Evaluation of Effect of Biologically Synthesized Ethanolic Extract of Propolis-Loaded Poly(-Lactic-co-Glycolic Acid) Nanoparticles on Wound Healing in Diabetic Rats

Wound healing is interaction of a complex cascade of cellular/biochemical actions leading to restoration of structural and functional integrity with regain of injured tissues strength. This study was aimed at evaluation of application of ethanolic extract of propolis-loaded poly(-lactic-co-glycolic acid) nanoparticles (EEP-PLGA NPs) on wound healing in diabetic rats. Sixty rats were randomized into four groups of 15 rats each: In control group (Control) diabetic wound was treated with normal saline. In Carrier 1 group diabetic wound was treated with PLGA nanoparticles based solution. In Carrier 2 group the diabetic wound was treated with EEP. In Treatment group animals received EEP-PLGA NPs on the wound. Wound size was measured on 7, 14 and 21 days after surgery. The expression of p53, bcl-2, Caspase III, were evaluated using reverse-transcription PCR and Immunohistochemical staining. The Treatment group had significantly reduced the wound size compared to other groups ( P = 0.001). histological and morphometric studies, and mean rank of the qualitative studies demonstrated that there was significant difference between Treatment group and other groups ( P < .05). Observations demonstrated that ethanolic extract of propolis-loaded PLGA nanoparticles significantly shortened the inflammatory phase and accelerated the cellular proliferation. Accordingly, the animals in Treatment group revealed significantly ( P < .05) higher fibroblast distribution/one mm2 of wound area and rapid re epithelialization. The mRNA levels of bcl-2, p53 and caspase III were remarkably ( P < .05) higher in Treatment group compared to control and animals. The immunohistochemical analyzes confirmed the RT-PCR findings. EEP-PLGA NPs offered potential advantages in wound healing acceleration and improvement through angiogenesis stimulation, fibroblast proliferation and granulation tissue formation in early days of healing phases, acceleration in diabetic wound repair associated with earlier wound contraction and stability of damaged area by rearrangement of granulation tissue and collagen fibers.

Wound healing and Metabolite Profiling in Collagen-Chitosan Biomaterial-treated Chronic Wounds of Hansen’s Disease Patients

Aims: Impaired wound healing causes chronic ulcers in Hansen’s disease (HD) patients which are an unrecognized clinical manifestation and requires utmost care and attention for wound management. Collagen and chitosan biopolymers when synergistically combined produce a biologically active biomaterial for wound dressings. Hence, the aim was to prepare a collagen/chitosan (COL/CS) composite and characterize for wound healing potential in HD patients. Place and Duration of Study: CSIR-Central Leather Research Institute, Sardar Patel Road, Adyar, Chennai 600021, Southern Railway Headquarters Hospital, Constable Road, Ayanavaram, Chennai 600023, and Gremaltes Hospital, India between June 2013 and July 2020. Methodology: The HD wounds were measured by Planimetry in square cm and were also assessed for morphological structure of epidermis and collagen fiber arrangement by High Resolution- Scanning electron microscopy (HR-SEM). Proton Nuclear magnetic resonance spectroscopy (1H-NMR) for metabolite identification was studied in blood plasma samples of unwounded, untreated and treated HD patients Results: Size D (wound size on day of discharge) of the wounds were appreciably lower than Size 0 (wound size before biomaterial treatment) demonstrating efficient wound healing by the biomaterial. The morphological structure of the HD wounds showed healthy epidermal layer and thick fibers of collagen matrix in the treated wounds when compared to the controls. Key metabolites of metabolic pathways such as TCA cycle, creatine cycle and protein metabolism were identified by 1H-NMR spectroscopy Conclusion: The COL/CS wound dressing is a promising biomaterial for management of chronic wounds in Hansen’s disease.

