Remarkable Wound Healing Research Articles

Construction of piezoelectric, conductive and injectable hydrogels to promote wound healing through electrical stimulation.

Piezoelectric, conductive, and injectable hydrogel (SPG hydrogel) is constructed to rapidly close wounds, efficiently harvest biomechanical energy from animal motion, and generate electrical stimulation for electrotherapy of wound healing. 3-amino-4-methoxybenzoic acid (AMB) monomer was polymerized and grafted onto the gelatin, which was further crosslinked using EDC/NHS and embedded with strontium titanate nanoparticles (80.5 wt%), forming SPG hydrogel. This SPG hydrogel had high tissue adhesion ability, and could generate the output voltage (maximum output voltage 1 V) and current (maximum output current 0.5 nA) upon mechanical bending, promoting NIH-3T3 cell migration and proliferation. Upon application to the mice wound model, the SPG hydrogel rapidly closed the skin wound, smoothed the wound's appearance, reduced the remaining wound size, and increased epidermal thickness, demonstrating remarkable wound healing capabilities. This study suggests that the body motion-promoted electrotherapy offers a promising strategy for wound healing. STATEMENT OF SIGNIFICANCE: Piezoelectric nanomaterials are often incorporated into hydrogels to create piezoelectric hydrogels for wound healing. However, piezoelectric nanomaterials tend to agglomerate within the hydrogel matrix, and the hydrogel's low conductivity hinders efficient electron transfer. Together, both factors significantly reduce the piezoelectric effect. In this study, we developed an SPG hydrogel to improve the homogeneity and conductivity of the piezoelectric hydrogel. We first designed a conductive PG hydrogel and then immoblized piezoelectric STO nanoparticles within its matrix through coordination chemistry. Upon mechanical deformation, the uniformly distributed STO nanoparticles can generate electricity, which can efficiently transfer through the conductive matrix to the hydrogel's surface. This design shows great potential for wound healing applications.

Bio-friendly oleic acid-based ufasomal topical gel of rosuvastatin for diabetic wound healing: In-vitro, ex-Vivo, and in-Vivo evaluation

This study aimed to develop bio-friendly and biodegradable oleic acid-based ufasomes coated with chitosan for topical delivery of rosuvastatin for diabetic wound healing. Rosuvastatin was chosen as a suitable candidate due to its wound healing properties. Thin film hydration technique was implemented for the preparation of ufasomes at various concentrations of oleic acid. The most promising formulation (UF 5) was coated with chitosan. The effect of oleic acid and chitosan concentrations on vesicle Size, zeta-potential, polydispersity index, entrapment efficiency, and in-vitro drug release study was assessed. Optimum chitosan-coated ufasomal dispersion (CUF 3) was subjected to further characterizations, such as FT-IR, TEM, in-vitro release, broth microdilution susceptibility test, the effect of storage, ex-vivo skin permeability study, and wound healing efficiency in rats. Finally, CUF 3 was incorporated into chitosan gel base and examined for wound healing efficiency in rats. Uncoated ufasomal dispersion (UF 5) possessed the smallest vesicle Size (149.6 nm), the highest entrapment efficiency (79.48 %), an optimum zeta-potential (−35.78 mv), with polydispersity index of 0.18. FT-IR of coated ufasomes (CUF 3) reflected the effective coating of chitosan on the surface of ufasomes which coincided with the TEM image. Similar release profiles of UF 5 and CUF 3 were observed after 4 h of dissolution due to chitosan coating surrounding ufasomes. The cumulative percent of drug permeated across rat skin after 24 h for CUF 3 dispersion, and CUF 3 in chitosan gel were 11.21 % and 10.48 %, respectively, in comparison to 2.97 % in case of control gel. This was confirmed from the results of flux and permeability coefficient. A maximum skin retention and a controlled release effect with a reduced risk of systemic absorption of rosuvastatin were attained by CUF 3 in chitosan gel. Rosuvastatin encapsulated in ufasomal vesicles augmented the antimicrobial activity against Gram-negative and Gram-positive bacteria. A remarkable wound healing of CUF 3 in chitosan gel was confirmed by morphological and histopathological studies. Oleic acid-based ufasomes coated with chitosan could be a promising bio-friendly carrier for rosuvastatin to obtain a triple effect formulation for diabetic wound healing.

