam rolling seems sufficient to prevent further fatigue.

Thyrotropin-releasing hormone (TRH promotes wound re-epithelialisation in frog and human skin.

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Natalia T Meier

Full Text Available There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression. Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters.

Thyrotropin-Releasing Hormone (TRH) Promotes Wound Re-Epithelialisation in Frog and Human Skin

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Zhang, Guo-You; Emelianov, Vladimir; Paredes, Roberto; Debus, Sebastian; Augustin, Matthias; Funk, Wolfgang; Amaya, Enrique; Kloepper, Jennifer E.; Hardman, Matthew J.; Paus, Ralf

2013-01-01

There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters. PMID:24023889

Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

International Nuclear Information System (INIS)

Ribeiro, M.P.; Morgado, P.I.; Miguel, S.P.; Coutinho, P.; Correia, I.J.

2013-01-01

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine. - Highlights: • Evaluation of a hydrogel loaded with microparticles containing growth factors for wound healing • In vitro and in vivo assays were performed to characterize the properties of the skin substitute. • The monitoring of the wound healing process was done by macroscopic and histological analysis

Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

Energy Technology Data Exchange (ETDEWEB)

Ribeiro, M.P. [CICS-UBI, Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã (Portugal); UDI-IPG, Research Unit for Inland Development, Polytechnic Institute of Guarda, Guarda (Portugal); Morgado, P.I.; Miguel, S.P. [CICS-UBI, Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã (Portugal); Coutinho, P. [CICS-UBI, Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã (Portugal); UDI-IPG, Research Unit for Inland Development, Polytechnic Institute of Guarda, Guarda (Portugal); Correia, I.J., E-mail: icorreia@ubi.pt [CICS-UBI, Health Sciences Research Center, Faculty of Health Sciences, University of Beira Interior, Covilhã (Portugal)

2013-07-01

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine. - Highlights: • Evaluation of a hydrogel loaded with microparticles containing growth factors for wound healing • In vitro and in vivo assays were performed to characterize the properties of the skin substitute. • The monitoring of the wound healing process was done by macroscopic and histological analysis.

Multidisciplinary approaches to stimulate wound healing.

Science.gov (United States)

Businaro, Rita; Corsi, Mariangela; Di Raimo, Tania; Marasco, Sergio; Laskin, Debra L; Salvati, Bruno; Capoano, Raffaele; Ricci, Serafino; Siciliano, Camilla; Frati, Giacomo; De Falco, Elena

2016-08-01

New civil wars and waves of terrorism are causing crucial social changes, with consequences in all fields, including health care. In particular, skin injuries are evolving as an epidemic issue. From a physiological standpoint, although wound repair takes place more rapidly in the skin than in other tissues, it is still a complex organ to reconstruct. Genetic and clinical variables, such as diabetes, smoking, and inflammatory/immunological pathologies, are also important risk factors limiting the regenerative potential of many therapeutic applications. Therefore, optimization of current clinical strategies is critical. Here, we summarize the current state of the field by focusing on stem cell therapy applications in wound healing, with an emphasis on current clinical approaches being developed. These involve protocols for the ex vivo expansion of adipose tissue-derived mesenchymal stem cells by means of a patented Good Manufacturing Practice-compliant platelet lysate. Combinations of multiple strategies, including genetic modifications and stem cells, biomimetic scaffolds, and novel vehicles, such as nanoparticles, are also discussed as future approaches. © 2016 New York Academy of Sciences.

Different wound healing properties of dermis, adipose, and gingiva mesenchymal stromal cells.

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Boink, Mireille A; van den Broek, Lenie J; Roffel, Sanne; Nazmi, Kamran; Bolscher, Jan G M; Gefen, Amit; Veerman, Enno C I; Gibbs, Susan

2016-01-01

Oral wounds heal faster and with better scar quality than skin wounds. Deep skin wounds where adipose tissue is exposed, have a greater risk of forming hypertrophic scars. Differences in wound healing and final scar quality might be related to differences in mesenchymal stromal cells (MSC) and their ability to respond to intrinsic (autocrine) and extrinsic signals, such as human salivary histatin, epidermal growth factor, and transforming growth factor beta1. Dermis-, adipose-, and gingiva-derived MSC were compared for their regenerative potential with regards to proliferation, migration, and matrix contraction. Proliferation was assessed by cell counting and migration using a scratch wound assay. Matrix contraction and alpha smooth muscle actin was assessed in MSC populated collagen gels, and also in skin and gingival full thickness tissue engineered equivalents (reconstructed epithelium on MSC populated matrix). Compared to skin-derived MSC, gingiva MSC showed greater proliferation and migration capacity, and less matrix contraction in full thickness tissue equivalents, which may partly explain the superior oral wound healing. Epidermal keratinocytes were required for enhanced adipose MSC matrix contraction and alpha smooth muscle actin expression, and may therefore contribute to adverse scarring in deep cutaneous wounds. Histatin enhanced migration without influencing proliferation or matrix contraction in all three MSC, indicating that salivary peptides may have a beneficial effect on wound closure in general. Transforming growth factor beta1 enhanced contraction and alpha smooth muscle actin expression in all three MSC types when incorporated into collagen gels. Understanding the mechanisms responsible for the superior oral wound healing will aid us to develop advanced strategies for optimal skin regeneration, wound healing and scar formation. © 2015 by the Wound Healing Society.

LaFePdO3 perovskite automotive catalyst having a self-regenerative function

International Nuclear Information System (INIS)

Tanaka, Hirohisa; Tan, Isao; Uenishi, Mari; Taniguchi, Masashi; Kimura, Mareo; Nishihata, Yasuo; Mizuki, Jun'ichiro

2006-01-01

An automotive gasoline engine is operated close to the stoichiometric air-to-fuel ratio to convert the pollutant emissions simultaneously, accompanying with redox (reduction and oxidation) fluctuations in exhaust-gas composition through adjusting the air-to-fuel ratio. An innovative LaFe 0.95 Pd 0.05 O 3 perovskite catalyst, named 'the intelligent catalyst', has been developed, and which has a new self-regenerative function of the precious metal in the inherent fluctuations of automotive exhaust-gas. The LaFe 0.95 Pd 0.05 O 3 perovskite catalyst, La located at the A-site, was prepared by the alkoxide method. Pd located at the B-site of the perovskite lattice in the oxidative atmosphere, and segregated out to form small metallic particles in the reductive atmosphere. The catalyst retained a predominantly perovskite structure throughout a redox cycle of the exhaust-gas, while the local structure around Pd could be changed in a completely reversible manner. The agglomeration and growth of Pd particles is suppressed, even under the severe environment, as a result of the movement between inside and outside the perovskite lattice. It is revealed that the self-regenerative function of Pd occurs even at 200 deg. C, unexpectedly low temperature, in the LaFe 0.95 Pd 0.05 O 3 catalyst. Since the high catalytic activity is maintained, the great reduction of Pd loading has been achieved. The intelligent catalyst is expected as a new application of the rare earth, and then the technology is expected in the same way in the global standard of the catalyst designing

Fibrin glue as the cell-delivery vehicle for mesenchymal stromal cells in regenerative medicine.

Science.gov (United States)

Wu, Xiuwen; Ren, Jianan; Li, Jieshou

2012-05-01

The use of tissue-engineering techniques such as stem-cell therapy to renew injured tissues is a promising strategy in regenerative medicine. As a cell-delivery vehicle, fibrin glues (FG) facilitate cell attachment, growth and differentiation and, ultimately, tissue formation and organization by its three-dimensional structure. Numerous studies have provided evidence that stromal cells derived from bone marrow (bone marrow stromal cells; BMSC) and adipose tissue (adipose-derived stromal cells; ADSC) contain a population of adult multipotent mesenchymal stromal cells (MSC) and endothelial progenitor cells that can differentiate into several lineages. By combining MSC with FG, the implantation could take advantage of the mutual benefits. Researchers and physicians have pinned their hopes on stem cells for developing novel approaches in regenerative medicine. This review focuses on the therapeutic potential of MSC with FG in bone defect reconstruction, cartilage and tendon injury repair, ligament, heart and nerve regeneration, and, furthermore, wound healing.

Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function

DEFF Research Database (Denmark)

Mirastschijski, Ursula; Schnabel, Reinhild; Claes, Juliane

2010-01-01

applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined......, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP...... and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound...

Regenerative medicine in otorhinolaryngology.

Science.gov (United States)

Wormald, J C R; Fishman, J M; Juniat, S; Tolley, N; Birchall, M A

2015-08-01

Tissue engineering using biocompatible scaffolds, with or without cells, can permit surgeons to restore structure and function following tissue resection or in cases of congenital abnormality. Tracheal regeneration has emerged as a spearhead application of these technologies, whilst regenerative therapies are now being developed to treat most other diseases within otolaryngology. A systematic review of the literature was performed using Ovid Medline and Ovid Embase, from database inception to 15 November 2014. A total of 561 papers matched the search criteria, with 76 fulfilling inclusion criteria. Articles were predominantly pre-clinical animal studies, reflecting the current status of research in this field. Several key human research articles were identified and discussed. The main issues facing research in regenerative surgery are translation of animal model work into human models, increasing stem cell availability so it can be used to further research, and development of better facilities to enable implementation of these advances.

Positive in vitro wound healing effects of functional inclusion bodies of a lipoxygenase from the Mexican axolotl.

Science.gov (United States)

Stamm, Anne; Strauß, Sarah; Vogt, Peter; Scheper, Thomas; Pepelanova, Iliyana

2018-04-07

AmbLOXe is a lipoxygenase, which is up-regulated during limb-redevelopment in the Mexican axolotl, Ambystoma mexicanum, an animal with remarkable regeneration capacity. Previous studies have shown that mammalian cells transformed with the gene of this epidermal lipoxygenase display faster migration and wound closure rate during in vitro wound healing experiments. In this study, the gene of AmbLOXe was codon-optimized for expression in Escherichia coli and was produced in the insoluble fraction as protein aggregates. These inclusion bodies or nanopills were shown to be reservoirs containing functional protein during in vitro wound healing assays. For this purpose, functional inclusion bodies were used to coat cell culture surfaces prior cell seeding or were added directly to the medium after cells reached confluence. In both scenarios, AmbLOXe inclusion bodies led to faster migration rate and wound closure, in comparison to controls containing either no AmbLOXe or GFP inclusion bodies. Our results demonstrate that AmbLOXe inclusion bodies are functional and may serve as stable reservoirs of this enzyme. Nevertheless, further studies with soluble enzyme are also necessary in order to start elucidating the exact molecular substrates of AmbLOXe and the biochemical pathways involved in the wound healing effect.

A Cooperative Copper Metal-Organic Framework-Hydrogel System Improves Wound Healing in Diabetes.

Science.gov (United States)

Xiao, Jisheng; Chen, Siyu; Yi, Ji; Zhang, Hao; Ameer, Guillermo A

2017-01-05

Chronic non-healing wounds remain a major clinical challenge that would benefit from the development of advanced, regenerative dressings that promote wound closure within a clinically relevant time frame. The use of copper ions has shown promise in wound healing applications possibly by promoting angiogenesis. However, reported treatments that use copper ions require multiple applications of copper salts or oxides to the wound bed, exposing the patient to potentially toxic levels of copper ions and resulting in variable outcomes. Herein we set out to assess whether copper metal organic framework nanoparticles (HKUST-1 NPs) embedded within an antioxidant thermoresponsive citrate-based hydrogel would decrease copper ion toxicity and accelerate wound healing in diabetic mice. HKUST-1 and poly-(polyethyleneglycol citrate-co- N -isopropylacrylamide) (PPCN) were synthesized and characterized. HKUST-1 NP stability in a protein solution with and without embedding them in PPCN hydrogel was determined. Copper ion release, cytotoxicity, apoptosis, and in vitro migration processes were measured. Wound closure rates and wound blood perfusion were assessed in vivo using the splinted excisional dermal wound diabetic mouse model. HKUST-1 NP disintegrated in protein solution while HKUST-1 NPs embedded in PPCN (H-HKUST-1) were protected from degradation and copper ions were slowly released. Cytotoxicity and apoptosis due to copper ion release were significantly reduced while dermal cell migration in vitro and wound closure rates in vivo were significantly enhanced. In vivo , H-HKUST-1 induced angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. These results suggest that a cooperatively stabilized, copper ion-releasing H-HKUST-1 hydrogel is a promising innovative dressing for the treatment of chronic wounds.

Stem cell bioprinting for applications in regenerative medicine.

Science.gov (United States)

Tricomi, Brad J; Dias, Andrew D; Corr, David T

2016-11-01

Many regenerative medicine applications seek to harness the biologic power of stem cells in architecturally complex scaffolds or microenvironments. Traditional tissue engineering methods cannot create such intricate structures, nor can they precisely control cellular position or spatial distribution. These limitations have spurred advances in the field of bioprinting, aimed to satisfy these structural and compositional demands. Bioprinting can be defined as the programmed deposition of cells or other biologics, often with accompanying biomaterials. In this concise review, we focus on recent advances in stem cell bioprinting, including performance, utility, and applications in regenerative medicine. More specifically, this review explores the capability of bioprinting to direct stem cell fate, engineer tissue(s), and create functional vascular networks. Furthermore, the unique challenges and concerns related to bioprinting living stem cells, such as viability and maintaining multi- or pluripotency, are discussed. The regenerative capacity of stem cells, when combined with the structural/compositional control afforded by bioprinting, provides a unique and powerful tool to address the complex demands of tissue engineering and regenerative medicine applications. © 2016 New York Academy of Sciences.

Biomechanical Skin Property Evaluation for Wounds Treated With Synthetic and Biosynthetic Wound Dressings and a Newly Developed Collagen Matrix During Healing of Superficial Skin Defects in a Rat Models.

Science.gov (United States)

Held, Manuel; Engelke, Anne-Sophie; Tolzmann, Dascha Sophie; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Rothenberger, Jens

2016-09-01

There is a high prevalence of superficial wounds such as partial-thickness burns. Treatment of these wounds frequently includes temporary application of wound dressings. The aim of this study was to compare a newly developed collagen matrix with commonly used temporary skin dressings for treatment of partial-thickness skin defects. Through a skin dermatome, 42 standardized superficial skin defects were generated on the back of 28 adult male Lewis rats. The wounds were treated with a synthetic wound dressing (Suprathel, Polymedics Innovations Inc, Woodstock, GA) (n = 14), a biosynthetic skin dressing (Biobrane, Smith & Nephew, Hull, UK) (n = 14), or a newly developed bovine collagen matrix, Collagen Cell Carrier (Viscofan BioEngineering, Weinheim, Germany) (n = 14). Biomechanical properties of the skin were determined and compared every 10 days over a 3-month period of using the Cutometer MPA 580 (Courage + Khazaka Electronic GmbH, Cologne, Germany). As opposed to healthy skin, statistically significant differences were detected between days 10 and 30, and between days 60 and 80, for calculated elasticity (Ue), firmness of skin (R0), and overall elasticity (R8). After 3 months, no statistically significant differences in skin elasticity were detected between the different wound dressings. The presented results give an opportunity to compare the wound dressings used for treatment with respect to skin elasticity and reveal the potential of the bovine collagen matrix in the treatment of superficial skin defects; therefore the results facilitate further evaluation of collagen matrix in surgical applications and regenerative medicine.

Regenerative Engineering and Bionic Limbs.

Science.gov (United States)

James, Roshan; Laurencin, Cato T

2015-03-01

Amputations of the upper extremity are severely debilitating, current treatments support very basic limb movement, and patients undergo extensive physiotherapy and psychological counselling. There is no prosthesis that allows the amputees near-normal function. With increasing number of amputees due to injuries sustained in accidents, natural calamities and international conflicts, there is a growing requirement for novel strategies and new discoveries. Advances have been made in technological, material and in prosthesis integration where researchers are now exploring artificial prosthesis that integrate with the residual tissues and function based on signal impulses received from the residual nerves. Efforts are focused on challenging experts in different disciplines to integrate ideas and technologies to allow for the regeneration of injured tissues, recording on tissue signals and feed-back to facilitate responsive movements and gradations of muscle force. A fully functional replacement and regenerative or integrated prosthesis will rely on interface of biological process with robotic systems to allow individual control of movement such as at the elbow, forearm, digits and thumb in the upper extremity. Regenerative engineering focused on the regeneration of complex tissue and organ systems will be realized by the cross-fertilization of advances over the past thirty years in the fields of tissue engineering, nanotechnology, stem cell science, and developmental biology. The convergence of toolboxes crated within each discipline will allow interdisciplinary teams from engineering, science, and medicine to realize new strategies, mergers of disparate technologies, such as biophysics, smart bionics, and the healing power of the mind. Tackling the clinical challenges, interfacing the biological process with bionic technologies, engineering biological control of the electronic systems, and feed-back will be the important goals in regenerative engineering over the next

Skin wound healing in different aged Xenopus laevis.

Science.gov (United States)

Bertolotti, Evelina; Malagoli, Davide; Franchini, Antonella

2013-08-01

Xenopus froglets can perfectly heal skin wounds without scarring. To explore whether this capacity is maintained as development proceeds, we examined the cellular responses during the repair of skin injury in 8- and 15-month-old Xenopus laevis. The morphology and sequence of healing phases (i.e., inflammation, new tissue formation, and remodeling) were independent of age, while the timing was delayed in older frogs. At the beginning of postinjury, wound re-epithelialization occurred in form of a thin epithelium followed by a multilayered epidermis containing cells with apoptotic patterns and keratinocytes stained by anti-inducible nitric oxide synthase (iNOS) antibody. The inflammatory response, early activated by recruitment of blood cells immunoreactive to anti-tumor necrosis factor (TNF)-α, iNOS, transforming growth factor (TGF)-β1, and matrix metalloproteinase (MMP)-9, persisted over time. The dermis repaired by a granulation tissue with extensive angiogenesis, inflammatory cells, fibroblasts, and anti-α-SMA positive myofibroblasts. As the healing progressed, wounded areas displayed vascular regression, decrease in cellularity, and rearrangement of provisional matrix. The epidermis restored to a prewound morphology while granulation tissue was replaced by a fibrous tissue in a scar-like pattern. The quantitative PCR analysis demonstrated an up-regulated expression of Xenopus suppressor of cytokine signaling 3 (XSOCS-3) and Xenopus transforming growth factor-β2 (XTGF-β2) soon after wounding and peak levels were detected when granulation tissue was well developed with a large number of inflammatory cells. The findings indicate that X. laevis skin wound healing occurred by a combination of regeneration (in epidermis) and repair (in dermis) and, in contrast to froglet scarless wound healing, the growth to a more mature adult stage is associated with a decrease in regenerative capacity with scar-like tissue formation. Copyright © 2013 Wiley Periodicals, Inc.

Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer.

Science.gov (United States)

Ge, Yejing; Fuchs, Elaine

2018-05-01

Stem cells (SCs) govern tissue homeostasis and wound repair. They reside within niches, the special microenvironments within tissues that control SC lineage outputs. Upon injury or stress, new signals emanating from damaged tissue can divert nearby cells into adopting behaviours that are not part of their homeostatic repertoire. This behaviour, known as SC plasticity, typically resolves as wounds heal. However, in cancer, it can endure. Recent studies have yielded insights into the orchestrators of maintenance and lineage commitment for SCs belonging to three mammalian tissues: the haematopoietic system, the skin epithelium and the intestinal epithelium. We delineate the multifactorial determinants and general principles underlying the remarkable facets of SC plasticity, which lend promise for regenerative medicine and cancer therapeutics.

Regenerative medicine: looking backward 10 years further on.

Science.gov (United States)

Kemp, Paul

2016-12-01

The last decade has seen considerable changes in the Regenerative Medicine industry, but unfortunately the hope for numerous treatments that 'replace or regenerate human cells, tissues or organs to restore or establish normal function' has not yet emerged. In contrast to this, there have been major advances in the field of cellular immunotherapy though some do not consider these to be Regenerative Medicines. Regulatory changes have in some cases improved the route to a marketing license but they have not been matched by clarification of the complex, national reimbursement processes for cell-based treatments and this has adversely affected a number of leading Regenerative Medicine Companies. The review considers the direction that the industry may go in the future in relation to scientific, manufacturing and clinical strategies which may improve the rate of success of new therapies..

Functional electrospun fibers for the treatment of human skin wounds.

Science.gov (United States)

Wang, Jing; Windbergs, Maike

2017-10-01

Wounds are trauma induced defects of the human skin involving a multitude of endogenous biochemical events and cellular reactions of the immune system. The healing process is extremely complex and affected by the patient's physiological conditions, potential implications like infectious pathogens and inflammation as well as external factors. Due to increasing incidence of chronic wounds and proceeding resistance of infection pathogens, there is a strong need for effective therapeutic wound care. In this context, electrospun fibers with diameters in the nano- to micrometer range gain increasing interest. While resembling the structure of the native human extracellular matrix, such fiber mats provide physical and mechanical protection (including protection against bacterial invasion). At the same time, the fibers allow for gas exchange and prevent occlusion of the wound bed, thus facilitating wound healing. In addition, drugs can be incorporated within such fiber mats and their release can be adjusted by the material and dimensions of the individual fibers. The review gives a comprehensive overview about the current state of electrospun fibers for therapeutic application on skin wounds. Different materials as well as fabrication techniques are introduced including approaches for incorporation of drugs into or drug attachment onto the fiber surface. Against the background of wound pathophysiology and established therapy approaches, the therapeutic potential of electrospun fiber systems is discussed. A specific focus is set on interactions of fibers with skin cells/tissues as well as wound pathogens and strategies to modify and control them as key aspects for developing effective wound therapeutics. Further, advantages and limitations of controlled drug delivery from fiber mats to skin wounds are discussed and a future perspective is provided. Copyright © 2017 Elsevier B.V. All rights reserved.

Chitosan Dermal Substitute and Chitosan Skin Substitute Contribute to Accelerated Full-Thickness Wound Healing in Irradiated Rats

Directory of Open Access Journals (Sweden)

Abu Bakar Mohd Hilmi

2013-01-01

Full Text Available Wounds with full-thickness skin loss are commonly managed by skin grafting. In the absence of a graft, reepithelialization is imperfect and leads to increased scar formation. Biomaterials can alter wound healing so that it produces more regenerative tissue and fewer scars. This current study use the new chitosan based biomaterial in full-thickness wound with impaired healing on rat model. Wounds were evaluated after being treated with a chitosan dermal substitute, a chitosan skin substitute, or duoderm CGF. Wounds treated with the chitosan skin substitute showed the most re-epithelialization (33.2 ± 2.8%, longest epithelial tongue (1.62 ± 0.13 mm, and shortest migratory tongue distance (7.11 ± 0.25 mm. The scar size of wounds treated with the chitosan dermal substitute (0.13 ± 0.02 cm and chitosan skin substitute (0.16 ± 0.05 cm were significantly decreased (P<0.05 compared with duoderm (0.45 ± 0.11 cm. Human leukocyte antigen (HLA expression on days 7, 14, and 21 revealed the presence of human hair follicle stem cells and fibroblasts that were incorporated into and surviving in the irradiated wound. We have proven that a chitosan dermal substitute and chitosan skin substitute are suitable for wound healing in full-thickness wounds that are impaired due to radiation.

Phenotypic Screening Identifies Synergistically Acting Natural Product Enhancing the Performance of Biomaterial Based Wound Healing

Directory of Open Access Journals (Sweden)

Srinivasan Sivasubramanian

2017-07-01

Full Text Available The potential of multifunctional wound heal biomaterial relies on the optimal content of therapeutic constituents as well as the desirable physical, chemical, and biological properties to accelerate the healing process. Formulating biomaterials such as amnion or collagen based scaffolds with natural products offer an affordable strategy to develop dressing material with high efficiency in healing wounds. Using image based phenotyping and quantification, we screened natural product derived bioactive compounds for modulators of types I and III collagen production from human foreskin derived fibroblast cells. The identified hit was then formulated with amnion to develop a biomaterial, and its biophysical properties, in vitro and in vivo effects were characterized. In addition, we performed functional profiling analyses by PCR array to understand the effect of individual components of these materials on various genes such as inflammatory mediators including chemokines and cytokines, growth factors, fibroblast stimulating markers for collagen secretion, matrix metalloproteinases, etc., associated with wound healing. FACS based cell cycle analyses were carried out to evaluate the potential of biomaterials for induction of proliferation of fibroblasts. Western blot analyses was done to examine the effect of biomaterial on collagen synthesis by cells and compared to cells grown in the presence of growth factors. This work demonstrated an uncomplicated way of identifying components that synergistically promote healing. Besides, we demonstrated that modulating local wound environment using biomaterials with bioactive compounds could enhance healing. This study finds that the developed biomaterials offer immense scope for healing wounds by means of their skin regenerative features such as anti-inflammatory, fibroblast stimulation for collagen secretion as well as inhibition of enzymes and markers impeding the healing, hydrodynamic properties complemented

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

OpenAIRE

Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

2016-01-01

Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for bu...

Regenerative similariton laser

Directory of Open Access Journals (Sweden)

Thibault North

2016-05-01

Full Text Available Self-pulsating lasers based on cascaded reshaping and reamplification (2R are capable of initiating ultrashort pulses despite the accumulation of large amounts of nonlinearities in all-fiber resonators. The spectral properties of pulses in self-similar propagation are compatible with cascaded 2R regeneration by offset filtering, making parabolic pulses suitable for the design of a laser of this recently introduced class. A new type of regenerative laser giving birth to similaritons is numerically investigated and shows that this laser is the analog of regenerative sources based solely on self-phase modulation and offset filtering. The regenerative similariton laser does not suffer from instabilities due to excessive nonlinearities and enables ultrashort pulse generation in a simple cavity configuration.

Response of human limbal epithelial cells to wounding on 3D RAFT tissue equivalents: effect of airlifting and human limbal fibroblasts.

Science.gov (United States)

Massie, Isobel; Levis, Hannah J; Daniels, Julie T

2014-10-01

Limbal epithelial stem cell deficiency can cause blindness but may be treated by human limbal epithelial cell (hLE) transplantation, normally on human amniotic membrane. Clinical outcomes using amnion can be unreliable and so we have developed an alternative tissue equivalent (TE), RAFT (Real Architecture for 3D Tissue), which supports hLE expansion, and stratification when airlifted. Human limbal fibroblasts (hLF) may be incorporated into RAFT TEs, where they support overlying hLE and improve phenotype. However, the impact of neither airlifting nor hLF on hLE function has been investigated. hLE on RAFT TEs (±hLF and airlifting) were wounded using heptanol and re-epithelialisation (fluorescein diacetate staining), and percentage putative stem cell marker p63α and proliferative marker Ki67 expression (wholemount immunohistochemistry), measured. Airlifted, hLF- RAFT TEs were unable to close the wound and p63α expression was 7 ± 0.2% after wounding. Conversely, non-airlifted, hLF- RAFT TEs closed the wound within 9 days and p63α expression was higher at 22 ± 5% (p < 0.01). hLE on both hLF- and hLF+ RAFT TEs (non-airlifted) closed the wound and p63α expression was 26 ± 8% and 36 ± 3% respectively (ns). Ki67 expression by hLE increased from 1.3 ± 0.5% before wounding to 7.89 ± 2.53% post-wounding for hLF- RAFT TEs (p < 0.01), and 0.8 ± 0.08% to 17.68 ± 10.88% for hLF+ RAFT TEs (p < 0.05), suggesting that re-epithelialisation was a result of proliferation. These data suggest that neither airlifting nor hLF are necessarily required to maintain a functional epithelium on RAFT TEs, thus simplifying and shortening the production process. This is important when working towards clinical application of regenerative medicine products. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparative study of regenerative effects of mesenchymal stem cells derived from placental amnion, chorion and umbilical cord on dermal wounds.

Science.gov (United States)

Ertl, Juliane; Pichlsberger, Melanie; Tuca, Alexandru-Cristian; Wurzer, Paul; Fuchs, Jakob; Geyer, Stefan H; Maurer-Gesek, Barbara; Weninger, Wolfgang J; Pfeiffer, Dagmar; Bubalo, Vladimir; Parvizi, Daryousch; Kamolz, Lars-Peter; Lang, Ingrid

2018-05-01

Mesenchymal stem/stromal cells derived from human term placentas (PMSCs) are novel therapeutic agents and more topical than ever. Here we evaluated the effects of three types of PMSCs on wound healing in an in vivo mouse model: Amnion-derived MSCs (AMSCs), blood vessel-derived MSCs (BV-MSCs) from the chorionic plate and Wharton's jelly-derived MSCs (WJ-MSCs) from the umbilical cord. We topically applied PMSCs onto skin wounds in mice using the dermal substitute Matriderm ® as carrier and evaluated wound healing parameters. In addition, we investigated the effects of all PMSC types under co-application with placental endothelial cells (PLECs). After 8 days, we compared the percent of wound closure and the angiogenic potential between all groups. AMSCs, BV-MSCs and WJ-MSCs significantly induced a faster healing and a higher number of blood vessels in the wound when compared to controls (Matriderm ® -alone). PLECs did not further improve the advantageous effects of PMSC-treatment. Quantitative data and 3D analysis by high resolution episcopic microscopy confirmed a lower density of vessels in Matriderm ® /PMSCs/PLECs co-application compared to Matriderm ® /PMSCs treatment. Results indicate that all three PMSC types exert similar beneficial effects on wound closure and neovascularization in our mouse model. Using Matriderm ® as carrier for PMSCs propagates rapid cell migration towards the wound area that allows a fast and clinically practicable method for stem cell application. These promising effects warrant further investigation in clinical trials. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Determinants of midterm functional outcomes, wound healing, and resources used in a hospital-based limb preservation program.

Science.gov (United States)

Ramanan, Bala; Ahmed, Ayman; Wu, Bian; Causey, Marlin W; Gasper, Warren J; Vartanian, Shant M; Reyzelman, Alexander M; Hiramoto, Jade S; Conte, Michael S

2017-12-01

The objective of this study was to assess midterm functional status, wound healing, and in-hospital resource use among a prospective cohort of patients treated in a tertiary hospital, multidisciplinary Center for Limb Preservation. Data were prospectively gathered on all consecutive admissions to the Center for Limb Preservation from July 2013 to October 2014 with follow-up data collection through January 2016. Limbs were staged using the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) threatened limb classification scheme at the time of hospital admission. Patients with nonatherosclerotic vascular disorders, acute limb ischemia, and trauma were excluded. The cohort included 128 patients with 157 threatened limbs; 8 limbs with unstageable disease were excluded. Mean age (±standard deviation [SD]) was 66 (±13) years, and median follow-up duration (interquartile range) was 395 (80-635) days. Fifty percent (n = 64/128) of patients were readmitted at least once, with a readmission rate of 20% within 30 days of the index admission. Mean total number of admissions per patient (±SD) was 1.9 ± 1.2, with mean (±SD) cumulative length of stay (cLOS) of 17.1 (±17.9) days. During follow-up, 25% of limbs required a vascular reintervention, and 45% developed recurrent wounds. There was no difference in the rate of readmission, vascular reintervention, or wound recurrence by initial WIfI stage (P > .05). At the end of the study period, 23 (26%) were alive and nonambulatory; in 20%, functional status was missing. On both univariate and multivariate analysis, end-stage renal disease and prior functional status predicted ability to ambulate independently (P wound healing. Direct hospital (inpatient) cost per limb saved was significantly higher in stage 4 patients (P wound healing, or wound recurrence. Patients presenting with limb-threatening conditions require significant inpatient care, have a high frequency of repeated hospitalizations, and are at

Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

Science.gov (United States)

Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

2015-01-01

Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Role of Stem Cell Therapeutics in Wound Healing: Current Understanding and Future Directions.

Science.gov (United States)

Sorice, Sarah; Rustad, Kristine C; Li, Alexander Y; Gurtner, Geoffrey C

2016-09-01

Chronic wounds present unique challenges for healthcare providers as they place patients at increased risk for various morbidities and mortality. Advances in wound care technology have expanded the treatment options available for wound management, but few products fully address the underlying core deficiencies responsible for the development of poorly healing wounds. In the future, addressing these derangements will undoubtedly play a key role in the treatment of these patients. Broad enthusiasm has surrounded the field of stem cell biology, which has shown great promise in repairing damaged tissues across numerous disease phenotypes. In this review, we provide a comprehensive review of the literature and evaluate the present landscape of wound therapeutics while discussing the rationales and allure behind stem cell-based products. We further propose 2 challenges that remain as new stem cell-based therapies are being developed and as this technology moves toward clinical translation. Given the relatively young age of this newer technology in wound healing, numerous challenges continue to surround its effective use including identifying the ideal population of stem cells to use and determining the optimal cell delivery method. However, significant forward progress has been made, with several clinical trials beginning to demonstrate reliable clinical benefit. The upward trajectory of stem cell technologies provides an exciting opportunity to positively impact patient outcomes through the controlled application of regenerative cell-based therapy.

Biological Activity of Propolis-Honey Balm in the Treatment of Experimentally-Evoked Burn Wounds

Directory of Open Access Journals (Sweden)

Żaneta Jastrzębska-Stojko

2013-11-01

Full Text Available Medicines of biogenic origin with micro-organic, regenerative and analgesic properties are becoming more and more significant in the treatment of burn wounds. These properties are found in apitherapeutics such as propolis and honey—products collected and processed by a honey bee. Their effect on the course of the healing processes is multidirectional. The aim of the study was a histopathological and biochemical analysis of the processes of scar formation in experimentally evoked burn wounds in white pigs treated with the 1% and 3% Sepropol balms containing standardized extracts of propolis and honey. The results were compared with the therapeutic effects obtained with dermazin cream (1% silver sulfadiazine. The level of collagen was determined in the wounds treated with 1% and 3% Sepropol and compared with the collagen level in healthy skin and wounds treated with dermazin. Granulation and regenerated epithelium formation times were compared, with the 3% Sepropol being by far the most effective. The 3% Sepropol also increased the collagen level to 116% with the control sub-groups scoring between 80% and 98%. The results show the healing process of burn wounds in pigs treated with the Sepropol balm starts earlier and has a faster course than the standard dermazin therapy.

Débridement and Autologous Lipotransfer for Chronic Ulceration of the Diabetic Foot and Lower Limb Improves Wound Healing.

Science.gov (United States)

Stasch, Tilman; Hoehne, Julius; Huynh, Tuan; De Baerdemaeker, Randy; Grandel, Siegfried; Herold, Christian

2015-12-01

The application of autologous lipotransfer (fat grafting, lipofilling) in reconstructive surgery is steadily becoming more popular as evidence of the regenerative and reparative effects of fat becomes better known. The authors investigated the use of autologous lipotransfer for treatment of chronic diabetic and other foot and lower limb ulcers. Twenty-six patients with nonhealing wounds were treated with surgical débridement and autologous lipotransfer (using the débridement and autologous lipotransfer method). The mean age of the wounds before intervention was 16.7 months. Wound size after débridement averaged 5.1 ± 2.6 cm2. On average, 7.1 ± 3.3 cc of lipoaspirate was transferred into the wound area. Twenty-two of 25 wounds (88 percent) healed completely within a mean of 68.0 ± 33.0 days. A reduction of wound size by 50 percent was achieved after an average of 4 weeks. In one patient with an ulcer within particularly scarred tissues on the lower limb, a repeated session of lipotransfer led to complete wound healing after another 4 weeks. The authors describe a simple and useful technique to improve wound healing in diabetic feet and chronic lower limb ulcers with a background of peripheral vascular disease, where other interventional options to achieve wound healing have failed.

Saliva and wound healing.

Science.gov (United States)

Brand, Henk S; Ligtenberg, Antoon J M; Veerman, Enno C I

2014-01-01

Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In addition, saliva contains several proteins which play a role in the different stages of wound healing. Saliva contains substantial amounts of tissue factor, which dramatically accelerates blood clotting. Subsequently, epidermal growth factor in saliva promotes the proliferation of epithelial cells. Secretory leucocyte protease inhibitor inhibits the tissue-degrading activity of enzymes like elastase and trypsin. Absence of this protease inhibitor delays oral wound healing. Salivary histatins in vitro promote wound closure by enhancing cell spreading and cell migration, but do not stimulate cell proliferation. A synthetic cyclic variant of histatin exhibits a 1,000-fold higher activity than linear histatin, which makes this cyclic variant a promising agent for the development of a new wound healing medication. Conclusively, recognition of the many roles salivary proteins play in wound healing makes saliva a promising source for the development of new drugs involved in tissue regeneration.

Highly efficient local delivery of endothelial progenitor cells significantly potentiates angiogenesis and full-thickness wound healing.

Science.gov (United States)

Wang, Chenggui; Wang, Qingqing; Gao, Wendong; Zhang, Zengjie; Lou, Yiting; Jin, Haiming; Chen, Xiaofeng; Lei, Bo; Xu, Huazi; Mao, Cong

2018-03-15

Wound therapy with a rapid healing performance remains a critical clinical challenge. Cellular delivery is considered to be a promising approach to improve the efficiency of healing, yet problems such as compromised cell viability and functionality arise due to the inefficient delivery. Here, we report the efficient delivery of endothelial progenitor cells (EPCs) with a bioactive nanofibrous scaffold (composed of collagen and polycaprolactone and bioactive glass nanoparticles, CPB) for enhancing wound healing. Under the stimulation of CPB nanofibrous system, the viability and angiogenic ability of EPCs were significantly enhanced through the activation of Hif-1α/VEGF/SDF-1α signaling. In vivo, CPB/EPC constructs significantly enhanced the formation of high-density blood vessels by greatly upregulating the expressions of Hif-1α, VEGF, and SDF-1α. Moreover, owing to the increased local delivery of cells and fast neovascularization within the wound site, cell proliferative activity, granulation tissue formation, and collagen synthesis and deposition were greatly promoted by CPB/EPC constructs resulting in rapid re-epithelialization and regeneration of skin appendages. As a result, the synergistic enhancement of wound healing was observed from CPB/EPC constructs, which suggests the highly efficient delivery of EPCs. CPB/EPC constructs may become highly competitive cell-based therapeutic products for efficient impaired wound healing application. This study may also provide a novel strategy to develop bioactive cell therapy constructs for angiogenesis-related regenerative medicine. This paper reported a highly efficient local delivery of EPCs using bioactive glass-based CPB nanofibrous scaffold for enhancing angiogenesis and wound regeneration. In vitro study showed that CPB can promote the proliferation, migration, and tube formation of EPCs through upregulation of the Hif-1α/VEGF/SDF-1α signaling pathway, indicating that the bioactivity and angiogenic ability of

Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

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Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

2017-09-01

Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

Stem Cell Therapy: Repurposing Cell-Based Regenerative Medicine Beyond Cell Replacement.

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Napoli, Eleonora; Lippert, Trenton; Borlongan, Cesar V

2018-02-27

Stem cells exhibit simple and naive cellular features, yet their exact purpose for regenerative medicine continues to elude even the most elegantly designed research paradigms from developmental biology to clinical therapeutics. Based on their capacity to divide indefinitely and their dynamic differentiation into any type of tissue, the advent of transplantable stem cells has offered a potential treatment for aging-related and injury-mediated diseases. Recent laboratory evidence has demonstrated that transplanted human neural stem cells facilitate endogenous reparative mechanisms by initiating multiple regenerative processes in the brain neurogenic areas. Within these highly proliferative niches reside a myriad of potent regenerative molecules, including anti-inflammatory cytokines, proteomes, and neurotrophic factors, altogether representing a biochemical cocktail vital for restoring brain function in the aging and diseased brain. Here, we advance the concept of therapeutically repurposing stem cells not towards cell replacement per se, but rather exploiting the cells' intrinsic properties to serve as the host brain regenerative catalysts.

REGEN: Ancestral Genome Reconstruction for Bacteria.

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Yang, Kuan; Heath, Lenwood S; Setubal, João C

2012-07-18

Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deletion and replicon fission and fusion. The reconstruction can be performed by either a maximum parsimony or a maximum likelihood method. Gene content reconstruction is based on the concept of neighboring gene pairs. REGEN was designed to be used with any set of genomes that are sufficiently related, which will usually be the case for bacteria within the same taxonomic order. We evaluated REGEN using simulated genomes and genomes in the Rhizobiales order.

Thermo-economic optimization of Regenerative Organic Rankine Cycle for waste heat recovery applications

International Nuclear Information System (INIS)

Imran, Muhammad; Park, Byung Sik; Kim, Hyouck Ju; Lee, Dong Hyun; Usman, Muhammad; Heo, Manki

2014-01-01

Highlights: • Thermo-economic optimization of regenerative ORC is performed. • Optimization is performed using multi objective genetic algorithm. • Objective function is maximum cycle efficiency and minimum specific investment. • Evaporation pressure, pinch point and superheat are decision variables. • Sensitivity analysis is performed to investigate effect of decision variables. - Abstract: Organic Rankine Cycle (ORC) is low grade and waste heat conversion technology. The current article deal with the thermo-economic optimization of basic ORC and regenerative ORC for waste heat recovery applications under constant heat source condition. Thermal efficiency and specific investment cost of basic ORC, single stage regenerative and double stage regenerative ORC has been optimized by using Non-dominated Sorting Genetic Algorithm-II (NSGA-II). Maximum thermal efficiency and minimum specific investment cost were selected as objective functions and relative increase in thermal efficiency and cost has been analyzed taking the basic ORC as base case. The constraint set consist of evaporation pressure, superheat, pinch point temperature difference in evaporator and condenser. The optimization was performed for five different working fluids. The optimization result show that R245fa is best working under considered conditions and basic ORC has low specific investment cost and thermal efficiency compared to regenerative ORC. R245fa is low boiling organic fluid, which has high degree of thermal stability and compatible with common construction materials of ORC. The average increase in thermal efficiency from basic ORC to single stage regenerative ORC was 1.01% with an additional cost of 187 $/kW while from basic ORC to double stage regenerative ORC was 1.45% with an average increase in cost of 297 $/kW. The sensitivity analysis was also performed to investigate the effect of operating conditions which show that evaporation pressure has promising effect on thermal

In vivo evaluation of adipose- and muscle-derived stem cells as a treatment for nonhealing diabetic wounds using multimodal microscopy

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Li, Joanne; Pincu, Yair; Marjanovic, Marina; Bower, Andrew J.; Chaney, Eric J.; Jensen, Tor; Boppart, Marni D.; Boppart, Stephen A.

