Prolonged Inflammatory Phase Research Articles

An Immunoregulatory and Metabolism-Improving Injectable Hydrogel for Cardiac Repair After Myocardial Infarction

Abstract The hypoxia microenvironment post myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff-base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), following by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity via pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats’ infarcted cardiac, the 28 day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.

Composite Polysaccharide Hydrogel Loaded with Scutellaria baicalensis Extract for Diabetic Wound Treatment.

Diabetic wounds present significant burdens to both patients and the healthcare system due to their prolonged inflammatory phase and adverse microenvironment. Traditional Chinese medicine (TCM), particularly Scutellaria baicalensis extract (SE), has shown promise in wound healing. Herein, sesbania gum (SG) was oxidized and formed hydrogel with carboxymethyl chitosan (CMCS) through the imine bond. Then, SE was loaded into the hydrogel as a wound dressing (CMCS-OSG@SE hydrogel). In vitro experiments demonstrated the mechanical properties and ROS scavenging efficiency of the hydrogel, as well as the release of SE and its biocompatibility. In an vivo study, diabetic mice with S. aureus infection were used, and the CMCS--OSG@SE hydrogel dressing accelerated wound healing by promoting epidermal regeneration and collagen deposition. This composite polysaccharide hydrogel loaded with SE shows great potential for diabetic wound treatment.

A Randomized, Placebo-controlled, Double-blind Clinical Trial of Bacteriophage Cocktails in Chronic Wound Infections.

Chronic wounds are prevalent globally at endemic proportions. The common features associated with chronic wounds are prolonged inflammatory phase, infection with multidrug-resistant (MDR) bacteria, and subsequent biofilm formation. The present randomized-controlled trial (RCT) study was undertaken on chronic wounds of ≥6 weeks longer duration using customized phages to evaluate the efficacy and safety of bacteriophage therapy. The study was conducted from December 2021 to August 2023. Thirty patients in each of the arms (placebo and bacteriophage) were recruited with chronic wounds. The patients, both arms, received the conventional treatment of wound debridement, local antiseptics, and local and systemic antibiotics at the discretion of the treating surgeon. However, before applying the customized bacteriophage cocktail or placebo, the wound surface was thoroughly washed to remove the residual antiseptics. The phage cocktails or placebo were applied on alternate days. The wounds were evaluated using the Bates-Jensen Wound Assessment Tool for the progress of wound healing. A total of 93.3% of the wound became sterile in 39 days (median sterility time), followed by complete healing by the end of 90 days in the phage group. Contrary to this, 83.3% of those on placebo therapy remained colonized by original bacteria or additional new bacteria without healing for up to 90 days. With the well-designed RCT, we could conclude that customized bacteriophage therapy using bacteriophage cocktails will definitely cure the chronic wound, irrespective of age, sex, diabetes status, and infection by MDR bacteria.

In silico screening of phytoconstituents as potential anti-inflammatory agents targeting NF-κB p65: an approach to promote burn wound healing

Chronic burn wounds are frequently characterised by a prolonged and dysregulated inflammatory phase that is mediated by over-activation of NF-κB p65. Synthetic wound healing drugs used for treatment of inflammation are primarily associated with several shortcomings which reduce their therapeutic index. In this scenario, phytoconstituents that exhibit multifaceted biological activities including anti-inflammatory effects have emerged as a promising therapeutic alternative. However, identification and isolation of phytoconstituents from medicinal herbs is a cumbersome method that is linked to profound uncertainty. Hence, present study aimed to identify prospective phytoconstituents as inhibitors of RHD of NF-κB p65 by utilizing in silico approach. Virtual screening of 2821 phytoconstituents was performed against protein model. Out of 2821 phytoconstituents, 162 phytoconstituents displayed a higher binding affinity (≤ −8.0 kcal/mol). These 162 phytoconstituents were subjected to ADMET predictions, and 15 of them were found to satisfy Lipinski’s rule of five and showed favorable pharmacokinetic properties. Among these 15 phytoconstituents, 5 phytoconstituents with high docking scores i.e. silibinin, bismurrayaquinone A, withafastuosin B, yuccagenin, (+)-catechin 3-gallate were selected for molecular dynamics (MD) simulation analysis. Results of MD simulation indicated that withafastuosin B, (+)-catechin 3-gallate and yuccagenin produced a compact and stable complex with protein without significant variations in conformation. Relative binding energy analysis of best hit molecules indicate that withafastuosin B, and (+)-catechin 3-gallate exhibit high binding affinity with target protein among other lead molecules. Findings of study suggest that these phytoconstituents could serve as promising anti-inflammatory agents for treatment of burn wounds by inhibiting the RHD of NF-κB p65. Communicated by Ramaswamy H. Sarma