Phytochemical Analysis, Antimicrobial Screening and In Vitro Pharmacological Activity of Artemisia vestita Leaf Extract.

Artemisia vestita Wall. Ex Besser is a folklore medicinal plant that belongs to Asteraceae family and a treasure trove of drugs. The aim of this research study was to investigate the phytoconstituents, antimicrobial activity, antioxidant, anti-inflammatory, cytotoxicity and wound healing potential of A. vestita leaf extract (ALE). Phytochemical analysis of the ALE was carried out by Soxhlet extraction and GCMS (gas chromatography-mass spectrometry) analysis. Antimicrobial activity was performed by the agar well diffusion method against selected bacterial and fungal strains. Free radical scavenging potential was evaluated by DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric reducing antioxidant power) assays. Anti-inflammatory activity was performed by enzyme inhibition assay-COXII. The cytotoxicity of ALE on HaCaT cells was studied via MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. An in vitro scratch assay was performed for the evaluation of the wound healing property of ALE. It showed satisfactory antimicrobial activity against Staphylococcus aureus (14.2 ± 0.28 mm), Escherichia coli (17.6 ± 0.52 mm), Bacillus subtilis (13.1 ± 0.37 mm), Streptococcus pyogenes (17.3 ± 0.64 mm), Proteus mirabilis (9.4 ± 0.56 mm), Aspergillus niger (12.7 ± 0.53 mm), Aspergilus flavus (15.3 ± 0.25 mm) and Candida albicans (17.6 ± 0.11 mm). In ALE, 36 phytochemicals were detected by GCMS analysis, but 22 were dominant. Moreover, the ALE was effective in scavenging free radicals with different assays and exhibited reasonable anti-inflammatory activity. The MTT assay revealed that ALE had a cytotoxic effect on the HaCaT cells. The scratch assay showed 94.6% wound closure (after 24 h incubation) compared to the positive control Cipladine, which is remarkable wound healing activity. This is the first report on the wound healing property of A. vestita, which can serve as a potential agent for wound healing and extends knowledge on its therapeutic potential.

Experimental study of Pruthvisara taila in excised wound model in Wistar albino rats

Pruthvisara taila is a formulation indicated in the chikitsa of vrana as topical medicine in classical text Chakradatta. It contains Shuddha chitrakamoola, Shuddha vatsanabha, Shuddha karaveera, Nirgundi moola, Nadibeeja, Kanji and Karanja taila as the base. Aims and Objectives: Evaluation of wound healing property of Pruthvisara taila through experimental study. Methodology: Wound healing property in albino rats by excision wound healing model and its histopathology study. Results: Results of the study on the parameters assessed like percentage of wound contraction and histopathology study; percentage of wound closure was observed in Control group was 94.92%, in standard it was 93.73% and in test drug the percentage of wound contraction was 95.73%.The test drug, Pruthvisara taila showed more angiogenesis and formation of new blood vessels than standard group and in control group there was absence of formation of new blood vessels and proliferation of fibroblast cells. The control group did not show any collagen formation and scab formation the test drug Pruthvisara taila showed moderate formation and deposition compared to standard drug. Compared to control and standard group, the test drug, Pruthvisara taila selected in this study showed remarkable wound healing property in excised wound.

Poly(vinyl alcohol) /Alginate nanofibrous mats containing Malva Sylvestris extract: Synthesis, characterization, in vitro and in vivo assessments for burn wound applications

An important part of wound healing is providing effective wound care, coupled with preventing wound infection, which slows or disrupts healing. There are currently many herbal plants that have historical supernatural properties that show remarkable wound healing abilities. These herbal extracts have shown promising results when applied to electrospun nanofibrous mats platforms for wound healing. Accordingly, Malva Sylvestris extract (MS) was electrospun into polyvinyl alcohol/alginate nanofibrous mats (PVA/ALG). Field Emission Scanning Electron Microscopy (FESEM) demonstrated that the fiber diameter ranged from approximately 100–200 nm in nanofibrous mats, with a uniform appearance without beads. MS extract was detected in nanofibrous mats by Fourier Transform Infrared Spectroscopy (FTIR). A major benefit of incorporating MS extract into PVA/ALG nanofibrous mats is that their alterations have resulted in enhanced mechanical characteristics. The nanofibrous mats containing MS extracts showed significantly increased antibacterial efficacy against Gram-positive and Gram-negative bacteria. Based on the findings from in vivo experiments, the PVA/ALG/MS1 (M2) dressing demonstrated a wound closure rate of 93–94 % within 21 days of treatment in rats, indicating its significant potential for use as a wound dressing agent in the treatment of burn injuries. The combination of PVA, ALG, and MS1 in this nanofibrous mats exhibited beneficial properties, including biocompatibility, suitable mechanical strength, and the ability to promote cellular proliferation and angiogenesis, further validating its effectiveness as a wound healing dressing.