Efficacy of Mobiderm® Bandage in Compression Therapy for Venous Ulcers: A Prospective Case Series

Background: Venous leg ulcers severely affect patients’ quality of life due to its high morbidity and recurrent nature. Currently, compression therapy is the first-line treatment for venous leg ulcers. Aim: This study sought to evaluate the efficacy of the Mobiderm® technology developed by Thuasne in a prospective case series of venous leg ulcers. Methods: Nine patients ( N = 9) with venous leg ulcers were enrolled into this case series. Mobiderm® bandage was applied on to the affected limbs of the patients in the multi-component bandages system. The bandages were changed as frequent as the patients had their wound dressing for their standard treatment in a 12-week duration. Wound size and calf circumference were measured at week 0 and week 12. Paired sample t-test was used to compare the mean values of wound size and calf circumference pre- and post-treatment. Results: Reductions in wound size and calf circumference were observed in all nine patients (100%). Five patients were evaluable at week 12. The wound sizes significantly reduced by 27.2% to 53.2% ( p = 0.02), and the calf circumferences significantly reduced by 3.2% to 26.0% ( p = 0.02) after 12 weeks ( N = 5). Safety was unremarkable, with no occurrence of treatment-emergent-related adverse event. Conclusion: Mobiderm® bandage was reported to be effective in promoting wound healing and reducing swelling, suggesting it to be integrated in the compression therapy for the management of venous leg ulcers.

Regeneration of Damaged Epidermal and Neural Cells in Rats with Subcutaneous Wounds Injected with Platelet Rich Plasma and Multivitamins

Introduction: The scientific definition of Wound is the disruption of various characteristics of the anatomical, functional and cellular continuity of a living tissue. Platelet-rich plasma is a natural occurring blood element that contains a vast amount of platelets in a noticeable volume. The sole function of PRP is a protective mechanism which acts as an adhesive material to maintain hemostatic and tissue properties, it also acts as an immediate hemostatic agent in surgical applications being biocompatible, safe, and effective. The sole aim of this study is to investigate the effect of PRP combined with multivitamins on the regeneration process of superficial rat skin. Methodology: Thirty male rats were used in this experiment and were divided into 3 groups control n= 10, PRP n =10 and PRP and multivitamins n=10. Each group was subjected to a skin wound and received and a treatment of 1 mil of PRP only or 1 mil PRP and 1 mil multivitamins. Control groups received nothing. Wound size was measured for 15 days. Wound site was surgically removed and processed for histological examination after 15 days. Results: Wound area was reduced in all animal groups over time. There is a more significant increase (P>0.05) between treated rats with PRP and multivitamins injections and control groups on day 15 of the experiment. The results also show a significant increase (P>0.05) in wound size between PRP treated rats and control groups beginning on day 5 of the experiment. There was no statistical significance (P=0.05) in wound size between PRP treated rats and control rats in the first 5 days post wound initiation. Tissue from PRP treated rats shows normal histological appearance of both dermal and epidermal layers however there is a thickened stratum corneum indication of scar formation. Histological examination of PRP and multivitamin treated wounds shows normal histological architecture with normal dermal and epidermal appearance. Conclusion: Overall PRP and multivitamin administration subcutaneously in wound sites of male rats shows improvement and restoration of histological architecture. Reduction in wound site was reduced significantly in comparison with other groups.

Macroscopic, Histologic, and Immunomodulatory Response of Limb Wounds Following Intravenous Allogeneic Cord Blood-Derived Multipotent Mesenchymal Stromal Cell Therapy in Horses

Limb wounds are common in horses and often develop complications. Intravenous multipotent mesenchymal stromal cell (MSC) therapy is promising but has risks associated with intravenous administration and unknown potential to improve cutaneous wound healing. The objectives were to determine the clinical safety of administering large numbers of allogeneic cord blood-derived MSCs intravenously, and if therapy causes clinically adverse reactions, accelerates wound closure, improves histologic healing, and alters mRNA expression of common wound cytokines. Wounds were created on the metacarpus of 12 horses. Treatment horses were administered 1.51–2.46 × 108 cells suspended in 50% HypoThermosol FRS, and control horses were administered 50% HypoThermosol FRS alone. Epithelialization, contraction, and wound closure rates were determined using planimetric analysis. Wounds were biopsied and evaluated for histologic healing characteristics and cytokine mRNA expression. Days until wound closure was also determined. The results indicate that 3/6 of treatment horses and 1/6 of control horses experienced minor transient reactions. Treatment did not accelerate wound closure or improve histologic healing. Treatment decreased wound size and decreased all measured cytokines except transforming growth factor-β3. MSC intravenous therapy has the potential to decrease limb wound size; however, further work is needed to understand the clinical relevance of adverse reactions.

