Diabetic Wound Research Articles

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

A nature-based solution for regulating the inflammatory phase of diabetic wound healing using a cold atmospheric plasma

A nature-based solution for regulating the inflammatory phase of diabetic wound healing using a cold atmospheric plasma

Functionalised Sodium-Carboxymethylcellulose-Collagen Bioactive Bilayer as an Acellular Skin Substitute for Future Use in Diabetic Wound Management: The Evaluation of Physicochemical, Cell Viability, and Antibacterial Effects.

The wound healing mechanism is dynamic and well-orchestrated; yet, it is a complicated process. The hallmark of wound healing is to promote wound regeneration in less time without invading skin pathogens at the injury site. This study developed a sodium-carboxymethylcellulose (Na-CMC) bilayer scaffold that was later integrated with silver nanoparticles/graphene quantum dot nanoparticles (AgNPs/GQDs) as an acellular skin substitute for future use in diabetic wounds. The bilayer scaffold was prepared by layering the Na-CMC gauze onto the ovine tendon collagen type 1 (OTC-1). The bilayer scaffold was post-crosslinked with 0.1% (w/v) genipin (GNP) as a natural crosslinking agent. The physical and chemical characteristics of the bilayer scaffold were evaluated. The results demonstrate that crosslinked (CL) groups exhibited a high-water absorption capacity (>1000%) and an ideal water vapour evaporation rate (2000 g/m2 h) with a lower biodegradation rate and good hydrophilicity, compression, resilience, and porosity than the non-crosslinked (NC) groups. The minimum inhibitory concentration (MIC) of AgNPs/GQDs presented some bactericidal effects against Gram-positive and Gram-negative bacteria. The cytotoxicity tests on bilayer scaffolds demonstrated good cell viability for human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Therefore, the Na-CMC bilayer scaffold could be a potential candidate for future diabetic wound care.

Identifying the molecular mechanisms of action of wound healing properties of Mathan tailam and Mahamegarajanga tailam in Wistar albino rats: Evidence through IL-10/VEGF/TNF-α signalling pathways

The Siddha system of medicine (SSM) is the oldest medical science practised in the ancient period of the southern part of India and Sri Lanka. Many formulations were described for wound healing in the SSM, with specific diagnostic differentiation in the Siddha literature. Most preparations for wound healing were available in the form of oil-based formulations, especially for external usage. Mathan tailam (MT) and Mahamegarajanga tailam (MMRT) have been used by Siddha physicians and traditional practitioners to treat wounds. Mathan tailam is a popular regimen for skin lacerations, burns, skin infections, diabetic wounds, and dermatitis. Mahamegarajanga tailam has long been used by traditional vaidyars to treat cuts and burns. Both MT and MMRT are clinically well-appreciated drugs for wound healing and need to be studied for their mechanisms of action for scientific documentation. In an in vivo study on albino rats -excisional wound model, the histopathological changes, histo-immune response, biomarker analysis, and mRNA expression were studied and analysed. Wounds treated with MT and MMRT healed faster (p < 0.05) than the untreated group (CNT). Histological investigation showed rapid re-epithelialization, dense collagen deposition, increased enzymatic antioxidant activities and decreased lipid peroxidation in the MT and MMRT groups. mRNA expression reveals MT and MMRT-treated tissues able to induce convergent cell motility in wound space. Our study for the first time provides strong in vivo experimental evidence that Mathan tailam and Mahamegarajanga tailam play a crucial role in promoting skin tissue wound healing through IL-6/VEGF/TNF-α mediated mechanisms. Traditional practices continue to teach us valuable lessons, as seen by their continuous use in their locality for years.

Structurally Oriented Carbon Dots as ROS Nanomodulators for Dynamic Chronic Inflammation and Infection Elimination.