2016-08-01

Impaired skin wound healing is a significant comorbid condition of diabetes, which often results in nonhealing diabetic ulcers due to poor peripheral microcirculation, among other factors. The effectiveness of the regeneration of adipose-derived stem cells (ADSCs) and muscle-derived stem cells (MDSCs) was assessed using an integrated multimodal microscopy system equipped with two-photon fluorescence and second-harmonic generation imaging. These imaging modalities, integrated in a single platform for spatial and temporal coregistration, allowed us to monitor in vivo changes in the collagen network and cell dynamics in a skin wound. Fluorescently labeled ADSCs and MDSCs were applied topically to the wound bed of wild-type and diabetic (db/db) mice following punch biopsy. Longitudinal imaging demonstrated that ADSCs and MDSCs provided remarkable capacity for improved diabetic wound healing, and integrated microscopy revealed a more organized collagen remodeling in the wound bed of treated mice. The results from this study verify the regenerative capacity of stem cells toward healing and, with multimodal microscopy, provide insight regarding their impact on the skin microenvironment. The optical method outlined in this study, which has the potential for in vivo human use, may optimize the care and treatment of diabetic nonhealing wounds.

Regenerative Medicine: Advances from Developmental to Degenerative Diseases.

Science.gov (United States)

Blair, Nicholas F; Frith, Thomas J R; Barbaric, Ivana

2017-01-01

Chronic tissue and organ failure caused by an injury, disease, ageing or congenital defects represents some of the most complex therapeutic challenges and poses a significant financial healthcare burden. Regenerative medicine strategies aim to fulfil the unmet clinical need by restoring the normal tissue function either through stimulating the endogenous tissue repair or by using transplantation strategies to replace the missing or defective cells. Stem cells represent an essential pillar of regenerative medicine efforts as they provide a source of progenitors or differentiated cells for use in cell replacement therapies. Whilst significant leaps have been made in controlling the stem cell fates and differentiating them to cell types of interest, transitioning bespoke cellular products from an academic environment to off-the-shelf clinical treatments brings about a whole new set of challenges which encompass manufacturing, regulatory and funding issues. Notwithstanding the need to resolve such issues before cell replacement therapies can benefit global healthcare, mounting progress in the field has highlighted regenerative medicine as a realistic prospect for treating some of the previously incurable conditions.

Use of Vacuum Therapy in the Treatment of Wounds in Patients with Diabetic Foot Syndrome

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P.O. Herasymchuk

2016-03-01

Full Text Available Introduction. Acute and chronic wound defects of the lower extremities occurs in 15–25 % of patients with diabetes mellitus, serving as the direct cause of frequent amputations of lower extremities in 12 % of patients. One of the current and promising directions of wound healing is vacuum therapy. Objective. To study the effect of vacuum therapy on the course of acute and chronic wound process in patients with diabetic foot syndrome, depending on the pathogenic form of the injury, and on the basis of the findings to improve the outcomes of surgical treatment of the above-mentioned pathology. Materials and methods. The study involved 239 patients with complicated forms of diabetic foot syndrome. Monitoring of the wound progress is complemented by clinical, cytological, microbiological and morphological criteria. In the treatment of patients, we have used vacuum therapy device by Agat-Dnepr company. Vacuum therapy of wounds was carried out in the modes of negative pressure within 80–125 mmHg. Results. On the 2nd — 3rd day of vacuum treatment, there was a significant decrease of local manifestations of acute inflammation. At the same time, we have noted a significantly reduction in the amount of wound defects. There were positive changes from the side of wound microbial contamination defects. Application of continuous vacuum therapy in the treatment of wound defects greatly improved the performance of local microcirculation. Conclusions. Use of vacuum therapy in the combination treatment of acute and chronic wounds in patients with diabetic foot syndrome has a local and systemic action that enables to stabilize the course of wound process, to stimulate regenerative processes, to eliminate manifestations of endogenous intoxication and violations of immunological reactivity.

REGEN: Ancestral Genome Reconstruction for Bacteria

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João C. Setubal

2012-07-01

Full Text Available Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deletion and replicon fission and fusion. The reconstruction can be performed by either a maximum parsimony or a maximum likelihood method. Gene content reconstruction is based on the concept of neighboring gene pairs. REGEN was designed to be used with any set of genomes that are sufficiently related, which will usually be the case for bacteria within the same taxonomic order. We evaluated REGEN using simulated genomes and genomes in the Rhizobiales order.

Changes in Regenerative Capacity through Lifespan

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Maximina H. Yun

2015-10-01

Full Text Available Most organisms experience changes in regenerative abilities through their lifespan. During aging, numerous tissues exhibit a progressive decline in homeostasis and regeneration that results in tissue degeneration, malfunction and pathology. The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. Understanding how these mechanisms impact on regenerative processes is essential to devise therapeutic approaches to improve tissue regeneration and extend healthspan. This review offers an overview of how regenerative abilities change through lifespan in various organisms, the factors that underlie such changes and the avenues for therapeutic intervention. It focuses on established models of mammalian regeneration as well as on models in which regenerative abilities do not decline with age, as these can deliver valuable insights for our understanding of the interplay between regeneration and aging.

Bioprinting is changing regenerative medicine forever.

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Collins, Scott Forrest

2014-12-01

3D printing, or solid freeform fabrication, applied to regenerative medicine brings technologies from several industries together to help solve unique challenges in both basic science and tissue engineering. By more finely organizing cells and supporting structures precisely in 3D space, we will gain critical knowledge of cell-cell communications and cell-environment interactions. As we increase the scale, we will move toward complex tissue and organ structures where several cell phenotypes will functionally and structurally interact, thus recapitulating the form and function of native tissues and organs.

Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing

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Bhavani S. Kowtharapu

2018-02-01

Full Text Available Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM on corneal epithelial cell function along with substance P (SP. Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK, paxillin, vimentin, β-catenin and vasodilator-stimulated phosphoprotein (VASP phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, β1 and β3 whereas SFCM increased α4, α5, αV, β1 and β5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained

Human lactoferrin stimulates skin keratinocyte function and wound re-epithelialization.

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Tang, L; Wu, J J; Ma, Q; Cui, T; Andreopoulos, F M; Gil, J; Valdes, J; Davis, S C; Li, J

2010-07-01

Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. To study the potential role of hLF in wound re-epithelialization. The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12-O-tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing.

REGEN: Ancestral Genome Reconstruction for Bacteria

OpenAIRE

Yang, Kuan; Heath, Lenwood S.; Setubal, João C.

2012-01-01

Ancestral genome reconstruction can be understood as a phylogenetic study with more details than a traditional phylogenetic tree reconstruction. We present a new computational system called REGEN for ancestral bacterial genome reconstruction at both the gene and replicon levels. REGEN reconstructs gene content, contiguous gene runs, and replicon structure for each ancestral genome. Along each branch of the phylogenetic tree, REGEN infers evolutionary events, including gene creation and deleti...

Educational tool for modeling and simulation of a closed regenerative life support system

Science.gov (United States)

Arai, Tatsuya; Fanchiang, Christine; Aoki, Hirofumi; Newman, Dava J.

For long term missions on the moon and Mars, regenerative life support systems emerge as a promising key technology for sustaining successful explorations with reduced re-supply logistics and cost. The purpose of this study was to create a simple model of a regenerative life support system which allows preliminary investigation of system responses. A simplified regenerative life support system was made with MATLAB Simulink ™. Mass flows in the system were simplified to carbon, water, oxygen and carbon dioxide. The subsystems included crew members, animals, a plant module, and a waste processor, which exchanged mass into and out of mass reservoirs. Preliminary numerical simulations were carried out to observe system responses. The simplified life support system model allowed preliminary investigation of the system response to perturbations such as increased or decreased number of crew members. The model is simple and flexible enough to add new components, and also possible to numerically predict non-linear subsystem functions and responses. Future work includes practical issues such as energy efficiency, air leakage, nutrition, and plant growth modeling. The model functions as an effective teaching tool about how a regenerative advanced life support system works.

Regenerative Therapy for Retinal Disorders

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Narsis Daftarian

2010-01-01

Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

Controlled local drug delivery strategies from chitosan hydrogels for wound healing.

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Elviri, Lisa; Bianchera, Annalisa; Bergonzi, Carlo; Bettini, Ruggero

2017-07-01

The main target of tissue engineering is the preparation and application of adequate materials for the design and production of scaffolds, that possess properties promoting cell adhesion, proliferation and differentiation. The use of natural polysaccharides, such as chitosan, to prepare hydrogels for wound healing and controlled drug delivery is a research topic of wide and increasing interest. Areas covered: This review presents the latest results and challenges in the preparation of chitosan and chitosan-based scaffold/hydrogel for wound healing applications. A detailed overview of their behavior in terms of controlled drug delivery, divided by drug categories, and efficacy was provided and critically discussed. Expert opinion: The need to establish and exploit the advantages of natural biomaterials in combination with active compounds is playing a pivotal role in the regenerative medicine fields. The challenges posed by the many variables affecting tissue repair and regeneration need to be standardized and adhere to recognized guidelines to improve the quality of evidence in the wound healing process. Currently, different methodologies are followed to prepare innovative scaffold formulations and structures. Innovative technologies such as 3D printing or bio-electrospray are promising to create chitosan-based scaffolds with finely controlled structures with customizable shape porosity and thickness. Chitosan scaffolds could be designed in combination with a variety of polysaccharides or active compounds with selected and reproducible spacial distribution, providing active wound dressing with highly tunable controlled drug delivery.

Researches on regenerative medicine-current state and prospect.

Science.gov (United States)

Wang, Zheng-Guo; Xiao, Kai

2012-01-01

Since 1980s, the rapid development of tissue engineering and stem cell research has pushed regenerative medicine to a new fastigium, and regenerative medicine has become a noticeable research field in the international biology and medicine. In China, about 100 million patients need repair and regeneration treatment every year, while the number is much larger in the world. Regenerative medicine could provide effective salvation for these patients. Both Chinese Academy of Sciences and Chinese Academy of Engineering have made roadmaps of 2010-2050 and 2011-2030 for regenerative medicine. The final goal of the two roadmaps is to make China go up to leading position in most research aspects of regenerative medicine. In accord with this strategy, the government and some enterprises have invested 3-5 billion RMB (0.5-0.8 billion USD) for the research on regenerative medicine. In order to push the translation of regenerative medicine forward-from bench to bedside, a strategic alliance has been established, and it includes 27 top-level research institutes, medical institutes, colleges, universities and enterprises in the field of stem cell and regeneration medicine. Recently the journal, Science, has published a special issue-Regenerative Medicine in China, consisting of 35 papers dealing with stem cell and regeneration, tissue engineering and regeneration, trauma and regeneration and bases for tissue repair and regenerative medicine. It is predicated that a greater breakthrough in theory and practice of regenerative medicine will be achieved in the near future (20 to 30 years).

The mechanical fingerprint of murine excisional wounds.

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Pensalfini, Marco; Haertel, Eric; Hopf, Raoul; Wietecha, Mateusz; Werner, Sabine; Mazza, Edoardo

2018-01-01

A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue. Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy

Mechanical cues in orofacial tissue engineering and regenerative medicine

NARCIS (Netherlands)

Brouwer, K.M.; Lundvig, D.M.S.; Middelkoop, E.; Wagener, F.A.D.T.; Von den Hoff, J.W.

2015-01-01

Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of

Surface biology of collagen scaffold explains blocking of wound contraction and regeneration of skin and peripheral nerves.

Science.gov (United States)

Yannas, I V; Tzeranis, D; So, P T

2015-12-23

We review the details of preparation and of the recently elucidated mechanism of biological (regenerative) activity of a collagen scaffold (dermis regeneration template, DRT) that has induced regeneration of skin and peripheral nerves (PN) in a variety of animal models and in the clinic. DRT is a 3D protein network with optimized pore size in the range 20-125 µm, degradation half-life 14 ± 7 d and ligand densities that exceed 200 µM α1β1 or α2β1 ligands. The pore has been optimized to allow migration of contractile cells (myofibroblasts, MFB) into the scaffold and to provide sufficient specific surface for cell-scaffold interaction; the degradation half-life provides the required time window for satisfactory binding interaction of MFB with the scaffold surface; and the ligand density supplies the appropriate ligands for specific binding of MFB on the scaffold surface. A dramatic change in MFB phenotype takes place following MFB-scaffold binding which has been shown to result in blocking of wound contraction. In both skin wounds and PN wounds the evidence has shown clearly that contraction blocking by DRT is followed by induction of regeneration of nearly perfect organs. The biologically active structure of DRT is required for contraction blocking; well-matched collagen scaffold controls of DRT, with structures that varied from that of DRT, have failed to induce regeneration. Careful processing of collagen scaffolds is required for adequate biological activity of the scaffold surface. The newly understood mechanism provides a relatively complete paradigm of regenerative medicine that can be used to prepare scaffolds that may induce regeneration of other organs in future studies.

Biomaterials and Culture Technologies for Regenerative Therapy of Liver Tissue.

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Perez, Roman A; Jung, Cho-Rok; Kim, Hae-Won

2017-01-01

Regenerative approach has emerged to substitute the current extracorporeal technologies for the treatment of diseased and damaged liver tissue. This is based on the use of biomaterials that modulate the responses of hepatic cells through the unique matrix properties tuned to recapitulate regenerative functions. Cells in liver preserve their phenotype or differentiate through the interactions with extracellular matrix molecules. Therefore, the intrinsic properties of the engineered biomaterials, such as stiffness and surface topography, need to be tailored to induce appropriate cellular functions. The matrix physical stimuli can be combined with biochemical cues, such as immobilized functional groups or the delivered actions of signaling molecules. Furthermore, the external modulation of cells, through cocultures with nonparenchymal cells (e.g., endothelial cells) that can signal bioactive molecules, is another promising avenue to regenerate liver tissue. This review disseminates the recent approaches of regenerating liver tissue, with a focus on the development of biomaterials and the related culture technologies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regenerative endodontics: a comprehensive review.

Science.gov (United States)

Kim, S G; Malek, M; Sigurdsson, A; Lin, L M; Kahler, B

2018-05-19

The European Society of Endodontology and the American Association for Endodontists have released position statements and clinical considerations for regenerative endodontics. There is increasing literature on this field since the initial reports of Iwaya et al. (Dental Traumatology, 17, 2001, 185) and Banchs & Trope (Journal of Endodontics, 30, 2004, 196). Endogenous stem cells from an induced periapical bleeding and scaffolds using blood clot, platelet rich plasma or platelet-rich fibrin have been utilized in regenerative endodontics. This approach has been described as a 'paradigm shift' and considered the first treatment option for immature teeth with pulp necrosis. There are three treatment outcomes of regenerative endodontics; (i) resolution of clinical signs and symptoms; (ii) further root maturation; and (iii) return of neurogenesis. It is known that results are variable for these objectives, and true regeneration of the pulp/dentine complex is not achieved. Repair derived primarily from the periodontal and osseous tissues has been shown histologically. It is hoped that with the concept of tissue engineering, namely stem cells, scaffolds and signalling molecules, that true pulp regeneration is an achievable goal. This review discusses current knowledge as well as future directions for regenerative endodontics. Patient-centred outcomes such as tooth discolouration and possibly more appointments with the potential for adverse effects needs to be discussed with patients and parents. Based on the classification of Cvek (Endodontics and Dental Traumatology, 8, 1992, 45), it is proposed that regenerative endodontics should be considered for teeth with incomplete root formation although teeth with near or complete root formation may be more suited for conventional endodontic therapy or MTA barrier techniques. However, much is still not known about clinical and biological aspects of regenerative endodontics. © 2018 International Endodontic Journal. Published by

Two sides of the same coin: stem cells in cancer and regenerative medicine.

Science.gov (United States)

Ilmer, Matthias; Vykoukal, Jody; Recio Boiles, Alejandro; Coleman, Michael; Alt, Eckhard

2014-07-01

Multipotent stromal cells (MSCs) derived from bone marrow, adipose tissue, cord blood, and other origins have recently received much attention as potential therapeutic agents with beneficial immunomodulatory and regenerative properties. In their native tissue environment, however, such cells also appear to have essential functions in building and supporting tumor microenvironments, providing metastatic niches, and maintaining cancer hallmarks. Here, we consider the varied roles of these tissue-resident stroma-associated cells, synthesize recent and emerging discoveries, and discuss the role, potential, and clinical applications of MSCs in cancer and regenerative medicine.-Ilmer, M., Vykoukal, J., Recio Boiles, A., Coleman, M., Alt, E. Two sides of the same coin: stem cells in cancer and regenerative medicine. © FASEB.

Transition theory and its relevance to patients with chronic wounds.

Science.gov (United States)

Neil, J A; Barrell, L M

1998-01-01

A wound, in the broadest sense, is a disruption of normal anatomic structure and function. Acute wounds progress through a timely and orderly sequence of repair that leads to the restoration of functional integrity. In chronic wounds, this timely and orderly sequence goes awry. As a result, people with chronic wounds often face not only physiological difficulties but emotional ones as well. The study of body image and its damage as a result of a chronic wound fits well with Selder's transition theory. This article describes interviews with seven patients with chronic wounds. The themes that emerged from those interviews were compared with Selder's theory to describe patients' experience with chronic wounds as a transition process that can be identified and better understood by healthcare providers.

Microporous dermal-mimetic electrospun scaffolds pre-seeded with fibroblasts promote tissue regeneration in full-thickness skin wounds.

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Paul P Bonvallet

Full Text Available Electrospun scaffolds serve as promising substrates for tissue repair due to their nanofibrous architecture and amenability to tailoring of chemical composition. In this study, the regenerative potential of a microporous electrospun scaffold pre-seeded with dermal fibroblasts was evaluated. Previously we reported that a 70% collagen I and 30% poly(Ɛ-caprolactone electrospun scaffold (70:30 col/PCL containing 160 μm diameter pores had favorable mechanical properties, supported fibroblast infiltration and subsequent cell-mediated deposition of extracellular matrix (ECM, and promoted more rapid and effective in vivo skin regeneration when compared to scaffolds lacking micropores. In the current study we tested the hypothesis that the efficacy of the 70:30 col/PCL microporous scaffolds could be further enhanced by seeding scaffolds with dermal fibroblasts prior to implantation into skin wounds. To address this hypothesis, a Fischer 344 (F344 rat syngeneic model was employed. In vitro studies showed that dermal fibroblasts isolated from F344 rat skin were able to adhere and proliferate on 70:30 col/PCL microporous scaffolds, and the cells also filled the 160 μm pores with native ECM proteins such as collagen I and fibronectin. Additionally, scaffolds seeded with F344 fibroblasts exhibited a low rate of contraction (~14% over a 21 day time frame. To assess regenerative potential, scaffolds with or without seeded F344 dermal fibroblasts were implanted into full thickness, critical size defects created in F344 hosts. Specifically, we compared: microporous scaffolds containing fibroblasts seeded for 4 days; scaffolds containing fibroblasts seeded for only 1 day; acellular microporous scaffolds; and a sham wound (no scaffold. Scaffolds containing fibroblasts seeded for 4 days had the best response of all treatment groups with respect to accelerated wound healing, a more normal-appearing dermal matrix structure, and hair follicle regeneration

Regenerative endodontics: A state of the art

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Rashmi Bansal

2011-01-01

Full Text Available Scientific advances in the creation of restorative biomaterials, in vitro cell culture technology, tissue grafting, tissue engineering, molecular biology and the human genome project provide the basis for the introduction of new technologies into dentistry. Non-vital infected teeth have long been treated with root canal therapy (for mature root apex and apexification (for immature root apex, or doomed to extraction. Although successful, current treatments fail to re-establish healthy pulp tissue in these teeth. But, what if the non-vital tooth could be made vital once again? That is the hope offered by regenerative endodontics, an emerging field focused on replacing traumatized and diseased pulp with functional pulp tissue. Restoration of vitality of non-vital tooth is based on tissue engineering and revascularization procedures. The purpose of this article is to review these biological procedures and the hurdles that must be overcome to develop regenerative endodontic procedures.

Regenerative-filter-incinerator device

Energy Technology Data Exchange (ETDEWEB)

Rosebrock, T.L.

1977-10-18

A regenerative-filter-incinerator device, for use in the exhaust system of a diesel engine, includes a drum-like regenerative-heat exchanger-filter assembly rotatably mounted within a housing that is adapted to be installed directly in the exhaust gas stream discharged from a diesel engine as close to the engine as possible. The regenerative-heat exchanger-filter assembly provides an inner chamber which serves as a reaction chamber for the secondary combustion of exhaust gases including particulates discharged from the engine. The regenerative-heat exchanger-filter assembly includes separately rotatable heat exchange-filter elements pervious to radial flow of fluid therethrough and adapted to filter out particulates from the exhaust gases and to carry them into the reaction chamber. During engine operation, the reaction chamber is provided with a quantity of heat, as necessary, to effect secondary combustion of the exhaust gases and particulates by means of an auxiliary heat source and the heat generated within the reaction chamber is stored in the individual heat exchange-filter elements during the discharge of exhaust gases therethrough from the reaction chamber and this heat is then transferred to the inflowing volume of the exhaust gases so that, in effect, exhaust gas is discharged from the device at substantially the same temperature as it was during its inlet into the device from the engine.

Leptin promotes wound healing in the skin.

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Susumu Tadokoro

Full Text Available Leptin, a 16 kDa anti-obesity hormone, exhibits various physiological properties. Interestingly, skin wound healing was proven to delay in leptin-deficient ob/ob mice. However, little is known on the mechanisms of this phenomenon. In this study, we attempted to elucidate a role of leptin in wound healing of skin.Immunohistochemical analysis was performed to confirm the expression of the leptin receptor (Ob-R in human and mouse skin. Leptin was topically administered to chemical wounds created in mouse back skin along with sustained-release absorbable hydrogel. The process of wound repair was histologically observed and the area of ulceration was measured over time. The effect of leptin on the proliferation, differentiation and migration of human epidermal keratinocytes was investigated.Ob-R was expressed in epidermal cells of human and mouse skin. Topical administration of leptin significantly promoted wound healing. Histological analysis showed more blood vessels in the dermal connective tissues in the leptin-treated group. The proliferation, differentiation/function and migration of human epidermal keratinocytes were enhanced by exogenous leptin.Topically administered leptin was proven to promote wound healing in the skin by accelerating proliferation, differentiation/function and migration of epidermal keratinocytes and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the skin.

Regenerative braking system of PM synchronous motor

Science.gov (United States)

Gao, Qian; Lv, Chengxing; Zhao, Na; Zang, Hechao; Jiang, Huilue; Zhang, Zhaowen; Zhang, Fengli

2018-04-01

Permanent-magnet synchronous motor is widely adopted in many fields with the advantage of a high efficiency and a high torque density. Regenerative Braking Systems (RBS) provide an efficient method to assist PMSM system achieve better fuel economy and lowering exhaust emissions. This paper describes the design and testing of the regenerative braking systems of PMSM. The mode of PWM duty has been adjusted to control regenerative braking of PMSM using energy controller for the port-controlled Hamiltonian model. The simulation analysis indicates that a smooth control could be realized and the highest efficiency and the smallest current ripple could be achieved by Regenerative Braking Systems.

Effect of platelet lysate on human cells involved in different phases of wound healing.

Science.gov (United States)

Barsotti, Maria Chiara; Chiara Barsotti, Maria; Losi, Paola; Briganti, Enrica; Sanguinetti, Elena; Magera, Angela; Al Kayal, Tamer; Feriani, Roberto; Di Stefano, Rossella; Soldani, Giorgio

2013-01-01

Platelets are rich in mediators able to positively affect cell activity in wound healing. Aim of this study was to characterize the effect of different concentrations of human pooled allogeneic platelet lysate on human cells involved in the different phases of wound healing (inflammatory phase, angiogenesis, extracellular matrix secretion and epithelialization). Platelet lysate effect was studied on endothelial cells, monocytes, fibroblasts and keratinocytes, in terms of viability and proliferation, migration, angiogenesis, tissue repair pathway activation (ERK1/2) and inflammatory response evaluation (NFκB). Results were compared both with basal medium and with a positive control containing serum and growth factors. Platelet lysate induced viability and proliferation at the highest concentrations tested (10% and 20% v/v). Whereas both platelet lysate concentrations increased cell migration, only 20% platelet lysate was able to significantly promote angiogenic activity (pplatelet lysate concentrations activated important inflammatory pathways such as ERK1/2 and NFκB with the same early kinetics, whereas the effect was different for later time-points. These data suggest the possibility of using allogeneic platelet lysate as both an alternative to growth factors commonly used for cell culture and as a tool for clinical regenerative application for wound healing.

Regulators of pluripotency and their implications in regenerative medicine

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El-Badawy A

2015-04-01

Full Text Available Ahmed El-Badawy, Nagwa El-Badri Center of Excellence for Stem Cells and Regenerative Medicine, Zewail City of Science and Technology, Giza, Egypt Abstract: The ultimate goal of regenerative medicine is to replace damaged tissues with new functioning ones. This can potentially be accomplished by stem cell transplantation. While stem cell transplantation for blood diseases has been increasingly successful, widespread application of stem cell therapy in the clinic has shown limited results. Despite successful efforts to refine existing methodologies and to develop better ones for reprogramming, clinical application of stem cell therapy suffers from issues related to the safety of the transplanted cells, as well as the low efficiency of reprogramming technology. Better understanding of the underlying mechanism(s involved in pluripotency should accelerate the clinical application of stem cell transplantation for regenerative purposes. This review outlines the main decision-making factors involved in pluripotency, focusing on the role of microRNAs, epigenetic modification, signaling pathways, and toll-like receptors. Of special interest is the role of toll-like receptors in pluripotency, where emerging data indicate that the innate immune system plays a vital role in reprogramming. Based on these data, we propose that nongenetic mechanisms for reprogramming provide a novel and perhaps an essential strategy to accelerate application of regenerative medicine in the clinic. Keywords: dedifferentiation, transdifferentiation, reprogramming, pluripotency, microRNAs, epigenetic modifications, signaling pathways, toll-like receptors

Regenerative Perspective in Modern Dentistry

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Mihnea Ioan Nicolescu

2016-04-01

Full Text Available This review aims to trace the contour lines of regenerative dentistry, to offer an introductory overview on this emerging field to both dental students and practitioners. The crystallized depiction of the concept is a translational approach, connecting dental academics to scientific research and clinical utility. Therefore, this review begins by presenting the general features of regenerative medicine, and then gradually introduces the specific aspects of major dental subdomains, highlighting the progress achieved during the last years by scientific research and, in some cases, which has already been translated into clinical results. The distinct characteristics of stem cells and their microenvironment, together with their diversity in the oral cavity, are put into the context of research and clinical use. Examples of regenerative studies regarding endodontic and periodontal compartments, as well as hard (alveolar bone and soft (salivary glands related tissues, are presented to make the reader further acquainted with the topic. Instead of providing a conclusion, we will emphasize the importance for all dental community members, from young students to experienced dentists, of an early awareness rising regarding biomedical research progress in general and regenerative dentistry in particular.

Platelet-rich plasma to improve the bio-functionality of biomaterials.

Science.gov (United States)

Anitua, Eduardo; Tejero, Ricardo; Alkhraisat, Mohammad H; Orive, Gorka

2013-04-01

Growth factors and cytokines are active players in controlling the different stages of wound healing and tissue regeneration. Recent trends in personalized regenerative medicine involve using patient's own platelet-rich plasma for stimulating wound healing and tissue regeneration. This technology provides a complex cocktail of growth factors and even a fibrin scaffold with multiple biologic effects. In the last few years, an increasing number of studies provide evidence of the potential of combining platelet-rich plasma with different biomaterials in order to improve their properties, including handling, administration, bioactivity, and level of osseointegration, among others. In this review, we discuss the use of platelet-rich plasma as an alternative, easy, cost-effective, and controllable strategy for the release of high concentrations of many endogenous growth factors. Additionally, we provide an overview of the current progress and future directions of research combining different types of biomaterials with platelet-rich plasma in tissue engineering and regenerative medicine.

[Wound healing in the elderly].

Science.gov (United States)

Eming, S A; Wlaschek, M; Scharffetter-Kochanek, K

2016-02-01

Restoration of tissue integrity is essential for host defense and protection of the organism. The efficacy and quality of skin repair varies significantly over a person's lifetime. Whereas prenatal wound healing is characterized by regeneration and scarless healing, scarring, fibrosis, and loss of function are features of postnatal repair. In fact, aging is the prominent risk factor for chronic wounds, skin fragility, infections, comorbidities, and decreased quality of life. Current strategies for restoration of tissue integrity and wound therapy are not sufficient and require further investigation of the underlying pathomechanisms and the development of causal-based concepts.

STATISTIC, PROBABILISTIC, CORRELATION AND SPECTRAL ANALYSES OF REGENERATIVE BRAKING CURRENT OF DC ELECTRIC ROLLING STOCK

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A. V. Nikitenko

2014-04-01

Full Text Available Purpose. Defining and analysis of the probabilistic and spectral characteristics of random current in regenerative braking mode of DC electric rolling stock are observed in this paper. Methodology. The elements and methods of the probability theory (particularly the theory of stationary and non-stationary processes and methods of the sampling theory are used for processing of the regenerated current data arrays by PC. Findings. The regenerated current records are obtained from the locomotives and trains in Ukraine railways and trams in Poland. It was established that the current has uninterrupted and the jumping variations in time (especially in trams. For the random current in the regenerative braking mode the functions of mathematical expectation, dispersion and standard deviation are calculated. Histograms, probabilistic characteristics and correlation functions are calculated and plotted down for this current too. It was established that the current of the regenerative braking mode can be considered like the stationary and non-ergodic process. The spectral analysis of these records and “tail part” of the correlation function found weak periodical (or low-frequency components which are known like an interharmonic. Originality. Firstly, the theory of non-stationary random processes was adapted for the analysis of the recuperated current which has uninterrupted and the jumping variations in time. Secondly, the presence of interharmonics in the stochastic process of regenerated current was defined for the first time. And finally, the patterns of temporal changes of the correlation current function are defined too. This allows to reasonably apply the correlation functions method in the identification of the electric traction system devices. Practical value. The results of probabilistic and statistic analysis of the recuperated current allow to estimate the quality of recovered energy and energy quality indices of electric rolling stock in the

Multifunctional nanodiamonds in regenerative medicine: Recent advances and future directions.

Science.gov (United States)

Whitlow, Jonathan; Pacelli, Settimio; Paul, Arghya

2017-09-10

With recent advances in the field of nanomedicine, many new strategies have emerged for diagnosing and treating diseases. At the forefront of this multidisciplinary research, carbon nanomaterials have demonstrated unprecedented potential for a variety of regenerative medicine applications including novel drug delivery platforms that facilitate the localized and sustained release of therapeutics. Nanodiamonds (NDs) are a unique class of carbon nanoparticles that are gaining increasing attention for their biocompatibility, highly functional surfaces, optical properties, and robust physical properties. Their remarkable features have established NDs as an invaluable regenerative medicine platform, with a broad range of clinically relevant applications ranging from targeted delivery systems for insoluble drugs, bioactive substrates for stem cells, and fluorescent probes for long-term tracking of cells and biomolecules in vitro and in vivo. This review introduces the synthesis techniques and the various routes of surface functionalization that allow for precise control over the properties of NDs. It also provides an in-depth overview of the current progress made toward the use of NDs in the fields of drug delivery, tissue engineering, and bioimaging. Their future outlook in regenerative medicine including the current clinical significance of NDs, as well as the challenges that must be overcome to successfully translate the reviewed technologies from research platforms to clinical therapies will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Design, clinical translation and immunological response of biomaterials in regenerative medicine

Science.gov (United States)

Sadtler, Kaitlyn; Singh, Anirudha; Wolf, Matthew T.; Wang, Xiaokun; Pardoll, Drew M.; Elisseeff, Jennifer H.

2016-07-01

The field of regenerative medicine aims to replace tissues lost as a consequence of disease, trauma or congenital abnormalities. Biomaterials serve as scaffolds for regenerative medicine to deliver cells, provide biological signals and physical support, and mobilize endogenous cells to repair tissues. Sophisticated chemistries are used to synthesize materials that mimic and modulate native tissue microenvironments, to replace form and to elucidate structure-function relationships of cell-material interactions. The therapeutic relevance of these biomaterial properties can only be studied after clinical translation, whereby key parameters for efficacy can be defined and then used for future design. In this Review, we present the development and translation of biomaterials for two tissue engineering targets, cartilage and cornea, both of which lack the ability to self-repair. Finally, looking to the future, we discuss the role of the immune system in regeneration and the potential for biomaterial scaffolds to modulate immune signalling to create a pro-regenerative environment.

Development of a computer code for a regenerative Rankine cycle analysis

International Nuclear Information System (INIS)

Wi, Myung Hwan; Kim, Seong O; Choi, Seok Ki; Kim, Jin Hwan

2005-01-01

A regenerative Rankine cycle can increase the thermal efficiency of a steam system without increasing the steam pressure and temperature. The regenerative process involves heating the feedwater on its return trip to the steam generator by extracting steam at various stages of the turbine and transferring the energy to the feedwater via a feedwater heater. Some real plants use more than five feedwater heaters to enhance the cycle efficiency. However, the optimum number of feedwater heaters required is determined by balancing the efficiency improvement against the capital investment for a given cycle. In the present study, the computer code, TAOPCS, for the thermodynamic analysis of a regenerative steam cycle was developed to optimally design and accurately analyze the behavior of the power conversion system of Korea Advance Liquid Metal Reactor (KALIMER). In order to understand the functions and the characteristics of the code, the main features of the TAPCS were described and the example results are presented in this paper

Comparative energy analysis on a new regenerative Brayton cycle

International Nuclear Information System (INIS)

Goodarzi, M.

2016-01-01

Highlights: • New regenerative Brayton cycle has been introduced. • New cycle has higher thermal efficiency and lower exhausted heat per output power. • Regenerator may remain useful in the new cycle even at high pressure ratio. • New regenerative Brayton cycle is suggested for low pressure ratio operations. - Abstract: Gas turbines are frequently used for power generation. Brayton cycle is the basis for gas turbine operation and developing the alternative cycles. Regenerative Brayton cycle is a developed cycle for basic Brayton cycle with higher thermal efficiency at low to moderate pressure ratios. A new regenerative Brayton cycle has been introduced in the present study. Energy analysis has been conducted on ideal cycles to compare them from the first law of thermodynamics viewpoint. Comparative analyses showed that the new regenerative Brayton cycle has higher thermal efficiency than the original one at the same pressure ratio, and also lower heat absorption and exhausted heat per unite output power. Computed results show that new cycle improves thermal efficiency from 12% to 26% relative to the original regenerative Brayton cycle in the range of studied pressure ratios. Contrary to the original regenerative Brayton cycle, regenerator remains useful in the new regenerative Brayton cycle even at higher pressure ratio.

Molecular biology of wound healing

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Nalliappan Ganapathy

2012-01-01

Full Text Available Wound healing is a dynamic process that involves the integrated action of a number of cell types, the extra cellular matrix, and soluble mediators termed cytokines.In recent years considerable advances have been made in the research, knowledge, and understanding of growth factors. Growth factors are, in essence, proteins that communicate activities to cells. Their function is dependent on the receptor site they attach to. Growth factors were initially named for the type of response generated by them, but newer research has shown that many of these cells may accomplish many different types of response. A growth factor′s role in wound repair is a critical component of the successful resolution of a wound. Growth factors help regulate many of the activities involved in healing. The role and function of growth factor is an evolving area of science and offers the potential for treatment alternatives in the future.

Negative pressure wound therapy via vacuum-assisted closure following partial foot amputation: what is the role of wound chronicity?

Science.gov (United States)

Armstrong, David G; Lavery, Lawrence A; Boulton, Andrew J M

2007-03-01

Randomised clinical trials (RCTs) to evaluate diabetic foot wound therapies have systematically eliminated large acute wounds from evaluation, focusing only on smaller chronic wounds. The purpose of this study was to evaluate the proportion and rate of wound healing in acute and chronic wounds after partial foot amputation in individuals with diabetes treated with negative pressure wound therapy (NPWT) delivered by the vacuum-assisted closure (VAC) device or with standard wound therapy (SWT). This study constitutes a secondary analysis of patients enrolled in a 16-week RCT of NPWT: 162 open foot amputation wounds (mean wound size = 20.7 cm(2)) were included. Acute wounds were defined as the wounds less than 30 days after amputation, whereas chronic wounds as the wounds greater than 30 days. Inclusion criteria consisted of individuals older than 18 years, presence of a diabetic foot amputation wound up to the transmetatarsal level and adequate perfusion. Wound size and healing were confirmed by independent, blinded wound evaluators. Analyses were done on an intent-to-treat basis. There was a significantly higher proportion of acute wounds (SWT = 59; NPWT = 63) than chronic wounds (SWT = 26; NPWT = 14), evaluated in this clinical trial (P = 0.001). There was no significant difference in the proportion of acute and chronic wounds achieving complete wound closure in either treatment group. Despite this finding, the Kaplan-Meier curves demonstrated statistically significantly faster healing in the NPWT group in both acute (P = 0.030) and chronic wounds (P = 0.033). Among the patients treated with NPWT via the VAC, there was not a significant difference in healing as a function of chronicity. In both the acute and the chronic wound groups, results for patients treated with NPWT were superior to those for the patients treated with SWT. These results appear to indicate that wound duration should not deter the clinician from using this modality to treat complex wounds.

Leaf and shoot water content and leaf dry matter content of Mediterranean woody species with different post-fire regenerative strategies.

Science.gov (United States)

Saura-Mas, S; Lloret, F

2007-03-01

Post-fire regeneration is a key process in Mediterranean shrubland dynamics, strongly determining the functional properties of the community. In this study, a test is carried out to determine whether there is co-variation between species regenerative types and functional attributes related to water use. An analysis was made of the seasonal variations in leaf relative water content (RWC), leaf dry matter content (LDMC), leaf moisture (LM) and live fine fuel moisture (LFFM) in 30 woody species of a coastal shrubland, with different post-fire regenerative strategies (seeding, resprouting or both). RWC results suggest that the studied resprouters have more efficient mechanisms to reduce water losses and maintain water supply between seasons. In contrast, seeders are more drought tolerant. LDMC is higher in resprouters over the course of the year, suggesting a more efficient conservation of nutrients. The weight of the phylogenetic constraint to understand differences between regenerative strategies tends to be important for LDMC, while it is not the case for variables such as RWC. Groups of species with different post-fire regenerative strategies (seeders and resprouters) have different functional traits related to water use. In addition to the role of phylogenetical constraints, these differences are also likely to be related to the respective life history characteristics. Therefore, the presence and abundance of species with different post-fire regenerative responses influence the functional properties of the communities.

Inflammation and wound healing: The role of the macrophage

Science.gov (United States)

Koh, Timothy J.; DiPietro, Luisa Ann

2013-01-01

The macrophage is a prominent inflammatory cell in wounds, but its role in healing remains incompletely understood. Macrophages have been described to have many functions in wounds, including host defense, the promotion and resolution of inflammation, the removal of apoptotic cells, and the support of cell proliferation and tissue restoration following injury. Recent studies suggest that macrophages exist in several different phenotypic states within the healing wound, and that the influence of these cells on each stage of repair varies with the specific phenotypes. While the macrophage is beneficial to the repair of normally healing wounds, this pleotropic cell type may promote excessive inflammation and/or fibrosis in certain circumstances. Emerging evidence suggests that macrophage dysfunction is a component of the pathogenesis of non-healing and poorly healing wounds. Due to advances in the understanding of this multi-functional cell, the macrophage continues to be an attractive therapeutic target both to reduce fibrosis and scarring, and to improve healing of chronic wounds. PMID:21740602

Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.

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Barbara Gawronska-Kozak

Full Text Available Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process.

Microscale Regenerative Heat Exchanger

Science.gov (United States)

Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

2006-01-01

The device described herein is designed primarily for use as a regenerative heat exchanger in a miniature Stirling engine or Stirling-cycle heat pump. A regenerative heat exchanger (sometimes called, simply, a "regenerator" in the Stirling-engine art) is basically a thermal capacitor: Its role in the Stirling cycle is to alternately accept heat from, then deliver heat to, an oscillating flow of a working fluid between compression and expansion volumes, without introducing an excessive pressure drop. These volumes are at different temperatures, and conduction of heat between these volumes is undesirable because it reduces the energy-conversion efficiency of the Stirling cycle.

The Impact of Biomechanics in Tissue Engineering and Regenerative Medicine

Science.gov (United States)

Butler, David L.; Goldstein, Steven A.; Guo, X. Edward; Kamm, Roger; Laurencin, Cato T.; McIntire, Larry V.; Mow, Van C.; Nerem, Robert M.; Sah, Robert L.; Soslowsky, Louis J.; Spilker, Robert L.; Tranquillo, Robert T.

2009-01-01

Biomechanical factors profoundly influence the processes of tissue growth, development, maintenance, degeneration, and repair. Regenerative strategies to restore damaged or diseased tissues in vivo and create living tissue replacements in vitro have recently begun to harness advances in understanding of how cells and tissues sense and adapt to their mechanical environment. It is clear that biomechanical considerations will be fundamental to the successful development of clinical therapies based on principles of tissue engineering and regenerative medicine for a broad range of musculoskeletal, cardiovascular, craniofacial, skin, urinary, and neural tissues. Biomechanical stimuli may in fact hold the key to producing regenerated tissues with high strength and endurance. However, many challenges remain, particularly for tissues that function within complex and demanding mechanical environments in vivo. This paper reviews the present role and potential impact of experimental and computational biomechanics in engineering functional tissues using several illustrative examples of past successes and future grand challenges. PMID:19583462

Regenerative Braking System for Series Hybrid Electric City Bus

OpenAIRE

Zhang, Junzhi; Lu, Xin; Xue, Junliang; Li, Bos

2008-01-01

Regenerative Braking Systems (RBS) provide an efficient method to assist hybrid electric buses achieve better fuel economy while lowering exhaust emissions. This paper describes the design and testing of three regenerative braking systems, one of which is a series regenerative braking system and two of which are parallel regenerative braking systems. The existing friction based Adjustable Braking System (ABS) on the bus is integrated with each of the new braking systems in order to ensure bus...