A Comparative Study of Efficacy of Povidone Iodine Versus Super Oxidized Solution in Lower Limb Ulcers

BACKGROUND Wounds and their management are important in the practice of surgery. Super oxidised solution is a recent concept in wound management. It is an aqueous solution which is electrochemically processed which is non-toxic, non-irrigating and is having a neutral pH. Povidone iodine is the most common topical wound care product used in surgical practice. Both are affordable solutions for the patients. There are very few studies comparing the efficacy. In this study, we wanted to compare the efficacy of super oxidised solution and povidone iodine in the management of lower limb ulcers. METHODS A prospective study was conducted on 100 patients who were randomized into two groups. Group A was treated with super oxidized solution and Group B were treated with povidone iodine. Assessments of wounds were done on various days (1, 3, 5, 7, 9, 12, 15, 18, 21). Various outcomes of data were analysed using statistical analysis. RESULTS The average percentage reduction in wound size on day 21 was 47 % in Group A compared to 24 % in Group B. Early appearance of granulation tissue, disinfection, decrease in wound size, and less duration of hospital stay was achieved in Group A. CONCLUSIONS The results were more favourable towards super oxidised solution than povidone iodine. In this comparative study, super oxidized solution had faster efficacy and wound healing in patients than povidone iodine. KEY WORDS Super Oxidized Solution, Ulcer, Povidone Iodine.

Management of hard-to-heal leg ulcers with an acid-oxidising solution versus standard of care: the MACAN study

Objective: The efficacy of available wound dressings in the treatment of hard-to-heal wounds is limited. A new therapeutic approach using an acid-oxidising solution (AOS) was developed. Its effect on healing progress, tolerability and safety properties were investigated in a clinical study, and compared with standard of care (SOC) wound dressings. The study aimed to demonstrate the non-inferiority of AOS to SOC in terms of wound healing progress. Method: This open-label, randomised controlled trial was conducted at two study centres in Austria with patients with either infected or non-infected hard-to-heal leg ulcers of different aetiology. Patients were treated for six weeks either with AOS or SOC wound dressings. Outcome assessments included the percentage of granulation and re-epithelialisation tissue, wound size reduction, changes in wound pH, infection control and wound pain, local tolerability and adverse events (AEs). Healing time and rate were also assessed. Results: A total of 50 patients took part. In the AOS group, wounds exhibited higher amounts of granulation and re-epithelialisation tissue, and a faster and more pronounced wound size reduction compared with wounds in the SOC group. In the AOS-treated versus SOC-treated patients, a greater percentage of complete healing of hard-to-heal ulcers was achieved by the end of the study period (32% versus 8%, respectively). Furthermore, the wound pH decreased significantly faster in these wounds (p<0.0001). In all patients with infected leg ulcers, local infection was overcome more rapidly under AOS treatment. In the AOS group, one AE and no serious adverse events (SAEs) were detected versus 24 AEs and two SAEs in the SOC group. Conclusion: In this study, AOS proved to be a highly effective treatment to support wound healing in infected or non-infected hard-to-heal leg ulcers of different aetiology. Efficacy was found to be not only non-inferior but superior to SOC wound dressings. Furthermore, tolerability and safety profiles were favourable for AOS.

Assessment of wound area reduction on chronic wounds in dogs with photobiomodulation therapy: A randomized controlled clinical trial

