Treatment Of Chronic Skin Ulcers Research Articles

Network Pharmacology Study on Herb Pair Bletilla striata-Galla chinensis in the Treatment of Chronic Skin Ulcers.

Herb-paired Bletilla striata-Galla chinensis (BS-GC) is a classic combination of topical traditional Chinese medicine formulae in the treatment of chronic skin ulcers (CSUs). The aim of this study is to explore the effective active ingredients of BS-GC, as well as the core targets and signal transduction pathways of its action on CSUs. The ingredients of BS-GC were obtained from TCMSP and HERB databases. The targets of all active ingredients were retrieved from the SwissTargetPrediction database. The targets of CSUs were obtained from OMIM, GeneCards, Drugbank, and DisGeNET databases. A drug-disease target protein-protein interaction (PPI) network was constructed to select the most core targets, and an herb-ingredient-target network was built by utilizing Cytoscape 3.7.2. Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) analysis and verified the results of network pharmacology through molecular docking. A total of 40 active ingredients from the herb pair BS-GC were initially screened, and a total of 528 targets were retrieved. Meanwhile, the total number of CSU targets was 1032. Then, the number of common targets between BS-GC and CSUs was 107. The 13 core targets of herb pair BS-GC with CSUs were filtered out according to the PPI network, including AKT1, TNF, EGFR, BCL2, HIF1A, MMP-9, etc. The 5 main core active ingredients were 1-(4-Hydroxybenzyl)-2-methoxy-9,10-dihydrophenanthrene-4,7-diol, 1-(4- Hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene-2,7-diol, physcion, dihydromyricetin, and myricetin. The main biological processes were inflammation, oxidative stress, and immune response, involving the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, NF-κB signaling pathway, and calcium signaling pathway. Molecular docking results showed good binding activity between the 5 main core active ingredients and 13 core targets. This study predicted the core targets and signal transduction pathways in the treatment of CSUs to provide a reference for further molecular mechanism research.

Formulation development of collagen/chitosan-based porous scaffolds for skin wounds repair and regeneration

Herein we developed a hydrogel based porous cross-linked scaffold intended for the treatment of chronic skin ulcers. It is made of collagen, the most abundant protein of mammals ECM, and chitosan, a natural polysaccharide endowed with numerous positive cues for wound repair. Different cross-linking methods, namely UV irradiation with the addition of glucose, addition of tannic acid as cross-linking agent and ultrasonication, were employed to prepare a cross-linked hydrogel with a highly interconnected 3D internal structure. The variables considered critical to obtain a suitable system for the envisaged application are the composition of hydrogels, especially the concentration of chitosan, and the concentration ratio between chitosan and collagen. Stable systems, characterized by high porosity, were obtained thanks to the use of freeze-drying process. To assess the influence of the above-mentioned variables on scaffold mechanical properties, a Design of Experiments (DoE) approach was exploited, which resulted in the identification of the best hydrogel composition. In vitro and in vivo assays on a fibroblast model cell line and on a murine model, respectively, demonstrated scaffold biocompatibility, biomimicry, and safety.

RANDOMISED CONTROLLED TRIAL OF TOPICAL MUPIROCIN VERSUS CONVENTIONAL DRESSING IN CHRONIC SKIN ULCERS

Objectives:The objective of this study was to carry out a head-to-head comparison of mupirocin versus conventional dressings in the treatment of chronic skin ulcers with respect to both effectiveness and safety. To compare Aim: the efcacy of mupirocin in chronic wounds in terms of Reduced wound healing time, Size of the ulcer. A open-label, randomised, controlled tria Materials and Methods: l was carried out with patients suffering from skin ulcers of Wagner grading 1 or 2 persisting for over 4 weeks. 60 patients were recruited in total 30 participants treated with mupirocin 2% and 30 treated with combined conventional dressing. Treatment-emergent adverse reactions that were reported by patients or observed by the investigators were recorded. A total of 60 patients of which 44 were males a Results: nd 16 were female patients. The wound healing was better in the group treated with mupirocin and the duration of hospital stay was signicantly shorter. Patient compliance was found to be similar in both groups On the basis of the statistical analysis of our study we come to t Conclusion: he conclusion that mupirocin dressing is advantageous than conventional dressing in terms of Decreased wound surface area Decreased duration of hospital stay

A Retrospective Self-Controlled Study Evaluating the Prophylactic Effects of CACIPLIQ20 on Postsurgical Scars.