In situ photo-crosslinking silk fibroin based hydrogel accelerates diabetic wound healing through antibacterial and antioxidant

Bacterial infection and excessive reactive oxygen species (ROS) in diabetic wounds lead to a prolonged inflammatory phase, and injuries are highly susceptible to developing into chronic wounds. Improving the poor microenvironment is vital to achieving effective diabetic wound healing. In this work, methacrylated silk fibroin (SFMA) was combined with ε-polylysine (EPL) and manganese dioxide nanoparticles (BMNPs) to form an SF@(EPL-BM) hydrogel with in situ forming, antibacterial and antioxidant properties. EPL imparted high antibacterial activity (>96 %) to the hydrogel. BMNPs and EPL showed good scavenging activity against a variety of free radicals. SF@(EPL-BM) hydrogel had low cytotoxicity and could alleviate H2O2-induced oxidative stress in L929 cells. In diabetic wounds infected with Staphylococcus aureus (S. aureus), the SF@(EPL-BM) hydrogel exhibited better antibacterial properties and reduced wound ROS levels more significantly than that of the control in vivo. In this process, the pro-inflammatory factor TNF-α was down-regulated, and the vascularization marker CD31 was up-regulated. H&E and Masson staining showed a rapid transition from the inflammatory to the proliferative phase of the wounds, with significant new tissue and collagen deposition. These results confirm that this multifunctional hydrogel dressing holds well potential for chronic wound healing.

All-Natural Immunomodulatory Bioadhesive Hydrogel Promotes Angiogenesis and Diabetic Wound Healing by Regulating Macrophage Heterogeneity.

Macrophages are highly heterogeneous and exhibit a diversity of functions and phenotypes. They can be divided into pro-inflammatory macrophages (M1) and anti-inflammatory macrophages (M2). Diabetic wounds are characterized by a prolonged inflammatory phase and difficulty in healing due to the accumulation of pro-inflammatory (M1) macrophages in the wound. Therefore, hydrogel dressings with macrophage heterogeneity regulation function hold great promise in promoting diabetic wound healing in clinical applications. However, the precise conversion of pro-inflammatory M1 to anti-inflammatory M2 macrophages by simple and biosafe approaches is still a great challenge. Here, an all-natural hydrogel with the ability to regulate macrophage heterogeneity is developed to promote angiogenesis and diabetic wound healing. The protocatechuic aldehyde hybridized collagen-based all-natural hydrogel exhibits good bioadhesive and antibacterial properties as well as reactive oxygen species scavenging ability. More importantly, the hydrogel is able to convert M1 macrophages into M2 macrophages without the need for any additional ingredients or external intervention. This simple and safe immunomodulatory approach shows great application potential for shortening the inflammatory phase of diabetic wound repair and accelerating wound healing.

Evaluation of in vitro anti-inflammatory effect of PLAY® on UC-MSCs: A COX-2 expression study