Dual network composite hydrogels with robust antibacterial and antifouling capabilities for efficient wound healing.

Wound dressings play a critical role in the wound healing process; however, conventional dressings often address singular functions, lacking versatility in meeting diverse wound healing requirements. Herein, dual-network, multifunctional hydrogels (PSA/CS-GA) have been designed and synthesized through a one-pot approach. The in vitro and in vivo experiments demonstrate that the optimized hydrogels have exceptional antifouling properties, potent antibacterial effects and rapid hemostatic capabilities. Notably, in a full-thickness rat wound model, the hydrogel group displays a remarkable wound healing rate exceeding 95% on day 10, surpassing both the control group and the commercial 3M group. Furthermore, the hydrogels exert an anti-inflammatory effect by reducing inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), enhance the release of the vascular endothelial growth factor (VEGF) to promote blood vessel proliferation, and augment collagen deposition in the wound, thus effectively accelerating wound healing in vivo. These innovative hydrogels present a novel and highly effective approach to wound healing.

In situ formed tissue-adhesive carboxymethyl chitosan hydrogels through photoclick chemistry for wound healing

Chitosan-based hydrogels crosslinked through covalent bonds have been extensively researched for their remarkable wound healing properties. However, their practical application has been limited due to the complexity of the preparation process and weak tissue-adhesive strength. In this study, we present a straightforward method for producing tissue-adhesive carboxymethyl chitosan hydrogels consisting of a single component, without the need for an initiator, catalyst, or external crosslinking agent. We synthesized o-nitrobenzyl alcohol-conjugated carboxymethyl chitosan and utilized 365 nm LED light irradiation to self-crosslink the hydrogels through photo-triggered o-nitrobenzyl alcohol and primary amine cyclization. The resulting o-nitrosobenzaldehyde groups not only covalently crosslinked carboxymethyl chitosan chains but also formed robust covalent bonds with the amino groups from the tissue surface, resulting in enhanced adhesion. Furthermore, the hydrogels demonstrated favorable biocompatibility. In vivo studies using a mice full-thickness defect model demonstrated that the hydrogel significantly accelerated wound healing, indicating their potential as a wound repair dressing.

Novel Physically-Crosslinked Caffeine and Vitamin C-Loaded PVA/Aloe Vera Hydrogel Membranes for Topical Wound Healing: Synthesis, Characterization and In-Vivo Wound Healing Tests

Novel physically-crosslinked PVA membranes blended with Aloe vera extract were fabricated by solution-casting method. Physically-crosslinking process is depending on the rearrangement of PVA chains forming intermolecular hydrogen bonding with removal of water molecules using propanol as a stabilizing agent. The structure of crosslinked membranes was characterized by FT-IR, SEM, TGA, and XRD analyses and confirmed via gel faction and swelling ratio studies. Caffeine and vitamin C loaded-PVA/Aloe vera membranes were bio-assessed in terms of their impact on the wound healing using Wistar albino rats as an animal model. In vitro evaluation includes protein adsorption showed that the fabricated membranes improved significantly the wound healing ability via enhancing the tissue platelet aggregation. In addition, resulting adequate in vitro release behavior for the loaded ingredients in the potential application. In-vivo results displayed that rats full-thickness wounds were remarkably reduced after PVA/Aloe vera/Vitamin C membranes treatment, as shown by a reduction in the area of the wounds when compared to wounds treated with cotton gauze and PVA/Aloe vera membranes. Furthermore, the treated wounds with PVA/Aloevera/caffeine show more wound closer comparing to that incorporate vitamin C and the PVA/Aloevera incorporated both caffeine and vitamin C give the most significant healing that show reappearance of hair covered the wound area. Histological examinations of wounds covered in membranes showed a successful re-epithelialization, demonstrating caffeine's and vitamin C’s efficacy. These results demonstrated that, PVA/Aloe Vera/Caffeine and PVA/Aloe vera/vitamin C membrane have remarkable wound healing and skin regeneration properties.Graphical

Fluoride-activated photothermal system for promoting bacteria-infected wound healing

Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F− + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.