CACIPLIQ20 (OTR3, Paris, France) is a medical device used for the treatment of chronic skin ulcers. It contains a heparan sulfate mimetic that accelerates tissue healing by stabilizing matrix proteins and protecting heparin-binding growth factors. In humans, an open self-controlled study suggested that the topical application of CACIPLIQ20 optimizes skin healing following surgery. To expand previous findings using a different CACIPLIQ20 administration regimen. Twenty-four females were referred for breast-reduction surgery. Each patient had their own control with 1 CACIPLIQ20-treated and 1 saline-treated control breast. The treated side (right or left) was randomly assigned by the operating surgeon. Scar appearance was assessed by 6 independent raters using a global visual scar comparison scale based on scar photographs. All raters were blinded toward the CACIPLIQ20-treated side. The follow-up period following surgery ranged from 1 to 12 months with a median follow-up of 6 months. Overall, there was a mean improvement of 15.2% (SD = 26.7) in favor of CACIPLIQ20 (P = .016). On the CACIPLIQ20-treated side, the mean score per patient was above 20% in 11 patients and above 30% improvement in 8 cases. In contrast, only 3 patients were considered improved by at least 20% on the control side and only 1 above 30%. A comparison of different application regimens suggested that the best trend was obtained with a single administration of CACIPLIQ20 at Day 0. In conclusion, CACIPLIQ20 could represent an interesting scar prophylactic therapy, based on a single administration at the time of surgery, and without any known adverse effects.

Pinoresinol stimulates keratinocyte proliferation and downregulates TNF-α secretion in peripheral blood mononuclear cells: An experimental in vitro study.

Natural coniferous resins are used in traditional medicine for the treatment of skin wounds. Coniferous wood resins ("callus" resin) are a mixture of abietic (resin) acids, lignans such as pinoresinol, and p-coumaric acid. The wound-healing properties of resins are thought to be related to their antimicrobial properties, but also to their effects on cell proliferation and inflammation. The purpose of this study was to identify and investigate the effects of novel aqueous dispersions of resin and its main components in the proliferation of human primary keratinocytes in vitroand in the expression of proinflammatory cytokines in human peripheral blood mononuclear cells. The proliferation studies were performed under low and high calcium conditions with or without added growth stimulators at the time points of 2and 6 days using AlamarBlue Cell Viability Reagent. The cytokine release assay was carried out by incubating the cells with the test articles for 18 h, after which the levels of tumor necrosis factor-α(TNF-α),interleukin-1β (IL-1β), IL-6, and IL-8 were measured in the supernatant by enzyme-linked immunosorbent assay. Resin and the purified lignan PINO, but not p-coumaric acid or abietic acid (industrial tall oil rosin), enhanced the proliferation of human keratinocytes in vitroand inhibited the expression of TNF-α, and to a lesser extent the expression of IL-1β in peripheral blood mononuclear cells. In this study, novel aqueous dispersions of spruce resin were used to investigate the effects of main resin components on keratinocyte proliferation and on the expression of key proinflammatory cytokines known to be associated with chronic wounds. The observations suggest that lignans, such as PINO, but not resin acids, are the components of resins that mediate the proliferative and TNF-α-suppressing effects. Lignans including PINO were identified as novel potential compounds in the treatment of chronic skin ulcers.

Therapeutic Effect and Mechanism of Negative Pressure Wound Therapy with Huoxue Shengji Decoction Instillation for Chronic Skin Ulcers.