Wound healing is an intricate process consisting of multiple phases, each of which is indispensable for requisite tissue repair. Timely initiation and resolution of each overlapping phase is critical in aiding the wound healing cascade. A prolonged inflammatory phase causes overexpression of proteolytic mediators, resulting in extracellular matrix (ECM) degradation and increased oxidative stress. This imbalance in inflammatory mediators, ECM degradation, and upregulated levels of reactive oxygen species retards cell proliferation and migration, resulting in delayed tissue repair and the development of chronic wounds. Cyclooxygenase-2 (COX-2) is a potent inflammatory mediator that plays a pivotal role in the wound healing process at different stages of the tissue repair cascade. Overexpression of COX-2 during the tissue repair process impairs the wound healing cascade and contributes to the formation of chronic wounds. PLAY® is an in-house product of International Stem Cell Services Limited (iCREST) that is a human blood-platelet cocktail of natural growth factors and bioactive modulators. In our study, we hypothesized that PLAY® decreases inflammation in phorbol myristate acetate (PMA)- and 5-fluorouracil (5-FU)- stimulated umbilical cord derived mesenchymal stem cells (UC-MSCs) by downregulating COX-2 expression to its basal levels. We used an experimentally induced inflammatory in vitro model to produce enhanced COX-2 expression in mesenchymal stem cells (MSCs) and PLAY® showed a significant decrease in COX-2 levels in PMA induced UC-MSCs, providing evidence for an innate anti-inflammatory effect of PLAY® and a potential role in accelerated wound healing.

579 Clinical grade human pluripotent stem cells derived engineered skin substitutes promote keratinocytes wound closure in vitro

Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as consequence of a prolonged inflammatory phase during the healing process. They are extremely hard to heal and persist as a significant health care problem due to the absence of effective treatment and the uprising number of patients. Indeed, there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds. Development in skin engineering leads to a small catalogue of available substitute manufactured in Good Manufacturing Practices compliant (GMPc) conditions. Those substitutes are produced using primary cells that could limit their use due to restricted sourcing. Here, we propose GMPc protocols to produce functional populations of keratinocytes and fibroblasts derived from pluripotent stem cells to reconstruct the associated dermo-epidermal substitute with plasma based fibrin matrix. In addition, this manufactured composite skin is biologically active and enhances in vitro wounding of keratinocytes. The proposed composite skin open new perspectives for skin replacement using allogeneic substitute.

Recent Advancement of Functional Hydrogels toward Diabetic Wound Management.

Wound healing is a dynamic, orchestrated process comprising partially overlapping phases of hemostasis, inflammation, proliferation, and remodeling. This programmed process, dysregulated in diabetic individuals, results in chronic diabetic wounds. The normal process of healing halts at the inflammatory stage, and this prolonged inflammatory phase is characteristic of diabetic wounds. There are a few U.S. Food & Drug Administration approved skin substitutes; dermal matrixes are commercially available to manage diabetic wounds. However, expensiveness and nonresponsiveness in a few instances are the major limitations of such modalities. To address the issues, several treatment strategies have been exploited to treat chronic wounds; among them hydrogel-based systems showed promise due to favorable properties such as excellent absorption capabilities, porous structure, tunable mechanical strength, and biocompatibility. In the past two decades, hydrogels have become one of the most acceptable systems in the field of wound dressing material, offering single functionality to multifunctionality. This review focuses on the advancement of functional hydrogels explored for diabetic wound management. The process of diabetic wound healing is discussed in the light of the normal healing process, and the role of macrophages in the process is explained. This review also discusses the different approaches to treat diabetic wounds using functional hydrogels, along with their future opportunities.

Ionic liquid-based non-releasing antibacterial, anti-inflammatory, high-transparency hydrogel coupled with electrical stimulation for infected diabetic wound healing

Bacterial colonization , prolonged inflammatory phase , angiogenesis difficulties, collagen deposition deficiency, and other serious complications can impede the infected wound repair process, particularly for infected wounds of diabetic patients. Electrical stimulation (ES), as an attractive emerging therapy, has been widely carried out for promoting skin regeneration. Herein, we constructed a conductive antibacterial multifunctional hydrogel combined with exogenous ES as a strategy for Staphylococcus aureus -infected wound healing. The hydrogel is composed of an ionic liquid (1-Vinyl-3-butylimidazolium bromide, [VBIM]Br) polymer network and a polyvinyl alcohol (PVA)-borax dynamic borate network. The [VBIM]Br conferred the hydrogel with excellent electrical conductivity to favor the introduction of ES therapy for wound healing. Moreover, the ionic liquid polymer network endowed the hydrogel with anti-bacterial abilities to kill bacteria, anti-inflammatory capacities to shorten the inflammation period, high transparency to observe the healing process, and excellent protein absorption ability. The dynamic borate bonds in the PVA network provided the hydrogel with self-healing and tissue adhesion properties. Furthermore, the [VBIM]Br composite hydrogel coupled with exogenous ES promoted cell proliferation , migration, angiogenesis, and collagen deposition, which demonstrated great potential in chronic diabetic infected wound repair. • Dual-network triple-crosslinked hydrogel with multifunction is prepared and characterized. • Hydrogel exhibits excellent conductivity, antibacterial, anti-inflammatory, and high-transparency properties. • Hydrogel combined with ES promotes infected wound healing in the diabetic rat model. • This study provides a promising and effective strategy for infected diabetic wound management.