Wound Healing Effectivity of Ageratum conyzoides L. Leaf Ethanolic Extract (Purple Flower Type), Centella asiatica (L.) Urban Leaf Ethanolic Extract, and Astaxanthin Combination Gel Preparation in Diabetic Animal Model

The diabetic wounds are one of the global burden diseases. In our previous study, Ageratum conyzoides L. leaf ethanolic extract (purple flower type) 10%, Centella asiatica (L.) Urban leaf ethanolic extract 5%, and astaxanthin 0.1% combination gel preparation showed remarkable wound healing effectivity. However, this wound healing effectivity in the diabetic condition is still unknown. There were three groups used, namely negative group (placebo/gel base), positive group (oxoferin/tetrachlorodecaoxide), and test group (Ageratum conyzoides L. leaf ethanolic extract (purple flower type) 10%, Centella asiatica (L.) Urban leaf ethanolic extract 5%, and astaxanthin 0.1%). Each group consisted of three male Wistar rats. We conducted diabetes induction with alloxan (175 mg/Kg BW i.p) and followed by an incision 1.5 cm on the back. All of these groups were given treatment once daily and monitored for 14 days. The results of the study showed the test group indicated significantly better effectivity than positive and negative groups (p<0.05). The percentages of the wound healing effectivity of the test, positive and negative groups were 62.74%, 51.77%, and 41.65%, respectively. Ageratum conyzoides L. leaf ethanolic extract (purple flower type) 10%, Centella asiatica (L.) Urban leaf ethanolic extract 5%, and astaxanthin 0.1% combination gel preparation has excellent potential to be developed as a commercial product to treat diabetic wound conditions.

In Vivo Evaluation of the Wound Healing Potential of the Aerial Parts of Globularia arabica Aqueous and Methanol Extracts Grown in Jordan

Globularia arabica is a wild, rare, and endangered medicinal plant that is used in folk medicine in Jordan. This study aimed to assess the wound healing potential, total phenol and flavonoid contents, antioxidant activity, and cytotoxic potential of G. arabica extracts that were extracted from the aerial parts. In vivo wound healing assays were performed using an excision wound model in rats. Animals were treated with a hydrogel formula enriched with plant extracts in two different concentrations (2% and 5%). The results demonstrated that wound healing activity was improved and statistically significant (p < 0.05) after topical application of both doses of 2% (w/v) and 5% (w/v) of methanolic (ME) and aqueous extracts (AE) of aerial parts of G. arabica. The total phenol and flavonoid contents were appreciably associated with the reductive capacities of both extracts. With respect to the DPPH, the IC50 was 26.54 mg/mL for AE, while for ME; it was 18.77 mg/mL, ME and AE were selectively noncytotoxic on PDL fibroblasts.ME was exceptionally more effective than AE, exhibiting pronounced viability reduction propensities for aggressively resistant CACO2 cancer cells. While AE was ascribed more substantial growth inhibition properties in T47D breast adenocarcinoma. In conclusion, the study revealed that the ME and AE of G. arabica displayed remarkable wound healing activity, corroborating its traditional use. Moreover, phytochemical fingerprinting of both crude extracts can associate G. arabica'smaximal biological and pharmacological effects with bioactive metabolites.

In vitro wound healing potential of cyclohexane extract of Onosma dichroantha Boiss. based on bioassay-guided fractionation

Onosma dichroantha Boiss. is a biennial herb used in traditional medicine in Iran for healing wounds and burns. Our previous study demonstrated that cyclohexane extract of O. dichroantha Boiss. enhanced wound healing in vitro. The aim of the present study was to identify the active fractions and compounds responsible for this effect through bio-guided fractionation followed by three in vitro tests for anti-inflammation, proliferation, and migration (scratch test). Fractionation of the CE extract yielded six fractions (Fr. A to Fr. F). Fr. F showed the most remarkable wound healing activity in three assays. Fr. F was further fractionated into five subfractions (FF-SUB1 to FF-SUB5). FF-SUB1 and FF-SUB2 were selected for further purification based on their wound healing activity. The major components, F. F1 to F. F5, were isolated from these two subfractions and identified as acetylshikonin, deoxyshikonin, β, β-dimethylacrylshikonin, β-hydroxyisovalerylshikonin, and trans-anethole of the active subfractions. Bioassay-guided fractionation revealed that naphthoquinone derivatives, as an active component, are responsible for the wound healing properties of the fractions and subfractions of cyclohexane extract of O. dichroantha roots. The findings indicate that these fractions and subsections, as well as purified compounds, have a high potential for further investigation as an effective therapeutic agent in wound healing using in vivo models.