Active Magnetic Regenerative Liquefier

Energy Technology Data Exchange (ETDEWEB)

Barclay, John A. [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Oseen-Send, Kathryn [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ferguson, Luke [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Pouresfandiary, Jamshid [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Cousins, Anand [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Ralph, Heather [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States); Hampto, Tom [Heracles Energy Corporation d.b.a. Prometheus Energy, Washington, DC (United States)

2016-01-12

This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

Hypoperfusion and Wound Healing: Another Dimension of Wound Assessment.

Science.gov (United States)

Smollock, Wendy; Montenegro, Paul; Czenis, Amy; He, Yuan

2018-02-01

To examine the correlation between mean arterial pressure (MAP) and wound healing indices and describe an analytical process that can be used accurately and prospectively when evaluating all types of skin ulcerations. A correlational study in a long-term-care facility.Participants (N = 230) were adults residing in a long-term-care facility with an average age of 77.8 years (range, 35-105). Assessment through both an index of wound healing and wound surface area. Signs of wound healing included a reduction of surface area and surface necrosis and increased granulation or epithelialization. Aggregate analyses for all wound locations revealed a positive correlation between the MAP and index of wound healing (r = 0.86, n = 501, P wound healing was noted for all wound locations in this data set when MAP values were 80 mm Hg or less (r = 0.95, n = 141, P wounds and MAP of less than 80 mm Hg yielded a very strong positive correlation. The data indicated that as perfusion decreased, wounds within the sample population declined (r = 0.93, n = 102, P wound healing or worsened wounds. A predictability of wounds stalling or declining related to the MAP was observed, regardless of topical treatment or standard-of-care interventions. Therefore, the data also suggest that remediating states of low perfusion should take precedence in making treatment decisions.

A small peptide with potential ability to promote wound healing.

Directory of Open Access Journals (Sweden)

Jing Tang

Full Text Available Wound-healing represents a major health burden, such as diabetes-induced skin ulcers and burning. Many works are being tried to find ideal clinical wound-healing biomaterials. Especially, small molecules with low cost and function to promote production of endogenous wound healing agents (i.e. transforming growth factor beta, TGF-β are excellent candidates. In this study, a small peptide (tiger17, c[WCKPKPKPRCH-NH2] containing only 11 amino acid residues was designed and proved to be a potent wound healer. It showed strong wound healing-promoting activity in a murine model of full thickness dermal wound. Tiger17 exerted significant effects on three stages of wound healing progresses including (1 the induction of macrophages recruitment to wound site at inflammatory reaction stage; (2 the promotion of the migration and proliferation both keratinocytes and fibroblasts, leading to reepithelialization and granulation tissue formation; and (3 tissue remodeling phase, by promoting the release of transforming TGF-β1 and interleukin 6 (IL-6 in murine macrophages and activating mitogen-activated protein kinases (MAPK signaling pathways. Considering its easy production, store and transfer and function to promote production of endogenous wound healing agents (TGF-β, tiger17 might be an exciting biomaterial or template for the development of novel wound-healing agents.

Wound healing in animal models: review article

Directory of Open Access Journals (Sweden)

Fariba Jaffary

2017-10-01

Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

The regenerative medicine coalition. Interview with Frank-Roman Lauter.

Science.gov (United States)

Lauter, Frank-Roman

2012-11-01

Frank-Roman Lauter, Secretary General of the recently launched Regenerative Medicine Coalition, explains how the coalition was formed and what they hope to achieve. Frank-Roman Lauter has served as Secretary General of the Regenerative Medicine Coalition since 2012, and as Head of Business Development at Berlin-Brandenburg Center for Regenerative Therapies since 2007. Frank-Roman Lauter's interest is the organization of academic infrastructures to promote efficient translation of research findings into new therapies. He co-organizes joined strategy development for regenerative medicine clusters from seven European countries (FP7-EU Project) and has initiated cooperation between the California Institute for Regenerative Medicine and the German Federal Ministry for Education & Research, resulting in a joined funding program. Recently, he cofounded the international consortium of Regenerative Medicine translational centers (RMC; www.the-rmc.org ). Trained as a molecular biologist at the Max-Planck Institute in Berlin-Dahlem and at Stanford, he has 16 years of experience as an entrepreneur and life science manager in Germany and the USA.

Wound care centers

Science.gov (United States)

Pressure ulcer - wound care center; Decubitus ulcer - wound care center; Diabetic ulcer - wound care center; Surgical wound - wound ... Common types of non-healing wounds include: Pressure sores Surgical ... flow, or swollen legs Certain wounds may not heal well due to: ...

Regenerative Endodontics: Barriers and Strategies for Clinical Translation

OpenAIRE

Kim, Sahng G.; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y.; Yang, Rujing; Zhou, Xuedong; Mao, Jeremy J.

2012-01-01

Despite a great deal of enthusiasm and effort, regenerative endodontics has encountered substantial challenges towards clinical translation. Recent adoption by the American Dental Association (ADA) of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for the majority of endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other orga...

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure

Science.gov (United States)

Finosh, G.T.; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed. PMID:23507781

Phosphorous-Containing Polymers for Regenerative Medicine

Science.gov (United States)

Watson, Brendan M.; Kasper, F. Kurtis; Mikos, Antonios G.

2014-01-01

Disease and injury have resulted in a large, unmet need for functional tissue replacements. Polymeric scaffolds can be used to deliver cells and bioactive signals to address this need for regenerating damaged tissue. Phosphorous-containing polymers have been implemented to improve and accelerate the formation of native tissue both by mimicking the native role of phosphorous groups in the body and by attachment of other bioactive molecules. This manuscript reviews the synthesis, properties, and performance of phosphorous-containing polymers that can be useful in regenerative medicine applications. PMID:24565855

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization

DEFF Research Database (Denmark)

Kruse, Carla R; Singh, Mansher; Targosinski, Stefan

2017-01-01

primary keratinocyte and fibroblast function in vitro and on wound healing in vivo. In vitro, primary human keratinocytes and fibroblasts were cultured in different levels of pH (5.5-12.5) and the effect on cell viability, proliferation, and migration was studied. A rat full-thickness wound model was used...... to investigate the effect of pH (5.5-9.5) on wound healing in vivo. The effect of pH on inflammation was monitored by measuring IL-1 α concentrations from wounds and cell cultures exposed to different pH environments. Our results showed that both skin cell types tolerated wide range of pH very well. They further...... demonstrated that both acidic and alkaline environments decelerated cell migration in comparison to neutral environments and interestingly alkaline conditions significantly enhanced cell proliferation. Results from the in vivo experiments indicated that a prolonged, strongly acidic wound environment prevents...

[PERSONALIZED APPROACH TO PATIENT WITH CHRONIC WOUND IN FAMILY MEDICINE].

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Sinožić, T; Katić, M; Kovačević, J

2016-01-01

It can be said that the occurrence and development of wounds, healing, delayed healing, and the notion of chronic wound are some of the basic characteristics of all living beings. When it comes to people, there are a number of processes that take place during wound healing, and even under ideal circumstances, they create a functionally less valuable skin tissue, along with structural and functional changes. Fibrosis in the form of hypertrophic scars and keloids, contractures and adhesions are examples of excessive healing. Microcirculation is significantly different from healthy skin circulation with consequential formation of local hypoxia and stagnation in lymph flow with edema. Poor functionality of the scar tissue, particularly in the areas exposed to stronger forces, can cause forming of wounds. Such wounds are hard to heal despite the inexistence of other possible reasons for delayed healing, precisely because of their poor functionality and placement. The presence of wound requiring long-term treatment affects all areas of patient life and leads to decline in the quality of life. Exemplified by case presentation of a patient with post-traumatic wound in the scar area, in our office we showed a model of care based on the principle of overall personalized care with the biopsychosocial approach. Diagnostic and therapeutic procedures included wound assessment, biofilm and lymphedema detection, assessment of the patient’s psychosocial status, risk factors for wound healing, vascular ultrasound diagnostics, carboxytherapy as specialized adjuvant therapy, use of modern wound dressings, and compression therapy. Supportive psychotherapy was conducted in positive communication environment during treatment. In this way, in an atmosphere of cooperation with the patient, it was possible not only to influence the process of wound healing as the primary objective, but also to improve the quality of the patient’s life, as well as to influence our professional

Design of An Energy Efficient Hydraulic Regenerative circuit

Science.gov (United States)

Ramesh, S.; Ashok, S. Denis; Nagaraj, Shanmukha; Adithyakumar, C. R.; Reddy, M. Lohith Kumar; Naulakha, Niranjan Kumar

2018-02-01

Increasing cost and power demand, leads to evaluation of new method to increase through productivity and help to solve the power demands. Many researchers have break through to increase the efficiency of a hydraulic power pack, one of the promising methods is the concept of regenerative. The objective of this research work is to increase the efficiency of a hydraulic circuit by introducing a concept of regenerative circuit. A Regenerative circuit is a system that is used to speed up the extension stroke of the double acting single rod hydraulic cylinder. The output is connected to the input in the directional control value. By this concept, increase in velocity of the piston and decrease the cycle time. For the research, a basic hydraulic circuit and a regenerative circuit are designated and compared both with their results. The analysis was based on their time taken for extension and retraction of the piston. From the detailed analysis of both the hydraulic circuits, it is found that the efficiency by introducing hydraulic regenerative circuit increased by is 5.3%. The obtained results conclude that, implementing hydraulic regenerative circuit in a hydraulic power pack decreases power consumption, reduces cycle time and increases productivity in a longer run.

PRMT7 Preserves Satellite Cell Regenerative Capacity

Directory of Open Access Journals (Sweden)

Roméo Sébastien Blanc

2016-02-01

Full Text Available Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells, which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7−/− adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7-CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7-deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7-mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity.

Multispectral imaging of acute wound tissue oxygenation

Directory of Open Access Journals (Sweden)

Audrey Huong

2017-05-01

Full Text Available This paper investigates the appropriate range of values for the transcutaneous blood oxygen saturation (StO2 of granulating tissues and the surrounding tissue that can ensure timely wound recovery. This work has used a multispectral imaging system to collect wound images at wavelengths ranging between 520nm and 600nm with a resolution of 10nm. As part of this research, a pilot study was conducted on three injured individuals with superficial wounds of different wound ages at different skin locations. The StO2 value predicted for the examined wounds using the Extended Modified Lambert–Beer model revealed a mean StO2 of 61±10.3% compared to 41.6±6.2% at the surrounding tissues, and 50.1±1.53% for control sites. These preliminary results contribute to the existing knowledge on the possible range and variation of wound bed StO2 that are to be used as indicators of the functioning of the vasomotion system and wound health. This study has concluded that a high StO2 of approximately 60% and a large fluctuation in this value should precede a good progression in wound healing.

Application of Three - dimensional Wound Analyzer in the Small Wound Area Measurement during the Process of Wound Healing.

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Sheng, Jiajun; Li, Haihang; Jin, Jian; Liu, Tong; Ma, Bing; Liu, Gongcheng; Zhu, Shihui

2018-02-20

The objective of this study was to determinate the reliability of 3-dimensional wound analyzer (3-DWMD) in the wound area measurement for animal small area in the process of wound healing. Seven Sprague-Dawley rats were used to establish the skin defect model. And the wound area and time consumption were measured on days 0, 5, 10, 15 using 3-DWMD, investigators, and planimetry method. The measurement results using 3-DWMD and investigators were analyzed comparative with that using planimetry method separately. A total 46 wounds, including 32 irregular wounds and regular 14 wounds, were measured. No matter calculating the irregular wounds or the regular wounds, there was no significant difference between 3-DWMD group and planimetry group in measuring wound area (P > 0.05). However, a statistically significant difference was found in time-consuming for measuring wound area between 3-DWMD group and planimetry group (P area, and its measurement results were consistent with planimetry method. Therefore, such measuring equipment has clinical reference value for measuring precision area of the wound in the process of wound healing.

Preliminary thermodynamic study of regenerative Otto based cycles with zero NOx emissions operating with adiabatic and polytropic expansion

International Nuclear Information System (INIS)

Garcia, Ramon Ferreiro; Carril, Jose Carbia; Romero Gomez, Javier; Romero Gomez, Manuel

2016-01-01

Highlights: • Efficient polytropic expansion based Otto cycle. • Thermal efficiency is due to the inherent regeneration. • Low temperature combustion with zero NOx emissions. - Abstract: The aim of the paper is to demonstrate that a regenerative Otto cycle with adiabatic or polytropic expansion can achieve improved performance over traditional Otto engines, even exceeding the Carnot factor. Thus, the work deals with a novel regenerative Otto based internal combustion engine which differs from the conventional Otto thermal cycles in that the process of heat conversion into mechanical work is performed obeying a polytropic path function instead of the conventional adiabatic expansion without regeneration. Design characteristics concern the fact that combustion at constant volume is carried out undergoing large air excess so that the top combustion temperature is significantly lower than in conventional Otto cycles and consequently NOx emissions are neglected. Furthermore, during the polytropic expansion based path function, heat is absorbed by being submitted to a controlled heat flow rate, to achieve the desired polytropic expansion. The analysis of the regenerative Otto based on polytropic expansion is presented and results are compared with a regenerative Otto based on the adiabatic expansion and CF. The results show that a relevant advantage of the proposed regenerative Otto with polytropic expansion over the regenerative Otto cycle with adiabatic expansion involves performance enhancement within a wide range of combustion pressures, temperatures and regeneration capacities. Thus, thermal efficiency and specific work as function of the top combustion pressure ranges are of 71.95–58.43% and 143.5–173.6 kJ/kg respectively, when combustion pressures vary between 105 kPa and 200 kPa and CF is 60.8% (lower than the thermal efficiency). The successful results involving a compact engine structure, technically and economically viable, promises a new generation

Skin Wound Healing: An Update on the Current Knowledge and Concepts.

Science.gov (United States)

Sorg, Heiko; Tilkorn, Daniel J; Hager, Stephan; Hauser, Jörg; Mirastschijski, Ursula

2017-01-01

The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. Although wound healing mechanisms and specific cell functions in wound

The molecular biology in wound healing & non-healing wound.

Science.gov (United States)

Qing, Chun

2017-08-01

The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Aarhus Regenerative Orthopaedics Symposium (AROS)

DEFF Research Database (Denmark)

Foldager, Casper B.; Bendtsen, Michael; Berg, Lise C.

2016-01-01

to musculoskeletal pain and disability. The Aarhus Regenerative Orthopaedics Symposium (AROS) 2015 was motivated by the need to address regenerative challenges in an ageing population by engaging clinicians, basic scientists, and engineers. In this position paper, we review our contemporary understanding of societal......, patient-related, and basic science-related challenges in order to provide a reasoned roadmap for the future to deal with this compelling and urgent healthcare problem. © 2017 The Author(s). Published by Taylor & Francis on behalf of the Nordic Orthopedic Federation....

Aging influences wound healing in patients with chronic lower extremity wounds treated in a specialized Wound Care Center.

Science.gov (United States)

Wicke, Corinna; Bachinger, Andreas; Coerper, Stephan; Beckert, Stefan; Witte, Maria B; Königsrainer, Alfred

2009-01-01

With the dramatic increase in the aging population, the study and care of wounds in the elderly have become priority topics for both researchers and clinicians. The effects of aging on wound healing in humans have remained controversial. The study was a 5-year epidemiological evaluation of standardized data collected regularly during patients' visits at a specialized Wound Care Center with the aim to determine the key factors influencing the healing of chronic lower extremity wounds. In this analysis of 1,158 chronic wounds, the frequency of wound closure was statistically significantly lower in older patients compared with younger patients. The share of closed wounds decreased by nearly 25% in the elderly patients (>or=70 years). The relationship between the patient's age and the proportion of wound closure was nonlinear. The effect of aging on the frequency of wound closure of chronic wounds became clinically apparent after age 60. The chronicity of the wounds was illustrated by their recurrent nature, their long duration, the presence of multiple wounds, and the frequency of concurrent infection. Comorbidity was documented by the coprevalence of up to three underlying diseases related to impaired wound healing. The present study clearly showed that aging affects chronic wound healing negatively.

Deficiency of liver-derived insulin-like growth factor-I (IGF-I) does not interfere with the skin wound healing rate

Science.gov (United States)

Narayanan, Sampath; Grünler, Jacob; Sunkari, Vivekananda Gupta; Calissendorff, Freja S.; Ansurudeen, Ishrath; Illies, Christopher; Svensson, Johan; Jansson, John-Olov; Ohlsson, Claes; Brismar, Kerstin; Catrina, Sergiu-Bogdan

2018-01-01

Objective IGF-I is a growth factor, which is expressed in virtually all tissues. The circulating IGF-I is however derived mainly from the liver. IGF-I promotes wound healing and its levels are decreased in wounds with low regenerative potential such as diabetic wounds. However, the contribution of circulating IGF-I to wound healing is unknown. Here we investigated the role of systemic IGF-I on wound healing rate in mice with deficiency of liver-derived IGF-I (LI-IGF-I-/- mice) during normal (normoglycemic) and impaired wound healing (diabetes). Methods LI-IGF-I-/- mice with complete inactivation of the IGF-I gene in the hepatocytes were generated using the Cre/loxP recombination system. This resulted in a 75% reduction of circulating IGF-I. Diabetes was induced with streptozocin in both LI-IGF-I-/- and control mice. Wounds were made on the dorsum of the mice, and the wound healing rate and histology were evaluated. Serum IGF-I and GH were measured by RIA and ELISA respectively. The expression of IGF-I, IGF-II and the IGF-I receptor in the skin were evaluated by qRT-PCR. The local IGF-I protein expression in different cell types of the wounds during wound healing process was analyzed using immunohistochemistry. Results The wound healing rate was similar in LI-IGF-I-/- mice to that in controls. Diabetes significantly delayed the wound healing rate in both LI-IGF-I-/- and control mice. However, no significant difference was observed between diabetic animals with normal or reduced hepatic IGF-I production. The gene expression of IGF-I, IGF-II and IGF-I receptor in skin was not different between any group of animals tested. Local IGF-I levels in the wounds were similar between of LI-IGF-I-/- and WT mice although a transient reduction of IGF-I expression in leukocytes in the wounds of LI-IGF-I-/- was observed seven days post wounding. Conclusion Deficiency in the liver-derived IGF-I does not affect wound healing in mice, neither in normoglycemic conditions nor in

Regenerative braking strategies, vehicle safety and stability control systems: critical use-case proposals

Science.gov (United States)

Oleksowicz, Selim A.; Burnham, Keith J.; Southgate, Adam; McCoy, Chris; Waite, Gary; Hardwick, Graham; Harrington, Cian; McMurran, Ross

2013-05-01

The sustainable development of vehicle propulsion systems that have mainly focused on reduction of fuel consumption (i.e. CO2 emission) has led, not only to the development of systems connected with combustion processes but also to legislation and testing procedures. In recent years, the low carbon policy has made hybrid vehicles and fully electric vehicles (H/EVs) popular. The main virtue of these propulsion systems is their ability to restore some of the expended energy from kinetic movement, e.g. the braking process. Consequently new research and testing methods for H/EVs are currently being developed. This especially concerns the critical 'use-cases' for functionality tests within dynamic events for both virtual simulations, as well as real-time road tests. The use-case for conventional vehicles for numerical simulations and road tests are well established. However, the wide variety of tests and their great number (close to a thousand) creates a need for selection, in the first place, and the creation of critical use-cases suitable for testing H/EVs in both virtual and real-world environments. It is known that a marginal improvement in the regenerative braking ratio can significantly improve the vehicle range and, therefore, the economic cost of its operation. In modern vehicles, vehicle dynamics control systems play the principal role in safety, comfort and economic operation. Unfortunately, however, the existing standard road test scenarios are insufficient for H/EVs. Sector knowledge suggests that there are currently no agreed tests scenarios to fully investigate the effects of brake blending between conventional and regenerative braking as well as the regenerative braking interaction with active driving safety systems (ADSS). The paper presents seven manoeuvres, which are considered to be suitable and highly informative for the development and examination of H/EVs with regenerative braking capability. The critical manoeuvres presented are considered to be

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

Directory of Open Access Journals (Sweden)

Paulina Krzyszczyk

2018-05-01

Full Text Available Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes to anti-inflammatory (M2-like phenotypes. Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1 expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds.

The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes

Science.gov (United States)

Krzyszczyk, Paulina; Schloss, Rene; Palmer, Andre; Berthiaume, François

2018-01-01

Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation—the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds. PMID:29765329

A survey of dental residents' expectations for regenerative endodontics.

Science.gov (United States)

Manguno, Christine; Murray, Peter E; Howard, Cameron; Madras, Jonathan; Mangan, Stephen; Namerow, Kenneth N

2012-02-01

The objective was to survey a group of dental residents regarding their expectations for using regenerative endodontic procedures as part of future dental treatments. After institutional review board approval, the opinions of 32 dentists who were having postgraduate residency training to become specialists in a dental school were surveyed. The survey had 40 questions about professional status, ethical beliefs, judgment, and clinical practice. It was found that 83.9% of dentists had no continuing education or training in stem cells or regenerative endodontic procedures. Results showed that 96.8% of dentists are willing to receive training to be able to provide regenerative endodontic procedures for their patients. Of the total group, 49.1% of dentists already use membranes, scaffolds, or bioactive materials to provide dental treatment. It was determined that 47.3% of dentists agree that the costs of regenerative procedures should be comparable with current treatments. It was also found that 55.1% of dentists were unsure whether regenerative procedures would be successful. Dentists are supportive of using regenerative endodontic procedures in their dental practice, and they are willing to undergo extra training and to buy new technology to provide new procedures. Nevertheless, dentists also need more evidence for the effectiveness and safety of regenerative treatments before they will be recommended for most patients. Copyright © 2012. Published by Elsevier Inc.

Impaired cutaneous wound healing in mice lacking tetranectin

DEFF Research Database (Denmark)

Iba, Kousuke; Hatakeyama, Naoko; Kojima, Takashi

2009-01-01

disruption of the tetranectin gene to elucidate the biological function of tetranectin. In this study, we showed that wound healing was markedly delayed in tetranectin-null mice compared with wild-type mice. A single full-thickness incision was made in the dorsal skin. By 14 days after the incision......, the wounds fully healed in all wild-type mice based on the macroscopic closure; in contrast, the progress of wound healing in the tetranectin null mice appeared to be impaired. In histological analysis, wounds of wild-type mice showed complete reepithelialization and healed by 14 days after the incision....... However, those of tetranectin-null mice never showed complete reepithelialization at 14 days. At 21 days after the injury, the wound healed and was covered with an epidermis. These results supported the fact that tetranectin may play a role in the wound healing process....

Endothelial Jagged-1 Is Necessary for Homeostatic and Regenerative Hematopoiesis

Directory of Open Access Journals (Sweden)

Michael G. Poulos

2013-09-01

Full Text Available The bone marrow (BM microenvironment is composed of multiple niche cells that, by producing paracrine factors, maintain and regenerate the hematopoietic stem cell (HSC pool (Morrison and Spradling, 2008. We have previously demonstrated that endothelial cells support the proper regeneration of the hematopoietic system following myeloablation (Butler et al., 2010; Hooper et al., 2009; Kobayashi et al., 2010. Here, we demonstrate that expression of the angiocrine factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and regenerative hematopoiesis through a Notch-dependent mechanism. Conditional deletion of Jagged-1 in endothelial cells (Jag1(ECKO mice results in a profound decrease in hematopoiesis and premature exhaustion of the adult HSC pool, whereas quantification and functional assays demonstrate that loss of Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together, these data demonstrate that the instructive function of endothelial-specific Jagged-1 is required to support the self-renewal and regenerative capacity of HSCs in the adult BM vascular niche.

Three-dimensional wound measurements for monitoring wound healing

DEFF Research Database (Denmark)

Bisgaard Jørgensen, Line; Møller Jeppesen, Sune; Halekoh, Ulrich

Telemedicine is increasingly used for monitoring wound healing. Three-dimensional (3D) measurement methods enable clinicians to assess wound healing with respect to all dimensions. However, the currently available methods are inaccurate, costly or complicated to use. To address these issues, a 3D......-WAM camera was developed. This camera is able to measure wound size (2D area, 3D area, perimeter and volume) and to assess wound characteristics....

[Aesthetic effect of wound repair with flaps].

Science.gov (United States)

Tan, Qian; Zhou, Hong-Reng; Wang, Shu-Qin; Zheng, Dong-Feng; Xu, Peng; Wu, Jie; Ge, Hua-Qiang; Lin, Yue; Yan, Xin

2012-08-01

To investigate the aesthetic effect of wound repair with flaps. One thousand nine hundred and ninety-six patients with 2082 wounds hospitalized from January 2004 to December 2011. These wounds included 503 deep burn wounds, 268 pressure sores, 392 soft tissue defects caused by trauma, 479 soft tissue defects due to resection of skin cancer and mole removal, 314 soft tissue defects caused by scar excision, and 126 other wounds. Wound area ranged from 1.5 cm x 1.0 cm to 30.0 cm x 22.0 cm. Sliding flaps, expanded flaps, pedicle flaps, and free flaps were used to repair the wounds in accordance with the principle and timing of wound repair with flaps. Five flaps showed venous congestion within 48 hours post-operation, 2 flaps of them improved after local massage. One flap survived after local heparin wet packing and venous bloodletting. One flap survived after emergency surgical embolectomy and bridging with saphenous vein graft. One flap showed partial necrosis and healed after skin grafting. The other flaps survived well. One thousand three hundred and twenty-one patients were followed up for 3 months to 2 years, and flaps of them were satisfactory in shape, color, and elasticity, similar to that of normal skin. Some patients underwent scar revision later with good results. Application of suitable flaps in wound repair will result in quick wound healing, good function recovery, and satisfactory aesthetic effect.

Characterization of Aeromonas hydrophila Wound Pathotypes by Comparative Genomic and Functional Analyses of Virulence Genes

Science.gov (United States)

Grim, Christopher J.; Kozlova, Elena V.; Sha, Jian; Fitts, Eric C.; van Lier, Christina J.; Kirtley, Michelle L.; Joseph, Sandeep J.; Read, Timothy D.; Burd, Eileen M.; Tall, Ben D.; Joseph, Sam W.; Horneman, Amy J.; Chopra, Ashok K.; Shak, Joshua R.

2013-01-01

ABSTRACT Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966T, and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966T. The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966T and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. PMID:23611906

Lumican as a multivalent effector in wound healing.

Science.gov (United States)

Karamanou, Konstantina; Perrot, Gwenn; Maquart, Francois-Xavier; Brézillon, Stéphane

2018-03-01

Wound healing, a complex physiological process, is responsible for tissue repair after exposure to destructive stimuli, without resulting in complete functional regeneration. Injuries can be stromal or epithelial, and most cases of wound repair have been studied in the skin and cornea. Lumican, a small leucine-rich proteoglycan, is expressed in the extracellular matrices of several tissues, such as the cornea, cartilage, and skin. This molecule has been shown to regulate collagen fibrillogenesis, keratinocyte phenotypes, and corneal transparency modulation. Lumican is also involved in the extravasation of inflammatory cells and angiogenesis, which are both critical in stromal wound healing. Lumican is the only member of the small leucine-rich proteoglycan family expressed by the epithelia during wound healing. This review summarizes the importance of lumican in wound healing and potential methods of lumican drug delivery to target wound repair are discussed. The involvement of lumican in corneal wound healing is described based on in vitro and in vivo models, with critical emphasis on its underlying mechanisms of action. Similarly, the expression and role of lumican in the healing of other tissues are presented, with emphasis on skin wound healing. Overall, lumican promotes normal wound repair and broadens new therapeutic perspectives for impaired wound healing. Copyright © 2018. Published by Elsevier B.V.

Effect of aging on wound healing: current concepts.

Science.gov (United States)

Pittman, Joyce

2007-01-01

The population is aging, and advanced age is commonly identified as a risk factor for delayed wound healing. Therefore, it is important for WOC nurses to be knowledgeable about how aging affects the wound healing and repair process, and strategies they can use to promote healing in the elderly population. Impaired wound healing in the aged is due partly to comorbidities common among the elderly, but evidence also suggests that inherent differences in cellular structure and function may impair tissue repair and regeneration as well. This article will address the effect of aging on wound healing, with a particular focus on processes of cellular senescence and related factors hypothesized to result in slowed or impaired wound healing in the elderly.

Temporomandibular Joint Regenerative Medicine

Directory of Open Access Journals (Sweden)

Xavier Van Bellinghen

2018-02-01

Full Text Available The temporomandibular joint (TMJ is an articulation formed between the temporal bone and the mandibular condyle which is commonly affected. These affections are often so painful during fundamental oral activities that patients have lower quality of life. Limitations of therapeutics for severe TMJ diseases have led to increased interest in regenerative strategies combining stem cells, implantable scaffolds and well-targeting bioactive molecules. To succeed in functional and structural regeneration of TMJ is very challenging. Innovative strategies and biomaterials are absolutely crucial because TMJ can be considered as one of the most difficult tissues to regenerate due to its limited healing capacity, its unique histological and structural properties and the necessity for long-term prevention of its ossified or fibrous adhesions. The ideal approach for TMJ regeneration is a unique scaffold functionalized with an osteochondral molecular gradient containing a single stem cell population able to undergo osteogenic and chondrogenic differentiation such as BMSCs, ADSCs or DPSCs. The key for this complex regeneration is the functionalization with active molecules such as IGF-1, TGF-β1 or bFGF. This regeneration can be optimized by nano/micro-assisted functionalization and by spatiotemporal drug delivery systems orchestrating the 3D formation of TMJ tissues.

Overcoming immunological barriers in regenerative medicine.

Science.gov (United States)

Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A

2014-08-01

Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists.

Regenerative endodontics--Creating new horizons.

Science.gov (United States)

Dhillon, Harnoor; Kaushik, Mamta; Sharma, Roshni

2016-05-01

Trauma to the dental pulp, physical or microbiologic, can lead to inflammation of the pulp followed by necrosis. The current treatment modality for such cases is non-surgical root canal treatment. The damaged tissue is extirpated and the root canal system prepared. It is then obturated with an inert material such a gutta percha. In spite of advances in techniques and materials, 10%-15% of the cases may end in failure of treatment. Regenerative endodontics combines principles of endodontics, cell biology, and tissue engineering to provide an ideal treatment for inflamed and necrotic pulp. It utilizes mesenchymal stem cells, growth factors, and organ tissue culture to provide treatment. Potential treatment modalities include induction of blood clot for pulp revascularization, scaffold aided regeneration, and pulp implantation. Although in its infancy, successful treatment of damaged pulp tissue has been performed using principles of regenerative endodontics. This field is dynamic and exciting with the ability to shape the future of endodontics. This article highlights the fundamental concepts, protocol for treatment, and possible avenues for research in regenerative endodontics. © 2015 Wiley Periodicals, Inc.

MSCs-derived exosomes: cell-secreted nanovesicles with regenerative potential

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Ana Marote

2016-08-01

Full Text Available Exosomes are membrane-enclosed nanovesicles (30-150 nm that shuttle active cargoes between different cells. These tiny extracellular vesicles have been recently isolated from mesenchymal stem cells (MSCs conditioned medium, a population of multipotent cells identified in several adult tissues. MSCs paracrine activity has been already shown to be the key mediator of their elicited regenerative effects. On the other hand, the individual contribution of MSCs-derived exosomes for these effects is only now being unraveled. The administration of MSCs-derived exosomes has been demonstrated to restore tissue function in multiple diseases/injury models and to induce beneficial in vitro effects, mainly mediated by exosomal-enclosed miRNAs. Additionally, the source and the culture conditions of MSCs have been shown to influence the regenerative responses induced by exosomes. Therefore, these studies reveal that MSCs-derived exosomes hold a great potential for cell-free therapies that are safer and easier to manipulate than cell-based products. Nevertheless, this is an emerging research field and hence, further studies are required to understand the full dimension of this complex intercellular communication system and how it can be optimized to take full advantage of its therapeutic effects. In this mini-review, we summarize the most significant new advances in the regenerative properties of MSCs-derived exosomes and discuss the molecular mechanisms underlying these effects.

Wound-Related Allergic/Irritant Contact Dermatitis.

Science.gov (United States)

Alavi, Afsaneh; Sibbald, R Gary; Ladizinski, Barry; Saraiya, Ami; Lee, Kachiu C; Skotnicki-Grant, Sandy; Maibach, Howard

2016-06-01

To provide information from a literature review about the prevention, recognition, and treatment for contact dermatitis. This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. After participating in this educational activity, the participant should be better able to:1. Identify signs and symptoms of and diagnostic measures for contact dermatitis.2. Identify causes and risks for contact dermatitis.3. Select appropriate treatment for contact dermatitis and its prevention. Contact dermatitis to wound care products is a common, often neglected problem. A review was conducted to identify articles relevant to contact dermatitis.A PubMed English-language literature review was conducted for appropriate articles published between January 2000 and December 2015.Contact dermatitis is both irritant (80% of cases) or allergic (20% of cases). Frequent use of potential contact allergens and impaired barrier function of the skin can lead to rising sensitization in patients with chronic wounds. Common known allergens to avoid in wound care patients include fragrances, colophony, lanolin, and topical antibiotics.Clinicians should be cognizant of the allergens in wound care products and the potential for sensitization. All medical devices, including wound dressings, adhesives, and bandages, should be labeled with their complete ingredients, and manufacturers should be encouraged to remove common allergens from wound care products, including topical creams, ointments, and dressings.

The dissolution kinetics of magnetite under regenerative conditions

International Nuclear Information System (INIS)

Ranganathan, S.

2004-01-01

Dissolution studies of magnetite were carried out under regenerative conditions in dilute chemical decontamination formulations. During regeneration of the formulation, the H + from the strong acid cation exchange resin gets released and the metal is absorbed on the resin. The efficiency of the regenerative process depends on the stability constants of the complexes involved and the selectivity on the ion exchange column. The regenerative condition helps to maintain a constant chelating agent concentration and pH during the dissolution experiment. Such a condition is ideal for obtaining data on the dissolution behaviour of the corrosion products with special application to actual reactor decontamination. The ethylenediaminetetraacetic acid (EDTA) based formulation used was found to be ineffective due to the high stability constant of Fe(III)-EDTA complex, which is not easily cleaved by the cation exchange resin. Hence, knowledge of the kinetics of magnetite dissolution under regenerative condition is of primary importance. The 2,6-pyridinedicarboxylic acid formulation is found to be better for the dissolution of Fe 3 O 4 in both static and regenerative modes in the presence of reductants than nitrilotriacetic acid and EDTA. (orig.)

The dissolution kinetics of magnetite under regenerative conditions

Energy Technology Data Exchange (ETDEWEB)

Ranganathan, S. [New Brunswick Univ., Frederiction (Canada). Dept. of Chemical Engineering; Raghavan, P.S.; Gopalan, R.; Srinivasan, M.P.; Narasimhan, S.V. [Water and Steam Chemistry Lab. of Bhabha Atomic Research Centre (BARC) (India)

2004-07-01

Dissolution studies of magnetite were carried out under regenerative conditions in dilute chemical decontamination formulations. During regeneration of the formulation, the H{sup +} from the strong acid cation exchange resin gets released and the metal is absorbed on the resin. The efficiency of the regenerative process depends on the stability constants of the complexes involved and the selectivity on the ion exchange column. The regenerative condition helps to maintain a constant chelating agent concentration and pH during the dissolution experiment. Such a condition is ideal for obtaining data on the dissolution behaviour of the corrosion products with special application to actual reactor decontamination. The ethylenediaminetetraacetic acid (EDTA) based formulation used was found to be ineffective due to the high stability constant of Fe(III)-EDTA complex, which is not easily cleaved by the cation exchange resin. Hence, knowledge of the kinetics of magnetite dissolution under regenerative condition is of primary importance. The 2,6-pyridinedicarboxylic acid formulation is found to be better for the dissolution of Fe{sub 3}O{sub 4} in both static and regenerative modes in the presence of reductants than nitrilotriacetic acid and EDTA. (orig.)

Exercise accelerates wound healing among healthy older adults: a preliminary investigation.

Science.gov (United States)

Emery, Charles F; Kiecolt-Glaser, Janice K; Glaser, Ronald; Malarkey, William B; Frid, David J

2005-11-01

Older adults are likely to experience delayed rates of wound healing, impaired neuroendocrine responsiveness, and increased daily stress. Exercise activity has been shown to have a positive effect on physiological functioning and psychological functioning among older adults. This study evaluated the effect of a 3-month exercise program on wound healing, neuroendocrine function, and perceived stress among healthy older adults. Twenty-eight healthy older adults (mean age 61.0 +/- 5.5 years) were assigned randomly to an exercise activity group (n = 13) or to a nonexercise control group (n = 15). One month following baseline randomization, after exercise participants had acclimated to the exercise routine, all participants underwent an experimental wound procedure. Wounds were measured 3 times per week until healed to calculate rate of wound healing. All participants completed assessments of exercise endurance, salivary cortisol, and self-reported stress prior to randomization and at the conclusion of the intervention. Exercise participants achieved significant improvements in cardiorespiratory fitness, as reflected by increased oxygen consumption (VO(2)max) and exercise duration. Wound healing occurred at a significantly faster rate in the exercise group [mean = 29.2 (9.0) days] than in the nonexercise group [38.9 (7.4) days; p =.012]. Exercise participants also experienced increased cortisol secretion during stress testing following the intervention. Group differences in wound healing and neuroendocrine responsiveness were found despite low levels of self-reported stress. A relatively short-term exercise intervention is associated with enhanced rates of wound healing among healthy older adults. Thus, exercise activity may be an important component of health care to promote wound healing.

Wound Healing Potential of Chlorogenic Acid and Myricetin-3-O-β-Rhamnoside Isolated from Parrotia persica

Directory of Open Access Journals (Sweden)

Sara E. Moghadam

2017-09-01

Full Text Available Wound healing is a complex physiological process that is controlled by a well-orchestrated cascade of interdependent biochemical and cellular events, which has spurred the development of therapeutics that simultaneously target these active cellular constituents. We assessed the potential of Parrotia persica (Hamamelidaceae in wound repair by analyzing the regenerative effects of its two main phenolic compounds, myricetin-3-O-β-rhamnoside and chlorogenic acid. To accomplish this, we performed phytochemical profiling and characterized the chemical structure of pure compounds isolated from P. persica, followed by an analysis of the biological effects of myricetin-3-O-β-rhamnoside and chlorogenic acid on three cell types, including keratinocytes, fibroblasts, and endothelial cells. Myricetin-3-O-β-rhamnoside and chlorogenic acid exhibited complementary pro-healing properties. The percentage of keratinocyte wound closure as measured by a scratch assay was four fold faster in the presence of 10 µg/mL chlorogenic acid, as compared to the negative control. On the other hand, myricetin-3-O-β-rhamnoside at 10 µg/mL was more effective in promoting fibroblast migration, demonstrating a two-fold higher rate of closure compared to the negative control group. Both compounds enhanced the capillary-like tube formation of endothelial cells in an in vitro angiogenesis assay. Our results altogether delineate the potential to synergistically accelerate the fibroblastic and remodelling phases of wound repair by administering appropriate amounts of myricetin-3-O-β-rhamnoside and chlorogenic acid.

Artificial organs versus regenerative medicine: is it true?

Science.gov (United States)

Nosé, Yukihiko; Okubo, Hisashi

2003-09-01

Individuals engaged in the fields of artificial kidney and artificial heart have often mistakenly stated that "the era of artificial organs is over; regenerative medicine is the future." Contrarily, we do not believe artificial organs and regenerative medicine are different medical technologies. As a matter of fact, artificial organs developed during the last 50 years have been used as a bridge to regeneration. The only difference between regenerative medicine and artificial organs is that artificial organs for the bridge to regeneration promote tissue regeneration in situ, instead of outside the body (for example, vascular prostheses, neuroprostheses, bladder substitutes, skin prostheses, bone prostheses, cartilage prostheses, ligament prostheses, etc.). All of these artificial organs are successful because tissue regeneration over a man-made prosthesis is established inside the patient's body (artificial organs to support regeneration). Another usage of the group of artificial organs for the bridge to regeneration is to sustain the functions of the patient's diseased organs during the regeneration process of the body's healthy tissues and/or organs. This particular group includes artificial kidney, hepatic assist, respiratory assist, and circulatory assist. Proof of regeneration of these healthy tissues and/or organs is demonstrated in the short-term recovery of end-stage organ failure patients (artificial organs for bridge to regeneration). A third group of artificial organs for the bridge to regeneration accelerates the regenerating process of the patient's healthy tissues and organs. This group includes neurostimulators, artificial blood (red cells) blood oxygenators, and plasmapheresis devices, including hemodiafiltrators. So-called "therapeutic artificial organs" fall into this category (artificial organs to accelerate regeneration). Thus, almost all of today's artificial organs are useful in the bridge to regeneration of healthy natural tissues and organs

Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

Science.gov (United States)

2015-11-01

1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

Effect of platelet lysate on human cells involved in different phases of wound healing.