Clinical Grade Human Pluripotent Stem Cell-Derived Engineered Skin Substitutes Promote Keratinocytes Wound Closure In Vitro.

Chronic wounds, such as leg ulcers associated with sickle cell disease, occur as a consequence of a prolonged inflammatory phase during the healing process. They are extremely hard to heal and persist as a significant health care problem due to the absence of effective treatment and the uprising number of patients. Indeed, there is a critical need to develop novel cell- and tissue-based therapies to treat these chronic wounds. Development in skin engineering leads to a small catalogue of available substitutes manufactured in Good Manufacturing Practices compliant (GMPc) conditions. Those substitutes are produced using primary cells that could limit their use due to restricted sourcing. Here, we propose GMPc protocols to produce functional populations of keratinocytes and fibroblasts derived from pluripotent stem cells to reconstruct the associated dermo-epidermal substitute with plasma-based fibrin matrix. In addition, this manufactured composite skin is biologically active and enhances in vitro wounding of keratinocytes. The proposed composite skin opens new perspectives for skin replacement using allogeneic substitute.

The Role of Hemodynamic Shear Stress in Healing Chronic Wounds

Wounds continue to pose significant challenges to clinicians. Data based on randomized controlled trials from the US Wound Registry showed that less than 50% of wounds heal in an unpredictable period of time. Chronic wounds are difficult to heal, with multiple barriers to healing that include inadequate nutrient flow, an inflammatory-coagulation vicious cycle, redox imbalance, and anatomical, physiological, and biochemical dysfunction in the endothelium. In clinical practice, wounds that fail to heal within an appropriate time are at higher risk for deterioration as well as development of infection that further complicates the pathology. Wounds complicated by deep abscess and osteomyelitis often result in amputation. Higher level amputations, below the knee and above the knee, are associated with increased morbidity and mortality rates. However, the most consequential barrier to healing is the prolonged inflammatory phase, which prevents progression to the proliferation phase of wound healing. Diabetic foot ulcers are especially difficult to heal because of angiopathy, hypoxia and ischemia, AGEs, and other factors related to impaired hemodynamics. Restoration of physiological levels of blood flow to DFUs will concomitantly bring about normalization of laminar SS on the endothelium. These multifaceted healing mechanisms, specifically related to the effects of vascular SS on the endothelium, are reviewed here. Such mechanisms involve anti-inflammation, anticoagulation, antioxidation, vasodilation, and angiogenesis. A concluding inference is made that if normalized SS could be produced in the vasculature serving chronic wounds, the sequential healing processes would be enhanced.

The impact of acetylcholinesterase inhibitors on ileus and gut motility following abdominal surgery: a clinical review.

Postoperative ileus is a common complication in the days following colorectal surgery occurring in up to 50% of patients. When prolonged, this complication results in significant morbidity and mortality, doubling the total costs of hospital stay. Postoperative ileus (POI) results from the prolonged inflammatory phase that is mediated in part by the cholinergic anti-inflammatory pathway. Acetylcholinesterase inhibitors, such as neostigmine and pyridostigmine, delay the degradation of acetylcholine at the synaptic cleft. This increase in acetylcholine has been shown to increase gut motility. They have been effective in the treatment of acute colonic pseudo-obstruction, but there is limited evidence for the use of these medications for reducing the incidence of POI. This review was conducted to summarise the evidence of acetylcholinesterase inhibitors' effect on gut motility and discuss their potential use as part of an enhanced recovery protocols to prevent or treat POI.

A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes

Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1β and IL-6), enhanced anti-inflammatory factors (TGF-β1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.