Background and Aim: Chronic wounds are a clinical problem and require intensive standard wound care. However, this is sometimes insufficient to promote healing. Photobiomodulation therapy (PBMT) can be used as an adjunctive therapy to improve wound healing. Various PBMT devices with different properties and parameter settings as well as different animal species can influence a variety of clinical outcomes. This study aims to assess the use of 830 nm PBMT or simultaneous superpulsed and multiple wavelengths (SPMW; 660, 875, and 905 nm) PBMT on chronic wounds in client-owned dogs. Materials and Methods: This study included 21 client-owned dogs with chronic wounds allocated into three groups: (1) Control group (C) treated with irrigated saline and without PBMT (n=7); (2) L1 group treated with irrigated saline together with the radiation of 830 nm PBMT (n=7); and (3) L2 group treated with irrigated saline together with the radiation of simultaneous SPMW-PBMT (n=7). Wound healing was assessed on the basis of wound size reduction as a percentage of wound area every 2nd day for 15 days using image analysis software (ImageJ software®, National Institutes of Health, Rockville, Maryland, USA). Results: A significant difference in the percentage of wound area reduction was noted between the C and PBMT groups (L1 and L2; p<0.05). The average percentages of wound area reduction at the end of the study (15 days) were 42.39±20.58, 56.98±24.82, and 61.81±27.18 in the C, L1, and L2 groups, respectively. A steady decrease in wound size was noted in both PBMT and non-PBMT groups, and coefficients were 7.77, 8.95, and 10.01 in the C, L1, and L2 groups, respectively. The percentage of wound area reduction was found to be significantly different between the PBMT and non-BPMT groups on day 7 (p<0.05). Conclusion: Based on the results of the current study, using either 830 nm PBMT or simultaneous SPMW-PBMT can accelerate the chronic wound healing process in dogs with a significant reduction in wound area. Therefore, it can be used as an adjunctive therapy to improve wound healing in dogs with reduced treatment duration.

Identification of preoperative predictors for acute postsurgical pain and for pain at three months after surgery: a prospective observational study

Identifying patients at risk is the start of adequate perioperative pain management. We aimed to identify preoperative predictors for acute postsurgical pain (APSP) and for pain at 3 months after surgery to develop prediction models. In a prospective observational study, we collected preoperative predictors and the movement-evoked numerical rating scale (NRS-MEP) of postoperative pain at day 1, 2, 3, 7, week 1, 6 and 3 months after surgery from patients with a range of surgical procedures. Regression analyses of data of 2258 surgical in- and outpatients showed that independent predictors for APSP using the mean NRS-MEP over the first three days after surgery were hospital admittance, female sex, higher preoperative pain, younger age, pain catastrophizing, anxiety, higher score on functional disability, highest categories of expected pain, medical specialty, unknown wound size, and wound size > 10 cm compared to wound size ≤ 10 cm (RMSE = 2.11). For pain at three months, the only predictors were preoperative pain and a higher score on functional disability (RMSE = 1.69). Adding pain trajectories improved the prediction of pain at three months (RMSE = 1.37). Our clinically applicable prediction models can be used preoperatively to identify patients at risk, as well as in the direct postoperative period.

Copper Ions Ameliorated Thermal Burn-Induced Damage in ex vivo Human Skin Organ Culture

<b><i>Introduction:</i></b> The zone of stasis is formed around the coagulation zone following skin burning and is characterized by its unique potential for salvation. The cells in this zone may die or survive depending on the severity of the burn and therefore are target for the local treatments of burns. Their low survival rate is consistent with decreased tissue perfusion, hypotension, infection, and/or edema, resulting in a significant increase in the wound size following burning. Copper is an essential trace mineral needed for the normal function of almost all body tissues, including the skin. <b><i>Objective:</i></b> The aim of the work was to study the effect copper ions have on skin burn pathophysiology. <b><i>Methods:</i></b> Skin obtained from healthy patients undergoing abdominoplasty surgery was cut into 8 × 8 mm squares, and round 0.8-mm diameter burn wounds were inflicted on the skin explants. The burned and control intact skin samples were cultured up to 27 days after wounding. Immediately following injury and then again every 48 h, saline only or containing 0.02 or 1 µM copper ions was added onto the skin explant burn wounds. <b><i>Results:</i></b> We found that exposing the wounded sites immediately after burn infliction to 0.02 or 1 µM copper ions reduced the deterioration of the zone of stasis and the increase in wound size. The presence of the copper ions prevented the dramatic increase of pro-inflammatory cytokines (interleukin (IL)-6 and IL-8) and transforming growth factor beta-1 that followed skin burning. We also detected re-epithelialization of the skin tissue and a greater amount of collagen fibers upon copper treatment. <b><i>Conclusion:</i></b> The deterioration of the zone of stasis and the increase in wound size following burning may be prevented or reduced by using copper ion-based therapeutic interventions.