Directory of Open Access Journals (Sweden)

Maria Chiara Barsotti

Full Text Available BACKGROUND: Platelets are rich in mediators able to positively affect cell activity in wound healing. Aim of this study was to characterize the effect of different concentrations of human pooled allogeneic platelet lysate on human cells involved in the different phases of wound healing (inflammatory phase, angiogenesis, extracellular matrix secretion and epithelialization. METHODOLOGY/PRINCIPAL FINDINGS: Platelet lysate effect was studied on endothelial cells, monocytes, fibroblasts and keratinocytes, in terms of viability and proliferation, migration, angiogenesis, tissue repair pathway activation (ERK1/2 and inflammatory response evaluation (NFκB. Results were compared both with basal medium and with a positive control containing serum and growth factors. Platelet lysate induced viability and proliferation at the highest concentrations tested (10% and 20% v/v. Whereas both platelet lysate concentrations increased cell migration, only 20% platelet lysate was able to significantly promote angiogenic activity (p<0.05 vs. control, comparably to the positive control. Both platelet lysate concentrations activated important inflammatory pathways such as ERK1/2 and NFκB with the same early kinetics, whereas the effect was different for later time-points. CONCLUSION/SIGNIFICANCE: These data suggest the possibility of using allogeneic platelet lysate as both an alternative to growth factors commonly used for cell culture and as a tool for clinical regenerative application for wound healing.

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment.

Science.gov (United States)

Xiao, Yun; Ahadian, Samad; Radisic, Milica

2017-02-01

Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different biochemical (e.g., growth factors, peptides, DNA, and RNA) and biophysical (e.g., topographical guidance, pressure, electrical stimulation, and pulsed electromagnetic field) cues providing a functional and instructive acellular matrix to heal diabetic chronic wounds. The biochemical and biophysical signals generally regulate cell-matrix interactions and cell behavior and function inducing the tissue regeneration for chronic wounds. Some technologies and devices have already been developed and used in the clinic employing biochemical and biophysical cues for wound healing applications. These technologies can be integrated with smart biomaterials to deliver therapeutic agents to the wound tissue in a precise and controllable manner. This review provides useful guidance in understanding molecular mechanisms and signals in the healing of diabetic chronic wounds and in designing instructive biomaterials to treat them.

Development of a wound healing index for patients with chronic wounds.

Science.gov (United States)

Horn, Susan D; Fife, Caroline E; Smout, Randall J; Barrett, Ryan S; Thomson, Brett

2013-01-01

Randomized controlled trials in wound care generalize poorly because they exclude patients with significant comorbid conditions. Research using real-world wound care patients is hindered by lack of validated methods to stratify patients according to severity of underlying illnesses. We developed a comprehensive stratification system for patients with wounds that predicts healing likelihood. Complete medical record data on 50,967 wounds from the United States Wound Registry were assigned a clear outcome (healed, amputated, etc.). Factors known to be associated with healing were evaluated using logistic regression models. Significant variables (p healing for each wound type. Some variables predicted significantly in nearly all models: wound size, wound age, number of wounds, evidence of bioburden, tissue type exposed (Wagner grade or stage), being nonambulatory, and requiring hospitalization during the course of care. Variables significant in some models included renal failure, renal transplant, malnutrition, autoimmune disease, and cardiovascular disease. All models validated well when applied to the holdout sample. The "Wound Healing Index" can validly predict likelihood of wound healing among real-world patients and can facilitate comparative effectiveness research to identify patients needing advanced therapeutics. © 2013 by the Wound Healing Society.

Cooperative Control of Regenerative Braking and Antilock Braking for a Hybrid Electric Vehicle

Directory of Open Access Journals (Sweden)

Guodong Yin

2013-01-01

Full Text Available A new cooperative braking control strategy (CBCS is proposed for a parallel hybrid electric vehicle (HEV with both a regenerative braking system and an antilock braking system (ABS to achieve improved braking performance and energy regeneration. The braking system of the vehicle is based on a new method of HEV braking torque distribution that makes the antilock braking system work together with the regenerative braking system harmoniously. In the cooperative braking control strategy, a sliding mode controller (SMC for ABS is designed to maintain the wheel slip within an optimal range by adjusting the hydraulic braking torque continuously; to reduce the chattering in SMC, a boundary-layer method with moderate tuning of a saturation function is also investigated; based on the wheel slip ratio, battery state of charge (SOC, and the motor speed, a fuzzy logic control strategy (FLC is applied to adjust the regenerative braking torque dynamically. In order to evaluate the performance of the cooperative braking control strategy, the braking system model of a hybrid electric vehicle is built in MATLAB/SIMULINK. It is found from the simulation that the cooperative braking control strategy suggested in this paper provides satisfactory braking performance, passenger comfort, and high regenerative efficiency.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine

Science.gov (United States)

Samsonraj, Rebekah M.; Raghunath, Michael; Nurcombe, Victor; Hui, James H.

2017-01-01

Abstract Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self‐renewal and differentiation into tissue‐specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age‐related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone‐forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical‐grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173–2185 PMID:29076267

Regenerative Hydride Heat Pump

Science.gov (United States)

Jones, Jack A.

1992-01-01

Hydride heat pump features regenerative heating and single circulation loop. Counterflow heat exchangers accommodate different temperatures of FeTi and LaNi4.7Al0.3 subloops. Heating scheme increases efficiency.

Combined hydraulic and regenerative braking system

Science.gov (United States)

Venkataperumal, R.R.; Mericle, G.E.

1979-08-09

A combined hydraulic and regenerative braking system and method for an electric vehicle is disclosed. The braking system is responsive to the applied hydraulic pressure in a brake line to control the braking of the vehicle to be completely hydraulic up to a first level of brake line pressure, to be partially hydraulic at a constant braking force and partially regenerative at a linearly increasing braking force from the first level of applied brake line pressure to a higher second level of brake line pressure, to be partially hydraulic at a linearly increasing braking force and partially regenerative at a linearly decreasing braking force from the second level of applied line pressure to a third and higher level of applied line pressure, and to be completely hydraulic at a linearly increasing braking force from the third level to all higher applied levels of line pressure.

Regenerative agriculture: merging farming and natural resource conservation profitably.

Science.gov (United States)

LaCanne, Claire E; Lundgren, Jonathan G

2018-01-01

Most cropland in the United States is characterized by large monocultures, whose productivity is maintained through a strong reliance on costly tillage, external fertilizers, and pesticides (Schipanski et al., 2016). Despite this, farmers have developed a regenerative model of farm production that promotes soil health and biodiversity, while producing nutrient-dense farm products profitably. Little work has focused on the relative costs and benefits of novel regenerative farming operations, which necessitates studying in situ , farmer-defined best management practices. Here, we evaluate the relative effects of regenerative and conventional corn production systems on pest management services, soil conservation, and farmer profitability and productivity throughout the Northern Plains of the United States. Regenerative farming systems provided greater ecosystem services and profitability for farmers than an input-intensive model of corn production. Pests were 10-fold more abundant in insecticide-treated corn fields than on insecticide-free regenerative farms, indicating that farmers who proactively design pest-resilient food systems outperform farmers that react to pests chemically. Regenerative fields had 29% lower grain production but 78% higher profits over traditional corn production systems. Profit was positively correlated with the particulate organic matter of the soil, not yield. These results provide the basis for dialogue on ecologically based farming systems that could be used to simultaneously produce food while conserving our natural resource base: two factors that are pitted against one another in simplified food production systems. To attain this requires a systems-level shift on the farm; simply applying individual regenerative practices within the current production model will not likely produce the documented results.

Analysis of the rate of maturogenesis of a traumatized Cvek's stage 3 anterior tooth treated with platelet-rich fibrin as a regenerative tool using three-dimensional cone-beam computed tomography: an original case report.

Science.gov (United States)

Solomon, Raji Viola; Faizuddin, Umrana; Guniganti, Sushma Shravani; Waghray, Shefali

2015-01-01

Regenerative endodontic procedures are biologically based procedures which deal with the regeneration of pulp-like tissue, more idealistically the pulp-dentin complex. The regeneration of this pulp-dentin complex in an infected necrotic tooth with an open apex is possible only when the canal is effectively disinfected. Though there are various procedures for treating open apex ranging from Ca(OH) 2 apexification, mineral trioxide aggregate apexification and surgical approach, regeneration of tissues has always taken superior hand over the repair of tissues. The mechanics behind the regenerative endodontic procedures is that despite the tooth being necrotic, some pulp tissue can survive apically which under favorable conditions proliferate to aid in the process of regeneration. In the past 2 decades, an increased understanding of the physiological roles of platelets in wound healing and after tissue injury has led to the idea of using platelets as therapeutic tools in the field regenerative endodontics. In the present case report with an open apex, high sterilization protocol is followed using triple antibiotic paste as intra-canal medicament, followed which platelet rich fibrin is used as the regenerative material of choice. Over an 18-month follow-up period, clinically patient is asymptomatic and radiographically there is complete regression of the periapical lesion and initiation of the root end closure.

Autonomous Operation of Super-Regenerative Receiver in BAN

NARCIS (Netherlands)

Kalyanasundaram, P.; Huang, L.; Dolmans, G.; Imamura, K.

2012-01-01

Super-regenerative receiver is one of the potential candidates to achieve ultra low power wireless communication in body area network (BAN). The main limitations of the super-regenerative receiver include the difficulty in choosing a good quench waveform to optimize its sensitivity and selectivity,

Managing painful chronic wounds: the Wound Pain Management Model

DEFF Research Database (Denmark)

Price, Patricia; Fogh, Karsten; Glynn, Chris

2007-01-01

of the pain experience: location, duration, intensity, quality, onset and impact on activities of daily living. Holistic management must be based on a safe and effective mix of psychosocial approaches together with local and systemic pain management. It is no longer acceptable to ignore or inadequately...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...... document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr...

Adaptive controller for regenerative and friction braking system

Science.gov (United States)

Davis, Roy I.

1990-01-01

A regenerative and friction braking system for a vehicle having one or more roadwheels driven by an electric traction motor includes a driver responsive device for producing a brake demand signal having a magnitude corresponding to the level of braking force selected by the driver and friction and regenerative brakes operatively connected with the roadwheels of the vehicle. A system according to this invention further includes control means for operating the friction and regenerative braking subsystems so that maximum brake torques sustainable by the roadwheels of the vehicle without skidding or slipping will not be exceeded.

Wound repair during arm regeneration in the red starfish Echinaster sepositus

KAUST Repository

Ben Khadra, Yousra

2015-06-24

Starfish can regenerate entire arms following their loss by both autotomic and traumatic amputation. Although the overall regenerative process has been studied several times in different asteroid species, there is still a considerable gap of knowledge as far as the detailed aspects of the repair phase at tissue and cellular level are concerned, particularly in post-traumatic regeneration. The present work is focused on the arm regeneration model in the Mediterranean red starfish Echinaster sepositus; in order to describe the early cellular mechanisms of arm regeneration following traumatic amputation, different microscopy techniques were employed. In E. sepositus, the repair phase was characterized by prompt wound healing by a syncytial network of phagocytes and re-epithelialisation followed by a localized subepidermal oedematous area formation. Scattered and apparently undifferentiated cells, intermixed with numerous phagocytes, were frequently found in the wound area during these first stages of regeneration and extensive dedifferentiation phenomena were seen at the level of the stump, particularly in the muscle bundles. A true localized blastema did not form. Our results confirm that regeneration in asteroids mainly relies on morphallactic processes, consisting in extensive rearrangement of the existing tissues which contribute to the new tissues through cell dedifferentiation, re-differentiation and/or migration. This article is protected by copyright. All rights reserved.

State of the art: stem cells in equine regenerative medicine.

Science.gov (United States)

Lopez, M J; Jarazo, J

2015-03-01

According to Greek mythology, Prometheus' liver grew back nightly after it was removed each day by an eagle as punishment for giving mankind fire. Hence, contrary to popular belief, the concept of tissue and organ regeneration is not new. In the early 20th century, cell culture and ex vivo organ preservation studies by Alexis Carrel, some with famed aviator Charles Lindbergh, established a foundation for much of modern regenerative medicine. While early beliefs and discoveries foreshadowed significant accomplishments in regenerative medicine, advances in knowledge within numerous scientific disciplines, as well as nano- and micromolecular level imaging and detection technologies, have contributed to explosive advances over the last 20 years. Virtually limitless preparations, combinations and applications of the 3 major components of regenerative medicine, namely cells, biomaterials and bioactive molecules, have created a new paradigm of future therapeutic options for most species. It is increasingly clear, however, that despite significant parallels among and within species, there is no 'one-size-fits-all' regenerative therapy. Likewise, a panacea has yet to be discovered that completely reverses the consequences of time, trauma and disease. Nonetheless, there is no question that the promise and potential of regenerative medicine have forever altered medical practices. The horse is a relative newcomer to regenerative medicine applications, yet there is already a large body of work to incorporate novel regenerative therapies into standard care. This review focuses on the current state and potential future of stem cells in equine regenerative medicine. © 2014 EVJ Ltd.

The role of nuclear hormone receptors in cutaneous wound repair.

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Rieger, Sandra; Zhao, Hengguang; Martin, Paige; Abe, Koichiro; Lisse, Thomas S

2015-01-01

The cutaneous wound repair process involves balancing a dynamic series of events ranging from inflammation, oxidative stress, cell migration, proliferation, survival and differentiation. A complex series of secreted trophic factors, cytokines, surface and intracellular proteins are expressed in a temporospatial manner to restore skin integrity after wounding. Impaired initiation, maintenance or termination of the tissue repair processes can lead to perturbed healing, necrosis, fibrosis or even cancer. Nuclear hormone receptors (NHRs) in the cutaneous environment regulate tissue repair processes such as fibroplasia and angiogenesis. Defects in functional NHRs and their ligands are associated with the clinical phenotypes of chronic non-healing wounds and skin endocrine disorders. The functional relationship between NHRs and skin niche cells such as epidermal keratinocytes and dermal fibroblasts is pivotal for successful wound closure and permanent repair. The aim of this review is to delineate the cutaneous effects and cross-talk of various nuclear receptors upon injury towards functional tissue restoration. Copyright © 2014 John Wiley & Sons, Ltd.

Differential expression of myofibroblasts on CO2 laser wounds and scalpel wounds: an experimental model

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Machado, R. M.; Oliveira, C. R. B.; Vitória, L. A.; Xavier, F. C. A.; Pinheiro, A. L. B.; Freitas, A. C.; Ramalho, L. M. P.

2018-04-01

Wound contraction of both traumatic and surgical origin may reduce or limit the function of the tissue. Myofibroblasts are cells involved on the process of wound contraction, which is smaller on CO2 Laser wounds. The aims of this study were to quantitative and statistically assess the presence of myofibroblasts on both conventional and CO2 Laser wounds. Thirty-two animals (rattus norvegicus) were divided into four groups and operated using either the CO2 Laser (groups A1 and A2) or conventional scalpel (groups B1 and B2). The animals were sacrificed eight days post-operatively (groups: A1 and B1) and 14th days after surgery (groups: A2 and B2). The spec imens we re routinely processed to wax and stained with a-Smooth Muscle Actin (aSMA) and analyzed under light microscopy (40X). Two standard areas around the wound of each slide were selected and used to count the number of myofribroblasts present using a calibrated eyepiece and a graticule. The number of myofibroblasts at day eight was significantly higher than at day 14th. Comparison of the two techniques at day eight showed significant differences between the two groups (Laser, p=0.007 and scalpel, p=0.001). The number of cells present on group B1 was significantly higher than group A1 (p=0.001). However at the 14th day there was no such difference (p=0,072). It is concluded that the small number of myofibroblasts at day eight after wounding with the CO2 Lasermay be the reason why contraction on this wound is smaller than the one observed in conventional surgery.

Nanotoxicity in Systemic Circulation and Wound Healing.

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Bakshi, Mandeep Singh

2017-06-19

Nanotoxicity of nanomaterials is an important issue in view of their potential applications in systemic circulation and wound healing dressing. This account specifically deals with several characteristic features of different nanomaterials which induce hemolysis and how to make them hemocompatible. The shape, size, and surface functionalities of naked metallic as well as nonmetallic nanoparticles surfaces are responsible for the hemolysis. An appropriate coating of biocompatible molecules dramatically reduces hemolysis and promotes their ability as safe drug delivery vehicles. The use of coated nanomaterials in wound healing dressing opens several new strategies for rapid wound healing processes. Properly designed nanomaterials should be selected to minimize the nanotoxicity in the wound healing process. Future directions need new synthetic methods for engineered nanomaterials for their best use in nanomedicine and nanobiotechnology.

Platelet rich fibrin - a novel acumen into regenerative endodontic therapy

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Kavita Hotwani

2014-02-01

Full Text Available Research into regenerative dentistry has added impetus onto the field of molecular biology. It can be documented as a prototype shift in the therapeutic armamentarium for dental disease. Regenerative endodontic procedures are widely being added to the current armamentarium of pulp therapy procedures. The regenerative potential of platelets has been deliberated. A new family of platelet concentrates called the platelet rich fibrin (PRF has been recently used by several investigators and has shown application in diverse disciplines of dentistry. This paper is intended to add light on the various prospects of PRF and clinical insights to regenerative endodontic therapy.

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

International Nuclear Information System (INIS)

Akita, S.; Yoshimoto, H.; Ohtsuru, A.; Hirano, A.; Yamashita, S.

2012-01-01

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6±14.9 y (52-89 y), with mean radiation dose of 75.0±35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6±1.3 x 10 7 cells were obtained. All cases healed uneventfully after 6.6±3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9±0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds. (authors)

Autologous adipose-derived regenerative cells are effective for chronic intractable radiation injuries

Energy Technology Data Exchange (ETDEWEB)

Akita, S; Yoshimoto, H [Div. of Plastic and Reconstructive Surgery, Dept. of Developmental and Reconstructive Medicine, Nagasaki Univ., Graduate School of Biomedical and Sciences, Nagasaki (Japan); Ohtsuru, A [Takashi Nagai Memorial International Hibakusha Medical Center, Nagasaki Univ. Hospital, Nagasaki (Japan); Hirano, A [Div. of Plastic and Reconstructive Surgery, Dept. of Developmental and Reconstructive Medicine, Nagasaki Univ., Graduate School of Biomedical and Sciences, Nagasaki (Japan); Yamashita, S [Takashi Nagai Memorial International Hibakusha Medical Center, Nagasaki Univ. Hospital, Nagasaki (Japan); Dept. of Molecular Medicine, Atomic Bomb Disease Inst., Nagasaki Univ. School of Medicine, Nagasaki (Japan)

2012-07-01

Effective therapy for chronic radiation injuries, such as ulcers, is prone to infection. Stiffness is expected since the therapeutic radiation often involves wider and deeper tissues and often requires extensive debridement and reconstruction, which are not sometimes appropriate for elderly and compromised hosts. Autologous adipose-derived regenerative cells (ADRCs) are highly yielding, forming relatively elderly aged consecutive 10 cases, 63.6{+-}14.9 y (52-89 y), with mean radiation dose of 75.0{+-}35.4 Gy (50-120 Gy) were included with at least 10-month follow-up. Minimal debridement and ADRC injection in the wound bed and margin along with the injection of mixture of fat and ADRCs in the periphery were tested for efficacy and regenerated tissue quality by clinically as well as imaging by computed tomography and magnetic resonance imaging. Uncultured ADRCs of 1.6{+-}1.3 x 10{sup 7} cells were obtained. All cases healed uneventfully after 6.6{+-}3.2 weeks (2-10 weeks) post-operatively. The done site morbidity was negligible and without major complications, such as paralysis or massive haematoma. The regenerated tissue quality was significantly superior to the pre-operative one and the mixture of fat and ADRCs connected to the intact tissue was very soft and pliable. Mean follow-up at 1.9{+-}0.8 y (0.9-2.9 y) revealed no recurrence or new ulceration after treatment. Thus, the ADRCs treatment for decades-long radiation injuries is effective, safe and improves the quality of wounds. (authors)

An Intelligent Regenerative Braking Strategy for Electric Vehicles

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Zhibin Song

2011-09-01

Full Text Available Regenerative braking is an effective approach for electric vehicles (EVs to extend their driving range. A fuzzy-logic-based regenerative braking strategy (RBS integrated with series regenerative braking is developed in this paper to advance the level of energy-savings. From the viewpoint of securing car stability in braking operations, the braking force distribution between the front and rear wheels so as to accord with the ideal distribution curve are considered to prevent vehicles from experiencing wheel lock and slip phenomena during braking. Then, a fuzzy RBS using the driver’s braking force command, vehicle speed, battery SOC, battery temperature are designed to determine the distribution between friction braking force and regenerative braking force to improve the energy recuperation efficiency. The experimental results on an “LF620” prototype EV validated the feasibility and effectiveness of regenerative braking and showed that the proposed fuzzy RBS was endowed with good control performance. The maximum driving range of LF620 EV was improved by 25.7% compared with non-RBS conditions.

Evaluation strategy of regenerative braking energy for supercapacitor vehicle.

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Zou, Zhongyue; Cao, Junyi; Cao, Binggang; Chen, Wen

2015-03-01

In order to improve the efficiency of energy conversion and increase the driving range of electric vehicles, the regenerative energy captured during braking process is stored in the energy storage devices and then will be re-used. Due to the high power density of supercapacitors, they are employed to withstand high current in the short time and essentially capture more regenerative energy. The measuring methods for regenerative energy should be investigated to estimate the energy conversion efficiency and performance of electric vehicles. Based on the analysis of the regenerative braking energy system of a supercapacitor vehicle, an evaluation system for energy recovery in the braking process is established using USB portable data-acquisition devices. Experiments under various braking conditions are carried out. The results verify the higher efficiency of energy regeneration system using supercapacitors and the effectiveness of the proposed measurement method. It is also demonstrated that the maximum regenerative energy conversion efficiency can reach to 88%. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Recent considerations in regenerative endodontic treatment approaches

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Hacer Aksel

2014-09-01

Conclusion: Although the regenerative treatment approaches have good clinical outcomes in the majority of case reports, the outcomes are unpredictable. Since the current clinical protocols for regenerative endodontics do not fully fulfill the triad of tissue engineering ((growth factors, scaffold and stem cells, further translational studies are required to achieve more pulp- and dentin-like tissue in the root canal system to achieve pulp regeneration.

Extrafloral nectar secretion from wounds of Solanum dulcamara.

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Lortzing, Tobias; Calf, Onno W; Böhlke, Marlene; Schwachtje, Jens; Kopka, Joachim; Geuß, Daniel; Kosanke, Susanne; van Dam, Nicole M; Steppuhn, Anke

2016-04-25

Plants usually close wounds rapidly to prevent infections and the loss of valuable resources such as assimilates(1). However, herbivore-inflicted wounds on the bittersweet nightshade Solanum dulcamara appear not to close completely and produce sugary wound secretions visible as droplets. Many plants across the plant kingdom secrete sugary nectar from extrafloral nectaries(2) to attract natural enemies of herbivores for indirect defence(3,4). As ants forage on wound edges of S. dulcamara in the field, we hypothesized that wound secretions are a form of extrafloral nectar (EFN). We show that, unlike EFN from known nectaries, wound secretions are neither associated with any specific structure nor restricted to certain locations. However, similar to EFN, they are jasmonate-inducible and the plant controls their chemical composition. Wound secretions are attractive for ants, and application of wound secretion mimics increases ant attraction and reduces herbivory on S. dulcamara plants in a natural population. In greenhouse experiments, we reveal that ants can defend S. dulcamara from two of its native herbivores, slugs and flea beetle larvae. Since nectar is defined by its ecological function as a sugary secretion involved in interactions with animals(5), such 'plant bleeding' could be a primitive mode of nectar secretion exemplifying an evolutionary origin of structured extrafloral nectaries.

Dual function of active constituents from bark of Ficus racemosa L in wound healing.

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Bopage, Nisansala Swarnamali; Kamal Bandara Gunaherath, G M; Jayawardena, Kithsiri Hector; Wijeyaratne, Sushila Chandrani; Abeysekera, Ajita Mahendra; Somaratne, Seneviratne

2018-01-25

Different parts including the latex of Ficus racemosa L. has been used as a medicine for wound healing in the Ayurveda and in the indigenous system of medicine in Sri Lanka. This plant has been evaluated for its wound healing potential using animal models. The aim of this study was to obtain an insight into the wound healing process and identify the potential wound healing active substance/s present in F. racemosa L. bark using scratch wound assay (SWA) as the in-vitro assay method. Stem bark extracts of F. racemosa were evaluated using scratch wound assay (SWA) on Baby Hamster Kidney (BHK 21) and Madin-Darby Canine Kidney (MDCK) cell lines and Kirby Bauer disc diffusion assay on common bacteria and fungi for cell migration enhancing ability and antimicrobial activity respectively. Dichloromethane and hexanes extracts which showed cell migration enhancement activity on SWA were subjected to bioactivity directed fractionation using column chromatography followed by preparative thin layer chromatography to identify the compounds responsible for the cell migration enhancement activity. Dichloromethane and hexanes extracts showed cell migration enhancement activity on both cell lines, while EtOAc and MeOH extracts showed antibacterial activity against Staphylococcus and Bacillus species and antifungal activity against Saccharomyces spp. and Candida albicans. Lupeol (1) and β-sitosterol (2) were isolated as the potential wound healing active compounds which exhibited significant cell migration enhancement activity on BHK 21 and MDCK cell lines (> 80%) in par with the positive control, asiaticoside at a concentration of 25 μM. The optimum concentration of each compound required for the maximum wound healing has been determined as 30 μM and 35 μM for 1 and 2 respectively on both cell lines. It is also established that lupeol acetate (3) isolated from the hexanes extract act as a pro-drug by undergoing hydrolysis into lupeol in the vicinity of cells. Different

Clay nanoparticles for regenerative medicine and biomaterial design: A review of clay bioactivity.

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Mousa, Mohamed; Evans, Nicholas D; Oreffo, Richard O C; Dawson, Jonathan I

2018-03-01

Clay nanoparticles, composites and hydrogels are emerging as a new class of biomaterial with exciting potential for tissue engineering and regenerative medicine applications. Clay particles have been extensively explored in polymeric nanocomposites for self-assembly and enhanced mechanical properties as well as for their potential as drug delivery modifiers. In recent years, a cluster of studies have explored cellular interactions with clay nanoparticles alone or in combination with polymeric matrices. These pioneering studies have suggested new and unforeseen utility for certain clays as bioactive additives able to enhance cellular functions including adhesion, proliferation and differentiation, most notably for osteogenesis. This review examines the recent literature describing the potential effects of clay-based nanomaterials on cell function and examines the potential role of key clay physicochemical properties in influencing such interactions and their exciting possibilities for regenerative medicine. Copyright © 2018 Elsevier Ltd. All rights reserved.

Removal of the basement membrane enhances corneal wound healing.

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Pal-Ghosh, Sonali; Pajoohesh-Ganji, Ahdeah; Tadvalkar, Gauri; Stepp, Mary Ann

2011-12-01

Recurrent corneal erosions are painful and put patients' vision at risk. Treatment typically begins with debridement of the area around the erosion site followed by more aggressive treatments. An in vivo mouse model has been developed that reproducibly induces recurrent epithelial erosions in wild-type mice spontaneously within two weeks after a single 1.5 mm corneal debridement wound created using a dulled-blade. This study was conducted to determine whether 1) inhibiting MMP9 function during healing after dulled-blade wounding impacts erosion development and 2) wounds made with a rotating-burr heal without erosions. Oral or topical inhibition of MMPs after dulled-blade wounding does not improve healing. Wounds made by rotating-burr heal with significantly fewer erosions than dulled-blade wounds. The localization of MMP9, β4 integrin and basement membrane proteins (LN332 and type VII collagen), immune cell influx, and reinnervation of the corneal nerves were compared after both wound types. Rotating-burr wounds remove the anterior basement membrane centrally but not at the periphery near the wound margin, induce more apoptosis of corneal stromal cells, and damage more stromal nerve fibers. Despite the fact that rotating-burr wounds do more damage to the cornea, fewer immune cells are recruited and significantly more wounds resolve completely. Copyright © 2011 Elsevier Ltd. All rights reserved.

Regenerative endodontics: barriers and strategies for clinical translation.

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Mao, Jeremy J; Kim, Sahng G; Zhou, Jian; Ye, Ling; Cho, Shoko; Suzuki, Takahiro; Fu, Susan Y; Yang, Rujing; Zhou, Xuedong

2012-07-01

Regenerative endodontics has encountered substantial challenges toward clinical translation. The adoption by the American Dental Association of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for most endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation. Copyright © 2012 Elsevier Inc. All rights reserved.

PKCδ inhibition normalizes the wound-healing capacity of diabetic human fibroblasts.

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Khamaisi, Mogher; Katagiri, Sayaka; Keenan, Hillary; Park, Kyoungmin; Maeda, Yasutaka; Li, Qian; Qi, Weier; Thomou, Thomas; Eschuk, Danielle; Tellechea, Ana; Veves, Aris; Huang, Chenyu; Orgill, Dennis Paul; Wagers, Amy; King, George L

2016-03-01

Abnormal fibroblast function underlies poor wound healing in patients with diabetes; however, the mechanisms that impair wound healing are poorly defined. Here, we evaluated fibroblasts from individuals who had type 1 diabetes (T1D) for 50 years or more (Medalists, n = 26) and from age-matched controls (n = 7). Compared with those from controls, Medalist fibroblasts demonstrated a reduced migration response to insulin, lower VEGF expression, and less phosphorylated AKT (p-AKT), but not p-ERK, activation. Medalist fibroblasts were also functionally less effective at wound closure in nude mice. Activation of the δ isoform of protein kinase C (PKCδ) was increased in postmortem fibroblasts from Medalists, fibroblasts from living T1D subjects, biopsies of active wounds of living T1D subjects, and granulation tissues from mice with streptozotocin-induced diabetes. Diabetes-induced PKCD mRNA expression was related to a 2-fold increase in the mRNA half-life. Pharmacologic inhibition and siRNA-mediated knockdown of PKCδ or expression of a dominant-negative isoform restored insulin signaling of p-AKT and VEGF expression in vitro and improved wound healing in vivo. Additionally, increasing PKCδ expression in control fibroblasts produced the same abnormalities as those seen in Medalist fibroblasts. Our results indicate that persistent PKCδ elevation in fibroblasts from diabetic patients inhibits insulin signaling and function to impair wound healing and suggest PKCδ inhibition as a potential therapy to improve wound healing in diabetic patients.

Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine.

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Samsonraj, Rebekah M; Raghunath, Michael; Nurcombe, Victor; Hui, James H; van Wijnen, Andre J; Cool, Simon M

2017-12-01

Mesenchymal stem cells (MSC) hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. MSCs orchestrate tissue development, maintenance and repair, and are useful for musculoskeletal regenerative therapies to treat age-related orthopedic degenerative diseases and other clinical conditions. Importantly, MSCs produce secretory factors that play critical roles in tissue repair that support both engraftment and trophic functions (autocrine and paracrine). The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Quality control and release criteria for MSCs should include cell surface markers, differentiation potential, and other essential cell parameters. For example, cell surface marker profiles (surfactome), bone-forming capacities in ectopic and orthotopic models, as well as cell size and granularity, telomere length, senescence status, trophic factor secretion (secretome), and immunomodulation, should be thoroughly assessed to predict MSC utility for regenerative medicine. We propose that these and other functionalities of MSCs should be characterized prior to use in clinical applications as part of comprehensive and uniform guidelines and release criteria for their clinical-grade production to achieve predictably favorable treatment outcomes for stem cell therapy. Stem Cells Translational Medicine 2017;6:2173-2185. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Pharmacological effect of Ageratina pichinchensis on wound healing in diabetic rats and genotoxicity evaluation.

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Romero-Cerecero, Ofelia; Zamilpa, Alejandro; Díaz-García, Edgar Rolando; Tortoriello, Jaime

2014-10-28

Among the main causes affecting the wound healing process, we find diabetes mellitus, which is due to the occurrence of a prolonged inflammation phase, defects in angiogenesis, and a diminution in fibroblast proliferation. The species Ageratina pichinchensis has been utilized in Mexican traditional medicine for the treatment of skin wounds. Pharmacological models have demonstrated that an extract obtained from this species improves wound healing and, through a clinical study, it was evidenced that the extract (in a pharmaceutical form) is effective in the treatment of patients with chronic venous ulcers. The 7-O-(β-D-glucopyranosyl)-galactin compound was recently identified as responsible for the pharmacological activity. The objective of the present study was to evaluate the wound healing activity of an aqueous extract and another hexane-ethyl acetate extract from Ageratina pichinchensis (both standardized in the active compound) in a diabetic foot ulcer rat model, as well as evaluating the possible genotoxic effects produced by the same species. Rats with streptozotocin-induced diabetes were submitted (under anesthesia with pentobarbital) to a circular lesion on the skin (excisional) on the rear of the paw. All animals were topically treated daily until healing. 5-methyl-1 phenyl-2-(1H) Pyridone was used as a positive control treatment. Once the wound was healed, a skin sample was obtained and utilized for histopathological analysis. The possible genotoxic effects produced by the extract, in a model of spermatozoid viability and morphology, were evaluated. The results showed that 100% of animals treated with Ageratina pichinchensis extracts presented wound healing between days 4 and 11 of treatment, while in the positive control group (treated with 5-methyl-1 phenyl-2-(1H) pyridone) and in the negative control group (vehicle), only 70% and 40%, respectively, exhibited wound healing at day 11. Histological analysis demonstrated evidences of an active regenerative

Clinical considerations for regenerative endodontic procedures.

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Geisler, Todd M

2012-07-01

The management of a tooth with incomplete root maturation and a necrotic pulp is an endodontic and a restorative challenge. Apexification procedures alone leave the tooth in a weakened state and at risk for reinfection. Regenerative endodontic procedures potentially offer advantages, including the possibility of hard tissue deposition and continued root development. Case studies have reported regeneration of human pulplike tissues in vivo, but there is no protocol that reliably regenerates pulplike tissue. This article summarizes historical, current, and future regenerative treatment approaches. Copyright © 2012 Elsevier Inc. All rights reserved.

PLATELET-RICH PLASMA (PRP AND ITS APPLICATION IN THE TREATMENT OF CHRONIC AND HARD-TO-HEAL SKIN WOUNDS. A Review.

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Tsvetan Sokolov

2015-12-01

Full Text Available In the last few years various methods are being applied in the use of platelet-rich plasma (PRP during treatment in different orthopedic disease. They allow improvement of local biological condition and regeneration of different types of tissues. PRP is a modern treatment strategy with worldwide recognition. There is a high concentration of platelet growth factors in small amounts of plasma. PRP and its various forms have become one of the best methods to support the healing process of various tissues. PRP is used in regenerative medicine, because it provides two of three components (growth factors and scaffolds necessary for complete tissue regeneration. The particular reason for the appearance of lesions is important in order to select an appropriate treatment method and technical application. PRP may be used for treatment of various chronic and hard-to-heal cutaneous wounds, especially when standard conventional therapy is not good enough and surgical treatment is not possible. It reduces the duration, cost of treatment and the hospital stay. There is reduction of wound pain after starting the treatment, reduced risk of blood-borne disease transmission, wound healing is restored, and local immunity is activated.

Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

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Tom J. Burdon

2011-01-01

Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis

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Hindi, Sajedah M.; Kumar, Ashok

2015-01-01

Satellite cells are a stem cell population within adult muscle and are responsible for myofiber regeneration upon injury. Satellite cell dysfunction has been shown to underlie the loss of skeletal muscle mass in many acquired and genetic muscle disorders. The transcription factor paired box-protein-7 (PAX7) is indispensable for supplementing the reservoir of satellite cells and driving regeneration in normal and diseased muscle. TNF receptor–associated factor 6 (TRAF6) is an adaptor protein and an E3 ubiquitin ligase that mediates the activation of multiple cell signaling pathways in a context-dependent manner. Here, we demonstrated that TRAF6-mediated signaling is critical for homeostasis of satellite cells and their function during regenerative myogenesis. Selective deletion of Traf6 in satellite cells of adult mice led to profound muscle regeneration defects and dramatically reduced levels of PAX7 and late myogenesis markers. TRAF6 was required for the activation of MAPKs ERK1/2 and JNK1/2, which in turn activated the transcription factor c-JUN, which binds the Pax7 promoter and augments Pax7 expression. Moreover, TRAF6/c-JUN signaling repressed the levels of the microRNAs miR-1 and miR-206, which promote differentiation, to maintain PAX7 levels in satellite cells. We also determined that satellite cell–specific deletion of Traf6 exaggerates the dystrophic phenotype in the mdx (a mouse model of Duchenne muscular dystrophy) mouse by blunting the regeneration of injured myofibers. Collectively, our study reveals an essential role for TRAF6 in satellite stem cell function. PMID:26619121

Low Intensity Laser Therapy Applied in the Healing of Wounds

Science.gov (United States)

Kahn, Fred; Matthews, Jeffrey

2009-06-01

Objective: The aim of this study was to determine the outcomes of Low Intensity Laser Therapy (LILT) on wound healing for patients presenting with pain, compromised neurological and physical function and tissue damage associated with vascular/diabetic ulcerations of the lower extremity. Methods: A retrospective case review of six patients treated with LILT (GaAlAs SLD, 660 nm, 750 mW, 3.6 J/cm2; GaAlAs SLD, 840 nm, 1,500 mW, 6.48 J/cm2; GaAlAs laser, 830 nm, 75 mW, 270 J/cm2) was conducted of clinical features including pain, measured by visual analogue scale (VAS), motor function, measured by range of motion (ROM) and visual outcome, measured by wound dimensions for six patients (n = 6; 5 males, 1 female; age = 67.83 years). Results: Significant progress with regard to alleviation of pain (ΔVAS = -5), improvements in motor function (ΔROM = +40%), epithelialization (wound closure rate = 3%/week) and complete wound closure was achieved. No recurrence of pathology at least one month post cessation of therapy was evident (x¯% reduction in wound area = 100%). Conclusions: LILT achieved consistent, effective and clear endpoints, was cost effective, created no adverse effects and ultimately led to the salvage of extremities.

Repairing quite swimmingly: advances in regenerative medicine using zebrafish.

Science.gov (United States)

Goessling, Wolfram; North, Trista E

2014-07-01

Regenerative medicine has the promise to alleviate morbidity and mortality caused by organ dysfunction, longstanding injury and trauma. Although regenerative approaches for a few diseases have been highly successful, some organs either do not regenerate well or have no current treatment approach to harness their intrinsic regenerative potential. In this Review, we describe the modeling of human disease and tissue repair in zebrafish, through the discovery of disease-causing genes using classical forward-genetic screens and by modulating clinically relevant phenotypes through chemical genetic screening approaches. Furthermore, we present an overview of those organ systems that regenerate well in zebrafish in contrast to mammalian tissue, as well as those organs in which the regenerative potential is conserved from fish to mammals, enabling drug discovery in preclinical disease-relevant models. We provide two examples from our own work in which the clinical translation of zebrafish findings is either imminent or has already proven successful. The promising results in multiple organs suggest that further insight into regenerative mechanisms and novel clinically relevant therapeutic approaches will emerge from zebrafish research in the future. © 2014. Published by The Company of Biologists Ltd.

Center for Neuroscience & Regenerative Medicine

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Federal Laboratory Consortium — The Center for Neuroscience and Regenerative Medicine (CNRM) was established as a collaborative intramural federal program involving the U.S. Department of Defense...

Conference Report: 6th Annual International Symposium on Regenerative Rehabilitation.

Science.gov (United States)

Loghmani, M Terry; Roche, Joseph A

2018-04-03

The 6th International Symposium on Regenerative Rehabilitation, hosted by the Alliance for Regenerative Rehabilitation Research and Training (AR 3 T), included a preconference meeting of institutional representatives of the International Consortium of Regenerative Rehabilitation, keynote talks from distinguished scientists, platform and poster presentations from experts and trainees, panel discussions and postconference workshops. The following priorities were identified: increasing rigor in basic, preclinical and clinical studies, especially the use of better controls; developing better outcome measures for preclinical and clinical trials; focusing on developing more tissue-based interventions versus cell-based interventions; including regenerative rehabilitation in curricula of professional programs like occupational and physical therapy; and developing better instruments to quantify rehabilitative interventions.

A high-power compact regenerative amplifier FEL

International Nuclear Information System (INIS)

Nguyen, D.C.; Sheffield, R.L.; Fortgang, C.M.; Kinross-Wright, J.M.; Ebrahim, N.A.; Goldstein, J.C.

1997-01-01

The Regenerative Amplifier FEL (RAFEL) is a new FEL approach aimed at achieving the highest optical power from a compact rf-linac FEL. The key idea is to feed back a small fraction ( 5 in single pass) wiggler to enable the FEL to reach saturation in a few passes. This paper summarizes the design of a high-power compact regenerative amplifier FEL and describes the first experimental demonstration of the RAFEL concept

Early Orthodontic Tooth Movement into Regenerative Bony Defects: A Case Report.

Science.gov (United States)

Tsai, Hui-Chen; Yao, Chung-Chen Jane; Wong, Man-Ying

Early orthodontic tooth movement following regenerative surgery is controversial. In this case, during protraction of the maxillary right first premolar to substitute for the long-term missing maxillary right canine, Bio-Oss and Bio-Gide were used for lateral ridge augmentation at the area of the maxillary right lateral incisor and to cover the denuded surface at the buccal side of the first premolar. Orthodontic tooth movement (OTM) commenced 2 weeks after regenerative surgery. After 8 months, new bone formation was observed on the root surface of the first premolar during implant surgery. A cone beam computed tomography scan taken 1.5 years postsurgery revealed good maintenance of regenerative bone at the same site. This satisfactory outcome of early OTM following regenerative surgery suggests biomechanical stimulation may not jeopardize the regenerative effect.

Human neonatal cardiovascular progenitors: unlocking the secret to regenerative ability.

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Tania I Fuentes

Full Text Available Although clinical benefit can be achieved after cardiac transplantation of adult c-kit+ or cardiosphere-derived cells for myocardial repair, these stem cells lack the regenerative capacity unique to neonatal cardiovascular stem cells. Unraveling the molecular basis for this age-related discrepancy in function could potentially transform cardiovascular stem cell transplantation. In this report, clonal populations of human neonatal and adult cardiovascular progenitor cells were isolated and characterized, revealing the existence of a novel subpopulation of endogenous cardiovascular stem cells that persist throughout life and co-express both c-kit and isl1. Epigenetic profiling identified 41 microRNAs whose expression was significantly altered with age in phenotypically-matched clones. These differences were correlated with reduced proliferation and a limited capacity to invade in response to growth factor stimulation, despite high levels of growth factor receptor on progenitors isolated from adults. Further understanding of these differences may provide novel therapeutic targets to enhance cardiovascular regenerative capacity.