Background Negative pressure wound therapy (NPWT) with instillation (NPWTi) is a new treatment for chronic skin ulcers (CSUs), but the choice of perfusate is still investigated. The clinical application of Huoxue Shengji (HXSJ) decoction has been proved to promote the formation of granulation. The formation of fresh granulation, angiogenesis, and proliferation of vascular endothelial cells are closely related. The purpose of this study was to observe the clinical efficacy of NWPT with HXSJ decoction instillation in the treatment of CSUs and to explore the potential mechanism by which HXSJ decoction promotes proliferation of vascular endothelial cells at the cellular level. Methods In the clinical study, the random number table was used to divide the patients into three groups (patients were numbered by visit time and assigned a random number and grouped by the remainder after the random number was divided by 3, and when the number of patients in one group reached 20, the enrolment of this group is stopped), including NPWT combined with HXSJ decoction instillation (group A), NPWT combined with normal saline instillation (group B), and NPWT (group C). Related indexes were examined, including the wound cavity volume, bacterial culture, histopathology examination, time periods of debridement, repair methods, and the time of ulcer healing. In the basic research, the effect of HXSJ decoction on the proliferation of HUVECs was analysed by CCK-8 assay and RT-PCR and western blot were used to quantify the VEGF and VEGFR-2 expression in the relevant signalling pathway. Results There was no significant difference in the improvement rate of invasive cavity volume (P > 0.05) between groups A and B, but a significant difference was observed between groups A and C (P < 0.05). There was no significant difference in microbial reduction among groups (all P > 0.05). Histopathological examination showed that the microvascular count in group A was significantly higher than that in groups B and C (both P < 0.01) and there was no statistical difference between groups B and C (P > 0.05). There were no significant differences in the number of invasive lesions and repair methods among the groups (all P > 0.05). The healing time of group A was significantly faster than those of groups B and C (compared to group B, P < 0.05; compared to group C, P < 0.01), and there was no statistical difference between groups B and C (P > 0.05). In the cellular experiments, concentration screening was performed and 125 μg/mL HXSJ decoction showed the most significant effect on the proliferation of HUVECs and also enhanced the expression of VEGF and VEGFR-2. Conclusion HXSJ decoction can enhance the expression of VEGF and VEGFR-2 and promote the proliferation of HUVECs. Treatment with NWPT with HXSJ decoction instillation can further reduce the wound cavity volume; meanwhile, it can promote blood vessel formation in ulcer wounds, thus accelerating the healing of CSUs.

Clinical Studies on Platelet-Rich Plasma Therapy for Chronic Cutaneous Ulcers: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Significance: Platelet-rich plasma (PRP) may be a potential drug for treatment of chronic refractory ulcers, which increase the risk of systemic infection and local canceration. However, the efficacy and safety of clinical application of PRP are still controversial. Thus, this study was aimed to assess the efficacy and safety of PRP in patients with chronic ulcers. Recent Advances: For this meta-analysis, Cochrane's Library, MEDLINE, EMBASE, PubMed, Web of Science, and CINAHL (Cumulate Index to Nursing and Allied Health Literature) databases were searched. Results were pooled using a random-effects model. The primary outcome was the proportion of completely healed chronic ulcers. Critical Issues: Seventeen randomized controlled trials were included. Compared with the control group, PRP significantly increased the fraction of healed ulcers (pooled risk ratio [RR] = 1.50; 95% confidence interval [CI] = 1.20 to 1.87; I2 = 47.8%). In autologous PRP (APRP) and homologous PRP (HPRP) subgroups, there were statistical differences between the control group versus treatment subgroup (pooled RR = 1.30, 95% CI = 1.10 to 1.54, I2 = 25.7%; pooled RR = 3.53, 95% CI = 1.94 to 6.43, I2 = 0.0%, respectively). In terms of percent of chronic ulcers area healed, there was a statistically significant difference between the PRP-treated group versus the control group (standard mean difference [SMD] = 1.37, 95% CI = 0.91 to 1.82, I2 = 22.1%). As for PRP safety, there existed a statistically significant difference between the APRP subgroup and the HPRP subgroup, respectively (pooled RR = 0.58; 95% CI = 0.35 to 0.98; I2 = 0.0%) and (pooled RR = 4.12; 95% CI = 1.55 to 10.96; I2 = 6.8%). Future Directions: Our findings shows that PRP may be a beneficial treatment of chronic skin ulcers and that APRP may be much safer than HPRP.

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing.

The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

CGF treatment of leg ulcers: A randomized controlled trial

BackgroundConcentrated Growth Factors (CGF) is a concentration of second generation autologous growth factors compared to platelet rich plasma (PRP) and represents a multifactorial stimulation system that can be used for the management and treatment of chronic skin ulcers.AimThe aim of this work is to evaluate the additional benefits of the CGF compared to the standard of dressing and its effects on the dynamics of the healing process.MethodsAutologous CGFs were obtained from 100 patients with chronic mixed ulcers (venous ulcers in patients with II stage claudication) of the lower limbs in a multicentric controlled randomized study.ResultsThe results showed a significant advantage in the use of CGF in association with cleansing and selective compression in the healing time and stabilization of mixed ulcers of the lower extremities.ConclusionsThese results support the CGF’s clinical use for improving clinical outcomes in mixed ulcers of the legs.