Evaluation of the Wound Healing Potential of Hypericum triquetrifolium Turra: An Experimental Animal Study and Histopathological Examination

The wound healing potential of the aerial parts of Hypericum triquetrifolium Turra (Hypericaceae) was evaluated using an in vivo excision wound model in rats. Adult male Sprague Dawley rats were randomly assigned into seven groups; blank vehicles (olive oil and petroleum jelly), negative control, treatments [H. triquetrifolium ethanolic extract in petroleum jelly (5% and 10%) and H. triquetrifolium olive oil macerate (100 and 200 g/L)], and positive control (MEBO). Treatments were applied topically once daily until the wounds had completely healed. Wound areas and contraction rates were calculated, and full-thickness samples of the healed skin were collected for histopathological examination. H. triquetrifolium ointment (5%) showed the best wound healing activity with statistically significant differences when compared with the MEBO, petroleum jelly, and the negative control groups. Tissue sections were histopathologically examined in terms of re-epithelialization, granulation tissue development, collagen deposition, inflammatory cell infiltration, angiogenesis, and ulcer formation to support the in vivo excision wound model findings. H. triquetrifolium ointment (5%) showed the best histopathological scores in both re-epithelialization and ulcer formation. For quality control purposes, a high-performance liquid chromatography (HPLC) method was used to quantify key marker compounds in the extract, namely hypericin and rutin which showed a content of 0.64% and 4.46% (w/w), respectively. Based on the experimental results, H. triquetrifolium ointment (5%) exhibits remarkable wound healing properties at various stages of the wound healing process. Further investigations to prove its safety and efficacy in different types of wounds and to uncover its cellular mechanisms are warranted.

Faster and Protective Wound Healing Mechanistic of Para‐Coumaric Acid Loaded Liver ECM Scaffold Cross‐linked with Acellular Marine Kelp

AbstractDecellularized liver‐derived extracellular matrix is a unique combination of a complex milieu of growth factors and proteins that stimulate biochemical, physical, and mechanical cues to the cells. However, the lack of mechanical strength hindering the applicability of extracellular matrix (ECM) is an outstanding challenge. Herein, to deal with this problem, decellularized kelp is introduced as a crosslinking material thereby strengthening the physical structure of ECM for its utilization as a wound‐healing material. Consequently, a significant architectural change is observed in the ECM by forming a solid‐shaped scaffold. Nevertheless, the hindrance of high pH is addressed by incorporating the acidic drug p‐coumaric acid. To evaluate the innate regenerative abilities, the scaffolds are applied to rat excisional wounds. A remarkable wound healing capability is demonstrated by both the EK scaffolds, but a faster regeneration is achieved with only EK‐20@cou. The speculated hypothesis is that the incorporation of p‐coumaric acid can offer many additional bioactive benefits to the scaffold such as remarkable biocompatibility, antioxidant, and anti‐bacterial properties that are deliberately supported by the in vitro results. In silico molecular simulations (MS) validated that p‐Cou released from the EK‐20@Cou scaffold is accountable for the observed extraordinary regenerative behavior as compared to EK‐20(PW).

In-vivo Wound Healing and Anti-Inflammatory Activity of the Solvent Fraction of Zehneria scabra L.F. Sond (Cucurbitaceae) Leaves.