The selective elimination of cytotoxic ROS while retaining essential ones is pivotal in the management of chronic inflammation. Co-occurring bacterial infection further complicates the conditions, necessitating precision and an efficacious treatment strategy. Herein, the dynamic ROS nanomodulators are rationally constructed through regulating the surface states of herbal carbon dots (CDs) for on-demand inflammation or infection elimination. The phenolic OH containing CDs derived from honeysuckle (HOCD) and dandelion (DACD) demonstrated appropriate redox potentials, ensuring their ability to scavenge cytotoxic ROS such as ·OH and ONOO-, while invalidity toward essential ones such as O2·-, H2O2, and NO. This enables efficient treatment of chronic inflammation without affecting essential ROS signal pathways. The surface C-N/C═N of CDs derived from taxus leaves (TACD) and DACD renders them with suitable band structures, facilitating absorption in the red region and efficient generation of O2·- upon light irradiation for sterilization. Specifically, the facilely prepared DACD demonstrates fascinating dynamic ROS modulating ability, making it highly suitable for addressing concurrent chronic inflammation and infection, such as diabetic wound infection. This dynamic ROS regulation strategy facilitates the realization of the precise and efficient treatment of chronic inflammation and infection with minimal side effects, holding immense potential for clinical practice.

Human adipose‐derived multipotent stromal cells enriched with IL‐10 modRNA improve diabetic wound healing: Trigger the macrophage phenotype shift

AbstractDiabetic wounds present a significant challenge in regenerative medicine due to impaired healing, characterized by prolonged inflammation and deficient tissue repair, primarily caused by a skewed pro‐inflammatory macrophage phenotype. This study investigates the therapeutic potential of interleukin‐10 (IL‐10) chemically modified mRNA (modRNA)‐enriched human adipose‐derived multipotent stromal cells (hADSCs) in a well‐established murine model of diabetic wounds. The modRNAs used in this study were chemically modified using N1‐methylpseudouridine‐5′‐triphosphate (m1Ψ) by substituting uridine‐5‐triphosphate. In vitro experiments demonstrated that IL‐10 modRNA‐transfected hADSCs effectively modulated macrophage polarization towards an anti‐inflammatory phenotype. In vivo experiments with a well‐established murine model demonstrated that transplantation of hADSCsmodIL‐10 on postoperative day 5 (POD5) significantly improved wound healing outcomes, including accelerated wound closure, enhanced re‐epithelialization, promoted M2 polarization, improved collagen deposition, and increased neovascularization. This study concludes that IL‐10 modRNA‐enriched hADSCs offer a promising therapeutic approach for diabetic wound healing, with the timing of IL‐10 administration playing a crucial role in its effectiveness. These cells modulate macrophage polarization and promote tissue repair, demonstrating their potential for improving the management of diabetic wounds.

Oxygen-Propelled Dual-Modular Microneedles with Dopamine-Enhanced RNA Delivery for Regulating Each Stage of Diabetic Wounds.

Diabetic wounds are characterized by the disruption and cessation of essential healing stages, which include hemostasis, inflammation, proliferation, and remodeling. However, traditional treatments for diabetic wounds concentrate on individual stages of the healing process. Herein, this study utilizes mask-mediated sequential polymerization and varied cross-linking techniques to develop dual-modular microneedles (MNs) with fast- and slow-module, exhibiting varying degradation rates tailored for the full spectrum of diabetic wound healing. First, MNs incorporating calcium ions and dopamine synergistically promote rapid hemostasis. Second, fast-module physically cross-linked MNs rapidly D-mannose/dopamine-enhanced tripolyphosphate-quaternized chitosan (mDTC) nanoparticles (NPs) loaded with microRNA-147 (miRNA-147) to manage inflammation and oxidative stress in diabetic wounds. Additionally, dopamine in these NPs enhances their internalization and safeguards miRNA-147 from oxidative stress and RNase degradation. Finally, slow-module chemically cross-linked MNs facilitate the continuous release of deferoxamine (DFO) and dopamine, accelerating angiogenesis and tissue regeneration during the proliferation and remodeling stages. Manganese/dopamine-enhanced calcium peroxide NPs within the MNs initiate a blast-like generation of oxygen bubbles, not only enhancing the delivery of miRNA-mDTC NPs and DFO but also alleviating tissue hypoxia. Consequently, dual-modular MNs are instrumental in promoting rapid and complete healing of diabetic wounds through all stages of healing.