Advancing pig cloning technologies towards application in regenerative medicine.

Science.gov (United States)

Nagashima, H; Matsunari, H; Nakano, K; Watanabe, M; Umeyama, K; Nagaya, M

2012-08-01

Regenerative medicine is expected to make a significant contribution by development of novel therapeutic treatments for intractable diseases and for improving the quality of life of patients. Many advances in regenerative medicine, including basic and translational research, have been developed and tested in experimental animals; pigs have played an important role in various aspects of this work. The value of pigs as a model species is being enhanced by the generation of specially designed animals through cloning and genetic modifications, enabling more sophisticated research to be performed and thus accelerating the clinical application of regenerative medicine. This article reviews the significant aspects of the creation and application of cloned and genetically modified pigs in regenerative medicine research and considers the possible future directions of the technology. We also discuss the importance of reproductive biology as an interface between basic science and clinical medicine. © 2012 Blackwell Verlag GmbH.

The effectiveness of platelet-rich plasma on the skin wound healing process: A comparative experimental study in sheep

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Daikh Badis

2018-06-01

Full Text Available Aim: The therapeutic evaluation of the biological effect of platelet-rich plasma (PRP used as a surgical adjunct to maintain the inflammatory process and to potentiate tissue healing, make the subject of recent research in regenerative medicine. This study was designed to evaluate the healing activity of PRP by its topical application on the skin experimentally injured in a sheep model. Materials and Methods: The study was conducted on 9 adult and clinically healthy males sheep. PRP was obtained by a protocol of double centrifugation of whole blood from each animal. After sterile skin preparation, full-thickness excisional wounds (20 mm x 20 mm were created on the back of each animal. The animals were randomly divided into three equal groups of three sheep for each. In Group I, the wounds were treated with PRP, in Group II; wounds were treated with Asiaticoside; in Group III, wounds were treated with saline solution. The different treatments were administered topically every 3 days. Morphometric measurements of the contraction surface of the wounds and histopathological biopsies were carried out at the 3rd, 7th, 14th, 21st, and 28th days of healing. Results: The results of the morphometric data obtained revealed that it was significant differences recorded at the 7th and 14th day of healing in favor for animals of Group I. Semi-quantitative histopathological evaluation showed that PRP reduces inflammation during 3 first days post-surgical and promotes epithelialization in 3 weeks of healing. Conclusion: We concluded that topical administration of PRP obtained by double centrifugation protocol could potentially improve the skin healing process in sheep.

Limb Regeneration in Axolotl: Is It Superhealing?

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Stéphane Roy

2006-01-01

Full Text Available The ability of axolotls to regenerate their limbs is almost legendary. In fact, urodeles such as the axolotl are the only vertebrates that can regenerate multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list goes on throughout their lives. It is therefore surprising to realize, although we have known of their regenerative potential for over 200 years, how little we understand the mechanisms behind this achievement of adult tissue morphogenesis. Many observations can be drawn between regeneration and other disciplines such as development and wound healing. In this review, we present new developments in functional analysis that will help to address the role of specific genes during the process of regeneration. We also present an analysis of the resemblance between wound healing and regeneration, and discuss whether axolotls are superhealers. A better understanding of these animals' regenerative capacity could lead to major benefits by providing regenerative medicine with directions on how to develop therapeutic approaches leading to regeneration in humans.

A Clinicoepidemiological Profile of Chronic Wounds in Wound Healing Department in Shanghai.

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Sun, Xiaofang; Ni, Pengwen; Wu, Minjie; Huang, Yao; Ye, Junna; Xie, Ting

2017-03-01

The aim of the study was to update the clinical database of chronic wounds in order to derive an evidence based understanding of the condition and hence to guide future clinical management in China. A total of 241 patients from January 1, 2011 to April 30, 2016 with chronic wounds of more than 2 weeks' duration were studied in wound healing department in Shanghai. Results revealed that among all the patients the mean age was 52.5 ± 20.2 years (range 2-92 years). The mean initial area of wounds was 30.3 ± 63.0 cm 2 (range 0.25-468 cm 2 ). The mean duration of wounds was 68.5 ± 175.2 months (range 0.5-840 months). The previously reported causes of chronic wounds were traumatic or surgical wounds (n = 82, 34.0%), followed by pressure ulcers (n = 59, 24.5%). To study the effects of age, patients were divided into 2 groups: less than 60 years (wounds etiology between the 2 age groups was analyzed, and there was significant statistical difference ( P wounds, chi-square test was used. There were significant differences in the factor of wound infection. ( P = .035, 95% CI = 0.031-0.038) Regarding therapies, 72.6% (n = 175) of the patients were treated with negative pressure wound therapy. Among all the patients, 29.9% (n = 72) of them were completely healed when discharged while 62.7% (n = 150) of them improved. The mean treatment cost was 12055.4 ± 9206.3 Chinese Yuan (range 891-63626 Chinese Yuan). In conclusion, traumatic or surgical wounds have recently become the leading cause of chronic wounds in Shanghai, China. Etiology of the 2 age groups was different. Infection could significantly influence the wound outcome.

Physicochemical properties of radiation-sterilized honey alginate wound dressing for exudating wounds

International Nuclear Information System (INIS)

Asa, Anie Day DC.; De Guzman, Zenaida M.; Baldos, Davison T.; Asaad, Celia O.

2013-01-01

Honey is a well-known natural cure in promoting healing of wounds. Alginate, on the other hand, is a polysaccharide with pharmaceutical applications such as wound dressing and control release drugs. Calcium-alginate wound dressings have a gel-forming capability. in that, upon ion exchange between calcium ions in the dressing, and sodium ions in wound fluid, the dressing transforms into a gel. Cross-linked alginate gels can absorb would fluid, and also maintain a moist environment to the wound area. Combined with anti-microbial properties of honey and absorption and gelling properties of alginate, a honey alginate wound dressing is developed and irradiated for sterility. Its physicochemical properties are then analyzed. The honey-alginate wound dressing has lower pH (4.40±0.02) than alginate alone dressings (5.40±0.04) which is more favorable for wound healing. The dressing also has low moisture content (10.25±1.11%). Analysis of moisture vapour transmission rate shows a general increase with time for 48 hours. The wound dressing also has an absorbency of 19.00±1.80 g/100 cm 2 with a gel fraction of 18.44±0.63%. The rate of absorption analysis, meanwhile, shows a very rapid absorption rate upon exposure to wound fluid. After some time, a decrease in rate is observed which is accounted to the release of honey to the wound environment. For tensile strength, irradiation causes an effect in tensile strength in machine direction but is insignificant for cross machine direction. Physicochemical properties of the radiation-sterilized honey alginate wound dressing e.g. acidic pH, absorbency, moisture vapor permeability and absorption rate ascertain its characteristic as a good wound dressing for exudating wounds. Its low moisture content, meanwhile, allows for longer shelf-life of the developed product. (author)

Integration of regenerative shock absorber into vehicle electric system

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Zhang, Chongxiao; Li, Peng; Xing, Shaoxu; Kim, Junyoung; Yu, Liangyao; Zuo, Lei

2014-03-01

Regenerative/Energy harvesting shock absorbers have a great potential to increase fuel efficiency and provide suspension damping simultaneously. In recent years there's intensive work on this topic, but most researches focus on electricity extraction from vibration and harvesting efficiency improvement. The integration of electricity generated from regenerative shock absorbers into vehicle electric system, which is very important to realize the fuel efficiency benefit, has not been investigated. This paper is to study and demonstrate the integration of regenerative shock absorber with vehicle alternator, battery and in-vehicle electrical load together. In the presented system, the shock absorber is excited by a shaker and it converts kinetic energy into electricity. The harvested electricity flows into a DC/DC converter which realizes two functions: controlling the shock absorber's damping and regulating the output voltage. The damping is tuned by controlling shock absorber's output current, which is also the input current of DC/DC converter. By adjusting the duty cycles of switches in the converter, its input impedance together with input current can be adjusted according to dynamic damping requirements. An automotive lead-acid battery is charged by the DC/DC converter's output. To simulate the working condition of combustion engine, an AC motor is used to drive a truck alternator, which also charges the battery. Power resistors are used as battery's electrical load to simulate in-vehicle electrical devices. Experimental results show that the proposed integration strategy can effectively utilize the harvested electricity and power consumption of the AC motor is decreased accordingly. This proves the combustion engine's load reduction and fuel efficiency improvement.

Giant hepatic regenerative nodules in Alagille syndrome

Energy Technology Data Exchange (ETDEWEB)

Rapp, Jordan B. [Lewis Katz School of Medicine at Temple University, Department of Radiology, Temple University Hospital, Philadelphia, PA (United States); Bellah, Richard D.; Anupindi, Sudha A. [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); Maya, Carolina [The Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Pawel, Bruce R. [University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (United States); The Children' s Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Philadelphia, PA (United States)

2017-02-15

Children with Alagille syndrome undergo surveillance radiologic examinations as they are at risk for developing cirrhosis and hepatocellular carcinoma. There is limited literature on the imaging of liver masses in Alagille syndrome. We report the ultrasound (US) and magnetic resonance imaging (MRI) appearances of incidental benign giant hepatic regenerative nodules in this population. To describe the imaging findings of giant regenerative nodules in patients with Alagille syndrome. A retrospective search of the hospital database was performed to find all cases of hepatic masses in patients with Alagille syndrome during a 10-year period. Imaging, clinical charts, laboratory data and available pathology were reviewed and analyzed and summarized for each patient. Twenty of 45 patients with confirmed Alagille syndrome had imaging studies. Of those, we identified six with giant focal liver masses. All six patients had large central hepatic masses that were remarkably similar on US and MRI, in addition to having features of cirrhosis. In each case, the mass was located in hepatic segment VIII and imaging showed the mass splaying the main portal venous branches at the hepatic hilum, as well as smaller portal and hepatic venous branches coursing through them. On MRI, signal intensity of the mass was isointense to liver on T1-weighted sequences in four of six patients, but hyperintense on T1 in two of six patients. In all six cases, the mass was hypointense on T2- weighted sequences. The mass post-contrast was isointense to adjacent liver in all phases in five the cases. Five out of six patients had pathological correlation demonstrating preserved ductal architecture confirming the final diagnosis of a regenerative nodule. Giant hepatic regenerative nodules with characteristic US and MR features can occur in patients with Alagille syndrome with underlying cirrhosis. Recognizing these lesions as benign giant hepatic regenerative nodules should, thereby, mitigate any need for

Giant hepatic regenerative nodules in Alagille syndrome

International Nuclear Information System (INIS)

Rapp, Jordan B.; Bellah, Richard D.; Anupindi, Sudha A.; Maya, Carolina; Pawel, Bruce R.

2017-01-01

Children with Alagille syndrome undergo surveillance radiologic examinations as they are at risk for developing cirrhosis and hepatocellular carcinoma. There is limited literature on the imaging of liver masses in Alagille syndrome. We report the ultrasound (US) and magnetic resonance imaging (MRI) appearances of incidental benign giant hepatic regenerative nodules in this population. To describe the imaging findings of giant regenerative nodules in patients with Alagille syndrome. A retrospective search of the hospital database was performed to find all cases of hepatic masses in patients with Alagille syndrome during a 10-year period. Imaging, clinical charts, laboratory data and available pathology were reviewed and analyzed and summarized for each patient. Twenty of 45 patients with confirmed Alagille syndrome had imaging studies. Of those, we identified six with giant focal liver masses. All six patients had large central hepatic masses that were remarkably similar on US and MRI, in addition to having features of cirrhosis. In each case, the mass was located in hepatic segment VIII and imaging showed the mass splaying the main portal venous branches at the hepatic hilum, as well as smaller portal and hepatic venous branches coursing through them. On MRI, signal intensity of the mass was isointense to liver on T1-weighted sequences in four of six patients, but hyperintense on T1 in two of six patients. In all six cases, the mass was hypointense on T2- weighted sequences. The mass post-contrast was isointense to adjacent liver in all phases in five the cases. Five out of six patients had pathological correlation demonstrating preserved ductal architecture confirming the final diagnosis of a regenerative nodule. Giant hepatic regenerative nodules with characteristic US and MR features can occur in patients with Alagille syndrome with underlying cirrhosis. Recognizing these lesions as benign giant hepatic regenerative nodules should, thereby, mitigate any need for

Micro-Scale Regenerative Heat Exchanger

Science.gov (United States)

Moran, Matthew E.; Stelter, Stephan; Stelter, Manfred

2004-01-01

A micro-scale regenerative heat exchanger has been designed, optimized and fabricated for use in a micro-Stirling device. Novel design and fabrication techniques enabled the minimization of axial heat conduction losses and pressure drop, while maximizing thermal regenerative performance. The fabricated prototype is comprised of ten separate assembled layers of alternating metal-dielectric composite. Each layer is offset to minimize conduction losses and maximize heat transfer by boundary layer disruption. A grating pattern of 100 micron square non-contiguous flow passages were formed with a nominal 20 micron wall thickness, and an overall assembled ten-layer thickness of 900 microns. Application of the micro heat exchanger is envisioned in the areas of micro-refrigerators/coolers, micropower devices, and micro-fluidic devices.

Erich Regener and the ionisation maximum of the atmosphere

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Carlson, P.; Watson, A. A.

2014-12-01

In the 1930s the German physicist Erich Regener (1881-1955) did important work on the measurement of the rate of production of ionisation deep under water and in the atmosphere. Along with one of his students, Georg Pfotzer, he discovered the altitude at which the production of ionisation in the atmosphere reaches a maximum, often, but misleadingly, called the Pfotzer maximum. Regener was one of the first to estimate the energy density of cosmic rays, an estimate that was used by Baade and Zwicky to bolster their postulate that supernovae might be their source. Yet Regener's name is less recognised by present-day cosmic ray physicists than it should be, largely because in 1937 he was forced to take early retirement by the National Socialists as his wife had Jewish ancestors. In this paper we briefly review his work on cosmic rays and recommend an alternative naming of the ionisation maximum. The influence that Regener had on the field through his son, his son-in-law, his grandsons and his students, and through his links with Rutherford's group in Cambridge, is discussed in an appendix. Regener was nominated for the Nobel Prize in Physics by Schrödinger in 1938. He died in 1955 at the age of 73.

Electrolyte for batteries with regenerative solid electrolyte interface

Science.gov (United States)

Xiao, Jie; Lu, Dongping; Shao, Yuyan; Bennett, Wendy D.; Graff, Gordon L.; Liu, Jun; Zhang, Ji-Guang

2017-08-01

An energy storage device comprising: an anode; and a solute-containing electrolyte composition wherein the solute concentration in the electrolyte composition is sufficiently high to form a regenerative solid electrolyte interface layer on a surface of the anode only during charging of the energy storage device, wherein the regenerative layer comprises at least one solute or solvated solute from the electrolyte composition.

Image acquisition and planimetry systems to develop wounding techniques in 3D wound model

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Kiefer Ann-Kathrin

2017-09-01

Full Text Available Wound healing represents a complex biological repair process. Established 2D monolayers and wounding techniques investigate cell migration, but do not represent coordinated multi-cellular systems. We aim to use wound surface area measurements obtained from image acquisition and planimetry systems to establish our wounding technique and in vitro organotypic tissue. These systems will be used in our future wound healing treatment studies to assess the rate of wound closure in response to wound healing treatment with light therapy (photobiomodulation. The image acquisition and planimetry systems were developed, calibrated, and verified to measure wound surface area in vitro. The system consists of a recording system (Sony DSC HX60, 20.4 M Pixel, 1/2.3″ CMOS sensor and calibrated with 1mm scale paper. Macro photography with an optical zoom magnification of 2:1 achieves sufficient resolution to evaluate the 3mm wound size and healing growth. The camera system was leveled with an aluminum construction to ensure constant distance and orientation of the images. The JPG-format images were processed with a planimetry system in MATLAB. Edge detection enables definition of the wounded area. Wound area can be calculated with surface integrals. To separate the wounded area from the background, the image was filtered in several steps. Agar models, injured through several test persons with different levels of experience, were used as pilot data to test the planimetry software. These image acquisition and planimetry systems support the development of our wound healing research. The reproducibility of our wounding technique can be assessed by the variability in initial wound surface area. Also, wound healing treatment effects can be assessed by the change in rate of wound closure. These techniques represent the foundations of our wound model, wounding technique, and analysis systems in our ongoing studies in wound healing and therapy.

Conducted healing to treat large skin wounds.

Science.gov (United States)

Salgado, M I; Petroianu, A; Alberti, L R; Burgarelli, G L; Barbosa, A J A

2013-01-01

Improvement of the healing process to provide better aesthetical and functional results continues to be a surgical challenge. This study compared the treatment of skin wounds by means of conducted healing (an original method of treatment by secondary healing) and by the use of autogenous skin grafts. Two skin segments, one on each side of the dorsum,were removed from 17 rabbits. The side that served as a graft donor site was left open as to undergo conducted healing (A)and was submitted only to debridement and local care with dressings. The skin removed from the side mentioned above was implanted as a graft (B) to cover the wound on the other side. Thus, each animal received the two types of treatment on its dorsum (A and B). The rabbits were divided into two groups according to the size of the wounds: Group 1 - A and B (4 cm2)and Group 2 - A and B (25 cm2). The healing time was 19 days for Group 1 and 35 days for Group 2. The final macro- and microscopic aspects of the healing process were analysed comparatively among all subgroups. The presence of inflammatory cells, epidermal cysts and of giant cells was evaluated. No macro- or microscopic differences were observed while comparing the wounds that underwent conducted healing and those in which grafting was employed, although the wounds submitted to conducted healing healed more rapidly. Conducted wound healing was effective for the treatment of skin wounds. Celsius.

Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications.

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Ojeh, Nkemcho; Pastar, Irena; Tomic-Canic, Marjana; Stojadinovic, Olivera

2015-10-23

The skin is the largest organ of the body and has an array of functions. Skin compartments, epidermis, and hair follicles house stem cells that are indispensable for skin homeostasis and regeneration. These stem cells also contribute to wound repair, resulting in restoration of tissue integrity and function of damaged tissue. Unsuccessful wound healing processes often lead to non-healing wounds. Chronic wounds are caused by depletion of stem cells and a variety of other cellular and molecular mechanisms, many of which are still poorly understood. Current chronic wound therapies are limited, so the search to develop better therapeutic strategies is ongoing. Adult stem cells are gaining recognition as potential candidates for numerous skin pathologies. In this review, we will discuss epidermal and other stem cells present in the skin, and highlight some of the therapeutic applications of epidermal stem cells and other adult stem cells as tools for cell/scaffold-based therapies for non-healing wounds and other skin disorders. We will also discuss emerging concepts and offer some perspectives on how skin tissue-engineered products can be optimized to provide efficacious therapy in cutaneous repair and regeneration.

Regenerative therapy and tissue engineering for the treatment of end-stage cardiac failure: new developments and challenges.

Science.gov (United States)

Finosh, G T; Jayabalan, Muthu

2012-01-01

Regeneration of myocardium through regenerative therapy and tissue engineering is appearing as a prospective treatment modality for patients with end-stage heart failure. Focusing on this area, this review highlights the new developments and challenges in the regeneration of myocardial tissue. The role of various cell sources, calcium ion and cytokine on the functional performance of regenerative therapy is discussed. The evolution of tissue engineering and the role of tissue matrix/scaffold, cell adhesion and vascularisation on tissue engineering of cardiac tissue implant are also discussed.

Teaching wound care to family medicine residents on a wound care service

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Little SH

2013-08-01

Full Text Available Sahoko H Little,1,2 Sunil S Menawat,1,3 Michael Worzniak,1 Michael D Fetters2 1Oakwood Annapolis Family Medicine Residency, Wayne, Michigan, USA; 2University of Michigan, Department of Family Medicine, Ann Arbor, Michigan, USA; 3Ghent Family Medicine Residency, Eastern Virginia Medical School, Norfolk, Virginia, USA Abstract: Primary care physicians often care for patients with chronic wounds, and they can best serve patients if they have knowledge and proficient skills in chronic wound care, including sharp debridement. The Oakwood Annapolis Family Medicine Residency in Michigan, USA developed a Wound Care Service, incorporating wound care training during the surgical rotation. Effectiveness of the wound care training was evaluated through pre- and posttesting of residents, to assess changes in knowledge and comfort in treating chronic wounds. The results demonstrate significant improvement in residents’ knowledge and comfort in wound care. This innovation demonstrates the feasibility of educating residents in chronic wound care through hands-on experience. Keywords: wound care education, primary care, residency education, surgery rotation, curriculum development

Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila

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Patterson, Rachel A.; Juarez, Michelle T.; Hermann, Anita; Sasik, Roman; Hardiman, Gary; McGinnis, William

2013-01-01

After injury to the animal epidermis, a variety of genes are transcriptionally activated in nearby cells to regenerate the missing cells and facilitate barrier repair. The range and types of diffusible wound signals that are produced by damaged epidermis and function to activate repair genes during epidermal regeneration remains a subject of very active study in many animals. In Drosophila embryos, we have discovered that serine protease function is locally activated around wound sites, and is also required for localized activation of epidermal repair genes. The serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier. We developed a trypsin wounding treatment as an amplification tool to more fully understand the changes in the Drosophila transcriptome that occur after epidermal injury. By comparing our array results with similar results on mammalian skin wounding we can see which evolutionarily conserved pathways are activated after epidermal wounding in very diverse animals. Our innovative serine protease-mediated wounding protocol allowed us to identify 8 additional genes that are activated in epidermal cells in the immediate vicinity of puncture wounds, and the functions of many of these genes suggest novel genetic pathways that may control epidermal wound repair. Additionally, our data augments the evidence that clean puncture wounding can mount a powerful innate immune transcriptional response, with different innate immune genes being activated in an interesting variety of ways. These include puncture-induced activation only in epidermal cells in the immediate vicinity of wounds, or in all epidermal cells, or specifically in the fat body, or in multiple tissues. PMID:23637905

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering.

Science.gov (United States)

Ogueri, Kenneth S; Escobar Ivirico, Jorge L; Nair, Lakshmi S; Allcock, Harry R; Laurencin, Cato T

2017-03-01

The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately, be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly (lactide-co-glycolide) (PLAGA). Laurencin and co-workers has demonstrated the exploitation of the synthetic flexibility of Polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of this new

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

Science.gov (United States)

Ogueri, Kenneth S.; Escobar Ivirico, Jorge L.; Nair, Lakshmi S.; Allcock, Harry R.; Laurencin, Cato T.

2017-01-01

The occurrence of musculoskeletal tissue injury or disease and the subsequent functional impairment is at an alarming rate. It continues to be one of the most challenging problems in the human health care. Regenerative engineering offers a promising transdisciplinary strategy for tissues regeneration based on the convergence of tissue engineering, advanced materials science, stem cell science, developmental biology and clinical translation. Biomaterials are emerging as extracellular-mimicking matrices designed to provide instructive cues to control cell behavior and ultimately, be applied as therapies to regenerate damaged tissues. Biodegradable polymers constitute an attractive class of biomaterials for the development of scaffolds due to their flexibility in chemistry and the ability to be excreted or resorbed by the body. Herein, the focus will be on biodegradable polyphosphazene-based blend systems. The synthetic flexibility of polyphosphazene, combined with the unique inorganic backbone, has provided a springboard for more research and subsequent development of numerous novel materials that are capable of forming miscible blends with poly (lactide-co-glycolide) (PLAGA). Laurencin and co-workers has demonstrated the exploitation of the synthetic flexibility of Polyphosphazene that will allow the design of novel polymers, which can form miscible blends with PLAGA for biomedical applications. These novel blends, due to their well-tuned biodegradability, and mechanical and biological properties coupled with the buffering capacity of the degradation products, constitute ideal materials for regeneration of various musculoskeletal tissues. Lay Summary Regenerative engineering aims to regenerate complex tissues to address the clinical challenge of organ damage. Tissue engineering has largely focused on the restoration and repair of individual tissues and organs, but over the past 25 years, scientific, engineering, and medical advances have led to the introduction of

Diabetic foot wounds: the value of negative pressure wound therapy with instillation.

Science.gov (United States)

Dalla Paola, Luca

2013-12-01

Chronic wounds such as diabetic foot wounds are a tremendous burden to the health care system and often require a multidisciplinary approach to prevent amputations. Advanced technologies such as negative pressure wound therapy (NPWT) and bioengineered tissues have been successfully used in the treatment of these types of complex wounds. However, the introduction of NPWT with instillation (NPWTi) has provided an alternative treatment for treating complex and difficult-to-heal wounds. This article provides an overview of NPWT and the new NPWTi system and describes preliminary experience using NPWTi on patients with complicated infected diabetic foot wounds after surgical debridement and in a multidisciplinary setting. © 2013 The Author. International Wound Journal © 2013 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Biofilms in wounds

DEFF Research Database (Denmark)

Cooper, R A; Bjarnsholt, Thomas; Alhede, M

2014-01-01

Following confirmation of the presence of biofilms in chronic wounds, the term biofilm became a buzzword within the wound healing community. For more than a century pathogens have been successfully isolated and identified from wound specimens using techniques that were devised in the nineteenth...... extracellular polymeric substances (EPS). Cells within such aggregations (or biofilms) display varying physiological and metabolic properties that are distinct from those of planktonic cells, and which contribute to their persistence. There are many factors that influence healing in wounds and the discovery...... of biofilms in chronic wounds has provided new insight into the reasons why. Increased tolerance of biofilms to antimicrobial agents explains the limited efficacy of antimicrobial agents in chronic wounds and illustrates the need to develop new management strategies. This review aims to explain the nature...

A prospective randomized evaluation of negative-pressure wound dressings for diabetic foot wounds.

Science.gov (United States)

Eginton, Mark T; Brown, Kellie R; Seabrook, Gary R; Towne, Jonathan B; Cambria, Robert A

2003-11-01

Optimal treatment for large diabetic foot wounds is ill defined. The purpose of this study was to compare the rate of wound healing with the Vacuum Assisted Closure device trade mark (VAC) to conventional moist dressings in the treatment of large diabetic foot wounds. Diabetics with significant soft tissue defects of the foot were considered for enrollment. Patients were randomized to receive either moist gauze dressings or VAC treatments for 2 weeks, after which they were treated with the alternative dressing for an additional 2 weeks. Wounds were photographed weekly and wound dimensions calculated in a blinded fashion with spatial analysis software. Percent change in wound dimensions were calculated and compared for each weekly assessment and over 2 weeks of therapy with each dressing type. Ten patients were enrolled in the trial, but two were lost to follow-up and two were withdrawn. Complete data were available for analysis on seven wounds in six patients. Average length, width, and depth of the wounds at initiation of the trial was 7.7, 3.5, and 3.1 cm, respectively. Only the wound depth was significantly decreased over the weeks of the trial to 1.2 cm ( p VAC dressings decreased the wound volume and depth significantly more than moist gauze dressings (59% vs. 0% and 49% vs. 8%, respectively). VAC dressings were associated with a decrease in all wound dimensions while wound length and width increased with moist dressings. In summary, over the first several weeks of therapy, VAC dressings decreased wound depth and volume more effectively than moist gauze dressings. Negative-pressure wound treatment may accelerate closure of large foot wounds in the diabetic patient.

Tissue-specific composite cell aggregates drive periodontium tissue regeneration by reconstructing a regenerative microenvironment.

Science.gov (United States)

Zhu, Bin; Liu, Wenjia; Zhang, Hao; Zhao, Xicong; Duan, Yan; Li, Dehua; Jin, Yan

2017-06-01

Periodontitis is the most common cause of periodontium destruction. Regeneration of damaged tissue is the expected treatment goal. However, the regeneration of a functional periodontal ligament (PDL) insertion remains a difficulty, due to complicated factors. Recently, periodontal ligament stem cells (PDLSCs) and bone marrow-derived mesenchymal stem cells (BMMSCs) have been shown to participate in PDL regeneration, both pathologically and physiologically. Besides, interactions affect the biofunctions of different derived cells during the regenerative process. Therefore, the purpose of this study was to discuss the different derived composite cell aggregate (CA) systems of PDLSCs and BMMSCs (iliac-derived or jaw-derived) for periodontium regeneration under regenerative microenvironment reconstruction. Our results showed although all three mono-MSC CAs were compacted and the cells arranged regularly in them, jaw-derived BMMSC (JBMMSC) CAs secreted more extracellular matrix than the others. Furthermore, PDLSC/JBMMSC compound CAs highly expressed ALP, Col-I, fibronectin, integrin-β1 and periostin, suggesting that their biofunction is more appropriate for periodontal structure regeneration. Inspiringly, PDLSC/JBMMSC compound CAs regenerated more functional PDL-like tissue insertions in both nude mice ectopic and minipig orthotopic transplantation. The results indicated that the different derived CAs of PDLSCs/JBMMSCs provided an appropriate regenerative microenvironment facilitating a more stable and regular regeneration of functional periodontium tissue. This method may provide a possible strategy to solve periodontium defects in periodontitis and powerful experimental evidence for clinical applications in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The TMI Regenerative Solid Oxide Fuel Cell

Science.gov (United States)

Cable, Thomas L.; Ruhl, Robert C.; Petrik, Michael

1996-01-01

Energy storage and production in space requires rugged, reliable hardware which minimizes weight, volume, and maintenance while maximizing power output and usable energy storage. Systems generally consist of photovoltaic solar arrays which operate (during sunlight cycles) to provide system power and regenerate fuel (hydrogen) via water electrolysis and (during dark cycles) fuel cells convert hydrogen into electricity. Common configurations use two separate systems (fuel cell and electrolyzer) in conjunction with photovoltaic cells. Reliability, power to weight and power to volume ratios could be greatly improved if both power production (fuel cells) and power storage (electrolysis) functions can be integrated into a single unit. The solid oxide fuel cell (SOFC) based design integrates fuel cell and electrolyzer functions and potentially simplifies system requirements. The integrated fuel cell/electrolyzer design also utilizes innovative gas storage concepts and operates like a rechargeable 'hydrogen-oxygen battery'. Preliminary research has been completed on improved H2/H20 electrode (SOFC anode/electrolyzer cathode) materials for regenerative fuel cells. Tests have shown improved cell performance in both fuel and electrolysis modes in reversible fuel cell tests. Regenerative fuel cell efficiencies, ratio of power out (fuel cell mode) to power in (electrolyzer mode), improved from 50 percent using conventional electrode materials to over 80 percent. The new materials will allow a single SOFC system to operate as both the electolyzer and fuel cell. Preliminary system designs have also been developed to show the technical feasibility of using the design for space applications requiring high energy storage efficiencies and high specific energy. Small space systems also have potential for dual-use, terrestrial applications.

Regenerative endodontics: A way forward.

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Diogenes, Anibal; Ruparel, Nikita B; Shiloah, Yoav; Hargreaves, Kenneth M

2016-05-01

Immature teeth are susceptible to infections due to trauma, anatomic anomalies, and caries. Traditional endodontic therapies for immature teeth, such as apexification procedures, promote resolution of the disease and prevent future infections. However, these procedures fail to promote continued root development, leaving teeth susceptible to fractures. Regenerative endodontic procedures (REPs) have evolved in the past decade, being incorporated into endodontic practice and becoming a viable treatment alternative for immature teeth. The authors have summarized the status of regenerative endodontics on the basis of the available published studies and provide insight into the different levels of clinical outcomes expected from these procedures. Substantial advances in regenerative endodontics are allowing a better understanding of a multitude of factors that govern stem cell-mediated regeneration and repair of the damaged pulp-dentin complex. REPs promote healing of apical periodontitis, continued radiographic root development, and, in certain cases, vitality responses. Despite the clinical success of these procedures, they appear to promote a guided endodontic repair process rather than a true regeneration of physiological-like tissue. Immature teeth with pulpal necrosis with otherwise poor prognosis can be treated with REPs. These procedures do not preclude the possibility of apexification procedures if attempts are unsuccessful. Therefore, REPs may be considered first treatment options for immature teeth with pulpal necrosis. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Topical Negative Pressure Therapy in Wound Care: Effectiveness and guidelines for clinical application

NARCIS (Netherlands)

C.M. Moues-Vink (Chantal)

2009-01-01

textabstractThe aim in the treatment of any type of wound is to achieve normal and timely healing. Complicated wound healing may affect functional ability and almost always involves appearance or “looks” despite reconstructive measures. Recent figures on either the incidence of wounds or the

Analysis of the rate of maturogenesis of a traumatized Cvek′s stage 3 anterior tooth treated with platelet-rich fibrin as a regenerative tool using three-dimensional cone-beam computed tomography: An original case report

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Raji Viola Solomon

2015-01-01

Full Text Available Regenerative endodontic procedures are biologically based procedures which deal with the regeneration of pulp-like tissue, more idealistically the pulp-dentin complex. The regeneration of this pulp-dentin complex in an infected necrotic tooth with an open apex is possible only when the canal is effectively disinfected. Though there are various procedures for treating open apex ranging from Ca(OH 2 apexification, mineral trioxide aggregate apexification and surgical approach, regeneration of tissues has always taken superior hand over the repair of tissues. The mechanics behind the regenerative endodontic procedures is that despite the tooth being necrotic, some pulp tissue can survive apically which under favorable conditions proliferate to aid in the process of regeneration. In the past 2 decades, an increased understanding of the physiological roles of platelets in wound healing and after tissue injury has led to the idea of using platelets as therapeutic tools in the field regenerative endodontics. In the present case report with an open apex, high sterilization protocol is followed using triple antibiotic paste as intra-canal medicament, followed which platelet rich fibrin is used as the regenerative material of choice. Over an 18-month follow-up period, clinically patient is asymptomatic and radiographically there is complete regression of the periapical lesion and initiation of the root end closure.

Innate defense regulator peptide 1018 in wound healing and wound infection.

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Lars Steinstraesser

Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

Platelet concentrates: Bioengineering dentistry′s regenerative dreams

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Sushma Naag

2015-01-01

Full Text Available Technological advances in the fields of medicine and allied sciences had given much needed momentum into the field of molecular biology and regenerative medicine. They indeed provided a boost to innovate new yields for both hard tissue and soft tissue regeneration in dentistry. One among them is the use of platelet concentrates (platelet rich plasma [PRP], platelet rich fibrin [PRF]. Autologous concentrate of blood platelets with a suspension of growth factors offers an enhanced healing of hard and soft tissues. It is an auxiliary benefit for an operator to be aware of platelet concentrates and its healing properties for delivering unsurpassed oral health care to patients. The current article outlines the principles, objectives and clinical insight to the regenerative potential of platelet concentrates in various fields of dentistry. The search words of the PubMed data base were PRF and other permutations of keywords such as "PRP dentistry", PRF dentistry, PRF regenerative dentistry.

Modern and Convensional Wound Dressing to Interleukin 1 and Interleukin 6 in Diabetic wound

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Werna Nontji

2015-04-01

Full Text Available Introduction:Holistic wound care is one of the ways to prevent gangrene and amputation, modern wound dressing is more effective than convensional with increasing transforming growth factor and cytokine, especially interleukin. This study aims to identify the effectiveness of Modern and Convensional Wound Dressing to Interleukin 1 (IL-1 and Interleukin 6 (IL-6 in Diabetic wound. Method:A Quasi eksperimental pre-post with control group design was used. The intervention given was modern wound dressing and Control group by convensional wound dressing, This study was conducted in Makassar with 32 samples (16 in intervention group and 16 in control group. Result: The result of Pooled T- test showed that p = 0.00 (p < 0.05, it means that there was signifi cant correlation between modern wound dressing to IL-6 and IL-1 than Convensional wound dressing. Discussion: Process of wound healing was produced growth factor and cytokine (IL-1 and IL-6, it will stimulated by wound dressing, modern wound dressing (Calcium alginat can absorb wound drainage, non oklusive, non adhesif, and autolytic debridement. Keywords: Modern wound dressing, Interleukin 1 (IL-1, Interleukin 6 (IL-6

Peroxisome Proliferator-Activated Receptor (PPAR) in Regenerative Medicine: Molecular Mechanism for PPAR in Stem Cells' Adipocyte Differentiation.

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Xie, Qiang; Tian, Taoran; Chen, Zhaozhao; Deng, Shuwen; Sun, Ke; Xie, Jing; Cai, Xiaoxiao

2016-01-01

Regenerative medicine plays an indispensable role in modern medicine and many trials and researches have therefore been developed to fit our medical needs. Tissue engineering has proven that adipose tissue can widely be used and brings advantages to regenerative medicine. Moreover, a trait of adipose stem cells being isolated and grown in vitro is a cornerstone to various applications. Since the adipose tissue has been widely used in regenerative medicine, numerous studies have been conducted to seek methods for gaining more adipocytes. To investigate molecular mechanism for adipocyte differentiation, peroxisome proliferator-activated receptor (PPAR) has been widely studied to find out its functional mechanism, as a key factor for adipocyte differentiation. However, the precise molecular mechanism is still unknown. This review thus summarizes recent progress on the study of molecular mechanism and role of PPAR in adipocyte differentiation.

[Errors in wound management].

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Filipović, Marinko; Novinscak, Tomislav

2014-10-01

Chronic ulcers have adverse effects on the patient quality of life and productivity, thus posing financial burden upon the healthcare system. Chronic wound healing is a complex process resulting from the interaction of the patient general health status, wound related factors, medical personnel skill and competence, and therapy related products. In clinical practice, considerable improvement has been made in the treatment of chronic wounds, which is evident in the reduced rate of the severe forms of chronic wounds in outpatient clinics. However, in spite of all the modern approaches, efforts invested by medical personnel and agents available for wound care, numerous problems are still encountered in daily practice. Most frequently, the problems arise from inappropriate education, of young personnel in particular, absence of multidisciplinary approach, and inadequate communication among the personnel directly involved in wound treatment. To perceive them more clearly, the potential problems or complications in the management of chronic wounds can be classified into the following groups: problems mostly related to the use of wound coverage and other etiology related specificities of wound treatment; problems related to incompatibility of the agents used in wound treatment; and problems arising from failure to ensure aseptic and antiseptic performance conditions.

Tissue engineering and regenerative medicine: manufacturing challenges.

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Williams, D J; Sebastine, I M

2005-12-01

Tissue engineering and regenerative medicine are interdisciplinary fields that apply principles of engineering and life sciences to develop biological substitutes, typically composed of biological and synthetic components, that restore, maintain or improve tissue function. Many tissue engineering technologies are still at a laboratory or pre-commercial scale. The short review paper describes the most significant manufacturing and bio-process challenges inherent in the commercialisation and exploitation of the exciting results emerging from the biological and clinical laboratories exploring tissue engineering and regenerative medicine. A three-generation road map of the industry has been used to structure a view of these challenges and to define where the manufacturing community can contribute to the commercial success of the products from these emerging fields. The first-generation industry is characterised by its demonstrated clinical applications and products in the marketplace, the second is characterised by emerging clinical applications, and the third generation is characterised by aspirational clinical applications. The paper focuses on the cost reduction requirement of the first generation of the industry to allow more market penetration and consequent patient impact. It indicates the technological requirements, for instance the creation of three-dimensional tissue structures, and value chain issues in the second generation of the industry. The third-generation industry challenges lie in fundamental biological and clinical science. The paper sets out a road map of these generations to identify areas for research.

A Comprehensive Review of the Techniques on Regenerative Shock Absorber Systems

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Ran Zhang

2018-05-01

Full Text Available In this paper, the current technologies of the regenerative shock absorber systems have been categorized and evaluated. Three drive modes of the regenerative shock absorber systems, namely the direct drive mode, the indirect drive mode and hybrid drive mode are reviewed for their readiness to be implemented. The damping performances of the three different modes are listed and compared. Electrical circuit and control algorithms have also been evaluated to maximize the power output and to deliver the premium ride comfort and handling performance. Different types of parameterized road excitations have been applied to vehicle suspension systems to investigate the performance of the regenerative shock absorbers. The potential of incorporating nonlinearity into the regenerative shock absorber design analysis is discussed. The research gaps for the comparison of the different drive modes and the nonlinearity analysis of the regenerative shock absorbers are identified and, the corresponding research questions have been proposed for future work.

Leptin promotes wound healing in the oral mucosa.

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Umeki, Hirochika; Tokuyama, Reiko; Ide, Shinji; Okubo, Mitsuru; Tadokoro, Susumu; Tezuka, Mitsuki; Tatehara, Seiko; Satomura, Kazuhito

2014-01-01

Leptin, a 16 kDa circulating anti-obesity hormone, exhibits many physiological properties. Recently, leptin was isolated from saliva; however, its function in the oral cavity is still unclear. In this study, we investigated the physiological role of leptin in the oral cavity by focusing on its effect on wound healing in the oral mucosa. Immunohistochemical analysis was used to examine the expression of the leptin receptor (Ob-R) in human/rabbit oral mucosa. To investigate the effect of leptin on wound healing in the oral mucosa, chemical wounds were created in rabbit oral mucosa, and leptin was topically administered to the wound. The process of wound repair was histologically observed and quantitatively analyzed by measuring the area of ulceration and the duration required for complete healing. The effect of leptin on the proliferation, differentiation and migration of human oral mucosal epithelial cells (RT7 cells) was investigated using crystal violet staining, reverse transcription polymerase chain reaction (RT-PCR) and a wound healing assay, respectively. Ob-R was expressed in spinous/granular cells in the epithelial tissue and vascular endothelial cells in the subepithelial connective tissue of the oral mucosa. Topical administration of leptin significantly promoted wound healing and shortened the duration required for complete healing. Histological analysis of gingival tissue beneath the ulceration showed a denser distribution of blood vessels in the leptin-treated group. Although the proliferation and differentiation of RT7 cells were not affected by leptin, the migration of these cells was accelerated in the presence of leptin. Topically administered leptin was shown to promote wound healing in the oral mucosa by accelerating epithelial cell migration and enhancing angiogenesis around the wounded area. These results strongly suggest that topical administration of leptin may be useful as a treatment to promote wound healing in the oral mucosa.