Wounds continue to be a difficult clinical problem, with early and late consequences causing significant morbidity and death. As a result, proper wound management is critical. In addition to contemporary medicine, medicinal herbs serve an essential role in the treatment of wounds and bacterial infections. Z. scabra is a medicinal plant that has traditionally been used to treat wounds. However, there are no scientific reports on solvent fraction wound healing activities. As a result, the current study presents a scientific assessment of the wound healing ability of the solvent fractions of Z. scabra leaves. The leaves were crushed and macerated three times in 80% methanol. Chloroform, ethyl acetate, and aqueous fractions of simple ointment at 5% w/w and 10 percent w/w strengths were prepared using the fusion technique based on the British Pharmacopoeia. Excision and incision wound models were used to assess the solvent fractions' wound healing activities. The anti-inflammatory efficacy of crude and solvent fractions was tested in mice utilizing a carrageenan-induced hindpaw edema model. In rats, a test dose of 2000 mg/kg of the 10% w/w crude extract ointment was found to be safe. Groups treated with the 5% and 10% ethyl acetate fractions of the extract experienced significant (p<0.05 and p<0.01) wound reduction in the excision wound model. When compared to the negative control, the length of epithelization in groups treated with 10% ethyl acetate fraction and aqueous fractions of Z. scabra was statistically significant (p 0.001). By lowering the amount of carrageenan-induced paw edema, the leaf extract and the chloroform fraction of Z. scabra demonstrated a dose-dependent anti-inflammatory effect. The extract showed remarkable wound healing and anti-inflammatory activity and might be recommended for the treatment of many types of human wounds.

Assessment of solution stability and drug release properties of liposomal curcumin in peritoneal dialysis fluid and its synergistic antibacterial activity with vancomycin

Infectious Peritonitis associated with recurrent and persistent infections is the major cause of technique failure of life-sustaining peritoneal dialysis (PD) therapy used for treating patients with end-stage renal failure (ESRF). The infections -if diagnosed timely- are usually resolved with empiric antibiotic treatment. However, the treatment of infections associated with drug resistant bacteria or fungal infections remains challenging, poses a very serious problem to the health of PD patients, and is the leading cause of mortality and morbidity. Therefore, the development of alternate approaches other than antibiotics are required to keep up with the constantly changing and increasing multiple drug resistance (MDR) of bacterial strains. Curcumin exhibits anti-oxidative/anti-inflammatory potential and remarkable wound healing properties. It also has broad-spectrum anti-bacterial/anti-biofilm effects and its synergistic antibacterial activity with several antibiotics (including those used clinically for the treatment of PD associated infections) is well proven against variety of pathogenic infections including MDR strains. However, poor water-solubility of curcumin (<0.125 mg/L) remains a major barrier to achieve desirable bioavailability and further limit its therapeutic efficacy. Among the various drug carrier strategies, liposomal encapsulation has been found to be most promising mode to remarkably enhance the therapeutic index of curcumin by facilitating its gastric absorption, protecting its enzymatic degradation and allowing its slow release over time for maximum benefits. However, to date, the potential of liposomal curcumin has not been explored for the treatment of PD associated infections. Starting our efforts in this direction, a comprehensive assessment of solution stability and drug release properties of curcumin-loaded liposomal vesicles has been demonstrated in peritoneal dialysis fluid. The results clearly indicated an excellent solution stability of curcumin loaded inside liposome and the formulation affirms the regulated curcumin release enhancing the bioavailability. Further, we evaluated the synergistic antibacterial efficacy of curcumin-loaded liposomal formulation with vancomycin against the Staphylococcus aureus and Escherichia coli – pathogens (known for causing intra-peritoneal infections during PD). This synergy strategy resulted in outstanding improvement in bacterial inhibition efficacy of liposomal curcumin at significantly lowered doses. The results of the present study propose lipocurcumin as a potent antibiotic additive to vancomycin to cure PD-infections caused by antibiotic-resistant bacteria.

Drug Release and Cytotoxicity of Hyaluronic Acid and Zinc Oxide Gels, An In-Vitro Study

ABSTRACT Hyaluronic acid (HA) is a naturally occurring biopolymer, with a remarkable wound healing property. Zinc-oxide non-eugenol is a material widely used for periodontal dressing in dentistry. However, it has been reported that zinc oxide non-eugenol is toxic to osteoblasts and fibroblasts. Hence, the present study aimed to evaluate the drug release and cytotoxicity of HA and zinc-oxide gels. Hydrogels of HA and zinc oxide were formulated with carbopol as a carrier. In vitro drug release was performed by UV spectrophotometry, dialysis, and vial bag methods. Cytotoxicity assessment of HA and zinc-oxide gels was performed in human periodontal ligament fibroblasts (HPdLF) and human gingival fibroblasts (hGFs). An inverted phase-contrast microscope was used to assess the morphological changes. At 24 and 48 hr, HPdLF cells showed the highest viability in 0.1% low molecular weight-HA (LMW-HA) with a median value of 131.9, and hGFs showed the highest viability in 5% LMW-HA with a median of 129.56. The highest viability of HPdLF cells was observed in 5% high molecular weight-HA (HMW-HA), with a median value of 127.11. hGFs showed the highest viability in 1% HMW-HA with a median value of 97.99. Within the limitations of the present study, we concluded that LMW-HA is more efficient than HMW-HA. Both HPdLF and hGF cells showed complete cell morbidity with zinc-oxide hydrogels. Therefore, zinc oxide-based gels in concentrations as low as 9% could be toxic intraorally to soft tissues that harbor gingival and periodontal ligament fibroblasts.