Advancing self‐healing soy protein hydrogel with dynamic Schiff base and metal‐ligand bonds for diabetic chronic wound recovery

AbstractTo address the unique challenges of diabetic wound healing, wound dressings, particularly multifunctional hydrogels have garnered considerable interest. For the first time, a novel environmentally friendly soy protein‐based hydrogel is developed to accelerate the healing of diabetic chronic wounds. Specifically, this hydrogel framework is in direct formation through the dynamic Schiff base between oxidized guar gum and epigallocatechin‐3‐gallate (EGCG)‐modified soy protein isolate. Meantime, the addition of Ag+ enhances the cross‐linking of the hydrogel network by forming metal‐ligand bonds with the catechol groups in EGCG. Interestingly, the stretchability (up to 380%), swelling, and rheology properties of the hydrogel can be controlled by fine‐tuning the density of metal‐ligand bonds, endowing them with a high potential for precise matching. Additionally, various dynamic bonds endow hydrogel with excellent self‐healing ability, adhesiveness, and injectability. This hydrogel also exhibits good antibacterial properties, biocompatibility, and cell migration capabilities. Both in vivo and in vitro experiments demonstrated the outstanding anti‐inflammatory capacity of the hydrogel and its ability to modulate macrophage polarization. Consequently, the hydrogel has proven effective in promoting wound healing in a diabetic full‐thickness wound model through enhanced angiogenesis and collagen deposition. This eco‐friendly plant protein hydrogel offers a sustainable solution for wound care and environmental protection.

Elastic Nanofibrous Dressings with Mesenchymal Stem Cell-Recruiting and Protecting Characteristics for Promoting Diabetic Wound Healing.

Diabetic wounds that do not heal for a long time challenge global healthcare. Mesenchymal stem cell (MSC) therapy has positive significance in promoting diabetic wound healing. However, traditional MSC therapy involves exogenous MSCs, which brings many limitations and unsatisfactory treatment. Moreover, the maintenance of MSC viability and function is difficult because of the high level of reactive oxygen species (ROS) in diabetic wounds. Therefore, we developed a nanofibrous dressing to recruit and protect endogenous MSCs while avoiding the inherent disadvantages of exogenous MSCs. Ceria nanoparticles capable of ROS scavenging are integrated into the nanofibrous dressings, together with Apt19S, a DNA aptamer with affinity and selectivity for MSCs. In addition, the homogenization and freeze-drying technology give the nanofibrous dressings good elasticity, which protects the wound from external pressure. Further experiments in diabetic mice show that the dressing has excellent endogenous MSC recruitment and anti-inflammatory properties, thereby synergistically promoting diabetic wound healing. This study is expected to explore an efficient method of stem cell therapy, providing a new way to construct high-performance wound dressings.

Cuttlefish ink-derived melanin nanoparticle-embedded tremella fuciformis polysaccharide hydrogels for the treatment of MRSA-infected diabetic wounds

Diabetic wounds arise great attention as they are difficult to heal and easily suffer from serious bacterial infection. However, the overuse of antibiotics increases the resistance of bacteria and makes common drugs ineffective. Here, we developed a photothermal hydrogel (TFP/NP) composed of tremella fuciformis polysaccharides (TFPs) and cuttlefish ink-derived melanin nanoparticles (NPs). The NPs can produce reliable photothermal effects under near-infrared laser (NIR) irradiation and help to remove the bacteria in the wounds, while TFPs were able to form hydrogel frameworks which possessed anti-inflammatory effects and could be applied to promote wound healing. The TFP/NP hydrogels produced stable thermal effects under NIR irradiation and could continuously kill bacteria. The experiment on a full-layer skin wound sMRSA activity and could improve the healing efficiency. The wounds of the mice could be repaired within 14 days after reasonable treatment. In addition, the hydrogels play significant roles in promoting collagen deposition, anti-inflammation, angiogenesis, and cell proliferation during the therapeutic process. This research provides a simple and effective method for the therapy of bacterial infection wounds through the synergistic effect of TFPs and NPs.

Cerium dioxide nanozyme doped hybrid hydrogel with antioxidant and antibacterial abilities for promoting diabetic wound healing

Diabetic wounds are among the most severe chronic complications in patients with diabetes. Owing to the detrimental effects of high glucose and high levels of reactive oxygen species (ROS) in the wound microenvironment, diabetic wound healing is significantly challenging. To address the issues of elevated ROS levels and infection susceptibility in diabetic wounds, we designed a composite hydrogel system loaded with cerium dioxide nanoparticles (CeO2 NPs) and vancomycin. This hydrogel aimed to reshape the wound microenvironment by continuously consuming ROS and inhibiting infection. Experimental results demonstrated that the CeO2 NPs-loaded hydrogel demonstrated an 85.40% clearance rate of hydroxyl radicals (·OH) and achieved over 90% inhibition against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and effectively promoted the healing of diabetic mouse wounds. This cerium dioxide nanozyme hybrid hydrogel system can exert antioxidative and antibacterial effects and serve as a wound dressing to promote the healing of infected diabetic wounds.