649 Hypoxia-pretreatment as a possible approach to stimulate wound healing potentials of dermal fibroblasts in treatment of chronic skin ulcers

The development of new therapeutic approaches to chronic wounds hasn’t lost its relevance. In non-healing diabetic ulcers (diabetic foot) auto-transplantation (a common treatment approach) is not effective due to impaired fibroblast functionality and shifts in synthesis of ECM proteins (COL1, COL3, FN) and certain growth factors. It was shown that HIF1 (hypoxia-induced factor) is a key regulator of ECM remodeling by fibroblasts through control of collagen prolyl hydroxylase (P4HA1, P4HA2 – both required for collagen deposition) and lysylhydroxylase (PLOD2 – modulates collagen fibers strength) expression. Therefore, the use of hypoxia-stimulated fibroblasts (sFbs) may represent a reasonable treatment alternative in the maintenance of chronic diabetic wounds. Here, we evaluated the expression levels of wound healing-related genes and proteins in sFbs after 24h, 48h and 72h exposure to 1% O2. After a short-term (24/48h) exposure to hypoxia, sFbs exhibited a marked increase in expression of a number of genes as compared to 21% O2 culture: Hif1a – 7.4 and 16.9 fold respectively; Vegf1a – 21/60; Egln1 – 9/9; Egln2 – 6.5/5; Egln3 – 53/110; COL1 – 2.4/3; Fn – 3.3/1.7; P4HAa1 - 5.8/7.8; P4ha2 – 6.6/8.5; and Plod2 - 9/25 fold. In contrast, with a longer exposure to hypoxia (72h), activation was significantly diminished (Hif1a – 2 fold; Vegf1a – 6; Egln3 – 2.4) or completely abrogated (Egln1, Egln2, COL1, Fn, P4ha1, P4ha2, and Plod2). Importantly, at protein level, we observed only COLI (2 fold) stimulation by hypoxia. The stimulation of COLIII and Fn synthesis in sFb was detected only after a 6-18h period of their re-oxygenation. Based on our results, we propose that short-term stimulation of dermal fibroblasts (for example, immobilized on a biopolymer scaffold) by hypoxia could be beneficial for chronic diabetic wound treatment. (NRC Kurchatov Institute intramural grant supported research).

Il trattamento topico con una matrice contenente mesoglicano in associazione ad acido ialuronico nella gestione delle ulcere cutanee croniche degli arti inferiori/Topical treatment with a matrix containing mesoglycan in association with hyaluronic acid in the management of chronic skin ulcers of the lower limbs

Un’ulcera cutanea cronica degli arti inferiori rappresenta l’epifenomeno di varie situazioni patologiche che possono coinvolgere, a vari livelli e con diversi gradi di interessamento, i sistemi venoso, arterioso e linfatico della gamba. Recentemente sono state pubblicate numerose evidenze secondo cui i glicosaminoglicani (GAG) svolgono un ruolo importante nella riepitelizzazione delle ulcere cutanee croniche degli arti inferiori, in particolare per quanto riguarda le ulcere ad eziopatogenesi vascolare venosa o mista. In questo articolo riportiamo la nostra esperienza nel trattamento delle ulcere cutanee croniche degli arti inferiori con una metodica che prevede il debridement secondo il protocollo TIME, antisepsi con una soluzione di iodopovidone al 10% la successiva l’applicazione di una medicazione bioattiva contenente GAG e acido ialuronico. Questa metodica è stata confrontata con un’analoga metodica che prevede sempre lo stesso tipo di debridement e di antisepsi con soluzione di iodopovidone al 10% affiancata a una medicazione non bioattiva.&#x0D; A chronic skin ulcer in the lower limbs represents the epiphenomenon of pathologies that may involve, at various levels, the venous, arterial, lymphatic and nervous systems of the leg, which must be identified and adequately treated. Recently, there has been increasing evidence that glycosaminoglycans (GAGs) play a role in the re-epithelialization of chronic skin ulcerative wounds of the lower limbs, particularly as regards ulcers of venous and arterial vascular origin. In this paper we report our experience in the treatment of chronic skin ulcers with debridement according to the TIME Wound Bed Preparation protocol with application of a bioactive dressing containing GAGs and hyaluronic acid, compared to a technique using a standard dressing involving the cleansing of the wound with 10% povidone iodine solution.

Botulinum Toxin A Injection for Treatment of Chronic Skin Ulcer: A Case Series and Literature Review.