Bacterial exopolysaccharides-mediated synthesis of polymeric silver nanodots with remarkable wound healing properties

Bacterial exopolysaccharides have recently gained much attention due to their widespread biological and therapeutic actions. Here, we describe the process of obtaining exopolysaccharides (EPS) of Lactobacillus gasseri and its characterization using various analytical techniques. Results from gel permeation chromatography and GC-MS analysis revealed that EPS had an average molecular weight of 1.29 × 105 Da and was composed of glucose, mannose, arabinose, and maltose. The exopolysaccharide was observed to possess anti-oxidant, free radical scavenging, hydroxyl radical scavenging, and ferric cyanide reducing capabilities. The reducing tendency of EPS was utilized to synthesize silver nanodots (AgNDs). In comparison to chemically synthesized silver nanoparticles (AgNPs), EPS-mediated AgNDs were found to be smaller in size (5–7 nm vs. 10–40 nm) with more negative surface charge (−33.7 mV vs. −20.5 mV). Interestingly, the cell viability assays (in three different cell lines) demonstrated a dose-dependent response with AgNDs. However, we failed to observe a similar response using chemically synthesized AgNPs, suggesting aggregation of AgNPs at higher concentrations. Moreover, a cream-based formulation of AgNDs was prepared and evaluated for the in-vivo wound healing property. These beneficial properties make the exopolysaccharide a novel, sustainable and eco-friendly candidate for the synthesis of therapeutically active nanomaterials.

CaO-B2O3-SiO2 glass fibers for wound healing

It was reported by Jung and Day in 2011 that a cotton-like glass fiber pad made of borate glass 13-93B3 demonstrated a remarkable wound healing effect. It was approved for sale as a novel wound dressing in the management of acute and chronic wounds in 2016. However, the detailed mechanism of its wound healing effect has not been reported. In the present study, glass fibers of different composition in the system CaO-B2O3-SiO2 were prepared and their in vitro properties investigated to determine the role of the constituent components in wound healing. Fine glass fibers that were 0.6–2.0 μm in diameter were obtained by a melt blown method. However, these fibers were accompanied by small glass beads because of the low viscosity of the glass melts. 13-93B3 glass released an appreciable amount of borate and calcium ions into simulated body fluid (SBF). The amounts of these released ions decreased with partial replacement of the B2O3 in 13-93B3 with SiO2. The addition of large amounts of the borate and calcium ions into the culture medium decreased the viability of the L929 fibroblasts. Partial replacement of the B2O3 in 13-93B3 with SiO2 induced the formation of an apatite-like phase amenable to the adsorption of biological components on its surface in SBF. The wound healing effect of these glass fibers of different composition is worth examining in future animal experiments.

Unilateral zebrafish corneal injury induces bilateral cell plasticity supporting wound closure

The cornea, transparent and outermost structure of camera-type eyes, is prone to environmental challenges, but has remarkable wound healing capabilities which enables to preserve vision. The manner in which cell plasticity impacts wound healing remains to be determined. In this study, we report rapid wound closure after zebrafish corneal epithelium abrasion. Furthermore, by investigating the cellular and molecular events taking place during corneal epithelial closure, we show the induction of a bilateral response to a unilateral wound. Our transcriptomic results, together with our TGF-beta receptor inhibition experiments, demonstrate conclusively the crucial role of TGF-beta signaling in corneal wound healing. Finally, our results on Pax6 expression and bilateral wound healing, demonstrate the decisive impact of epithelial cell plasticity on the pace of healing. Altogether, our study describes terminally differentiated cell competencies in the healing of an injured cornea. These findings will enhance the translation of research on cell plasticity to organ regeneration.