Carbon dots-supported Zn single atom nanozymes for the catalytic therapy of diabetic wounds

Diabetic wound treatment continues to be a significant clinical issue due to higher levels of oxidative stress, susceptibility to bacterial infections, and chronic inflammatory responses during healing. We rationally developed and synthesized an ultra-small carbon dots (C-dots) loaded with zinc single-atom nanozyme (Zn/C-dots) with the aim of promoting wounds healing by nanocatalytic treatment, especially targeting its complex pathological microenvironment. Zinc single atoms and C-dots form a dual catalytic system with higher enzymatic activity. Furthermore, the Zn/C-dots nanozyme effectively enters cells, accumulates at mitochondria, and removes excess ROS, protecting cells from oxidative stress damage and limiting the release of pro-inflammatory cytokines, hence reducing inflammation. Zinc can synergistically increase the antibacterial action of C-dots (the effective antibacterial rate of 100 µg/mL Zn/C-dots was above 90 %). Unlike traditional C-dots, Zn/C-dots can cause endothelial cell migration and the formation of new blood vessels. In vitro cytotoxicity, blood compatibility, and in vivo toxicity studies of Zn/C-dots show that they are biocompatible. We subsequently utilized the Zn/C-dots nanozymes to treat diabetic rats' chronic wounds for external use, combining them with ROS-responsive hydrogels to create an antioxidative system (H-Zn/C-dots). The hydrogels anchored the Zn/C-dots nanozymes to the wound, allowing for long-term treatment. The results revealed that H-Zn/C-dots can considerably reduce inflammation, accelerate angiogenesis, collagen deposition, and promote tissue remodeling at the diabetic wound site. After 14 days, the wound area had decreased to approximately 9.19 %, making it a potential treatment. Statement of significanceAn ultra-small carbon dot with a zinc single-atom nanozyme was designed and manufactured. Zn/C-dots possess antibacterial, ROS-scavenging, and angiogenesis activities. In vivo, the multifunctional ROS-responsive hydrogel incorporating Zn/C-dots could speed up diabetic wound healing.

Salvianolic acid B improves diabetic skin wound repair through Pink1/Parkin-mediated mitophagy

Diabetic skin wound is a disturbing and rapidly evolving clinical issue. Here, we investigated how salvianolic acid B (Sal B) affected the diabetic wound healing process. Following Sal B administration, histopathological damage was investigated by H&E and Masson staining, and CD34, apoptosis and mitophagy markers were measured by immunofluorescence, immunohistochemistry, and western blotting. Migration, proliferation, and mitochondrial function of high glucose (HG) –induced HMEC-1 cells were measured. The effects of si-Parkin on endothelial cell migration, apoptosis and mitochondrial autophagy were examined. Sal B alleviated inflammatory cell infiltration and promoted angiogenesis in skin wound tissue. Apoptosis and mitophagy were ameliorated by Sal B in diabetic skin wound tissues and HG-induced HMEC-1 cells. Parkin inhibition impaired the migratorypromoted cell apoptosis and inhibited mitophagy of HMEC-1 cells. This finding demonstrated that Sal B promoted diabetic skin wound repair via Pink1/Parkin-mediated mitophagy, improved our understanding of the diabetic wound healing process.

Rhein-chitosan in situ hydrogel promotes wound healing in diabetic mice

Chronic inflammation and infection often lead to delayed healing in skin wounds of patients with diabetes, presenting a significant challenge in clinical wound repair. In an effort to tackle this issue, we explored the utilization of the natural compounds Rhein and chitosan in the creation of a crosslinked in situ gel. Developed as Rhein-chitosan in situ hydrogel (CS-Rh gel), this formulation has the ability to gel at body temperature, making it suitable for irregular wounds of varying shapes. Our experimental investigations have demonstrated its excellent biocompatibility, controlled release of Rhein, biodegradability, anti-inflammatory properties, antibacterial effect, as well as its ability to enhance keratinocyte proliferation and migration. Furthermore, in vivo studies have confirmed that CS-Rh gel can effectively mitigate tissue inflammation, promote collagen deposition, and significantly accelerate wound healing in diabetic mice within a short timeframe of two weeks. Consequently, this innovative approach holds promise as a viable therapeutic strategy for supporting the healing of diabetic wounds in a clinical setting.