Chronic skin ulcer (CSU) often combines with a variety of refractory factors that respond poorly to routine treatments. Botulinum toxin A (BTX-A) can be injected subcutaneously to improve the local blood supply, to reduce pain, and to promote wound healing. At present, few reports have mentioned BTX-A injection for chronic skin ulcer treatment. We observed the effect of four cases that used BTX-A to treat CSU and provided a brief review of the literature. Four cases of CSUs with 4 different causes were treated with BTX-A injection (4 U/cm2). The specific operation is as follows: local, multipoint, cyclic, equidistant, and subcutaneous injections with a depth of 6 to 8 mm. The ulcer area was significantly reduced. Subsequently, the ulcer healed within 20 to 48 days. Botulinum toxin A is recommended as an important treatment for chronic skin ulcer that can improve healing of skin ulcers with various etiologies.

Comparative study of topical mupirocin versus mupirocin with sucralfate combination in treatment of chronic skin ulcers

Comparative study of topical mupirocin versus mupirocin with sucralfate combination in treatment of chronic skin ulcers

Role of Hepatocyte Growth Factor in Wound Repair

Hepatocyte growth factor (HGF) is a multifunctional cytokine that is related to many diseases. HGF mainly contributes to cell migration,proliferation,and survival and regulates vascular angiogenesis,matrix deposition,and degradation of wound healing. HGF also promotes wound reepithelialization and reduces scar formation. This review article summarizes the role of HGF in wound repair and the relationship between HGF and other growth factors,especially when applied for the clinical treatment of chronic skin ulcers.

Transcutaneous oximetry and laser Doppler flowmetry values in patients with chronic skin ulcers treated with platelet rich plasma and stromal vascular fraction cells: a pilot study

Stromal vascular fraction cells (SVFs) hold great promise for use in regenerative medicine applications, as a result of their ability to promote the healing process through in situ differentiation and the secretion of paracrine factors. The aim of this paper was to evaluate whether and how the topical application of SVF with platelet-rich plasma (PRP) for the treatment of chronic skin ulcers modified the cutaneous perfusion of the treated areas. Perilesional laser Doppler flowmetry (LDF) and transcutaneous oximetry (tcpO2) values were recorded for a 3-month period in 15 patients with chronic skin ulcers of various etiologies, who had been previously treated with single co-administered perilesional and intralesional injections of SVF+PRP. No significant differences were found between pretreatment, 1 month, and 3 month posttreatment values regarding both LDF values (basal: p = 0.10 and declivous: p = 0.0976) and declivous tcpO2 levels (p = 0.0804). The only significant difference reported was between pretreatment and 3-month posttreatment basal tcpO2 levels (p = 0.0466). These results may reflect improved subcapillary circulation of the treated areas at 3 months postinjection, without a significant improvement in capillary perfusion. Level of Evidence: Level IV, therapeutic study.

Efficacy and safety of topical sevoflurane in the treatment of chronic skin ulcers.

Results of efficacy and safety assessments of topical sevoflurane use in patients with long-term treatment-refractory vascular ulcers are reported. Patients were randomly assigned to receive sevoflurane instillations (1 mL per cm2 of ulcer area 1-4 times daily) plus standard wound care (ulcer cleaning, debridement, and dressing changes) or standard care only. Topical sevoflurane was initiated during hospitalization, with self- or nurse-administered instillations continued after discharge. Study participants were evaluated at least once weekly for 1 month and then every 2 weeks for up to 90 days. The primary efficacy measures were debridement-related and overall pain (assessed using a 10-point visual analog scale), daily opioid use, and ulcer size; secondary measures were patient and clinician impressions of improvement and ulcer-related admissions during treatment. The primary safety endpoint was intolerable sevoflurane-related adverse effects. Compared with the group receiving standard care alone (n = 5), the sevoflurane group (n = 10) had significant (p = 0.001) reductions in mean ± S.D. scores for debridement-related pain on day 1 of treatment and at subsequent time points; the sevoflurane group also had significant reductions in overall pain, daily opioid use, and ulcer size. Outcomes in terms of patient- and clinician-rated improvement and emergency admissions also favored the sevoflurane group. Mild localized reddening in the area surrounding ulcers occurred in 4 sevoflurane-treated patients. Direct application of sevoflurane onto vascular ulcers resulted in an intense and long-lasting analgesia and was associated with a progressive reduction of ulcer size.