Nanomaterials Versus The Microbial Compounds With Wound Healing Property

Age and diabetes related slow-healing or chronic wounds may result in morbidity and mortality through persistent biofilms infections and prolonged inflammatory phase. Nano-materials [metal/metal oxide NPs (39%), lipid vehicles (21%), polymer NPs (19%), ceramic nanoparticles (NPs) (14%), and carbon nanomaterials (NMs) (7%)] can be introduced as a possible next-generation therapy because of either their intrinsic wound healing activity or via carrying bioactive compounds including, antibiotics, antioxidants, growth factor or stem cell. The nanomaterials have been shown to implicate in all four stages of wound healing including hemostasis (polymer NPs, ceramic NPs, nanoceria-6.1%), inflammation (liposome/vesicles/solid lipid NPs/polymer NPs/ceramic NPs/silver NPs/gold NPs/nanoceria/fullerenes/carbon-based NPs-32.7%), proliferation (vesicles/liposome/solid lipid NPs/gold NPs/silver NPs/iron oxide NPs/ceramic NPs/copper NPs/self-assembling elastin-like NPs/nanoceria/micelle/dendrimers/polymer NPs-57.1%), remodeling (iron oxide NPs/nanoceria-4.1%). Natural compounds from alkaloids, flavonoids, retinoids, volatile oil, terpenes, carotenoids, or polyphenolic compounds with proven antioxidant, anti-inflammatory, immunomodulatory, or antimicrobial characteristics are also well known for their potential to accelerate the wound healing process. In the current paper, we survey the potential and properties of nanomaterials and microbial compounds in improving the process of wound and scar healing. Finally, we review the potential biocompounds for incorporation to nano-material in perspective to designate more effective or multivalent wound healing natural or nano-based drugs.

The beneficial activity of curcumin and resveratrol loaded in nanoemulgel for healing of burn-induced wounds

Burns are complicated wounds characterized by prolonged and persistent inflammatory phase. The combination of nutraceuticals in nano-delivery systems is hypothesized to enhance therapeutic efficacy and achieve better healing outcome. In this regard, we investigated the combination of two polyphenols; curcumin and resveratrol, in a nanoemulsion based gel system (nanoemulgel). The ex-vivo skin deposition of the prepared nanoemulgels was measured, and their in-vivo burn healing potential was tested in rat-burn induced model by measurement of inflammatory markers, oxidative stress markers, amino acids and vitamin E levels, in addition to histopathological examination. The particle size of the nanoemulsions ranged from 167 to 180 nm with PDI less than 0.4 and negative zeta potential (−17 to −20 mV). Remarkable retention of the nutraceuticals in the skin when loaded alone or combined in nanoemulgels, reaching ≈60% of the applied dose was shown after 48 h. In vivo results proved the better burn healing outcome of the nanoemulgel formulation combining both curcumin and resveratrol, with histopathological features similar to normal control skin. Findings delineated the augmented burn healing potential of the nutraceuticals combination, and the promising delivery traits of the nanoemulgel dosage form, which can be further exploited with other nutraceuticals combinations.

A Concise Review on Tissue Engineered Artificial Skin Grafts for Chronic Wound Treatment: Can We Reconstruct Functional Skin Tissue In Vitro?

Chronic wounds occur as a consequence of a prolonged inflammatory phase during the healing process, which precludes skin regeneration. Typical treatment for chronic wounds includes application of autografts, allografts collected from cadaver, and topical delivery of antioxidant, anti-inflammatory, and antibacterial agents. Nevertheless, the mentioned therapies are not sufficient for extensive or deep wounds. Moreover, application of allogeneic skin grafts carries high risk of rejection and treatment failure. Advanced therapies for chronic wounds involve application of bioengineered artificial skin substitutes to overcome graft rejection as well as topical delivery of mesenchymal stem cells to reduce inflammation and accelerate the healing process. This review focuses on the concept of skin tissue engineering, which is a modern approach to chronic wound treatment. The aim of the article is to summarize common therapies for chronic wounds and recent achievements in the development of bioengineered artificial skin constructs, including analysis of biomaterials and cells widely used for skin graft production. This review also presents attempts to reconstruct nerves, pigmentation, and skin appendages (hair follicles, sweat glands) using artificial skin grafts as well as recent trends in the engineering of biomaterials, aiming to produce nanocomposite skin substitutes (nanofilled polymer composites) with controlled antibacterial activity. Finally, the article describes the composition, advantages, and limitations of both newly developed and commercially available bioengineered skin substitutes.