A Natural deep eutectic solvent as an effective material for dual debridement and antibiofilm effects in chronic wound treatment

In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU’s debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU’s de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU’s efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.

Anthocyanidin-Loaded Superabsorbent Self-Pumping Dressings for Macrophage Immunomodulation and Diabetic Wound Healing.

Management of diabetic chronic wound exudate is a serious challenge in healthcare worldwide since it is related to the speed of diabetic wound healing. However, current foam dressings not only absorb fluid to generate swelling and compress the wound to hinder wound healing but also are very thick and less comfortable to use. Herein, a superabsorbent self-pumping ultrathin dressing is reported to accelerate diabetic wound healing by achieving superior exudate absorption and management in an ultrathin state. The self-pumping dressing is composed of a drainage layer loaded with anthocyanidin and a thermoplastic polyurethane absorbent layer embedded with superabsorbent particles. The dressing realizes the self-pumping process of unidirectional exudate draining to the absorption layer through the drainage layer without significant dressing swelling to compress the diabetic wound. The dressing is experimentally proven to unidirectionally drain excessive exudate with inflammatory factors and modulate the conversion of macrophages from M1 to M2 in diabetic wounds, thereby promoting the healing of diabetic skin ulcers faster than commercial foam dressings. Therefore, the dressing provides a new idea and novel method for accelerating diabetic skin ulcer healing.

LSPR-enhanced photoresponsive antibacterial efficiency of Bi/MoS2-loaded fibrin gel for management of diabetic wounds

Chronic diabetic wounds present formidable challenges, marked by uncontrolled bacterial infections, prolonged inflammation, and impaired angiogenesis. The evolving landscape of photo-responsive antibacterial therapy holds great promise in addressing these multifaceted issues, with a particular focus on leveraging the distinctive properties of 2D heterojunction materials. In this investigation, we engineered composite sprayed hydrogels, seamlessly integrating Bi/MoS2 nano-heterojunctions. Capitalizing on the synergistic interplay between photocatalytic antibacterial and photothermal antibacterial mechanisms, the Bi/MoS2 heterojunction, guided by its localized surface plasmon resonance, demonstrated outstanding antibacterial efficacy within a mere 10-minute exposure to 808 nm near-infrared light. This accelerated sterilization both in vitro and in vivo, consequently expediting wound healing. The sprayed composite gel not only furnishes protective shielding for skin tissues but also fosters endothelial cell proliferation, vascularization, and angiogenesis. This safe and ultrafast sterilizing hydrogel presents immense potential for application in antimicrobial dressings, thereby offering a promising avenue for diabetic wound healing.

Penerapan Relaksasi Otot Progresif Terhadap Penurunan Tingkat Kecemasan pada Pasien Luka Kaki Diabetik

Background: Diabetic foot ulcers are one of the most common complications in patients with diabetes mellitus. Patients with diabetic foot wounds have various degrees of anxiety. One of the anxiety measurement tools is HARS (Hamilton Anxiety Rating Scale). Progressive muscle relaxation is one of the non-pharmacological treatments to reduce anxiety. Objective: To describe the results of the implementation of progressive muscle relaxation on anxiety levels in patients with diabetic foot wounds. Methods: This study used a descriptive research design case study approach by observing the anxiety level of diabetic foot wound patients on 2 respondents, carried out in the morning and evening for 5 consecutive days with a frequency of 15 minutes. The instruments used were HARS (Hamilton Anxiety Rating Scale) scale sheet, SOP (Standard Operating Procedure) progressive muscle relaxation, anxiety level observation sheet, stopwatch. Results: Results: There were changes in anxiety levels before and after progressive muscle relaxation in Mrs. S from moderate (27) to mild (15). While in Mrs. I from moderate (26) to mild (15). Conclusion: The application of progressive muscle relaxation can be useful for reducing anxiety levels in both diabetic foot wound patients.