Wound care matrices for chronic leg ulcers: role in therapy

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Sano H

2015-07-01

Full Text Available Hitomi Sano,1 Sachio Kouraba,2 Rei Ogawa11Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School, Tokyo, Japan; 2Sapporo Wound Care and Anti-Aging Laboratory, Sapporo, JapanAbstract: Chronic leg ulcers are a significant health care concern. Although deep wounds are usually treated by flap transfers, the operation is invasive and associates with serious complications. Skin grafts may be a less invasive means of covering wounds. However, skin grafts cannot survive on deep defects unless high-quality granulation tissue can first be generated in the defects. Technologies that generate high-quality granulation tissue are needed. One possibility is to use wound care matrices, which are bioengineered skin and soft tissue substitutes. Because they all support the healing process by providing a premade extracellular matrix material, these matrices can be termed “extracellular matrix replacement therapies”. The matrix promotes wound healing by acting as a scaffold for regeneration, attracting host cytokines to the wound, stimulating wound epithelialization and angiogenesis, and providing the wound bed with bioactive components. This therapy has lasting benefits as it not only helps large skin defects to be closed with thin skin grafts or patch grafts but also restores cosmetic appearance and proper function. In particular, since it acts as a layer that slides over the subcutaneous fascia, it provides skin elasticity, tear resistance, and texture. Several therapies and products employing wound care matrices for wound management have been developed recently. Some of these can be applied in combination with negative pressure wound therapy or beneficial materials that promote wound healing and can be incorporated into the matrix. To date, the clinical studies on these approaches suggest that wound care matrices promote spontaneous wound healing or can be used to facilitate skin grafting, thereby avoiding the need to use

Profiling wound healing with wound effluent: Raman spectroscopic indicators of infection

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Crane, Nicole J.; Elster, Eric A.

2012-01-01

The care of modern traumatic war wounds remains a significant challenge for clinicians. Many of the extremity wounds inflicted during Operation Enduring Freedom and Operation Iraqi Freedom are colonized or infected with multi-drug resistant organisms, particularly Acinetobacter baumannii. Biofilm formation and resistance to current treatments can significantly confound the wound healing process. Accurate strain identification and targeted drug administration for the treatment of wound bioburden has become a priority for combat casualty care. In this study, we use vibrational spectroscopy to examine wound exudates for bacterial load. Inherent chemical differences in different bacterial species and strains make possible the high specificity of vibrational spectroscopy.

Perivascular cells for regenerative medicine

NARCIS (Netherlands)

M. Crisan (Mihaela); M. Corselli (Mirko); W.C. Chen (William); B. Péault (Bruno)

2012-01-01

textabstractMesenchymal stem/stromal cells (MSC) are currently the best candidate therapeutic cells for regenerative medicine related to osteoarticular, muscular, vascular and inflammatory diseases, although these cells remain heterogeneous and necessitate a better biological characterization. We

Leptospermum Honey for Wound Care in an Extremely Premature Infant.

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Esser, Media

2017-02-01

Neonatal wound care is challenging due to the fragility and vulnerable skin structure. Neonates are often left susceptible to the forces of their environment, leaving them open to infection when skin injury occurs. Leptospermum honey has been used successfully in adult patients, with evidence lacking in the neonatal population. This case demonstrates the management of a difficult-to-heal wound in a 23-week gestation infant. Selecting the proper treatment and products for wound healing is challenging, with little evidence-based research available for the treatment of neonatal wounds. Leptospermum honey and other adult-driven dressings have been used for neonatal wound care as well as other adult-driven dressings. This case demonstrates the benefits of Leptospermum honey as an option for neonatal wounds. This case presents the treatment and healing of an extensive wound of a 23-week gestation neonate using a hydrogel product initially and then transitioning to a Leptospermum honey dressing due to suboptimal healing. Results of this treatment included quick healing time, little to no scarring, and no loss of movement or function to the affected extremities. The incorporation of Leptospermum honey for wound care has the potential to promote faster wound healing, with less scarring in the neonatal population. Adult wound care principles have been applied in the face of a weak evidence base relating to neonatal-specific cases. There is a need for continued research related to moist wound healing in the neonatal population, with resulting product and practice recommendations.

Pigment epithelium-derived factor as a multifunctional regulator of wound healing

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Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

2015-01-01

During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

Wound healing activity of Ipomoea batatas tubers (sweet potato

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Madhav Sonkamble

2011-10-01

Full Text Available Background: Ipomoea batatas (L. Lam. from the family Convolvulaceae is the world’s sixth largest food crop. The tubers of Ipomoea batatas commonly known as sweet potato are consumed as a vegetable globally. The tubers contain high levels of polyphenols such as anthocyanins and phenolic acids and vitamins A, B and C, which impart a potent antioxidant activity that can translate well to show wound healing effects. To check their effects on wound healing, the peels and peel bandage were tested on various injury models in rats in the present study.Methods: The methanolic extracts of the peels and peel bandage of Ipomoea batatas tubers (sweet potato were screened for wound healing by excision and incision wound models on Wistar rats. Three types of gel formulations were prepared, viz., gel containing 3.0% (w/w peel extract, gel containing 6.0% (w/w peel extract and gel containing 10% (w/w peel extract. Betadine (5% w/w povidone iodine cream was used as a reference standard. In the incision wound model, Tensile strength of the skin was measured. Epithelization time, wound contraction, hydroxyproline content of the scab, and ascorbic acid and malondialdehyde content of the plasma were determined in the excision wound model.Results: In the incision wound model, high tensile strength of the wounded skin was observed in animals treated with the peel extract gels and the peel bandage when compared with wounded control animals. The increase in tensile strength indicates the promotion of collagen fibers and that the disrupted wound surfaces are being firmly knit by collagen. In the excision wound model, significant wound closure was observed on the 4th day in rats treated with all three gel formulations when compared with the wounded control rats. A significant increase inFunctional Foods in Health and Disease 2011; 10:403-415hydroxyproline and ascorbic acid content in the gel-treated animals and a significant decrease in malondialdehyde content in the

The past, present and future of ligament regenerative engineering.

Science.gov (United States)

Mengsteab, Paulos Y; Nair, Lakshmi S; Laurencin, Cato T

2016-12-01

Regenerative engineering has been defined as the convergence of Advanced Materials Sciences, Stem Cell Sciences, Physics, Developmental Biology and Clinical Translation for the regeneration of complex tissues and organ systems. Anterior cruciate ligament (ACL) reconstruction necessitates the regeneration of bone, ligament and their interface to achieve superior clinical results. In the past, the ACL has been repaired with the use of autologous and allogeneic grafts, which have their respective drawbacks. Currently, investigations on the use of biodegradable matrices to achieve knee stability and permit tissue regeneration are making promising advancements. In the future, utilizing regenerative biology cues to induce an endogenous regenerative response may aid the enhancement of clinical ACL reconstruction outcomes.

Cardiovascular disease: primary prevention, disease modulation and regenerative therapy.

LENUS (Irish Health Repository)

Sultan, Sherif

2012-10-01

Cardiovascular primary prevention and regeneration programs are the contemporary frontiers in functional metabolic vascular medicine. This novel science perspective harnesses our inherent ability to modulate the interface between specialized gene receptors and bioavailable nutrients in what is labeled as the nutrient-gene interaction. By mimicking a natural process through the conveyance of highly absorbable receptor specific nutrients, it is feasible to accelerate cell repair and optimize mitochondrial function, thereby achieving cardiovascular cure. We performed a comprehensive review of PubMed, EMBASE and Cochrane Review databases for articles relating to cardiovascular regenerative medicine, nutrigenomics and primary prevention, with the aim of harmonizing their roles within contemporary clinical practice. We searched in particular for large-scale randomized controlled trials on contemporary cardiovascular pharmacotherapies and their specific adverse effects on metabolic pathways which feature prominently in cardiovascular regenerative programs, such as nitric oxide and glucose metabolism. Scientific research on \\'cardiovascular-free\\' centenarians delineated that low sugar and low insulin are consistent findings. As we age, our insulin level increases. Those who can decelerate the rapidity of this process are prompting their cardiovascular rejuvenation. It is beginning to dawn on some clinicians that contemporary treatments are not only failing to impact on our most prevalent diseases, but they may be causing more damage than good. Primary prevention programs are crucial elements for a better outcome. Cardiovascular primary prevention and regeneration programs have enhanced clinical efficacy and quality of life and complement our conventional endovascular practice.

Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects

Science.gov (United States)

Dai, Tianhong; Tanaka, Masamitsu; Huang, Ying-Ying; Hamblin, Michael R

2011-01-01

Since its discovery approximately 200 years ago, chitosan, as a cationic natural polymer, has been widely used as a topical dressing in wound management owing to its hemostatic, stimulation of healing, antimicrobial, nontoxic, biocompatible and biodegradable properties. This article covers the antimicrobial and wound-healing effects of chitosan, as well as its derivatives and complexes, and its use as a vehicle to deliver biopharmaceuticals, antimicrobials and growth factors into tissue. Studies covering applications of chitosan in wounds and burns can be classified into in vitro, animal and clinical studies. Chitosan preparations are classified into native chitosan, chitosan formulations, complexes and derivatives with other substances. Chitosan can be used to prevent or treat wound and burn infections not only because of its intrinsic antimicrobial properties, but also by virtue of its ability to deliver extrinsic antimicrobial agents to wounds and burns. It can also be used as a slow-release drug-delivery vehicle for growth factors to improve wound healing. The large number of publications in this area suggests that chitosan will continue to be an important agent in the management of wounds and burns. PMID:21810057

Regenerative Endodontics: A Road Less Travelled

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Bansal, Ramta; Mittal, Sunandan; Kumar, Tarun; Kaur, Dilpreet

2014-01-01

Although traditional approaches like root canal therapy and apexification procedures have been successful in treating diseased or infected root canals, but these modalities fail to re-establish healthy pulp tissue in treated teeth. Regeneration-based approaches aims to offer high levels of success by replacing diseased or necrotic pulp tissues with healthy pulp tissue to revitalize teeth. The applications of regenerative approaches in dental clinics have potential to dramatically improve patients’ quality of life. This review article offers a detailed overview of present regenerative endodontic approaches aiming to revitalize teeth and also outlines the problems to be dealt before this emerging field contributes to clinical treatment protocols. It conjointly covers the basic trilogy elements of tissue engineering. PMID:25478476

Telemedicine for wound management

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Ravi K Chittoria

2012-01-01

Full Text Available The escalating physiological, psychological, social and financial burdens of wounds and wound care on patients, families and society demand the immediate attention of the health care sector. Many forces are affecting the changes in health care provision for patients with chronic wounds, including managed care, the limited number of wound care therapists, an increasingly ageing and disabled population, regulatory and malpractice issues, and compromised care. The physician is also faced with a number of difficult issues when caring for chronic wound patients because their conditions are time consuming and high risk, represent an unprofitable part of care practice and raise issues of liability. Telemedicine enhances communication with the surgical wound care specialist. Digital image for skin lesions is a safe, accurate and cost-effective referral pathway. The two basic modes of telemedicine applications, store and forward (asynchronous transfer and real-time transmission (synchronous transfer, e.g. video conference, are utilized in the wound care setting. Telemedicine technology in the hands of an experienced physician can streamline management of a problem wound. Although there is always an element of anxiety related to technical change, the evolution of wound care telemedicine technology has demonstrated a predictable maturation process.

Personalized Regenerative Medicine

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Babak Arjmand

2017-03-01

Full Text Available Personalized medicine as a novel field of medicine refers to the prescription of specific therapeutics procedure for an individual. This approach has established based on pharmacogenetic and pharmacogenomic information and data. The terms precision and personalized medicines are sometimes applied interchangeably. However, there has been a shift from “personalized medicine” towards “precision medicine”. Although personalized medicine emerged from pharmacogenetics, nowadays it covers many fields of healthcare. Accordingly, regenerative medicine and cellular therapy as the new fields of medicine use cell-based products in order to develop personalized treatments. Different sources of stem cells including mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs have been considered in targeted therapies which could give many advantages. iPSCs as the novel and individual pluripotent stem cells have been introduced as the appropriate candidates for personalized cell therapies. Cellular therapies can provide a personalized approach. Because of person-to-person and population differences in the result of stem cell therapy, individualized cellular therapy must be adjusted according to the patient specific profile, in order to achieve best therapeutic results and outcomes. Several factors should be considered to achieve personalized stem cells therapy such as, recipient factors, donor factors, and the overall body environment in which the stem cells could be active and functional. In addition to these factors, the source of stem cells must be carefully chosen based on functional and physical criteria that lead to optimal outcomes.

From inflammation to wound healing: using a simple model to understand the functional versatility of murine macrophages.

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Childs, Lauren M; Paskow, Michael; Morris, Sidney M; Hesse, Matthias; Strogatz, Steven

2011-11-01

Macrophages are fundamental cells of the innate immune system. Their activation is essential for such distinct immune functions as inflammation (pathogen-killing) and tissue repair (wound healing). An open question has been the functional stability of an individual macrophage cell: whether it can change its functional profile between different immune responses such as between the repair pathway and the inflammatory pathway. We studied this question theoretically by constructing a rate equation model for the key substrate, enzymes and products of the pathways; we then tested the model experimentally. Both our model and experiments show that individual macrophages can switch from the repair pathway to the inflammation pathway but that the reverse switch does not occur.

Early regulation of axolotl limb regeneration.

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Makanae, Aki; Satoh, Akira

2012-10-01

Amphibian limb regeneration has been studied for a long time. In amphibian limb regeneration, an undifferentiated blastema is formed around the region damaged by amputation. The induction process of blastema formation has remained largely unknown because it is difficult to study the induction of limb regeneration. The recently developed accessory limb model (ALM) allows the investigation of limb induction and reveals early events of amphibian limb regeneration. The interaction between nerves and wound epidermis/epithelium is an important aspect of limb regeneration. During early limb regeneration, neurotrophic factors act on wound epithelium, leading to development of a functional epidermis/epithelium called the apical epithelial cap (AEC). AEC and nerves create a specific environment that inhibits wound healing and induces regeneration through blastema formation. It is suggested that FGF-signaling and MMP activities participate in creating a regenerative environment. To understand why urodele amphibians can create such a regenerative environment and humans cannot, it is necessary to identify the similarities and differences between regenerative and nonregenerative animals. Here we focus on ALM to consider limb regeneration from a new perspective and we also reported that focal adhesion kinase (FAK)-Src signaling controlled fibroblasts migration in axolotl limb regeneration. Copyright © 2012 Wiley Periodicals, Inc.

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

Science.gov (United States)

Marei, Mona K.; El Backly, Rania M.

2018-01-01

Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use. PMID:29770323

Dental Mesenchymal Stem Cell-Based Translational Regenerative Dentistry: From Artificial to Biological Replacement

Directory of Open Access Journals (Sweden)

Mona K. Marei

2018-05-01

Full Text Available Dentistry is a continuously changing field that has witnessed much advancement in the past century. Prosthodontics is that branch of dentistry that deals with replacing missing teeth using either fixed or removable appliances in an attempt to simulate natural tooth function. Although such “replacement therapies” appear to be easy and economic they fall short of ever coming close to their natural counterparts. Complications that arise often lead to failures and frequent repairs of such devices which seldom allow true physiological function of dental and oral-maxillofacial tissues. Such factors can critically affect the quality of life of an individual. The market for dental implants is continuously growing with huge economic revenues. Unfortunately, such treatments are again associated with frequent problems such as peri-implantitis resulting in an eventual loss or replacement of implants. This is particularly influential for patients having co-morbid diseases such as diabetes or osteoporosis and in association with smoking and other conditions that undoubtedly affect the final treatment outcome. The advent of tissue engineering and regenerative medicine therapies along with the enormous strides taken in their associated interdisciplinary fields such as stem cell therapy, biomaterial development, and others may open arenas to enhancing tissue regeneration via designing and construction of patient-specific biological and/or biomimetic substitutes. This review will overview current strategies in regenerative dentistry while overviewing key roles of dental mesenchymal stem cells particularly those of the dental pulp, until paving the way to precision/translational regenerative medicine therapies for future clinical use.

A conducive bioceramic/polymer composite biomaterial for diabetic wound healing.

Science.gov (United States)

Lv, Fang; Wang, Jie; Xu, Peng; Han, Yiming; Ma, Hongshi; Xu, He; Chen, Shijie; Chang, Jiang; Ke, Qinfei; Liu, Mingyao; Yi, Zhengfang; Wu, Chengtie

2017-09-15

Diabetic wound is a common complication of diabetes. Biomaterials offer great promise in inducing tissue regeneration for chronic wound healing. Herein, we reported a conducive Poly (caprolactone) (PCL)/gelatin nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) for diabetic wound healing. NAGEL bioceramic particles were well distributed in the inner of PCL/gelatin nanofibers via co-electrospinning process and the Si ions maintained a sustained release from the composite scaffolds during the degradation process. The nanofibrous scaffolds significantly promoted the adhesion, proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human keratinocytes (HaCaTs) in vitro. The in vivo study demonstrated that the scaffolds distinctly induced the angiogenesis, collagen deposition and re-epithelialization in the wound sites of diabetic mice model, as well as inhibited inflammation reaction. The mechanism for nanofibrous composite scaffolds accelerating diabetic wound healing is related to the activation of epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vivo and in vitro. Our results suggest that the released Si ions and nanofibrous structure of scaffolds have a synergetic effect on the improved efficiency of diabetic wound healing, paving the way to design functional biomaterials for tissue engineering and wound healing applications. In order to stimulate tissue regeneration for chronic wound healing, a new kind of conducive nanofibrous composite scaffold containing silicate-based bioceramic particles (Nagelschmidtite, NAGEL, Ca 7 P 2 Si 2 O 16 ) were prepared via co-electrospinning process. Biological assessments revealed that the NAGEL bioceramic particles could active epithelial to mesenchymal transition (EMT) and endothelial to mesenchymal transition (EndMT) pathway in vitro and in vivo. The new composite scaffold

Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiangyu; Niu, Yuqing [College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060 (China); Nanshan District Key lab for Biopolymers and Safety Evaluation, Shenzhen 518060 (China); Shenzhen Key Laboratory of Polymer Science and Technology, Shenzhen 518060 (China); Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen 518060 (China); Chen, Kevin C. [Multidisciplinary Research Center, Shantou University, Shantou, Guangdong 515063 (China); Chen, Shiguo, E-mail: csg@szu.edu.cn [College of Materials Science and Engineering, Shenzhen University, Shenzhen 518060 (China); Nanshan District Key lab for Biopolymers and Safety Evaluation, Shenzhen 518060 (China); Shenzhen Key Laboratory of Polymer Science and Technology, Shenzhen 518060 (China); Guangdong Research Center for Interfacial Engineering of Functional Materials, Shenzhen 518060 (China)

2017-02-01

A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50–130 μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13 days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization. - Highlights: • Rapid hemostatic and mild PUUF wound dressing was fabricated. • Low-toxic PUUF exhibited good water uptake that could build a regional moist environment beneficial for wound healing. • PUUF could promote wound healing and enhance re-epithelialization.

Insulin regulates multiple signaling pathways leading to monocyte/macrophage chemotaxis into the wound tissue

Directory of Open Access Journals (Sweden)

Yan Liu

2018-01-01

Full Text Available Wound healing is a complex process that involves sequential phases that overlap in time and space and affect each other dynamically at the gene and protein levels. We previously showed that insulin accelerates wound healing by stimulating faster and regenerative healing. One of the processes that insulin stimulates is an increase in monocyte/macrophage chemotaxis. In this study, we performed experiments in vivo and in vitro to elucidate the signaling transduction pathways that are involved in insulin-induced monocyte/macrophage chemotaxis. We found that insulin stimulates THP-1 cell chemotaxis in a dose-dependent and insulin receptor-dependent manner. We also show that the kinases PI3K-Akt, SPAK/JNK, and p38 MAPK are key molecules in the insulin-induced signaling pathways that lead to chemoattraction of the THP-1 cell. Furthermore, both PI3K-Akt and SPAK/JNK signaling involve Rac1 activation, an important molecule in regulating cell motility. Indeed, topical application of Rac1 inhibitor at an early stage during the healing process caused delayed and impaired healing even in the presence of insulin. These results delineate cell and molecular mechanisms involved in insulin-induced chemotaxis of monocyte/macrophage, cells that are critical for proper healing.

Reflective Self-Regenerative Systems Architecture Study

National Research Council Canada - National Science Library

Pu, Carlton; Blough, Douglas

2006-01-01

In this study, we develop the Reflective Self-Regenerative Systems (RSRS) architecture in detail, describing the internal structure of each component and the mutual invocations among the components...

A multi-centre clinical evaluation of reactive oxygen topical wound gel in 114 wounds.

Science.gov (United States)

Dryden, M; Dickinson, A; Brooks, J; Hudgell, L; Saeed, K; Cutting, K F

2016-03-01

This article reports the outcomes of the use of Surgihoney RO (SHRO), topical wound dressing in a multi-centre, international setting. The aims were to explore the clinical effects of SHRO, including a reduction in bacterial load and biofilm and improvement in healing in a variety of challenging non-healing and clinically infected wounds. This was a non-comparative evaluation, where both acute and chronic wounds with established delayed healing were treated with the dressing. Clinicians prospectively recorded wound improvement or deterioration, level of wound exudate, presence of pain, and presence of slough and necrosis. Analysis of this data provided information on clinical performance of the dressing. Semi-quantitative culture to assess bacterial bioburden was performed where possible. We recruited 104 patients, mean age 61 years old, with 114 wounds. The mean duration of wounds before treatment was 3.7 months and the mean duration of treatment was 25.7 days. During treatment 24 wounds (21%) healed and the remaining 90 (79%) wounds improved following application of the dressing. No deterioration in any wound was observed. A reduction in patient pain, level of wound exudate and in devitalised tissue were consistently reported. These positive improvements in wound progress were reflected in the wound cultures that showed a reduction in bacterial load in 39 out of the 40 swabs taken. There were two adverse events recorded: a stinging sensation following application of the dressing was experienced by 2 patients, and 2 elderly patients died of causes unrelated to the dressing or to the chronic wound. These patients' wounds and their response to SHRO have been included in the analysis. SHRO was well tolerated and shows great promise as an effective potent topical antimicrobial in the healing of challenging wounds. Matthew Dryden has become a shareholder in Matoke Holdings, the manufacturer of Surgihoney RO, since the completion of this study. Keith Cutting is a

Regenerative braking systems with torsional springs made of carbon nanotube yarn

International Nuclear Information System (INIS)

Liu, S; Martin, C; Livermore, C; Lashmore, D; Schauer, M

2014-01-01

The demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as an energy-storing actuator for regenerative braking systems. Originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing until failure. The maximum extractable energy density is measured to be as high as 6.13 kJ/kg. The tests also reveal structural reorganization and hysteresis in the torsional loading curves. A regenerative braking system is built to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yam's twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking system are up to 4.69 kJ/kg and 1.21 kW/kg, respectively. A slightly lower energy density of up to 1.23 kJ/kg and a 0.29 kW/kg mean power density are measured for the CNT yarns in a more complex system that mimics a unidirectional rotating regenerative braking mechanism. The lower energy densities for CNT yarns in the regenerative braking systems as compared with the yarns themselves reflect the frictional losses of the regenerative systems

Regenerative braking systems with torsional springs made of carbon nanotube yarn

Science.gov (United States)

Liu, S.; Martin, C.; Lashmore, D.; Schauer, M.; Livermore, C.

2014-11-01

The demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as an energy-storing actuator for regenerative braking systems. Originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing until failure. The maximum extractable energy density is measured to be as high as 6.13 kJ/kg. The tests also reveal structural reorganization and hysteresis in the torsional loading curves. A regenerative braking system is built to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yam's twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking system are up to 4.69 kJ/kg and 1.21 kW/kg, respectively. A slightly lower energy density of up to 1.23 kJ/kg and a 0.29 kW/kg mean power density are measured for the CNT yarns in a more complex system that mimics a unidirectional rotating regenerative braking mechanism. The lower energy densities for CNT yarns in the regenerative braking systems as compared with the yarns themselves reflect the frictional losses of the regenerative systems.

Wound healing and all-cause mortality in 958 wound patients treated in home care

DEFF Research Database (Denmark)

Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B. E.

2015-01-01

to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound...... healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died...

Regenerative Intelligent Brake Control for Electric Motorcycles

Directory of Open Access Journals (Sweden)

Juan Jesús Castillo Aguilar

2017-10-01

Full Text Available Vehicle models whose propulsion system is based on electric motors are increasing in number within the automobile industry. They will soon become a reliable alternative to vehicles with conventional propulsion systems. The main advantages of this type of vehicles are the non-emission of polluting gases and noise and the effectiveness of electric motors compared to combustion engines. Some of the disadvantages that electric vehicle manufacturers still have to solve are their low autonomy due to inefficient energy storage systems, vehicle cost, which is still too high, and reducing the recharging time. Current regenerative systems in motorcycles are designed with a low fixed maximum regeneration rate in order not to cause the rear wheel to slip when braking with the regenerative brake no matter what the road condition is. These types of systems do not make use of all the available regeneration power, since more importance is placed on safety when braking. An optimized regenerative braking strategy for two-wheeled vehicles is described is this work. This system is designed to recover the maximum energy in braking processes while maintaining the vehicle’s stability. In order to develop the previously described regenerative control, tyre forces, vehicle speed and road adhesion are obtained by means of an estimation algorithm. A based-on-fuzzy-logic algorithm is programmed to carry out an optimized control with this information. This system recuperates maximum braking power without compromising the rear wheel slip and safety. Simulations show that the system optimizes energy regeneration on every surface compared to a constant regeneration strategy.

Psoriasis and wound healing outcomes: A retrospective cohort study examining wound complications and antibiotic use.

Science.gov (United States)

Young, Paulina M; Parsi, Kory K; Schupp, Clayton W; Armstrong, April W

2017-11-15

Little is known about wound healing in psoriasis. We performed a cohort study examining differences in wound healing complications between patients with and without psoriasis. Psoriasis patients with traumatic wounds were matched 1:3 to non-psoriasis patients with traumatic wounds based on age, gender, and body mass index (BMI). We examined theincidence of wound complications including infection, necrosis, and hematoma as well as incident antibiotic use within three months following diagnosis of a traumatic wound. The study included 164 patients with traumatic wounds, comprised of 41 patients with psoriasis matched to 123 patients without psoriasis. No statistically significant differences were detected in the incidence of overall wound complications between wound patients with psoriasis and wound patients without psoriasis (14.6% versus. 13.0%, HR 1.18, CI 0.39-3.56). After adjustment for diabetes, peripheral vascular disease, and smoking, no statistically significant differences were detected in the incidence of overall wound complications between patients with and without psoriasis (HR 1.11, CI 0.34-3.58). Specifically, the adjusted rates of antibiotic use were not significantly different between those with and without psoriasis (HR 0.65, CI 0.29-1.46). The incidence of wound complications following traumatic wounds of the skin was found to be similar between patients with and without psoriasis.

A roentgenographic assessment of regenerative efficacy of bioactive Gengigel® in conjunction with amnion membrane in grade II furcation defect

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S Harveen Kalra

2015-01-01

Full Text Available Background: Nowadays, techniques are being developed to guide and instruct the specialized cellular components of the periodontium to participate in the regenerative process. This approach of reconstruction makes use of understanding of the development of the periodontium and the cellular processes that are involved. Hyaluronic acid is a naturally occurring non-sulfated high molecular weight glycosaminoglycan that forms a critical component of the extracellular matrix and contributes significantly to tissue hydrodynamics, cell migration, and proliferation. Hence, its administration to periodontal wound sites could achieve comparable beneficial effects in periodontal tissue regeneration. Hence, the purpose of the present case report was to assess roentgenographically, the regenerative capacity of Gengigel® in conjunction with bioactive amnion guided tissue regeneration (GTR membrane in a patient with Grade II furcation defect. Case Presentation: A patient complained of bleeding gums from the lower back tooth region, reportedly found Grade II furcation in the lower right mandibular first molar. After Phase, I therapy, Gengigel® along with bioactive amnion membrane was placed in the furcation area during the surgical phase. Roentgenographic assessment was done at 4 months and 6 months postoperatively. It resulted in complete defect-fill and loss of radiolucency at 6 months. Conclusion: Surgical placement of Gengigel® along with amnion membrane in the furcation defect can significantly improve the periodontal defect morphology.

Radionecrosis skin model induced an athymic mouse nude (Nu/Nu) for development of dermal-epidermal human substitute based regenerative therapy

International Nuclear Information System (INIS)

Mosca, Rodrigo Crespo

2014-01-01

The neoplasms incidence has increased significantly in recent years and continued population growth and aging will increase the statistics of this illness in the world's diseases. The cancer treatment usually consists in individual or combined use of chemotherapy, surgery and radiotherapy depending on the etiology of the tumor. In cases where radiotherapy is used in addition to the therapeutic effects of radiation, specific complications can occur, and in the skin, these complications can be present with a clinical expression ranging from erythema to radionecrosis, and this latter being the adverse effect with greater severity. The radionecrosis treatment consists in debridement necrotic areas and covering the surgical wounds. Autologous grafts are most commonly used for this covering, however when large areas are affected, allografts can be used for occlusive treatment and the keratinocytes and adipose derived stem cells (ADSC) addition becomes an alternative, due to the knowing for immunomodulatory and regenerative response. For that reason, aiming to simulate the radionecrosis adverse effects, an animal model of induced cutaneous radionecrosis was created, in athymic mouse Nude (Nu/Nu), for developing regenerative therapies based on human dermal-epidermal substitutes containing keratinocytes and ADSC, which proved occlusive as an efficient treatment, furthermore, having this radionecrosis animal model established, new possibilities for treatment of diseases involving dermal regeneration, can be tested. (author)

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, Susan R.

1994-01-01

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control.

A regenerative zinc-air fuel cell

Energy Technology Data Exchange (ETDEWEB)

Smedley, Stuart I. [Electrochemical Technology Development Ltd., Lower Hutt (New Zealand); Zhang, X. Gregory [Teck Cominco Metals Ltd., 2380 Speakman Drive, Mississauga, Ontario (Canada)

2007-03-20

The zinc regenerative fuel cell (ZRFC) developed by the former Metallic Power Inc. over the period from 1998 to 2004 is described. The component technologies and engineering solutions for various technical issues are discussed in relation to their functionality in the system. The system was designed to serve as a source of backup emergency power for remote or difficult to access cell phone towers during periods when the main power was interrupted. It contained a 12 cell stack providing 1.8 kW, a separate fuel tank containing zinc pellet fuel and electrolyte, and a zinc electrolyzer to regenerate the zinc pellets during standby periods. Offsite commissioning and testing of the system was successfully performed. The intellectual property of the ZRFC technology is now owned by Teck Cominco Metals Ltd. (author)

Methods of reconstruction of perineal wounds after abdominoperineal resection. Literature review

Directory of Open Access Journals (Sweden)

S. S. Gordeev

2017-01-01

Full Text Available The problem of wound closure after abdominoperineal resection to treat oncological diseases remains unsolved. Formation of a primary suture in the perineal wound can lead to multiple postoperative complications: seroma, abscess, wound disruption with subsequent perineal hernia. Chemoradiation therapy as a standard for locally advanced rectal or anal cancer doesn’t improve results of treatment of perineal wounds and increases duration of their healing. Currently, surgeons have several reconstructive and plastic techniques to improve both direct and long-term functional treatment results. In the article, the most common methods of allo- and autotransplantation are considered, benefits and deficiencies of various techniques are evaluated and analyzed.  

Three-Dimensional Printing and Cell Therapy for Wound Repair.

Science.gov (United States)

van Kogelenberg, Sylvia; Yue, Zhilian; Dinoro, Jeremy N; Baker, Christopher S; Wallace, Gordon G

2018-05-01

Significance: Skin tissue damage is a major challenge and a burden on healthcare systems, from burns and other trauma to diabetes and vascular disease. Although the biological complexities are relatively well understood, appropriate repair mechanisms are scarce. Three-dimensional bioprinting is a layer-based approach to regenerative medicine, whereby cells and cell-based materials can be dispensed in fine spatial arrangements to mimic native tissue. Recent Advances: Various bioprinting techniques have been employed in wound repair-based skin tissue engineering, from laser-induced forward transfer to extrusion-based methods, and with the investigation of the benefits and shortcomings of each, with emphasis on biological compatibility and cell proliferation, migration, and vitality. Critical issues: Development of appropriate biological inks and the vascularization of newly developed tissues remain a challenge within the field of skin tissue engineering. Future Directions: Progress within bioprinting requires close interactions between material scientists, tissue engineers, and clinicians. Microvascularization, integration of multiple cell types, and skin appendages will be essential for creation of complex skin tissue constructs.

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing.

Science.gov (United States)

Piperigkou, Zoi; Götte, Martin; Theocharis, Achilleas D; Karamanos, Nikos K

2017-10-24

Extracellular matrix (ECM) is a dynamic network of macromolecules, playing a regulatory role in cell functions, tissue regeneration and remodeling. Wound healing is a tissue repair process necessary for the maintenance of the functionality of tissues and organs. This highly orchestrated process is divided into four temporally overlapping phases, including hemostasis, inflammation, proliferation and tissue remodeling. The dynamic interplay between ECM and resident cells exerts its critical role in many aspects of wound healing, including cell proliferation, migration, differentiation, survival, matrix degradation and biosynthesis. Several epigenetic regulatory factors, such as the endogenous non-coding microRNAs (miRNAs), are the drivers of the wound healing response. microRNAs have pivotal roles in regulating ECM composition during wound healing and dermal regeneration. Their expression is associated with the distinct phases of wound healing and they serve as target biomarkers and targets for systematic regulation of wound repair. In this article we critically present the importance of epigenetics with particular emphasis on miRNAs regulating ECM components (i.e. glycoproteins, proteoglycans and matrix proteases) that are key players in wound healing. The clinical relevance of miRNA targeting as well as the delivery strategies designed for clinical applications are also presented and discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Platelet-rich plasma and adipose-derived mesenchymal stem cells for regenerative medicine-associated treatments in bottlenose dolphins (Tursiops truncatus.

Directory of Open Access Journals (Sweden)

Richard J Griffeth

Full Text Available Dolphins exhibit an extraordinary capacity to heal deep soft tissue injuries. Nevertheless, accelerated wound healing in wild or captive dolphins would minimize infection and other side effects associated with open wounds in marine animals. Here, we propose the use of a biological-based therapy for wound healing in dolphins by the application of platelet-rich plasma (PRP. Blood samples were collected from 9 different dolphins and a specific and simple protocol which concentrates platelets greater than two times that of whole blood was developed. As opposed to a commonly employed human protocol for PRP preparation, a single centrifugation for 3 minutes at 900 rpm resulted in the best condition for the concentration of dolphin platelets. By FACS analysis, dolphin platelets showed reactivity to platelet cell-surface marker CD41. Analysis by electron microscopy revealed that dolphin platelets were larger in size than human platelets. These findings may explain the need to reduce the duration and speed of centrifugation of whole blood from dolphins to obtain a 2-fold increase and maintain proper morphology of the platelets. For the first time, levels of several growth factors from activated dolphin platelets were quantified. Compared to humans, concentrations of PDGF-BB were not different, while TGFβ and VEGF-A were significantly lower in dolphins. Additionally, adipose tissue was obtained from cadaveric dolphins found along the Spanish Mediterranean coast, and adipose-derived mesenchymal stem cells (ASCs were successfully isolated, amplified, and characterized. When dolphin ASCs were treated with 2.5 or 5% dolphin PRP they exhibited significant increased proliferation and improved phagocytotic activity, indicating that in culture, PRP may improve the regenerative capacity of ASCs. Taken together, we show an effective and well-defined protocol for efficient PRP isolation. This protocol alone or in combination with ASCs, may constitute the basis of a

Molecular pathology of wound healing.

Science.gov (United States)

Kondo, Toshikazu; Ishida, Yuko

2010-12-15

Skin-wound healing is an orchestrated biological phenomena consisting of three sequential phases, inflammation, proliferation, and maturation. Many biological substances are involved in the process of wound repair, and this short and simplified overview of wound healing can be adopted to determine wound vitality or wound age in forensic medicine. With the development of genetically engineered animals, essential molecules for skin-wound healing have been identified. Especially, cytokines, and growth factors are useful candidates and markers for the determination of wound vitality or age. Moreover, bone marrow-derived progenitor cells would give significant information to wound age determination. In this review article, some interesting observations are presented, possibly contributing to the future practice of forensic pathologists. Copyright © 2010. Published by Elsevier Ireland Ltd.

Human resource development contributes to the creation of outstanding regenerative medicine products

Directory of Open Access Journals (Sweden)

Fusako Nishigaki

2017-12-01

Full Text Available Regenerative medicine is currently the focus of global attention. Countries all around the world are actively working to create new regenerative treatment modalities through pioneering research and novel technologies. This is wonderful news for patients who could not be treated with existing medical options. New venture businesses and companies are being established in regenerative medicine and their rapid industrialization is anticipated. However, to ensure high-quality products, human resources qualified in research and development and the manufacturing of these products are essential. The Forum for Innovative Regenerative Medicine (FIRM conducted a questionnaire of its industry members to examine the training and hiring of people in research and development, product creation, manufacturing, and more. Regenerative medicine is a brand new field; thus, many different businesses will need to cooperate together. People with a broad range of technical skills, abilities, and knowledge will be in demand, with various levels of expertise, from basic to advanced.

Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

Science.gov (United States)

Noguchi, Fumihito; Nakajima, Takeshi; Inui, Shigeki; Reddy, Janardan K; Itami, Satoshi

2014-01-01

MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/-)) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/-) and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/-) mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/-) mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/-) keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/-) keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/-) keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/-) keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/-) mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/-) mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/-) mice, indicating a decreased contribution of hair

Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.

Directory of Open Access Journals (Sweden)

Fumihito Noguchi

Full Text Available MED1 (Mediator complex subunit 1 is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1(epi-/- that develop epidermal hyperplasia. Herein, to investigate the function(s of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1(epi-/- and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1(epi-/- mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1(epi-/- mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1(epi-/- keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1(epi-/- keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1(epi-/- keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1(epi-/- keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1(epi-/- mice. On the other hand, skin wound healing in 6-month-old Med1(epi-/- mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1(epi-/- mice, indicating a decreased contribution of hair

Comparison of conventional gauze therapy with vacuum assisted closure wound therapy in acute traumatic wounds

International Nuclear Information System (INIS)

Naqvi, S.H.; Jalil, M.; Butt, Q.; Malik, Z.U

2013-01-01

Objective: To compare the Vacuum Assisted Closure (Vac) wound therapy with Conventional Gauze Therapy (CGT) in management of acute traumatic wounds on the basis of time taken to achieve a vital red wound ready for definitive surgical closure. Study Design: Randomized control trial. Place and Duration of Study: Department of Surgery Combined Military Hospital Rawalpindi from Mar 2009 to Sep 2009. Patients and Methods: This study included 82 patients of acute traumatic wounds. Patients were randomly allotted to group A, in which wound was treated with new method of vacuum assisted closure (VAC) wound therapy and to group B, in which wound was managed by conventional gauze therapy (CGT). Outcomes were measured by the presence of vital red wound ready to be closed by surgical intervention. Patients with concomitant systemic pathology were not included in study. Results: Comparison between the two groups revealed mean time for wound healing 13 days in group A and 16.9 days in group B with significant difference (p value =0.029). Conclusion: Vacuum assisted closure wound therapy is an effective method in reducing time of wound healing for definitive surgical closure. (author)

Bioprinting in Regenerative Medicine

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Manuela Monti

2016-02-01

Full Text Available Prof. Turksen is a very well known scientist in the stem cell biology field and he is also internationally known for his fundamental studies on claudin-6. In addition to his research activity he is editor for the Stem Cell Biology and Regenerative Medicine series (Humana Press and editor-in-chief of Stem Cell Reviews and Reports.....

Factors Affecting Wound Healing

Science.gov (United States)

Guo, S.; DiPietro, L.A.

2010-01-01

Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

Fuzzy logic electric vehicle regenerative antiskid braking and traction control system

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Cikanek, S.R.

1994-10-25

An regenerative antiskid braking and traction control system using fuzzy logic for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensor and determining if regenerative antiskid braking control, requiring hydraulic braking control, and requiring traction control are required. The processor then employs fuzzy logic based on the determined vehicle state and provides command signals to a motor controller to control operation of the electric traction motor and to the brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative braking control, hydraulic braking control, and traction control. 123 figs.

Characterization of Aeromonas hydrophila wound pathotypes by comparative genomic and functional analyses of virulence genes.

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Grim, Christopher J; Kozlova, Elena V; Sha, Jian; Fitts, Eric C; van Lier, Christina J; Kirtley, Michelle L; Joseph, Sandeep J; Read, Timothy D; Burd, Eileen M; Tall, Ben D; Joseph, Sam W; Horneman, Amy J; Chopra, Ashok K; Shak, Joshua R

2013-04-23

Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966(T), and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966(T). The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966(T) and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. Aeromonas hydrophila is a common aquatic bacterium that has increasingly been implicated in serious human infections. While many determinants of virulence have been identified in Aeromonas, rapid identification of pathogenic versus nonpathogenic

Wound Disruption Following Colorectal Operations.

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Moghadamyeghaneh, Zhobin; Hanna, Mark H; Carmichael, Joseph C; Mills, Steven; Pigazzi, Alessio; Nguyen, Ninh T; Stamos, Michael J

2015-12-01

Postoperative wound disruption is associated with high morbidity and mortality. We sought to identify the risk factors and outcomes of wound disruption following colorectal resection. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to examine the clinical data of patients who underwent colorectal resection from 2005 to 2013. Multivariate regression analysis was performed to identify risk factors of wound disruption. We sampled a total of 164,297 patients who underwent colorectal resection. Of these, 2073 (1.3 %) had wound disruption. Patients with wound disruption had significantly higher mortality (5.1 vs. 1.9 %, AOR: 1.46, P = 0.01). The highest risk of wound disruption was seen in patients with wound infection (4.8 vs. 0.9 %, AOR: 4.11, P disruption such as chronic steroid use (AOR: 1.71, P disruption compared to open surgery (AOR: 0.61, P disruption occurs in 1.3 % of colorectal resections, and it correlates with mortality of patients. Wound infection is the strongest predictor of wound disruption. Chronic steroid use, obesity, severe COPD, prolonged operation, non-elective admission, and serum albumin level are strongly associated with wound disruption. Utilization of the laparoscopic approach may decrease the risk of wound disruption when possible.

Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies

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Catherine D. McCusker

2014-06-01

Full Text Available Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

Biochemical and Biophysical Cues in Matrix Design for Chronic and Diabetic Wound Treatment

OpenAIRE

Xiao, Yun; Ahadian, Samad; Radisic, Milica

2017-01-01

Progress in biomaterial science and engineering and increasing knowledge in cell biology have enabled us to develop functional biomaterials providing appropriate biochemical and biophysical cues for tissue regeneration applications. Tissue regeneration is particularly important to treat chronic wounds of people with diabetes. Understanding and controlling the cellular microenvironment of the wound tissue are important to improve the wound healing process. In this study, we review different bi...

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study.

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Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

2015-10-01

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we determined which patient- and wound-related characteristics best predict time to complete wound healing and derived a prediction formula to estimate how long this may take. We selected 563 patients with acute wounds, documented in the WEC registry between 2007 and 2012. Wounds had existed for a median of 19 days (range 6-46 days). The majority of these were located on the leg (52%). Five significant independent predictors of prolonged wound healing were identified: wound location on the trunk [hazard ratio (HR) 0·565, 95% confidence interval (CI) 0·405-0·788; P = 0·001], wound infection (HR 0·728, 95% CI 0·534-0·991; P = 0·044), wound size (HR 0·993, 95% CI 0·988-0·997; P = 0·001), wound duration (HR 0·998, 95% CI 0·996-0·999; P = 0·005) and patient's age (HR 1·009, 95% CI 1·001-1·018; P = 0·020), but not diabetes. Awareness of the five factors predicting the healing of complex acute wounds, particularly wound infection and location on the trunk, may help caregivers to predict wound healing time and to detect, refer and focus on patients who need additional attention. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Induced pluripotent stem cells for regenerative medicine.

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Hirschi, Karen K; Li, Song; Roy, Krishnendu

2014-07-11

With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.

The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

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Mroz, Magdalena S; Lajczak, Natalia K; Goggins, Bridie J; Keely, Simon; Keely, Stephen J

2018-03-01

The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl - channels, whereas inhibition of CFTR activity with either CFTR- inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes

Regenerative engineering

CERN Document Server

Laurencin, Cato T

2013-01-01

Regenerative Engineering: The Future of Medicine Saadiq F. El-Amin III , MD , PhD; Joylene W.L. Thomas, MD ; Ugonna N. Ihekweazu, MD ; Mia D. Woods, MS; and Ashim Gupta, MSCell Biology Gloria Gronowicz, PhD and Karen Sagomonyants, DMDStem Cells and Tissue Regeneration Kristen Martins-Taylor, PhD; Xiaofang Wang, MD , PhD; Xue-Jun Li, PhD; and Ren-He Xu, MD , PhDIntroduction to Materials Science Sangamesh G. Kumbar, PhD and Cato T. Laurencin, MD , PhDBiomaterials A. Jon Goldberg, PhD and Liisa T. Kuhn, PhDIn Vitro Assessment of Cell-Biomaterial Interactions Yong Wang, PhDHost Response to Biomate

Macrophage Phenotypes Regulate Scar Formation and Chronic Wound Healing.

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Hesketh, Mark; Sahin, Katherine B; West, Zoe E; Murray, Rachael Z

2017-07-17

Macrophages and inflammation play a beneficial role during wound repair with macrophages regulating a wide range of processes, such as removal of dead cells, debris and pathogens, through to extracellular matrix deposition re-vascularisation and wound re-epithelialisation. To perform this range of functions, these cells develop distinct phenotypes over the course of wound healing. They can present with a pro-inflammatory M1 phenotype, more often found in the early stages of repair, through to anti-inflammatory M2 phenotypes that are pro-repair in the latter stages of wound healing. There is a continuum of phenotypes between these ranges with some cells sharing phenotypes of both M1 and M2 macrophages. One of the less pleasant consequences of quick closure, namely the replacement with scar tissue, is also regulated by macrophages, through their promotion of fibroblast proliferation, myofibroblast differentiation and collagen deposition. Alterations in macrophage number and phenotype disrupt this process and can dictate the level of scar formation. It is also clear that dysregulated inflammation and altered macrophage phenotypes are responsible for hindering closure of chronic wounds. The review will discuss our current knowledge of macrophage phenotype on the repair process and how alterations in the phenotypes might alter wound closure and the final repair quality.

Electromechanically Actuated Multifunctional Wireless Auxetic Device for Wound Management.

Science.gov (United States)

Mir, Mariam; Ansari, Umar; Ali, Murtaza Najabat; Iftikhar, Muhammad Hassan Ul; Qayyum, Faisal

2017-01-01

The design and fabrication of a wound healing device for chronic wounds, with multiple functions for controlled drug delivery and exudate removal, has been described in this paper. The structural features have been machined and modified through laser cutting in a biocompatible polymer cast. Miniaturized versions of electronically actuated (lead-screw and pulley) mechanisms are used for the specific purpose of controlled drug delivery. These mechanisms have been studied and tested, being controlled through a microcontroller setup. An auxetic polymeric barrier membrane has been used for restricting the drug quantities administered. Drug delivery mechanisms are powered wirelessly, through an external, active RF component; this communicates with a passive component that is buried inside the wound healing device. The exudate removal efficiency of the device has been assessed through several simple tests using simulated wound exudate. It has been found that reasonably precise quantities of drug dosages to be administered to the wound site can be controlled through both drug delivery mechanisms; however, the lead-screw mechanism provides a better control of auxetic barrier membrane actuation and hence controlled drug delivery. We propose that this device can have potential clinical significance in controlled drug delivery and exudate removal in the management of chronic wounds.

Gender affects skin wound healing in plasminogen deficient mice.

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Birgitte Rønø

Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

Recent advances in topical wound care

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Sujata Sarabahi

2012-01-01

Full Text Available There are a wide variety of dressing techniques and materials available for management of both acute wounds and chronic non-healing wounds. The primary objective in both the cases is to achieve a healed closed wound. However, in a chronic wound the dressing may be required for preparing the wound bed for further operative procedures such as skin grafting. An ideal dressing material should not only accelerate wound healing but also reduce loss of protein, electrolytes and fluid from the wound, and help to minimize pain and infection. The present dictum is to promote the concept of moist wound healing. This is in sharp contrast to the earlier practice of exposure method of wound management wherein the wound was allowed to dry. It can be quite a challenge for any physician to choose an appropriate dressing material when faced with a wound. Since wound care is undergoing a constant change and new products are being introduced into the market frequently, one needs to keep abreast of their effect on wound healing. This article emphasizes on the importance of assessment of the wound bed, the amount of drainage, depth of damage, presence of infection and location of wound. These characteristics will help any clinician decide on which product to use and where,in order to get optimal wound healing. However, there are no ′magical dressings′. Dressings are one important aspect that promotes wound healing apart from treating the underlying cause and other supportive measures like nutrition and systemic antibiotics need to be given equal attention.

Design Analysis And Applications Of A Regenerative Bicycle Ergometer

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Chukwuneke J. L.

2015-08-01

Full Text Available Man needs to do some form of physical work in other to remain healthy this work is similar to the work done by any machine or equipment and thus should be channeled to give useful output but rather it is usually dissipated into the environment in form of heat. The regenerative bicycle ergometer takes advantage of the greater power generated by the limbs and arms thus conserves converts and stores the energy dissipated by the rider with an ideal mechanical advantage of 7.6 it strategically uses simple mechanisms to magnify its work and then converts this mechanical energy into electrical energy by the use of a dynamo with a speed ratio of 108.5 and a transmission efficiency of 89 the rider pedals 27rpm to obtain the dynamos rated input of 2600rpm giving an output of 12.6volts. The regenerative bicycle ergometer is designed and constructed to perform all the core functions of a bicycle ergometer having an allowable load of 116.5kg and a maximum resistance of 65.33N which is equivalent to a mass of 6.66kg. The energy converted is stored in a 12volts battery making its use flexible clean and meeting the energy demands of man.

SPE (tm) regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications

Science.gov (United States)

Mcelroy, J. F.

1990-01-01

Viewgraphs on SPE regenerative hydrogen/oxygen fuel cells for extraterrestrial surface and microgravity applications are presented. Topics covered include: hydrogen-oxygen regenerative fuel cell energy storage system; electrochemical cell reactions; SPE cell voltage stability; passive water removal SPE fuel cell; fuel cell performance; SPE water electrolyzers; hydrophobic oxygen phase separator; hydrophilic/electrochemical hydrogen phase separator; and unitized regenerative fuel cell.

Tilapia Piscidin 4 (TP4 Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice

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Hang-Ning Huang

2015-05-01

Full Text Available Antimicrobial peptides (AMPs are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4, was isolated from Nile tilapia (Oreochromis niloticus; TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT and fibroblast cell line (Hs-68. In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF, transforming growth factor (TGF, and vascular endothelial growth factor (VEGF. The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.

Electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, S.R.

1995-09-12

An antiskid braking and traction control system for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes one or more sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensors and determining if regenerative antiskid braking control, requiring hydraulic braking control, or requiring traction control are required. The processor then employs a control strategy based on the determined vehicle state and provides command signals to a motor controller to control the operation of the electric traction motor and to a brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative antiskid braking control, hydraulic braking control, and traction control. 10 figs.

Electric vehicle regenerative antiskid braking and traction control system

Science.gov (United States)

Cikanek, Susan R.

1995-01-01

An antiskid braking and traction control system for an electric or hybrid vehicle having a regenerative braking system operatively connected to an electric traction motor, and a separate hydraulic braking system includes one or more sensors for monitoring present vehicle parameters and a processor, responsive to the sensors, for calculating vehicle parameters defining the vehicle behavior not directly measurable by the sensors and determining if regenerative antiskid braking control, requiring hydrualic braking control, or requiring traction control are required. The processor then employs a control strategy based on the determined vehicle state and provides command signals to a motor controller to control the operation of the electric traction motor and to a brake controller to control fluid pressure applied at each vehicle wheel to provide the appropriate regenerative antiskid braking control, hydraulic braking control, and traction control.

Regenerative strategies for the treatment of knee joint disabilities

CERN Document Server

Reis, Rui

2017-01-01

This book presents regenerative strategies for the treatment of knee joint disabilities. The book is composed of four main sections totaling 19 chapters which review the current knowledge on the clinical management and preclinical regenerative strategies. It examines the role of different natural-based biomaterials as scaffolds and implants for addressing different tissue lesions in the knee joint. Section one provides an updated and comprehensive discussion on articular cartilage tissue regeneration. Section two focuses on the important contributions for bone and osteochondral tissue engineering. Section three overview the recent advances on meniscus repair/regeneration strategies. Finally, section four further discusses the current strategies for treatment of ligament lesions. Each chapter is prepared by world know expert on their fields, so we do firmly believe that the proposed book will be a reference in the area of biomaterials for regenerative medicine.

Tissue engineering and microRNAs: future perspectives in regenerative medicine.

Science.gov (United States)

Gori, Manuele; Trombetta, Marcella; Santini, Daniele; Rainer, Alberto

2015-01-01

Tissue engineering is a growing area of biomedical research, holding great promise for a broad range of potential applications in the field of regenerative medicine. In recent decades, multiple tissue engineering strategies have been adopted to mimic and improve specific biological functions of tissues and organs, including biomimetic materials, drug-releasing scaffolds, stem cells, and dynamic culture systems. MicroRNAs (miRNAs), noncoding small RNAs that negatively regulate the expression of downstream target mRNAs, are considered a novel class of molecular targets and therapeutics that may play an important role in tissue engineering. Herein, we highlight the latest achievements in regenerative medicine, focusing on the role of miRNAs as key modulators of gene expression, stem cell self-renewal, proliferation and differentiation, and eventually in driving cell fate decisions. Finally, we will discuss the contribution of miRNAs in regulating the rearrangement of the tissue microenvironment and angiogenesis, and the range of strategies for miRNA delivery into target cells and tissues. Manipulation of miRNAs is an alternative approach and an attractive strategy for controlling several aspects of tissue engineering, although some issues concerning their in vivo effects and optimal delivery methods still remain uncovered.

Development of a Bayesian model to estimate health care outcomes in the severely wounded

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Alexander Stojadinovic

2010-08-01

Full Text Available Alexander Stojadinovic1, John Eberhardt2, Trevor S Brown3, Jason S Hawksworth4, Frederick Gage3, Douglas K Tadaki3, Jonathan A Forsberg5, Thomas A Davis3, Benjamin K Potter5, James R Dunne6, E A Elster31Combat Wound Initiative Program, 4Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA; 2DecisionQ Corporation, Washington, DC, USA; 3Regenerative Medicine Department, Combat Casualty Care, Naval Medical Research Center, Silver Spring, MD, USA; 5Integrated Department of Orthopaedics and Rehabilitation, 6Department of Surgery, National Naval Medical Center, Bethesda, MD, USABackground: Graphical probabilistic models have the ability to provide insights as to how clinical factors are conditionally related. These models can be used to help us understand factors influencing health care outcomes and resource utilization, and to estimate morbidity and clinical outcomes in trauma patient populations.Study design: Thirty-two combat casualties with severe extremity injuries enrolled in a prospective observational study were analyzed using step-wise machine-learned Bayesian belief network (BBN and step-wise logistic regression (LR. Models were evaluated using 10-fold cross-validation to calculate area-under-the-curve (AUC from receiver operating characteristics (ROC curves.Results: Our BBN showed important associations between various factors in our data set that could not be developed using standard regression methods. Cross-validated ROC curve analysis showed that our BBN model was a robust representation of our data domain and that LR models trained on these findings were also robust: hospital-acquired infection (AUC: LR, 0.81; BBN, 0.79, intensive care unit length of stay (AUC: LR, 0.97; BBN, 0.81, and wound healing (AUC: LR, 0.91; BBN, 0.72 showed strong AUC.Conclusions: A BBN model can effectively represent clinical outcomes and biomarkers in patients hospitalized after severe wounding, and is confirmed by 10-fold �

Healing of corneal epithelial wounds in marine and freshwater fish.

Science.gov (United States)

Ubels, J L; Edelhauser, H F

The corneal epithelium of a fish is in direct contact with the aquatic environment and is a barrier to movement of ions and water into and through the cornea. This tissue layer is thus important in maintenance of corneal transparency. When the epithelium is wounded, its protective function is lost and corneal transparency remains compromised until the epithelial barrier is re-established. This study was undertaken to investigate the healing response of the fish cornea to epithelial abrasion. Wounds were stained with fluorescein and photographed during healing. Wound areas were measured by planimetry. The cornea of the sculpin, a marine teleost, becomes edematous after wounding and heals at 2.54 to 3.42 mm2/hr. Nonswelling corneas of the elasmobranchs--dogfish shark and skate--heal at 1.29 mm2/hr, respectively. The wounded eye of the rainbow trout, a freshwater teleost, is stressed by the low osmolality of the environment. Severe corneal edema and cataracts develop following epithelial wounding, and the cornea heals at 0.64 mm2/hr. Although the healing rates in teleosts differ from those in mammals, histology shows that the corneal healing mechanism is essentially the same in fish and mammals.

Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds.

Science.gov (United States)

Galeano, Mariarosaria; Altavilla, Domenica; Bitto, Alessandra; Minutoli, Letteria; Calò, Margherita; Lo Cascio, Patrizia; Polito, Francesca; Giugliano, Giovanni; Squadrito, Giovanni; Mioni, Chiara; Giuliani, Daniela; Venuti, Francesco S; Squadrito, Francesco

2006-04-01

Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds. Randomized experiment. Research laboratory. C57BL/6 male mice weighing 25-30 g. Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 microL subcutaneously) or its vehicle alone (100 microl/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury.

Design and experiment study of a semi-active energy-regenerative suspension system

International Nuclear Information System (INIS)

Shi, Dehua; Chen, Long; Wang, Ruochen; Jiang, Haobin; Shen, Yujie

2015-01-01

A new kind of semi-active energy-regenerative suspension system is proposed to recover suspension vibration energy, as well as to reduce the suspension cost and demands for the motor-rated capacity. The system consists of an energy-regenerative damper and a DC-DC converter-based energy-regenerative circuit. The energy-regenerative damper is composed of an electromagnetic linear motor and an adjustable shock absorber with three regulating levels. The linear motor just works as the generator to harvest the suspension vibration energy. The circuit can be used to improve the system’s energy-regenerative performance and to continuously regulate the motor’s electromagnetic damping force. Therefore, although the motor works as a generator and damps the isolation without an external power source, the motor damping force is controllable. The damping characteristics of the system are studied based on a two degrees of freedom vehicle vibration model. By further analyzing the circuit operation characteristics under different working modes, the double-loop controller is designed to track the desired damping force. The external-loop is a fuzzy controller that offers the desired equivalent damping. The inner-loop controller, on one hand, is used to generate the pulse number and the frequency to control the angle and the rotational speed of the step motor; on the other hand, the inner-loop is used to offer the duty cycle of the energy-regenerative circuit. Simulations and experiments are conducted to validate such a new suspension system. The results show that the semi-active energy-regenerative suspension can improve vehicle ride comfort with the controllable damping characteristics of the linear motor. Meanwhile, it also ensures energy regeneration. (paper)

The wound debrider: a new monofilament fibre technology.

Science.gov (United States)

Haemmerle, Gilbert; Duelli, Heinz; Abel, Martin; Strohal, Robert

Debridement is a basic necessity to induce the functional process of tissue repair, especially in chronic wounds. In this pilot study the authors used a new debrider technology with specific monofilament fibres in a unique texture to evaluate its efficacy, safety and tolerability. In eleven patients, exhibiting all types of wound-associated debris (biofilms, slough, necrotic crusts and hyperkeratotic plaques), the debrider, wetted with physiological solution, was wiped without specific force over the wound for about 2-4 minutes. This led to removal of almost all debris leaving healthy granulation tissue intact, including small epithelialized islands of vital tissue. The procedure was without pain and adverse events. Scanning electron microscopic analyses identified the majority of the removed debris tightly packed within the monofilament texture. A surgeon who blindly assessed pictures taken before and after the debridement categorized all except one wound without the need for surgical debridement and ranked all the debridement results with the new debrider as 'very good' (best category). This formulates the basic concept that the new debrider-based technology is easy, fast, highly efficient, well tolerated and cost effective.

Comparison of advanced therapy medicinal product gingiva and skin substitutes and their in vitro wound healing potentials.

Science.gov (United States)

Boink, Mireille A; Roffel, Sanne; Breetveld, Melanie; Thon, Maria; Haasjes, Michiel S P; Waaijman, Taco; Scheper, Rik J; Blok, Chantal S; Gibbs, Susan

2018-02-01

Skin and oral mucosa substitutes are a therapeutic option for closing hard-to-heal skin and oral wounds. Our aim was to develop bi-layered skin and gingiva substitutes, from 3 mm diameter biopsies, cultured under identical conditions, which are compliant with current European regulations for advanced therapy medicinal products. We present in vitro mode of action methods to (i) determine viability: epithelial expansion, proliferation (Ki-67), metabolic activity (MTT assay); (ii) characterize skin and gingiva substitutes: histology and immunohistochemistry; and (iii) determine potency: soluble wound healing mediator release (enzyme-linked immunosorbent assay). Both skin and gingiva substitutes consist of metabolically active autologous reconstructed differentiated epithelium expanding from the original biopsy sheet on a fibroblast populated connective tissue matrix (donor dermis). Gingival epithelium expanded 1.7-fold more than skin epithelium during the 3 week culture period. The percentage of proliferating Ki-67-positive cells located in the basal layer of the gingiva substitute was >1.5-fold higher than in the skin substitute. Keratins 16 and 17, which are upregulated during normal wound healing, were expressed in both the skin and gingiva substitutes. Notably, the gingiva substitute secreted higher amounts of key cytokines involved in mitogenesis, motogenesis and chemotaxis (interleukin-6 > 23-fold, CXCL8 > 2.5-fold) as well as higher amounts of the anti-fibrotic growth factor, hepatocyte growth factor (>7-fold), compared with the skin substitute. In conclusion, while addressing the viability, characterization and potency of the tissue substitutes, important intrinsic differences between skin and gingiva were discovered that may explain in part the superior quality of wound healing observed in the oral mucosa compared with skin. Copyright © 2017 The Authors. Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

OpenAIRE

Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

2015-01-01

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we ...

Prospective regenerative medicine therapies for obstetric trauma-induced fecal incontinence.

Science.gov (United States)

Parmar, Nina; Kumar, Lalit; Emmanuel, Anton; Day, Richard M

2014-01-01

Fecal incontinence is a major public health issue that has yet to be adequately addressed. Obstetric trauma and injury to the anal sphincter muscles are the most common cause of fecal incontinence. New therapies are emerging aimed at repair or regeneration of sphincter muscle and restoration of continence. While regenerative medicine offers an attractive option for fecal incontinence there are currently no validated techniques using this approach. Although many challenges are yet to be resolved, the advent of regenerative medicine is likely to offer disruptive technologies to treat and possibly prevent the onset of this devastating condition. This article provides a review on regenerative medicine approaches for treating fecal incontinence and a critique of the current landscape in this area.

Negative pressure wound therapy for the treatment of infected wounds with exposed knee joint after patellar fracture.

Science.gov (United States)

Lee, Sang Yang; Niikura, Takahiro; Miwa, Masahiko; Sakai, Yoshitada; Oe, Keisuke; Fukazawa, Takahiro; Kawakami, Yohei; Kurosaka, Masahiro

2011-06-14

Treatment of soft tissue defects with exposed bones and joints, resulting from trauma, infection, and surgical complications, represents a major challenge. The introduction of negative pressure wound therapy has changed many wound management practices. Negative pressure wound therapy has recently been used in the orthopedic field for management of traumatic or open wounds with exposed bone, nerve, tendon, and orthopedic implants. This article describes a case of a patient with a large soft tissue defect and exposed knee joint, in which negative pressure wound therapy markedly improved wound healing. A 50-year-old man presented with an ulceration of his left knee with exposed joint, caused by severe wound infections after open reduction and internal fixation of a patellar fracture. After 20 days of negative pressure wound therapy, a granulated wound bed covered the exposed bones and joint.To our knowledge, this is the first report of negative pressure wound therapy used in a patient with a large soft tissue defect with exposed knee joint. Despite the chronic wound secondary to infection, healing was achieved through the use of the negative pressure wound therapy, thus promoting granulation tissue formation and closing the joint. We suggest negative pressure wound therapy as an alternative option for patients with lower limb wounds containing exposed bones and joints when free flap transfer is contraindicated. Our result added to the growing evidence that negative pressure wound therapy is a useful adjunctive treatment for open wounds around the knee joint. Copyright 2011, SLACK Incorporated.

Medicinal plants indications from herbal healers for wound treatment

OpenAIRE

Maria Willianne Alves do Nascimento; Regina Célia Sales Santos Veríssimo; Maria Lysete de Assis Bastos; Thaís Honório Lins Bernardo

2016-01-01

The objective was to identify medicinal plants indicated by commercial herbal healers for wound treatment, in street markets. A descriptive study conducted in a capital city in the northeast of Brazil, through interviews. The results indicate that plant commerce by healers of both genders, aged between 37 to 52 years, from those 69.3% learned about their function with family members. Forty-eight plant species were cited for wound treatment, between those, all participants cited Barbatimão and...

[Wound information management system: a standardized scheme for acquisition, storage and management of wound information].

Science.gov (United States)

Liu, Hu; Su, Rong-jia; Wu, Min-jie; Zhang, Yi; Qiu, Xiang-jun; Feng, Jian-gang; Xie, Ting; Lu, Shu-liang

2012-06-01

To form a wound information management scheme with objectivity, standardization, and convenience by means of wound information management system. A wound information management system was set up with the acquisition terminal, the defined wound description, the data bank, and related softwares. The efficacy of this system was evaluated in clinical practice. The acquisition terminal was composed of the third generation mobile phone and the software. It was feasible to get access to the wound information, including description, image, and therapeutic plan from the data bank by mobile phone. During 4 months, a collection of a total of 232 wound treatment information was entered, and accordingly standardized data of 38 patients were formed automatically. This system can provide standardized wound information management by standardized techniques of acquisition, transmission, and storage of wound information. It can be used widely in hospitals, especially primary medical institutions. Data resource of the system makes it possible for epidemiological study with large sample size in future.

Injury-activated glial cells promote wound healing of the adult skin in mice.

Science.gov (United States)

Parfejevs, Vadims; Debbache, Julien; Shakhova, Olga; Schaefer, Simon M; Glausch, Mareen; Wegner, Michael; Suter, Ueli; Riekstina, Una; Werner, Sabine; Sommer, Lukas

2018-01-16

Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.

Improved wound care product

DEFF Research Database (Denmark)

2012-01-01

The present invention pertains to use of sodium diacetate (NaHAc 2) as an antimicrobial agent against bacteria growing in biofilms. The aspects of the invention include a wound care product comprising sodium diacetate, a kit comprising a wound care product,and a methodof treating an infected wound....

Regenerative feedback resonant circuit

Science.gov (United States)

Jones, A. Mark; Kelly, James F.; McCloy, John S.; McMakin, Douglas L.

2014-09-02

A regenerative feedback resonant circuit for measuring a transient response in a loop is disclosed. The circuit includes an amplifier for generating a signal in the loop. The circuit further includes a resonator having a resonant cavity and a material located within the cavity. The signal sent into the resonator produces a resonant frequency. A variation of the resonant frequency due to perturbations in electromagnetic properties of the material is measured.

How wounds heal

Science.gov (United States)

... How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... bleed. For example, burns, some puncture wounds, and pressure sores do not bleed. Once the scab forms, your ...

The Ovonic regenerative fuel cell, a fundamentally new approach

International Nuclear Information System (INIS)

Ovshinsky, S.R.; Venkatesan, S.; Corrigan, D.A.

2004-01-01

The Ovonic Regenerative Fuel Cell utilizes Ovonic metal hydride materials in place of traditional noble metal catalysts in the hydrogen fuel electrode. This provides unique features including the ability to capture and utilize regenerative braking energy at high efficiency and the ability to operate for a significant period upon interruption of the hydrogen fuel supply. Additionally, this novel fuel cell does not use high price components, such as platinum catalysts, microporous membranes, and graphite bipolar plates, used in PEM fuel cells. Proof of concept has been demonstrated in full-size multicell prototypes delivering about 100 W power. The Ovonic Regenerative Fuel Cell is yet another component of ECD Ovonic technology contributing to the emerging hydrogen economy which already includes Uni-Solar PV solar cells, Ovonic solid-state hydrogen storage devices, and Ovonic nickel-metal hydride batteries from Cobasys, a joint venture between ECD Ovonics and ChevronTexaco. (author)

[Application of a hydrosurgery system in debridement of various types of burn wounds].

Science.gov (United States)

Li, M Y; Mao, Y G; Guo, G H; Liu, D W

2016-09-20

Burn wound healing is closely associated with the depth of wound and early debridement. The traditional ways of debridement have certain limitations and often result in poor appearance and function of repaired area. At present, the hydrosurgery system has been applied clinically in burn field. This paper summarizes advantages and disadvantages of application of the hydrosurgery system in debridement of burn wound with different depths, different periods, extraordinary region, and uncommon agent.

Filament wound structure and method

International Nuclear Information System (INIS)

Dritt, W.S.; Gerth, H.L.; Knight, C.E. Jr.; Pardue, R.M.

1977-01-01

A filament wound spherical structure is described comprising a plurality of filament band sets disposed about the surface of a mandrel with each band of each set formed of a continuous filament circumferentially wound about the mandrel a selected number of circuits and with each circuit of filament being wound parallel to and contiguous with an immediate previously wound circuit. Each filament band in each band set is wound at the same helix angle from the axis of revolution of the mandrel and all of the bands of each set are uniformly distributed about the mandrel circumference. The pole-to-equator wall thickness taper associated with each band set, as several contiguous band sets are wound about the mandrel starting at the poles, is accumulative as the band sets are nested to provide a complete filament wound sphere of essentially uniform thickness

Carbon nanotube torsional springs for regenerative braking systems

Science.gov (United States)

Liu, Sanwei; Martin, Corbin; Lashmore, David; Schauer, Mark; Livermore, Carol

2015-10-01

The modeling and demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as energy-storing actuators for regenerative braking systems. An originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing incrementally until failure. The measured average extractable energy density values are 2.9 kJ kg-1  ±  1.2 kJ kg-1 and 3.4 kJ kg-1  ±  0.4 kJ kg-1 for 1-ply CNT yarns and 2-ply CNT yarns, respectively. Additionally, a regenerative braking system is demonstrated to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yarn’s twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking setup are on average 3.3 kJ kg-1 and 0.67 kW kg-1, respectively, with maximum measured values of up to 4.7 kJ kg-1 and 1.2 kW kg-1, respectively. A slightly lower energy density of up to 1.2 kJ kg-1 and a 0.29 kW kg-1 mean power density are measured for CNT yarns in a more complex setup that mimics a unidirectional rotating regenerative braking mechanism.

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

Science.gov (United States)

Ayuk, Sandra Matabi; Abrahamse, Heidi; Houreld, Nicolette Nadene

2016-01-01

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.

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

Directory of Open Access Journals (Sweden)

Sandra Matabi Ayuk

2016-01-01

Full Text Available 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.

MFG-E8 Reprogramming of Macrophages Promotes Wound Healing by Increased bFGF Production and Fibroblast Functions.

Science.gov (United States)

Laplante, Patrick; Brillant-Marquis, Frédéric; Brissette, Marie-Joëlle; Joannette-Pilon, Benjamin; Cayrol, Romain; Kokta, Victor; Cailhier, Jean-François

2017-09-01

Macrophages are essential for tissue repair. They have a crucial role in cutaneous wound healing, participating actively in the inflammation phase of the process. Unregulated macrophage activation may, however, represent a source of excessive inflammation, leading to abnormal wound healing and hypertrophic scars. Our research group has shown that apoptotic endothelial and epithelial cells secrete MFG-E8, which has the ability to reprogram macrophages from an M1 (proinflammatory) to an M2 (anti-inflammatory, pro-repair) phenotype. Hence, we tested whether modulation of macrophage reprogramming would promote tissue repair. Using a mouse model of wound healing, we showed that the presence and/or addition of MFG-E8 favors wound closure associated with an increase in CD206-positive cells and basic fibroblast growth factor production in healing tissues. More importantly, adoptive transfer of ex vivo MFG-E8-treated macrophages promoted wound closure. We also observed that MFG-E8-treated macrophages produced basic fibroblast growth factor that is responsible for fibroblast migration and proliferation. Taken together, our results strongly suggest that MFG-E8 plays a key role in macrophage reprogramming in tissue healing through induction of an anti-inflammatory M2 phenotype and basic fibroblast growth factor production, leading to fibroblast migration and wound closure. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Biofilms and Wounds: An Identification Algorithm and Potential Treatment Options

Science.gov (United States)

Percival, Steven L.; Vuotto, Claudia; Donelli, Gianfranco; Lipsky, Benjamin A.

2015-01-01

Significance: The presence of a “pathogenic” or “highly virulent” biofilm is a fundamental risk factor that prevents a chronic wound from healing and increases the risk of the wound becoming clinically infected. There is presently no unequivocal gold standard method available for clinicians to confirm the presence of biofilms in a wound. Thus, to help support clinician practice, we devised an algorithm intended to demonstrate evidence of the presence of a biofilm in a wound to assist with wound management. Recent Advances: A variety of histological and microscopic methods applied to tissue biopsies are currently the most informative techniques available for demonstrating the presence of generic (not classified as pathogenic or commensal) biofilms and the effect they are having in promoting inflammation and downregulating cellular functions. Critical Issues: Even as we rely on microscopic techniques to visualize biofilms, they are entities which are patchy and dispersed rather than confluent, particularly on biotic surfaces. Consequently, detection of biofilms by microscopic techniques alone can lead to frequent false-negative results. Furthermore, visual identification using the naked eye of a pathogenic biofilm on a macroscopic level on the wound will not be possible, unlike with biofilms on abiotic surfaces. Future Direction: Lacking specific biomarkers to demonstrate microscopic, nonconfluent, virulent biofilms in wounds, the present focus on biofilm research should be placed on changing clinical practice. This is best done by utilizing an anti-biofilm toolbox approach, rather than speculating on unscientific approaches to identifying biofilms, with or without staining, in wounds with the naked eye. The approach to controlling biofilm should include initial wound cleansing, periodic debridement, followed by the application of appropriate antimicrobial wound dressings. This approach appears to be effective in removing pathogenic biofilms. PMID:26155381

Negative pressure wound therapy, staged excision and definitive closure with split-thickness skin graft for axillary hidradenitis suppurativa: a retrospective study.

Science.gov (United States)

Pearce, F B; Richardson, K A

2017-01-02

Bilateral axillary hidradenitis is a chronic, suppurative, and scarring disease that is most effectively treated by complete excision of all hair-bearing tissues. We assessed our staged procedure for excision and placement of a split-thickness skin graft for bilateral axillary hidradenitis in terms of costs, outcomes, and timing of excision. An IRB approved retrospective case analysis was performed on patients that underwent bilateral axillary hidradenitis skin excision with eventual placement of split-thickness skin grafting using the current LSUHSC/University Health hidradenitis surgical treatment protocol. Using ICD-9 codes (705.83) and CPT codes (11041, 11042, 11451, 11600, 11601, 11602, 11603, 11604) we reviewed cases performed at our institution from 1 January 2008 to 24 Febuary 2014 and we selected patients based on bilateral axillary involvement (alone) and >1 year history of active disease. Patients were excluded if resection of tissue encompassed regions outside of the immediately adjacent axillary. A total of seven patients matching criteria for bilateral axillary hidradenitis were selected for analysis. Clinical course, cost and surgical techniques were assessed. Of the seven patients, six required admission throughout their treatment due to lack of funding making use of negative pressure wound therapy at home not possible. These patients stayed an average of 10 days with a mean hospital charge of $35,178 and a mean hospital provider charge of $10,019. No recurrence was demonstrated. All patients attained full range of motion, post grafting. No patient required a further operation due to graft failure. Split-thickness skin grafting without use of bilayer dermal regenerative templates yielded definitive results with acceptable cosmesis and functionality, without the added cost of treatments such as a bilayer dermal regenerative template.

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract.

Directory of Open Access Journals (Sweden)

Alexander S Zevin

2016-09-01

Full Text Available The mechanism(s by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity.

Wounds, Functional Disability, and Indwelling Devices Are Associated With Cocolonization by Methicillin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci in Southeast Michigan

OpenAIRE

Flannery, Erika L.; Wang, Linda; Zöllner, Sebastian; Foxman, Betsy; Mobley, Harry L. T.; Mody, Lona

2011-01-01

Cocolonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) is a precursor to vancomycin-resistant S. aureus emergence. MRSA/VRE cocolonization incidence is higher among skilled nursing facility residents with functional disability and indwelling devices and occurs more frequently in wounds than other anatomical sites.

Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix Deposition.

Science.gov (United States)

Kunkemoeller, Britta; Kyriakides, Themis R

2017-10-20

Impaired wound healing is a major complication of diabetes, and can lead to development of chronic foot ulcers in a significant number of patients. Despite the danger posed by poor healing, very few specific therapies exist, leaving patients at risk of hospitalization, amputation, and further decline in overall health. Recent Advances: Redox signaling is a key regulator of wound healing, especially through its influence on the extracellular matrix (ECM). Normal redox signaling is disrupted in diabetes leading to several pathological mechanisms that alter the balance between reactive oxygen species (ROS) generation and scavenging. Importantly, pathological oxidative stress can alter ECM structure and function. There is limited understanding of the specific role of altered redox signaling in the diabetic wound, although there is evidence that ROS are involved in the underlying pathology. Preclinical studies of antioxidant-based therapies for diabetic wound healing have yielded promising results. Redox-based therapeutics constitute a novel approach for the treatment of wounds in diabetes patients that deserve further investigation. Antioxid. Redox Signal. 27, 823-838.

A survey of attitude and opinions of endodontic residents towards regenerative endodontics

Science.gov (United States)

Utneja, Shivani; Nawal, Ruchika Roongta; Ansari, Mohammed Irfan; Talwar, Sangeeta; Verma, Mahesh

2013-01-01

Aim: The objective of this survey was to study the level of awareness, current state of knowledge and opinions towards regenerative endodontic treatments amongst the endodontic residents of India. Settings and Design: Questionnaire based survey was designed. Materials and Methods: After approval from the organizing committee of 26th Federation of Operative Dentistry of India and 19th Indian Endodontic Society National conference 2011, 200 copies of the questionnaire were circulated amongst the endodontic residents in conservative dentistry and endodontics at various colleges across the country about regenerative endodontic procedures. The survey included profile of the respondents and consisted of 23 questions about their knowledge, attitude and opinions regarding use of these procedures as part of future dental treatment. Results: The survey showed that half the participants (50.6%) had received continued education in stem cells and/or regenerative dental treatments. The majority of participants were of the opinion (86.6%) that regenerative therapy should be incorporated into dentistry, and most of them (88%) were willing to acquire training in learning this new treatment strategy. The results indicated that half of the participants (52.6%) were already using some type of regenerative therapy in their clinical practice; however, with a majority of these limited to use of membranes, scaffolds or bioactive materials. Conclusions: These results reflect that endodontic residents are optimistic about the use of regenerative endodontic procedures; however, a need for more research and training was felt. PMID:23956532

Consequences of age on ischemic wound healing in rats: altered antioxidant activity and delayed wound closure.

Science.gov (United States)

Moor, Andrea N; Tummel, Evan; Prather, Jamie L; Jung, Michelle; Lopez, Jonathan J; Connors, Sarah; Gould, Lisa J

2014-04-01

Advertisements targeted at the elderly population suggest that antioxidant therapy will reduce free radicals and promote wound healing, yet few scientific studies substantiate these claims. To better understand the potential utility of supplemental antioxidant therapy for wound healing, we tested the hypothesis that age and tissue ischemia alter the balance of endogenous antioxidant enzymes. Using a bipedicled skin flap model, ischemic and non-ischemic wounds were created on young and aged rats. Wound closure and the balance of the critical antioxidants superoxide dismutase and glutathione in the wound bed were determined. Ischemia delayed wound closure significantly more in aged rats. Lower superoxide dismutase 2 and glutathione in non-ischemic wounds of aged rats indicate a basal deficit due to age alone. Ischemic wounds from aged rats had lower superoxide dismutase 2 protein and activity initially, coupled with decreased ratios of reduced/oxidized glutathione and lower glutathione peroxidase activity. De novo glutathione synthesis, to restore redox balance in aged ischemic wounds, was initiated as evidenced by increased glutamate cysteine ligase. Results demonstrate deficiencies in two antioxidant pathways in aged rats that become exaggerated in ischemic tissue, culminating in profoundly impaired wound healing and prolonged inflammation.

Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats.

Science.gov (United States)

Chen, Wei-Cheng; Liou, Shorong-Shii; Tzeng, Thing-Fong; Lee, Shiow-Ling; Liu, I-Min

2012-11-23

Lonicera japonica Thunb. (Caprifoliaceae), a widely used traditional Chinese medicinal plant, is used to treat some infectious diseases and it may have uses as a healthy food and applications in cosmetics and as an ornamental groundcover. The ethanol extract of the flowering aerial parts of L. japonica (LJEE) was investigated for its healing efficiency in a rat excision wound model. Excision wounds were inflicted upon three groups of eight rats each. Healing was assessed by the rate of wound contraction in skin wound sites in rats treated with simple ointment base, 10% (w/w) LJEE ointment, or the reference standard drug, 0.2% (w/w) nitrofurazone ointment. The effects of LJEE on the contents of hydroxyproline and hexosamine during healing were estimated. The antimicrobial activity of LJEE against microorganisms was also assessed. The in vivo anti-inflammatory activity of LJEE was investigated to understand the mechanism of wound healing. LJEE exhibited significant antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Candida albicans, and Candida tropicalis. The ointment formulation prepared with 10% (w/w) LJEE exhibited potent wound healing capacity as evidenced by the wound contraction in the excision wound model. The contents of hydroxyproline and hexosamine also correlated with the observed healing pattern. These findings were supported by the histopathological characteristics of healed wound sections, as greater tissue regeneration, more fibroblasts, and angiogenesis were observed in the 10% (w/w) LJEE ointment-treated group. The results also indicated that LJEE possesses potent anti-inflammatory activity, as it enhanced the production of anti-inflammatory cytokines that suppress proinflammatory cytokine production. The results suggest that the antimicrobial and anti-inflammatory activities of LJEE act synergistically to accelerate wound repair.

Combat Wound Initiative program.

Science.gov (United States)

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Wound Healing in Older Adults.

Science.gov (United States)

Gould, Lisa J; Fulton, Ana Tuya

2016-02-01

Impaired wound healing in the elderly represents a major clinical problem that is growing as our population ages. Wound healing is affected by age and by co-morbid conditions, particularly diabetes and obesity. This is particularly important in Rhode Island as the state has a very high percentage of vulnerable older adults. A multi- disciplinary approach that incorporates the skills of a comprehensive wound center with specialized nursing, geriatric medicine and palliative care will facilitate rapid wound healing, reduce costs and improve outcomes for our older adults that suffer from 'problem wounds'.

Elixir of Life: Thwarting Aging With Regenerative Reprogramming.