THE EFFECT OF EXTRACT FROM PLEROCERCOIDS OF GULL-TAPEWORM DIBOTHRIOCEPHALLUS DENDRITICUS ON WOUND HEALING IN MICE

In this work, the wound healing potential of the extract from plerocercoids of gulltapeworm D. dendriticus was first estimated in the mouse full-thickness wound model. Both the evaluation of wound closure rate and the histological characteristics of the healing process were performed. In the course of the study, the effect of the extract on contraction and epithelization of wound was not revealed. At the same time, the results of histological analysis showed that the epidermis in the group of mice whose wounds were treated with the extract was less differentiated, and the newly formed connective tissue was less mature than in the group of control animals. In addition, differences were found in the composition of leukocyte infiltrate in the granulation tissue of experimental animals – there was a significant increase in the number of eosinophils and a tendency to a lower content of neutrophils. The results obtained indicate that treatment of wounds with extract from plerocercoids slows down the reparative processes, which, however, does not lead to significant changes in the rate of wound contraction. Perhaps, this difference is due to a change in the early stages of healing: extract stimulates eosinophils migration to the area of damage, while the number of neutrophils decreases. This can lead to a prolonged inflammatory phase and the associated slowdown in repair.

Human beta defensins may be a multifactorial modulator in the management of diabetic wound.

Diabetic wound (DW) is considered as one of the serious complications associated with diabetes mellitus. Though some pharmacological approaches are available for managing DW, none of them has been reported to be very effective. Widely accepted options for its management include treatment of infection caused by various pathogens, wound debridement, reducing the period of the prolonged inflammatory phase, and supervision of the remodeling phase of wound healing. Satisfactory management of DW thus requires exploring new avenues for finding a potential therapeutic strategy. Literature shows that human beta defensins (HBDs) help in combating the insulin resistance by inhibiting the production of glucocorticoids, reducing chronic inflammation by acting through Toll-like receptor signaling pathway, and provoking cell migration, proliferation, angiogenesis, and stabilization of fibroblasts and keratinocytes, ultimately resulting in wound closure. In the present review, beneficial role of HBDs in the treatment of DW is discussed in detail.

WOUND HEALING PROPERTIES OF PURANA GHRITA WITH SPECIAL REFERENCE TO NON-HEALING DIABETIC ULCER- A case Study

Diabetic foot ulcer (DFU) is one of the major complications found in 15% of diabetics. It significantly reduces the quality of life. In DFU there is a prolonged inflammatory phase, delayed mature granulation tissue formation and reduction in wound tensile strength. The recommended line of treatment as per modern medicine includes Blood sugar control, removal of dead tissue & Wound dressing.According to Charak Samhita, Prameha Pidaka are caused due to upeksha (neglect) of underlying Prameha. Prameha Pidaka are of darun type and have 7 subtypes. Purana Ghrita plays significant role in wound healing in non-healing diabetic ulcer.Objective: To study the effect of Purana Ghrita in non-healing diabetic ulcer.Methods: In the case presented here, a male patient aged 70 years with type 2 diabetes, was admitted in the hospital for 2 months for the treatment of Non- healing diabetic ulcer on the sole of left foot. Allopathy treatment did not give desired results. Hence after 2 months of admittance, Ayurvedic treatment was introduced for DFU. Dressing of wound was done by mixture of Purana Ghrita, honey, Triphala Churna and Haridra Churna along with the dressing, Rasapachak, Raktapachak, Mansapachak, Gudmaradi vati, Aarogyavardhini vati & Sanjivani guti were used internally at different times. Result and Conclusion: With above mentioned treatment the non-healing diabetic ulcer healed and the patient was discharged after 30 days.Purana Ghrita has Vrana nashak qualities. It cleanses as well as heals i.e. it has Shodhan and Ropan properties.