Abstract Tu034: Endothelial cell regeneration by secretome obtained from P53 silenced bone marrow derived mesenchymal stromal cells (BM-MSCs)

Introduction: Diabetes is associated with impaired endothelial function. Studies have demonstrated that endothelial progenitor cells (EPCs) and mature endothelial cells (EC) are susceptible to apoptosis in hyperglycemic environment. Hyperglycemia leads to p53 gene over-expression and p53 gene silencing prior to hyperglycemia exposure prevents cellular senescence, improves mitochondrial function and helps vascular regeneration.. However, it is not possible to obtain sufficient quantities of secretome for therapeutic purposes from hematopoietic CD34+ve stem cells (HSCs). Our goal in this project was to test whether conditioned media (CM) obtained from p53 silenced human stem cells (other than CD34+ve cells) can also improve endothelial regeneration exposed to hyperglycemia. We compared CM obtained from adipose and bone marrow derived mesenchymal stem cells on endothelial regeneration Methods: Ad-human-P53 (TP53)-shRNA was used to silence P53 and Ad-scrambled-null-shRNA was used as control in bone marrow derived mesenchymal stromal cells. To collect conditioned media BM-MSCs were cultured in exosome free FBS media for 5 days, following transduction with Ad-p53sh or Ad-null, as the case may be. After transduction, cells were grown in media containing 2% exosome free FBS for only 48h and the collected supernatant was concentrated 10-fold to obtain the CM. Endothelial regeneration was tested using endothelial wound healing assay kit ( from Cell Biolabs # CBA-120-T). We compared CM obtained from null and p53sh in adipose and bone marrow derived MSCs on human endothelial cells in normal and high glucose conditions Results: We observed that CM from bone marrow derived MSCs increased the proliferation of endothelial cells in both normal and high glucose conditions, more so than adipose derived MSCs. We are currently studying the role of exosomes from this CM on cell proliferation and we are also analyzing the secretome (exosomal and non- exosomal fraction) by mass spectroscopy. Conclusion: P53 silenced BMMSC-CM appears to improve endothelial regeneration in hyperglycemia similar to the effect of p53-silenced HSCs. This maybe secondary to the fact that both these cells are derived from bone marrow and p53 silencing improves mitochondrial function. The CM obtained from BM-MSCs are in sufficient quantities and may have a prominent therapeutic role in treating diabetes vascular complications such as diabetic wound healing.

Mesalamine may be a Plausible Therapeutic Agent for the Management of Diabetic Wounds: A Computational Approach

Aim: Validation of mesalamine (MS) as a potential therapeutic agent in treating diabetic wound (DW) healing using in silico approach. Background: Diabetic wound (DW) is a serious consequence of diabetes that frequently results in the amputation of the affected organ. Maggot therapy, pressure off-loading, surgical intervention, glucose control, hyperbaric oxygen therapy, wound debridement, and other treatments are currently available for DW. However, the majority of people do not meet all DW requirements due to significant pathology and the high expense of the solutions. Objective: To address the issues with current conventional therapy, we reasoned that repurposing existing medication (MS) to a target receptor that plays a significant role in the progression of DW might be advantageous. Mesalamine (MS), also known as Mesalazine or 5- Aminosalicylic acid, is an aminosalicylate anti-inflammatory used to treat inflammatory bowel disease (IBD), ulcerative colitis (UC), inflamed anus or rectum. The complicated pathophysiology of DW, which includes prolonged inflammation, increased infection, decreased cell proliferation, and migration, is a serious issue. As a result, we chose the MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors as a universal target for treating the complex pathogenesis of DW. The use of MS as a therapeutic modulator on MMP-9, TNF-α, MurC, ParE, and GSK-3β receptors was studied in the current hypothetical investigation. Methods: Computational studies such as molecular docking and MMGBSA were performed by using the Schrödinger suite. Results: Computational investigations, such as molecular docking and MMGBSA were used to test our theory. It is clear from the in silico methods that MS has a higher binding affinity for the designated receptors. Hence, it is predicted that MS may be a good therapeutic agent to use in the treatment of DW. Conclusion: As a result of our findings, MS appears to be a unique therapeutic drug for the treatment of DW. However, further studies are highly required to take MS into clinical use.