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Beyret, Ergin; Martinez Redondo, Paloma; Platero Luengo, Aida; Izpisua Belmonte, Juan Carlos

2018-01-05

All living beings undergo systemic physiological decline after ontogeny, characterized as aging. Modern medicine has increased the life expectancy, yet this has created an aged society that has more predisposition to degenerative disorders. Therefore, novel interventions that aim to extend the healthspan in parallel to the life span are needed. Regeneration ability of living beings maintains their biological integrity and thus is the major leverage against aging. However, mammalian regeneration capacity is low and further declines during aging. Therefore, modalities that reinforce regeneration can antagonize aging. Recent advances in the field of regenerative medicine have shown that aging is not an irreversible process. Conversion of somatic cells to embryonic-like pluripotent cells demonstrated that the differentiated state and age of a cell is not fixed. Identification of the pluripotency-inducing factors subsequently ignited the idea that cellular features can be reprogrammed by defined factors that specify the desired outcome. The last decade consequently has witnessed a plethora of studies that modify cellular features including the hallmarks of aging in addition to cellular function and identity in a variety of cell types in vitro. Recently, some of these reprogramming strategies have been directly used in animal models in pursuit of rejuvenation and cell replacement. Here, we review these in vivo reprogramming efforts and discuss their potential use to extend the longevity by complementing or augmenting the regenerative capacity. © 2017 American Heart Association, Inc.

Regenerative Medicine for Periodontal and Peri-implant Diseases.

Science.gov (United States)

Larsson, L; Decker, A M; Nibali, L; Pilipchuk, S P; Berglundh, T; Giannobile, W V

2016-03-01

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions. © International & American Associations for Dental Research 2015.

Apitherapeutics and phage-loaded nanofibers as wound dressings with enhanced wound healing and antibacterial activity.

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Sarhan, Wessam A; Azzazy, Hassan Me

2017-09-01

Develop green wound dressings which exhibit enhanced wound-healing ability and potent antibacterial effects. Honey, polyvinyl alcohol, chitosan nanofibers were electrospun and loaded with bee venom, propolis and/or bacteriophage against the multidrug-resistant Pseudomonas aeruginosa and examined for their antibacterial, wound-healing ability and cytotoxicity. Among different formulations of nanofibers, honey, polyvinyl alcohol, chitosan-bee venom/bacteriophage exhibited the most potent antibacterial activity against all tested bacterial strains (Gram-positive and -negative strains) and achieved nearly complete killing of multidrug-resistant P. aeruginosa. In vivo testing revealed enhanced wound-healing results and cytotoxicity testing proved improved biocompatibility. The developed biocompatible nanofibers represent competitive wound-healing dressings with potent antibacterial and wound-healing activity.

LOX/Methane Regeneratively-Cooled Rocket Engine Development

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National Aeronautics and Space Administration — The purpose of this project is to advance the technologies required to build a subcritical regeneratively cooled liquid oxygen/methane rocket combustion chamber for...

The management of perineal wounds

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Ramesh k Sharma

2012-01-01

Full Text Available Management of perineal wounds can be very frustrating as these invariably get contaminated from the ano-genital tracts. Moreover, the apparent skin defect may be associated with a significant three dimensional dead space in the pelvic region. Such wounds are likely to become chronic and recalcitrant if appropriate wound management is not instituted in a timely manner. These wounds usually result after tumor excision, following trauma or as a result of infective pathologies like hideradenitis suppurativa or following thermal burns. Many options are available for management of perineal wounds and these have been discussed with illustrative case examples. A review of literature has been done for listing commonly instituted options for management of the wounds in perineum.

From regenerative dentistry to regenerative medicine: progress, challenges, and potential applications of oral stem cells

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Xiao L

2014-12-01

Full Text Available Li Xiao,1 Masanori Nasu2 1Department of Pharmacology, 2Research Center, The Nippon Dental University, Tokyo, Japan Abstract: Adult mesenchymal stem cells (MSCs and epithelial stem cells play essential roles in tissue repair and self-healing. Oral MSCs and epithelial stem cells can be isolated from adult human oral tissues, for example, teeth, periodontal ligament, and gingiva. Cocultivated adult oral epithelial stem cells and MSCs could represent some developmental events, such as epithelial invagination and tubular structure formation, signifying their potentials for tissue regeneration. Oral epithelial stem cells have been used in regenerative medicine over 1 decade. They are able to form a stratified cell sheet under three-dimensional culture conditions. Both experimental and clinical data indicate that the cell sheets can not only safely and effectively reconstruct the damaged cornea in humans, but also repair esophageal ulcer in animal models. Oral MSCs include dental pulp stem cells (DPSCs, stem cells from exfoliated deciduous teeth (SHED, stem cells from apical papilla (SCAP, periodontal ligament stem cells (PDLSCs, and mesenchymal stem cells from gingiva (GMSCs. They are widely applied in both regenerative dentistry and medicine. DPSCs, SHED, and SCAP are able to form dentin–pulp complex when being transplanted into immunodeficient animals. They have been experimentally used for the regeneration of dental pulp, neuron, bone muscle and blood vessels in animal models and have shown promising results. PDLSCs and GMSCs are demonstrated to be ideal cell sources for repairing the damaged tissues of periodontal, muscle, and tendon. Despite the abovementioned applications of oral stem cells, only a few human clinical trials are now underway to use them for the treatment of certain diseases. Since clinical use is the end goal, their true regenerative power and safety need to be further examined.Keywords: oral mesenchymal stem cells, oral

Preparation of SMART wound dressings based on colloidal microgels and textile fibres

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Cornelius, Victoria J.; Majcen, Natasa; Snowden, Martin J.; Mitchell, John C.; Voncina, Bojana

2007-01-01

Wound dressings and other types of wound healing technologies are experiencing fast-paced development and rapid growth. As the population ages, demand will continue to rise for advanced dressings used to treat chronic wounds, such as pressure ulcers, venous stasis ulcers, and diabetic ulcers. Moist wound dressings, which facilitate natural wound healing in a cost-effective manner, will be increasingly important. In commercially available hydrogel / gauze wound dressings the gel swells to adsorb wound excreta and provide an efficient non adhesive particle barrier. An alternative to hydrogels are microgels. Essentially discrete colloidal gel particles, as a result of their very high surface area to volume ratio compared to bulk gels, they have a much faster response to external stimuli such as temperature or pH. In response to either an increase or decrease in solvent quality these porous networks shrink and swell reversibly. When swollen the interstitial regions within the polymer matrix are available for further chemistry; such as the incorporation of small molecules. The reversible shrinking and swelling as a function of external stimuli provides a novel drug release system. As the environmental conditions of a wound change over its lifetime, tending to increase in pH if there is an infection combining these discrete polymeric particles with a substrate such as cotton, results in a smart wound dressing.

[Progress in stem cells and regenerative medicine].

Science.gov (United States)

Wang, Libin; Zhu, He; Hao, Jie; Zhou, Qi

2015-06-01

Stem cells have the ability to differentiate into all types of cells in the body and therefore have great application potential in regenerative medicine, in vitro disease modelling and drug screening. In recent years, stem cell technology has made great progress, and induced pluripotent stem cell technology revolutionizes the whole stem cell field. At the same time, stem cell research in our country has also achieved great progress and becomes an indispensable power in the worldwide stem cell research field. This review mainly focuses on the research progress in stem cells and regenerative medicine in our country since the advent of induced pluripotent stem cell technology, including induced pluripotent stem cells, transdifferentiation, haploid stem cells, and new gene editing tools.

Exploring the concept of a team approach to wound care: Managing wounds as a team.

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Moore, Zena; Butcher, Gillian; Corbett, Lisa Q; McGuiness, William; Snyder, Robert J; van Acker, Kristien

2014-05-01

Background - The growing prevalence and incidence of nonhealing acute and chronic wounds is a worrying concern. A major challenge is the lack of united services aimed at addressing the complex needs of individuals with wounds. However, the WHO argues that interprofessional collaboration in education and practice is key to providing the best patient care, enhancing clinical and health-related outcomes and strengthening the health system. It is based on this background that the team approach to wound care project was conceptualised. The project was jointly initiated and realised by the Association for the Advancement of Wound Care (AAWC-USA), the Australian Wound Management Association (AWMA) and the European Wound Management Association (EWMA). Aim - The aim of this project was to develop a universal model for the adoption of a team approach to wound care. Objective The overarching objective of this project was to provide recommendations for implementing a team approach to wound care within all clinical settings and through this to develop a model for advocating the team approach toward decision makers in national government levels. Method An integrative literature review was conducted. Using this knowledge, the authors arrived at a consensus on the most appropriate model to adopt and realise a team approach to wound care. Results - Eighty four articles met the inclusion criteria. Following data extraction, it was evident that none of the articles provided a definition for the terms multidisciplinary, interdisciplinary or transdisciplinary in the context of wound care. Given this lack of clarity within the wound care literature, the authors have here developed a Universal Model for the Team Approach to Wound Care to fill this gap in our current understanding. Conclusion - We advocate that the patient should be at the heart of all decision-making, as working with the Universal Model for the Team Approach to Wound Care begins with the needs of the patient. To

The use of negative pressure wound therapy in the treatment of infected wounds. Case studies

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Daniel de Alcântara Jones

Full Text Available ABSTRACT OBJECTIVE: To evaluate the results and benefits obtained from the topical use of negative pressure wound therapy (NPWT in patients with infected wounds. METHODS: This was a retrospective study of 20 patients (17 males and three females, mean age 42 years with infected wounds treated using NPWT. The infected wounds were caused by trauma. The treatment system used was VAC.(r (Vacuum Assisted Closure, KCI, San Antonio, United States applied to the wound in continuous mode from 100 to 125 mmHg. The parameters related to the wounds (location, number of VAC changes, the size of the defects in the soft parts, and the evolution of the state of the wound, length of hospital stay, length of intravenous antibiotic therapy, and complications related to the use of this therapy were evaluated. RESULTS: The mean length of the hospital stay, use of NPWT, and antibacterial therapy were 41 days, 22.5 days, and 20 days respectively. The use of the VAC led to a mean reduction of 29% in the wound area (95.65-68.1 cm2; p < 0.05. Only one patient did not show any improvement in the final appearance of the wound with complete eradication of the infection. No complication directly caused by NPWT was observed. CONCLUSION: NPWT stimulates infection-free scar tissue formation in a short time, and is a quick and comfortable alternative to conventional infected wounds treatment methods.

Efficient Healing Takes Some Nerve: Electrical Stimulation Enhances Innervation in Cutaneous Human Wounds.

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Emmerson, Elaine

2017-03-01

Cutaneous nerves extend throughout the dermis and epidermis and control both the functional and reparative capacity of the skin. Denervation of the skin impairs cutaneous healing, presenting evidence that nerves provide cues essential for timely wound repair. Sebastian et al. demonstrate that electrical stimulation promotes reinnervation and neural differentiation in human acute wounds, thus accelerating wound repair. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Lower limb revascularisation preceding surgical wound coverage - an interdisciplinary algorithm for chronic wound closure.

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Aust, M C; Spies, M; Guggenheim, M; Gohritz, A; Kall, S; Rosenthal, H; Pichlmaier, M; Oehlert, G; Vogt, P M

2008-08-01

Chronic wounds may occur or persist due to arterial insufficiency. Despite the high prevalence of arterial occlusive disease, a search of the literature has yielded a paucity of data on the benefit of interventions to recanalise lower extremity arteries prior to surgical closure of chronic wounds. To investigate the correlation of simple clinical examinations and apparative diagnostics for the detection of arterial occlusive disease of the lower extremity in patients with chronic wounds, and to evaluate the benefit of vascular procedures to optimise wound perfusion before surgical closure. During a 6-year period, 150 patients with chronic lower extremity wounds (no healing for more than 30 days) were included into this prospective study. All patients underwent palpation of foot pulses, Doppler sonography and measurement of occlusive pressures. Positive clinical findings were re-evaluated by angiography. All patients with peripheral extremity vessel occlusions underwent vascular interventions (percutaneous transluminal angioplasty with stenting, open thrombectomy or vascular bypass surgery) prior to surgical wound closure. In all 34 patients (21%) with missing foot pulses, suspicious Doppler signals or pathological occlusive pressure measurements, the clinical diagnosis of arterial occlusion was confirmed by angiography. An arterial pathology had previously been diagnosed in merely two of those patients. Nineteen patients underwent percutaneous transluminal angioplasty and 21 stents were implanted; in 10 cases, open thrombectomy or vascular bypasses were performed. In all 34 patients, sufficient peripheral recanalisation and improved wound perfusion were successfully achieved. For definitive wound closure, microsurgical tissue transplantation was performed in 15 patients. Angiography was performed prior to surgery. In 11 patients, regional or local flaps were used. Six patients received split skin grafting only; two wounds healed conservatively following vascular

Exosomal DMBT1 from human urine-derived stem cells facilitates diabetic wound repair by promoting angiogenesis.

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Chen, Chun-Yuan; Rao, Shan-Shan; Ren, Lu; Hu, Xiong-Ke; Tan, Yi-Juan; Hu, Yin; Luo, Juan; Liu, Yi-Wei; Yin, Hao; Huang, Jie; Cao, Jia; Wang, Zhen-Xing; Liu, Zheng-Zhao; Liu, Hao-Ming; Tang, Si-Yuan; Xu, Ran; Xie, Hui

2018-01-01

Chronic non-healing wounds represent one of the most common complications of diabetes and need advanced treatment strategies. Exosomes are key mediators of cell paracrine action and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of exosomes from human urine-derived stem cells (USC-Exos) on diabetic wound healing and the underlying mechanism. Methods: USCs were characterized by flow cytometry and multipotent differentiation potential analyses. USC-Exos were isolated from the conditioned media of USCs and identified by transmission electron microscopy and flow cytometry. A series of functional assays in vitro were performed to assess the effects of USC-Exos on the activities of wound healing-related cells. Protein profiles in USC-Exos and USCs were examined to screen the candidate molecules that mediate USC-Exos function. The effects of USC-Exos on wound healing in streptozotocin-induced diabetic mice were tested by measuring wound closure rates, histological and immunofluorescence analyses. Meanwhile, the role of the candidate protein in USC-Exos-induced regulation of angiogenic activities of endothelial cells and diabetic wound healing was assessed. Results: USCs were positive for CD29, CD44, CD73 and CD90, but negative for CD34 and CD45. USCs were able to differentiate into osteoblasts, adipocytes and chondrocytes. USC-Exos exhibited a cup- or sphere-shaped morphology with a mean diameter of 51.57 ± 2.93 nm and positive for CD63 and TSG101. USC-Exos could augment the functional properties of wound healing-related cells including the angiogenic activities of endothelial cells. USC-Exos were enriched in the proteins that are involved in regulation of wound healing-related biological processes. Particularly, a pro-angiogenic protein called deleted in malignant brain tumors 1 (DMBT1) was highly expressed in USC-Exos. Further functional assays showed that DMBT1 protein was required for USC

Wound Healing Effects of Rose Placenta in a Mouse Model of Full-Thickness Wounds

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Yang Woo Kim

2015-11-01

Full Text Available BackgroundRosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice.MethodsSixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta (250 µg was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF, vascular endothelial growth factor (VEGF, transforming growth factor-β1 (TGF-β1, and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test.Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-β1 expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA.ConclusionsRose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

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Engrav, Loren H; Tuggle, Christopher K; Kerr, Kathleen F; Zhu, Kathy Q; Numhom, Surawej; Couture, Oliver P; Beyer, Richard P; Hocking, Anne M; Carrougher, Gretchen J; Ramos, Maria Luiza C; Klein, Matthew B; Gibran, Nicole S

2011-04-20

Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1) there has been no validated animal model; 2) human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3) tissues typically have been homogenized, mixing cell populations; and 4) gene-by-gene studies are incomplete. We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative)/Yorkshire(non-pigmented non-fibroproliferative) porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. 1) The scars are still thick at forty-six weeks post wounding further validating the model. 2) The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3) The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

Functional genomics unique to week 20 post wounding in the deep cone/fat dome of the Duroc/Yorkshire porcine model of fibroproliferative scarring.

Directory of Open Access Journals (Sweden)

Loren H Engrav

Full Text Available BACKGROUND: Hypertrophic scar was first described over 100 years ago; PubMed has more than 1,000 references on the topic. Nevertheless prevention and treatment remains poor, because 1 there has been no validated animal model; 2 human scar tissue, which is impossible to obtain in a controlled manner, has been the only source for study; 3 tissues typically have been homogenized, mixing cell populations; and 4 gene-by-gene studies are incomplete. METHODOLOGY/PRINCIPAL FINDINGS: We have assembled a system that overcomes these barriers and permits the study of genome-wide gene expression in microanatomical locations, in shallow and deep partial-thickness wounds, and pigmented and non-pigmented skin, using the Duroc(pigmented fibroproliferative/Yorkshire(non-pigmented non-fibroproliferative porcine model. We used this system to obtain the differential transcriptome at 1, 2, 3, 12 and 20 weeks post wounding. It is not clear when fibroproliferation begins, but it is fully developed in humans and the Duroc breed at 20 weeks. Therefore we obtained the derivative functional genomics unique to 20 weeks post wounding. We also obtained long-term, forty-six week follow-up with the model. CONCLUSIONS/SIGNIFICANCE: 1 The scars are still thick at forty-six weeks post wounding further validating the model. 2 The differential transcriptome provides new insights into the fibroproliferative process as several genes thought fundamental to fibroproliferation are absent and others differentially expressed are newly implicated. 3 The findings in the derivative functional genomics support old concepts, which further validates the model, and suggests new avenues for reductionist exploration. In the future, these findings will be searched for directed networks likely involved in cutaneous fibroproliferation. These clues may lead to a better understanding of the systems biology of cutaneous fibroproliferation, and ultimately prevention and treatment of hypertrophic scarring.

The imperative for regenerative agriculture.

Science.gov (United States)

Rhodes, Christopher J

2017-03-01

A review is made of the current state of agriculture, emphasising issues of soil erosion and dependence on fossil fuels, in regard to achieving food security for a relentlessly enlarging global population. Soil has been described as "the fragile, living skin of the Earth", and yet both its aliveness and fragility have all too often been ignored in the expansion of agriculture across the face of the globe. Since it is a pivotal component in a global nexus of soil-water-air-energy, how we treat the soil can impact massively on climate change - with either beneficial or detrimental consequences, depending on whether the soil is preserved or degraded. Regenerative agriculture has at its core the intention to improve the health of soil or to restore highly degraded soil, which symbiotically enhances the quality of water, vegetation and land-productivity. By using methods of regenerative agriculture, it is possible not only to increase the amount of soil organic carbon (SOC) in existing soils, but to build new soil. This has the effect of drawing down carbon from the atmosphere, while simultaneously improving soil structure and soil health, soil fertility and crop yields, water retention and aquifer recharge - thus ameliorating both flooding and drought, and also the erosion of further soil, since runoff is reduced. Since food production on a more local scale is found to preserve the soil and its quality, urban food production should be seen as a significant potential contributor to regenerative agriculture in the future, so long as the methods employed are themselves 'regenerative'. If localisation is to become a dominant strategy for dealing with a vastly reduced use of fossil fuels, and preserving soil quality - with increased food production in towns and cities - it will be necessary to incorporate integrated ('systems') design approaches such as permaculture and the circular economy (which minimise and repurpose 'waste') within the existing urban infrastructure. In

Validation of a laser-assisted wound measurement device in a wound healing model.

Science.gov (United States)

Constantine, Ryan S; Bills, Jessica D; Lavery, Lawrence A; Davis, Kathryn E

2016-10-01

In the treatment and monitoring of a diabetic or chronic wound, accurate and repeatable measurement of the wound provides indispensable data for the patient's medical record. This study aims to measure the accuracy of the laser-assisted wound measurement (LAWM) device against traditional methods in the measurement of area, depth and volume. We measured four 'healing' wounds in a Play-Doh(®) -based model over five subsequent states of wound healing progression in which the model was irregularly filled in to replicate the healing process. We evaluated the LAWM device against traditional methods including digital photograph assessment with National Institutes of Health ImageJ software, measurements of depth with a ruler and weight-to-volume assessment with dental paste. Statistical analyses included analysis of variance (ANOVA) and paired t-tests. We demonstrate that there are significantly different and nearly statistically significant differences between traditional ruler depth measurement and LAWM device measurement, but there are no statistically significant differences in area measurement. Volume measurements were found to be significantly different in two of the wounds. Rate of percentage change was analysed for volume and depth in the wound healing model, and the LAWM device was not significantly different than the traditional measurement technique. While occasionally inaccurate in its absolute measurement, the LAWM device is a useful tool in the clinician's arsenal as it reliably measures rate of percentage change in depth and volume and offers a potentially aseptic alternative to traditional measurement techniques. © 2014 The Authors. International Wound Journal © 2014 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Carbon nanotube torsional springs for regenerative braking systems

International Nuclear Information System (INIS)

Liu, Sanwei; Martin, Corbin; Livermore, Carol; Lashmore, David; Schauer, Mark

2015-01-01

The modeling and demonstration of large stroke, high energy density and high power density torsional springs based on carbon nanotube (CNT) yarns is reported, as well as their application as energy-storing actuators for regenerative braking systems. An originally untwisted CNT yarn is cyclically loaded and unloaded in torsion, with the maximum rotation angle increasing incrementally until failure. The measured average extractable energy density values are 2.9 kJ kg −1   ±  1.2 kJ kg −1 and 3.4 kJ kg −1   ±  0.4 kJ kg −1 for 1-ply CNT yarns and 2-ply CNT yarns, respectively. Additionally, a regenerative braking system is demonstrated to capture the kinetic energy of a wheel and store it as elastic energy in twisted CNT yarns. When the yarn’s twist is released, the stored energy reaccelerates the wheel. The measured energy and mean power densities of the CNT yarns in the simple regenerative braking setup are on average 3.3 kJ kg −1 and 0.67 kW kg −1 , respectively, with maximum measured values of up to 4.7 kJ kg −1 and 1.2 kW kg −1 , respectively. A slightly lower energy density of up to 1.2 kJ kg −1 and a 0.29 kW kg −1 mean power density are measured for CNT yarns in a more complex setup that mimics a unidirectional rotating regenerative braking mechanism. (paper)

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

NARCIS (Netherlands)

Ubbink, Dirk T.; Lindeboom, Robert; Eskes, Anne M.; Brull, Huub; Legemate, Dink A.; Vermeulen, Hester

2015-01-01

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We

Predicting complex acute wound healing in patients from a wound expertise centre registry : a prognostic study

NARCIS (Netherlands)

Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

2015-01-01

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We

New evaluation methodology of regenerative braking contribution to energy efficiency improvement of electric vehicles

International Nuclear Information System (INIS)

Qiu, Chengqun; Wang, Guolin

2016-01-01

Highlights: • Two different contribution ratio evaluation parameters according to the deceleration braking process are proposed. • Methodologies for calculating the contribution made by regenerative brake to improve vehicle energy efficiency are proposed. • Road test results imply that the proposed parameters are effective. - Abstract: Comprehensive research is conducted on the design and control of a regenerative braking system for electric vehicles. The mechanism and evaluation methods of contribution brought by regenerative braking to improve electric vehicle’s energy efficiency are discussed and analyzed by the energy flow. Methodologies for calculating the contribution made by regenerative brake are proposed. Additionally a new regenerative braking control strategy called “serial 2 control strategy” is introduced. Moreover, two control strategies called “parallel control strategy” and “serial 1 control strategy” are proposed as the comparative control strategy. Furthermore, two different contribution ratio evaluation parameters according to the deceleration braking process are proposed. Finally, road tests are carried out under China typical city regenerative driving cycle standard with three different control strategies. The serial 2 control strategy offers considerably higher regeneration efficiency than the parallel strategy and serial 1 strategy.

New Advances Push Engineered Tissues Toward 3-D: Multidisciplinary Collaboration is Key to the Success of Regenerative Medicine.

Science.gov (United States)

Mertz, Leslie

2017-01-01

Although doctors still cannot simply order new, functioning organs for patients who need replacements, researchers in labs around the world are making the important advances in tissue engineering that set the stage for regenerative medicine as well as make other biomedical technologies possible.

Sinonasal Epithelial Wound Resealing in an In Vitro Model: Inhibition of Wound Closure with IL-4 Exposure

Science.gov (United States)

Wise, Sarah K.; Den Beste, Kyle A.; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma

2013-01-01

Background Prolonged healing and persistent inflammation following surgery for rhinosinusitis impacts patient satisfaction and healthcare resources. Cytokines interleukin (IL)-4, 5, and 13 are important mediators in Th2 inflammatory rhinosinusitis. Decreased wound healing has been demonstrated with Th2 cytokine exposure, but this has not been extensively studied in sinonasal epithelium. We hypothesized that in vitro exposure of primary sinonasal epithelial cell cultures to Th2 inflammatory cytokine IL-4 and IL-13 would impair wound resealing and decrease expression of annexin A2 at the wound edge. Methods Following 24-hour exposure to IL-4, 5, or 13 versus controls, sterile linear mechanical wounds were created in primary sinonasal epithelial cultures (n = 12 wounds per condition). Wounds were followed for 36 hours or until complete closure and residual wound areas were calculated by image analysis. Group differences in annexin A2 were assessed by immunofluorescence labeling, confocal microscopy, and Western blots. Results Significant wound closure differences were identified across cytokine exposure groups (pprotein levels were decreased in IL-4 treated wounds when compared to control wounds (p<0.01). Conclusions Th2 cytokine IL-4 decreases sinonasal epithelial wound closure in vitro. Annexin A2 is also diminished with IL-4 exposure. This supports the hypothesis that IL-4 exposure impairs sinonasal epithelial wound healing and may contribute to prolonged healing in Th2 inflammatory rhinosinusitis. PMID:23468432

In vivo performance of chitosan/soy-based membranes as wound-dressing devices for acute skin wounds.

Science.gov (United States)

Santos, Tírcia C; Höring, Bernhard; Reise, Kathrin; Marques, Alexandra P; Silva, Simone S; Oliveira, Joaquim M; Mano, João F; Castro, António G; Reis, Rui L; van Griensven, Martijn

2013-04-01

Wound management represents a major clinical challenge on what concerns healing enhancement and pain control. The selection of an appropriate dressing plays an important role in both recovery and esthetic appearance of the regenerated tissue. Despite the wide range of available dressings, the progress in the wound care market relies on the increasing interest in using natural-based biomedical products. Herein, a rat wound-dressing model of partial-thickness skin wounds was used to study newly developed chitosan/soy (cht/soy)-based membranes as wound-dressing materials. Healing and repair of nondressed, cht/soy membrane-dressed, and Epigard(®)-dressed wounds were followed macroscopically and histologically for 1 and 2 weeks. cht/soy membranes performed better than the controls, promoting a faster wound repair. Re-epithelialization, observed 1 week after wounding, was followed by cornification of the outermost epidermal layer at the second week of dressing, indicating repair of the wounded tissue. The use of this rodent model, although in impaired healing conditions, may enclose some drawbacks regarding the inevitable wound contraction. Moreover, being the main purpose the evaluation of cht/soy-based membranes' performance in the absence of growth factors, the choice of a clinically relevant positive control was limited to a polymeric mesh, without any growth factor influencing skin healing/repair, Epigard. These new cht/soy membranes possess the desired features regarding healing/repair stimulation, ease of handling, and final esthetic appearance-thus, valuable properties for wound dressings.

Vibration control of an energy regenerative seat suspension with variable external resistance

Science.gov (United States)

Ning, Donghong; Sun, Shuaishuai; Du, Haiping; Li, Weihua; Zhang, Nong

2018-06-01

In this paper, an energy regenerative seat suspension with a variable external resistance is proposed and built, and a semi-active controller for its vibration control is also designed and validated. The energy regenerative seat suspension is built with a three-phase generator and a gear reducer, which are installed in the scissors structure centre of the seat suspension, and the vibration energy is directly harvested from the rotary movement of suspension's scissors structure. The electromagnetic torque of the semi-active seat suspension actuator is controlled by an external variable resistor. An integrated model including the seat suspension's kinematics and the generator is built and proven to match the test result very well. A simplified experimental phenomenon model is also built based on the test results for the controller design. A state feedback H∞ controller is proposed for the regenerative seat suspension's semi-active vibration control. The proposed regenerative seat suspension and its controller are validated with both simulations and experiments. A well-tuned passive seat suspension is applied to evaluate the regenerative seat's performance. Based on ISO 2631-1, the frequency-weighted root mean square (FW-RMS) acceleration of the proposed seat suspension has a 22.84% reduction when compared with the passive one, which indicates the improvement of ride comfort. At the same time, the generated RMS power is 1.21 W. The proposed regenerative seat suspension can greatly improve the driver's ride comfort and has the potential to be developed to a self-powered semi-active system.

Fluorescence imaging of tryptophan and collagen cross-links to evaluate wound closure ex vivo

Science.gov (United States)

Wang, Ying; Ortega-Martinez, Antonio; Farinelli, Bill; Anderson, R. R.; Franco, Walfre

2016-02-01

Wound size is a key parameter in monitoring healing. Current methods to measure wound size are often subjective, time-consuming and marginally invasive. Recently, we developed a non-invasive, non-contact, fast and simple but robust fluorescence imaging (u-FEI) method to monitor the healing of skin wounds. This method exploits the fluorescence of native molecules to tissue as functional and structural markers. The objective of the present study is to demonstrate the feasibility of using variations in the fluorescence intensity of tryptophan and cross-links of collagen to evaluate proliferation of keratinocyte cells and quantitate size of wound during healing, respectively. Circular dermal wounds were created in ex vivo human skin and cultured in different media. Two serial fluorescence images of tryptophan and collagen cross-links were acquired every two days. Histology and immunohistology were used to validate correlation between fluorescence and epithelialization. Images of collagen cross-links show fluorescence of the exposed dermis and, hence, are a measure of wound area. Images of tryptophan show higher fluorescence intensity of proliferating keratinocytes forming new epithelium, as compared to surrounding keratinocytes not involved in epithelialization. These images are complementary since collagen cross-links report on structure while tryptophan reports on function. HE and immunohistology show that tryptophan fluorescence correlates with newly formed epidermis. We have established a fluorescence imaging method for studying epithelialization processes during wound healing in a skin organ culture model, our approach has the potential to provide a non-invasive, non-contact, quick, objective and direct method for quantitative measurements in wound healing in vivo.

Surgical Non-Regenerative Treatments for Peri-Implantitis: a Systematic Review

Directory of Open Access Journals (Sweden)

Ausra Ramanauskaite

2016-09-01

Full Text Available Objectives: The purposes of the present study were 1 to systematically review the literature on the surgical non-regenerative treatments of peri-implantitis and 2 to determine a predictable therapeutic option for the clinical management of peri-implantitis lesions. Material and Methods: The study search was performed on primary database MEDLINE and EMBASE from 2005 until 2016. Sequential screenings at the title, abstract, and full-text levels were performed. Clinical human studies in the English language that had reported changes in probing depth (PD and/or bleeding on probing (BOP and/or radiologic marginal bone level changes after peri-implantitis surgical non-regenerative treatment at 6-month follow-up or longer were included accordingly PRISMA guidelines. Results: The first electronic and hand search resulted in 765 citations. From 16 full-text articles reviewed, 6 were included in this systematic review. Surgical non-regenerative methods were found to be efficient in reducing clinical parameters. BOP and PD values were significantly decreased following implantoplasty and systematic administration of antibacterials, but not after local application of chemical compounds or diode laser. Similarly, significant improvement in clinical and radiographic parameters was found only after implantoplasty compared with resective surgery alone. We found significant heterogeneity in study designs and treatments provided among the pooled studies. All of the studies revealed an unclear or high risk of bias. Conclusions: Surgical non-regenerative treatment of peri-implantitis was found to be effective to reduce the soft tissue inflammation and decrease probing depth. More randomized controlled clinical trials are needed to assess the efficacy of surgical non-regenerative therapy of peri-implantitis.

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing.

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Zheng, Zhong; Zhang, Xinli; Dang, Catherine; Beanes, Steven; Chang, Grace X; Chen, Yao; Li, Chen-Shuang; Lee, Kevin S; Ting, Kang; Soo, Chia

2016-11-01

In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss- and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in late-gestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-β1 expression and scarless repair, while low Fm levels correlated with increased TGF-β1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FM-TGF-β1 nexus plays in fetal-type scarless skin repair. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Regenerative memory in time-delayed neuromorphic photonic resonators

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Romeira, B.; Avó, R.; Figueiredo, José M. L.; Barland, S.; Javaloyes, J.

2016-01-01

We investigate a photonic regenerative memory based upon a neuromorphic oscillator with a delayed self-feedback (autaptic) connection. We disclose the existence of a unique temporal response characteristic of localized structures enabling an ideal support for bits in an optical buffer memory for storage and reshaping of data information. We link our experimental implementation, based upon a nanoscale nonlinear resonant tunneling diode driving a laser, to the paradigm of neuronal activity, the FitzHugh-Nagumo model with delayed feedback. This proof-of-concept photonic regenerative memory might constitute a building block for a new class of neuron-inspired photonic memories that can handle high bit-rate optical signals.

Ocular progenitor cells and current applications in regenerative medicines – Review

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K. Gokuladhas

2017-06-01

Full Text Available The recent emerging field of regenerative medicine is to present solutions for chronic diseases which cannot be sufficiently repaired by the body's own mechanisms. Stem cells are undifferentiated biological cells and have the potential to develop into many different cell types in the body during early life and growth. Self renewal and totipotency are the characteristic features of stem cells and it holds a promising result for treating various diseases like diabetic foot ulcer, heart diseases, lung diseases, Autism, Skin diseases, arthritis including eye disease. Failure of complete recovery of eye diseases and complications that follow conventional treatments have shifted search to a new form of regenerative medicine using Stem cells. The ocular progenitor cells are remarkable in stem cell biology and replenishing degenerated cells despite being present in low quantity and quiescence in our body has a high therapeutic value. In this paper we have review the applications on ocular progenitor stem cells in treatment of human eye diseases and address the strategies that have been exploited in an effort to regain visual function in the advance treatment of stem cells without any side effects and also present the significance in advance stem cell research.

Aloe vera and Vitis vinifera improve wound healing in an in vivo rat burn wound model.

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Lin, Li-Xin; Wang, Peng; Wang, Yu-Ting; Huang, Yong; Jiang, Lei; Wang, Xue-Ming

2016-02-01

Aloe vera and Vitis vinifera have been traditionally used as wound healing agents. The present study aimed to investigate the effects of aloe emodin and resveratrol in the burn wound healing procedure. Burn wounds are common in developed and developing countries, however, in developing countries, the incidence of severe complications is higher and financial resources are limited. The results of the present study demonstrated that neither aloe emodin or resveratrol were cytotoxic to THP-1 macrophages at concentrations of 1, 100 and 500 ng/ml. A significant increase in wound-healing activity was observed in mice treated with the aloe emodin and resveratrol, compared with those which received control treatments. The levels of IL-1β in the exudates of the burn wound area of the treated mice increased in a time-dependent manner over 7 days following burn wound injury. At 10 days post-injury, steady and progressive wound healing was observed in the control animals. The present study confirmed that increased wound healing occurs following treatment with aloe emodin,, compared with resveratrol, providing support for the use of Aloe vera plants to improve burn wound healing.

Negative Pressure Wound Therapy in Maxillofacial Applications

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Adam J. Mellott

2016-09-01

Full Text Available Negative pressure wound therapy has greatly advanced the field of wound healing for nearly two decades, by providing a robust surgical adjunct technique for accelerating wound closure in acute and chronic wounds. However, the application of negative pressure wound therapy in maxillofacial applications has been relatively under utilized as a result of the physical articulations and contours of the head and neck that make it challenging to obtain an airtight seal for different negative pressure wound therapy systems. Adapting negative pressure wound therapies for maxillofacial applications could yield significant enhancement of wound closure in maxillofacial applications. The current review summarizes the basic science underlying negative pressure wound therapy, as well as specific maxillofacial procedures that could benefit from negative pressure wound therapy.

Scalp Wound Closure with K wires: An alternative easier method to scalp wound closure.

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Ramesh, S; Ajik, S

2012-12-01

Scalp defects and lacerations present a reconstructive challenge to plastic surgeons. Many methods have been described from the use of skin grafting to rotation flaps. Here we present a method of closure of a contaminated scalp wound with the use of Kirschner wires. In our case, closure of scalp laceration was made possible with the use of 1.4 Kirschner wires and cable tie/ zip tie fasteners. The duration to closure of wound was 10 days. In reconstructing the scalp defect, this method was found to adhere to principles of scalp reconstruction. There were no post operative complications found from the procedure. On initial application on the edge of the wound, tension applied caused the K wires to cut through the wound edge. On replacement of K wires 1cm away from wound edge the procedure was not plagued by any further complication. In conclusion we find scalp closure with Kirschner wires are a simple and effective method for scalp wound closure.

Bacterial Contribution in Chronicity of Wounds.

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Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

2017-04-01

A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

Chitosan-aluminum monostearate composite sponge dressing containing asiaticoside for wound healing and angiogenesis promotion in chronic wound.

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Phaechamud, Thawatchai; Yodkhum, Kotchamon; Charoenteeraboon, Juree; Tabata, Yasuhiko

2015-05-01

There are many factors that delay healing in chronic wounds including lowering level of growth factors and increasing exudate level comprising high amount of tissue destructive enzymes. Asiaticoside possesses interesting wound healing and angiogenic activities that are employed to stimulate tissue regeneration in wound healing application. This study attempted to develop chitosan-aluminum monostearate (Alst) composite sponge containing asiaticoside for use as an absorbent medical dressing in chronic wound. N-methyl-2-pyrrolidone (NMP) was used to enhance homogeneity of asiaticoside in the polymer composite matrix. The sponge dressings were prepared by lyophilization and dehydrothermal treatment (DHT). Functional group interaction, crystallinity, and morphology of the prepared sponges were investigated using FT-IR, PXRD, and SEM, respectively. Physicochemical properties, porosity, hydrophilic/hydrophobic properties and mechanical property, were evaluated. Wound dressing properties, water vapor transmission rate (WVTR), fluid absorbency, oxygen permeation (OP), and bio-adhesive property, were investigated. In vitro asiaticoside release study was conducted using immersion method. Cytotoxicity was studied in normal human dermal fibroblast (NHDF) and normal human epidermal keratinocyte (NHEK). Angiogenic activity of asiaticoside was evaluated using chick-chorioallantoic membrane (CAM) assay. FT-IR and PXRD results revealed the amidation after DHT to enhance the crystallinity of the prepared sponges. The prepared sponges had high porosity comprising high Alst-loaded amount that exhibited more compact structure. Alst enhanced hydrophobicity therefore it reduced the fluid absorption and WVTR together with bio-adhesion of the prepared sponge dressings. Porosity of all sponges was more than 85% therefore resulting in their high OP. Enhancing hydrophobicity of the material by Alst and more homogeneity caused by NMP eventually retarded the asiaticoside release for 7 days. The

risk factors for wound dehiscence

African Journals Online (AJOL)

group B included 17 patients (minor wound dehiscence,. 26.98%), and group C ... Conclusion With regard to the wound complications following the repair of .... appear to add extra protection for wound healing. (Table 1). Median time to ...

Modeling of anisotropic wound healing

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Valero, C.; Javierre, E.; García-Aznar, J. M.; Gómez-Benito, M. J.; Menzel, A.

2015-06-01

Biological soft tissues exhibit non-linear complex properties, the quantification of which presents a challenge. Nevertheless, these properties, such as skin anisotropy, highly influence different processes that occur in soft tissues, for instance wound healing, and thus its correct identification and quantification is crucial to understand them. Experimental and computational works are required in order to find the most precise model to replicate the tissues' properties. In this work, we present a wound healing model focused on the proliferative stage that includes angiogenesis and wound contraction in three dimensions and which relies on the accurate representation of the mechanical behavior of the skin. Thus, an anisotropic hyperelastic model has been considered to analyze the effect of collagen fibers on the healing evolution of an ellipsoidal wound. The implemented model accounts for the contribution of the ground matrix and two mechanically equivalent families of fibers. Simulation results show the evolution of the cellular and chemical species in the wound and the wound volume evolution. Moreover, the local strain directions depend on the relative wound orientation with respect to the fibers.

Enzymatic wound debridement; role of papaya in the management of post cesarean gaped wounds

International Nuclear Information System (INIS)

Nisa, M.U.

2012-01-01

Background: Enzymatic wound debridement is an emerging concept in facilitating the wound healing process. Papaya has de-sloughing, antibacterial and wound healing properties. It has been used in African countries since centuries for different medicinal pur-poses. Apart from anecdotal reports and few studies on chronic ulcers and burns, no planned studies are available to support its action in postoperative wound infection.Objectives: To compare efficacy and safety of papaya dressing with conventional wound dressing with povidone iodine in post cesarean section gaped wounds. Setting: Gynecology Unit 3, Sir Ganga Ram Hospital Lahore - Pakistan, over a period of six months(June 2012 to Nov 2012). Study Design: Randomized, quasi experimental stu-dy. Materials and Methods: The study sample included 60 patients with post cesarean section gaped wounds. The sample was divided into two groups; thirty patients as Group A or the study group received Papaya dressing and rest of thirty patients as Group B or the control group received Povidone iodine dressing. Wounds were thoroughly washed with saline and then mashed unripe papaya was spread over the whole area of wound in the study group and povidone iodine in the control group. Wounds were covered with sterile bandage for at least 48 hours in study group and 24 hours in the control group. The process was repeated till a clean base of wound with healthy granulation tis-sue was achieved suitable for secondary suture. The efficacy parameters studied were the duration of time needed to develop healthy granulation tissue and total duration of hospital stay which were compared bet-ween the two groups. Safety factors studied were the adverse effects of medications used in the study. Results: Out of 1200 cesarean sections done during study period, sixty (5%) were gaped in the post-operative period. Out of 60, 55 (90%) were emergency and only 5 (10%) were elective cesarean sections. All the sixty patients with postoperative gaped

Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

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Moris Topaz

2012-01-01

Full Text Available Regulated negative pressure-assisted wound therapy (RNPT should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound′s environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.