sepharose and Burns

Overcoming bacterial infections and promoting wound healing are significant challenges in clinical practice and fundamental research. This study developed a series of enzymatic crosslinking injectable hydrogels based on silk fibroin (SF), carboxymethyl cellulose (CMC), and agarose, with the addition of polydopamine functionalized graphene oxide (GO@PDA) to endow the hydrogel with suitable conductivity and antimicrobial activity. The hydrogels exhibited suitable gelation time, stable mechanical and rheological properties, high water absorbency, and hemostatic properties. Biocompatibility was also confirmed through various assays. After loading the antibiotic vancomycin hydrochloride, the hydrogels showed sustained release and good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The fast gelation time and desirable tissue-covering ability of the hydrogels allowed for a good hemostatic effect in a rat liver trauma model. In a rat full-thickness burn wound model, the hydrogels exhibited an excellent treatment effect, leading to significantly enhanced wound closure, collagen deposition, and granulation tissue formation, as well as neovascularization and anti-inflammatory effects. In conclusion, the antibacterial electroactive injectable hydrogel dressing, with its multifunctional properties, significantly promoted the in vivo wound healing process, making it an excellent candidate for full-thickness skin wound healing.

Topics: Animals; Anti-Bacterial Agents; Antioxidants; Burns; Carboxymethylcellulose Sodium; Fibroins; Hemostasis; Hemostatics; Hydrogels; Methicillin-Resistant Staphylococcus aureus; Rats; Sepharose; Skin; Wound Healing

Bioactive dressings are usually produced using natural or synthetic polymers. Recently, special attention has been paid to β-glucans that act as immunomodulators and have pro-healing properties. The aim of this research was to use β-1,3-glucan (curdlan) as a base for the production of bioactive dressing materials (curdlan/agarose and curdlan/chitosan) that were additionally enriched with vitamin C and/or hydrocortisone to improve healing of chronic and burn wounds. The secondary goal of the study was to compressively evaluate biological properties of the biomaterials. In this work, it was shown that vitamin C/hydrocortisone-enriched biomaterials exhibited faster vitamin C release profile than hydrocortisone. Consecutive release of the drugs is a desired phenomenon since it protects wounds against accumulation of high and toxic concentrations of the bioactive molecules. Moreover, biomaterials showed gradual release of low doses of the hydrocortisone, which is beneficial during management of burn wounds with hypergranulation tissue. Among all tested variants of biomaterials, dressing materials enriched with hydrocortisone and a mixture of vitamin C/hydrocortisone showed the best therapeutic potential since they had the ability to significantly reduce MMP-2 synthesis by macrophages and increase TGF-β1 release by skin cells. Moreover, materials containing hydrocortisone and its blend with vitamin C stimulated type I collagen deposition by fibroblasts and positively affected their migration and proliferation. Results of the experiments clearly showed that the developed biomaterials enriched with bioactive agents may be promising dressings for the management of non-healing chronic and burn wounds.

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Bandages; beta-Glucans; Burns; Collagen Type I; Drug Therapy, Combination; Fibroblasts; Humans; Hydrocortisone; Keratinocytes; Sepharose; Wound Healing

Wound infections cause inflammation, tissue damage, and delayed healing that can lead to invasive infection and even death. The efficacy of systemic antibiotics is limited due to poor tissue penetration that is especially a problem in burn and blast wounds where the microcirculation is disrupted. Topical administration of antimicrobials is an attractive approach because it prevents infection and avoids systemic toxicity, while hydrogels are an appealing vehicle for topical drug delivery. They are easy to apply to the wound site by being injectable, the drug release properties can be controlled, and their many characteristics, such as biodegradation, mechanical strength, and chemical and biological response to stimuli can be tailored. Hydrogels also create a moist wound environment that is beneficial for healing. The purpose of this study was to formulate an agarose hydrogel that contains high concentrations of minocycline or gentamicin and study its characteristics. Subsequently, the minocycline agarose hydrogel was tested in a porcine burn model and its effect as a prophylactic treatment was studied. The results demonstrated that 0.5% agarose in water was the optimal concentration in terms of viscosity and pH. Bench testing at room temperature demonstrated that both antibiotics remained stable in the hydrogel for at least 7 days and both antibiotics demonstrated sustained release over the time of the experiment. The porcine burn experiment showed that prophylactic treatment with the agarose minocycline hydrogel decreased the burn depth and reduced the number of bacteria as efficiently as the commonly used silver sulfadiazine cream.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Burns; Drug Stability; Gentamicins; Hydrogels; Hydrogen-Ion Concentration; Minocycline; Models, Animal; Rheology; Sepharose; Swine; Wound Healing; Wound Infection

In serum from 8 severely burned patients, haptoglobin (Hp), alpha 1-acid glycoprotein (AG) and alpha 1-antitrypsin (AT) were found to be increased by factors of 5, 6 and 2 respectively. Ceruloplasmin (Cp) was slightly decreased. In order to appreciate possible modifications to the structure of their attached N-glycans, whole sera were fractionated on concanavalin A (Con A)-Sepharose and respective glycoproteins measured by laser nephelometry using a monospecific antiserum. In the serum from normal as well as burned patients Hp was almost entirely bound to the immobilized lectin (but eluted with 300 mmol/l alpha 1-methylglucoside) and Cp was bound at about 92%. For AG, in contrast, the fraction without affinity for Con A, 25% in normal serum, decreased to 5% in patients, whereas the retained species increased in proportion. A very weakly reactive fraction (which was only retarded and eluted without alpha-methylglucoside) amounted to 72% in both types of serum. When reduced and alkylated, this intermediate fraction gave rise to both non-retained and retained species always in a proportion of about 1/3. On the whole one concludes that there is a significant shift for AG in burned patients towards species enriched in bi-antennary (Con A-reactive) glycans. For AT a minor part was not recognized by the lectin and about 27% was retarded. The latter, which increased in burned patients, gave rise mainly to retained species after reduction and alkylation. This again suggests a shift to bi-antennary glycans.

Topics: Acute-Phase Proteins; alpha 1-Antitrypsin; Blood Proteins; Burns; Ceruloplasmin; Chromatography, Affinity; Concanavalin A; Glycoproteins; Haptoglobins; Humans; Immunoglobulins; Isoelectric Focusing; Polysaccharides; Sepharose