Application of DoE approach in the development of mini-capsules, based on biopolymers and manuka honey polar fraction, as powder formulation for the treatment of skin ulcers

The aim of the present work was the development of a powder formulation for the delivery of manuka honey (MH) bioactive components in the treatment of chronic skin ulcers. In particular pectin (PEC)/chitosan glutamate (CS)/hyaluronic acid (HA) mini-capsules were obtained by inverse ionotropic gelation in presence of calcium chloride and subsequently freeze-dried. Optimization of unloaded (blank) formulation was performed using DoE approach. In a screening phase, the following three factors were investigated at two levels: CS (0.5–1% w/w), PEC (0.5–1% w/w) and HA (0.3–0.5% w/w) concentrations. For the optimization phase a “central composite design” was used. The response variables considered were: particle size, buffer (PBS) absorption and mechanical resistance. In a previously work two different MH fractions were investigated, in particular MH fraction 1 (Fr1), rich in polar substances (sugars, methylglyoxal (MGO), dicarbonyl compounds, …), was able to enhance human fibroblasts in vitro proliferation. In the present work, the loading of MH Fr1 into mini-capsules of optimized composition determined a significant increase in cell proliferation in comparison with the unloaded ones. Loaded particles showed antimicrobial activity against Staphylococcus aureus and Streptococcus pyogenes; they were also able to improve wound healing in vivo on a rat wound model.

Sponge-Like Dressings Based on the Association of Chitosan and Sericin for the Treatment of Chronic Skin Ulcers. I. Design of Experiments–Assisted Development

The aim of the present work was the development of sponge-like dressings based on chitosan glutamate (high molecular weight) and sericin for the treatment of chronic skin ulcers. Dressings were prepared by freeze-drying and glycine was added as cryoprotectant agent. Dressing development was assisted by design of experiments, using a simplex centroid design. Mechanical resistance, hydration propensity, viscous, and viscoelasticity properties of dressings were considered as response variables. The superimposition of the contour plots, calculated by the best fit model for each response variable, permitted to individuate a region of the factor space where the dressing of optimized quantitative composition was chosen. Such a dressing was able to absorb high amount of phosphate-buffered saline forming a gel characterized by rheological properties enabling both a lubricant and a protective effect. The optimized formulation was characterized by optimal mechanical properties and by cell proliferation and antioxidant activity on human fibroblast cell line.

Sponge-Like Dressings Based on the Association of Chitosan and Sericin for the Treatment of Chronic Skin Ulcers. II. Loading of the Hemoderivative Platelet Lysate

Platelet lysate (PL) was loaded into dressings based on chitosan glutamate (CSG) low and high molecular weight, sericin (Ser), and glycine (Gly). A synergic effect of Ser and PL on fibroblast proliferation was proved in vitro. Two different PL loading approaches were considered: the first provided to prepare dressings by freeze-drying a mixture of PL and CSG/Gly/Ser solution, the second approach consisted in the extemporarily loading of PL in the CSG/Gly/Ser freeze-dried dressings. As for the first approach, PL loading did not produce any variation in dressing mechanical properties. Such dressings absorbed a high amount (about 8-fold of dry weight) of phosphate-buffered saline (fluid mimicking wound exudate), forming a gel with pseudoplastic and elastic properties. Platelet-derived growth factor AB assay indicated that neither freeze-drying nor the excipients alter PL growth factor content. As for the second approach, mechanical and rheological properties of the gel formed upon PL absorption enabled to choose a PL loading of about 90 μL/cm2. Upon contact with fibroblasts, all PL loaded formulations increased the number not only of viable cells but also of those in the proliferative phase. Histological studies effected on human skin strips pointed out the positive effect of PL loaded dressings on dermal matrix reconstruction.

Efficacy of triethanolamine cream in the treatment of chronic skin ulcer: a clinical study

Objective To assess the efficacy and safety of triethanolamine cream for the treament of chronic skin ulcer.Methods Thirty-eight patients with chronic skin ulcer were classified into the test group and control group.The control group was routinely treated with debridement and dressing,while the test group was topically treated with triethanolamine cream besides debredement and dressing.Results After 8 weeks of treatment,the lesions healed in 18 (85.71％) patients in the test group and 8 (47.06％) patients in the control group,markedly improved in 2 (9.52％) patients in the test group and 2 (11.76％) patients in the control group,improved in 1 (4.76％) patient in the test group and 5 (29.41％) patients in the control group.The total response rate was significantly different between the test group and control group (95.24％ vs.58.82％,x2 =6.497,P ＜ 0.05).Both the time required for granulation tissue to generate and that for skin ulcer to heal were shorter in the test group than in the control group (both P ＜ 0.01).Conclusion Triethanolamine cream is a safe,effective,and well-tolerated treatment option for chronic skin ulcer. Key words: Ulcer; , Triethanolamine; Treatment outcome