Biological evaluation of critical bone defect regeneration using hydroxyapatite/ alginate composite granules.

PURPOSE: to evaluate biocompatibility and osteogenic potential of hydroxyapatite/alginate composite after its implantation on rat calvarian critical bone defect. METHODS: thirty adults male Wistar rats were randomly distributed into two groups: GHA - critical bone defect filled with hydroxyapatite/alginate composite granules (HA/Alg) and CG - critical bone defect without biomaterial; evaluated at biological points of 15, 45 and 120 days. RESULTS: the histomorphometrically analyses for GHA showed osteoid matrix deposition (OM) among the granules and towards the center of the defect in centripetal direction throughout the study, with evident new bone formation at 120 days, resulting in filling 4/5 of the initial bone defect. For CG, this finding was restricted to the edges of the bone margins and formation of connective tissue on the residual area was found in all biological points. Inflammatory response on GHA was chronic granulomatous type, discrete and regressive for all biological points. Throughout the study, the CG presented mononuclear inflammatory infiltrate diffuse and regressive. Histomorphometry analyses showed that OM percentage was evident for GHA group when compared to CG group in all analyzed periods (p > 0.05). CONCLUSIONS: the biomaterial evaluated at this study showed to be biocompatible, bioactive, osteoconductive and biodegradable synchronously with bone formation.

Platelet-rich fibrin (PRF) modified nano-hydroxyapatite/chitosan/gelatin/alginate scaffolds increase adhesion and viability of human dental pulp stem cells (DPSC) and osteoblasts derived from DPSC.

Bone tissue regeneration strategies have incorporated the use of natural polymers, such as hydroxyapatite (nHA), chitosan (CH), gelatin (GEL), or alginate (ALG). Additionally, platelet concentrates, such as platelet-rich fibrin (PRF) have been suggested to improve scaffold biocompatibility. This study aimed to develop scaffolds composed of nHA, GEL, and CH, with or without ALG and lyophilized PRF, to evaluate the scaffold's properties, growth factor release, and dental pulp stem cells (DPSC), and osteoblast (OB) derived from DPSC viability. Four scaffold variations were synthesized and lyophilized. Then, degradation, swelling profiles, and morphological analysis were performed. Furthermore, PDGF-BB and FGF-B growth factors release were quantified by ELISA, and cytotoxicity and cell viability were evaluated. The swelling and degradation profiles were similar in all scaffolds, with pore sizes ranging between 100 and 250 µm. FGF-B and PDGF-BB release was evidenced after 24 h of scaffold immersion in cell culture medium. DPSC and OB-DPSC viability was notably increased in PRF-supplemented scaffolds. The nHA-CH-GEL-PRF scaffold demonstrated optimal physical-biological characteristics for stimulating DPSC and OB-DPSC cell viability. These results suggest lyophilized PRF improves scaffold biocompatibility for bone tissue regeneration purposes.

Addition of synthetic polymers to a conventional cryoprotectant solution in the vitrification of bovine ovarian tissue.

Some synthetic polymers can be used at low concentrations to reduce the toxicity of conventional cryoprotectant agents. In this study we investigated whether the addition of synthetic polymers to a conventional cryoprotectant solution would improve the cryopreservation of bovine ovarian tissue. Freshly collected ovaries from ten adult crossbred cows were incised using a scalpel in the frontal section. From each cow, ovarian cortical slices of 1 mm thickness were divided into 30 fragments of 3 × 3 mm, of which 10 served as fresh controls, 10 were vitrified with conventional cryoprotectant agents (2.93 M glycerol, 27 % w/v; 4.35 M ethylene glycol, 27 % w/v), and 10 were vitrified using the same cryoprotectant agents in addition to synthetic polymers (0.2 % PVP K-12, 0.2 % SuperCool X-1000 ™ w/v and 0.4 % SuperCool Z-1000 ™ w/v). After warming, histology was used to assess follicular quantity and integrity, while in vitro culture of mechanically isolated follicles encapsulated in an alginate matrix was performed for 15 days to assess their growth and hormonal production. Vitrified ovarian tissues presented abnormal morphology, a higher percentage of atretic follicles, and their isolated follicles had lower survival rates and lower frequency of antrum formation during in vitro culture compared to those from fresh tissue. At the end of culture, the follicles that had been cryopreserved produced less estradiol and progesterone than the fresh ones. The addition of synthetic polymers during tissue vitrification did not modify any of these parameters. We conclude that, under the conditions of this study, the use of this combination of synthetic polymers for tissue vitrification did not enhance the preservation of the morphological or functional integrity of bovine ovarian follicles.

Fabrication and characterization of physically crosslinked alginate/chitosan-based hydrogel loaded with neomycin for the treatment of skin infections caused by Staphylococcus aureus.

Staphylococcus aureus is a pathogen widely involved in wound infection due to its ability to release several virulence factors that impair the skin healing process, as well as its mechanism of drug resistance. Herein, sodium alginate and chitosan were combined to produce a hydrogel for topical delivery of neomycin to combat S. aureus associated with skin complications. The hydrogel was formulated by combining sodium alginate (50 mg/mL) and chitosan (50 mg/mL) solutions in a ratio of 9:1 (HBase). Neomycin was added to HBase to achieve a concentration of 0.4 mg/mL (HNeo). The incorporation of neomycin into the product was confirmed by scanning electron microscopy, FTIR and TGA analysis. The hydrogels produced are homogeneous, have a high swelling capacity, and show biocompatibility using erythrocytes and fibroblasts as models. The formulations showed physicochemical and pharmacological stability for 60 days at 4 ± 2 °C. HNeo totally inhibited the growth of S. aureus after 4 h. The antimicrobial effects were confirmed using ex vivo (porcine skin) and in vivo (murine) wound infection models. Furthermore, the HNeo-treated mice showed lower severity scores than those treated with HBase. Taken together, the obtained results present a new low-cost bioproduct with promising applications in treating infected wounds.

3D Bioprinting of Biomimetic Alginate/Gelatin/Chondroitin Sulfate Hydrogel Nanocomposites for Intrinsically Chondrogenic Differentiation of Human Mesenchymal Stem Cells.

3D-printed hydrogel scaffolds biomimicking the extracellular matrix (ECM) are key in cartilage tissue engineering as they can enhance the chondrogenic differentiation of mesenchymal stem cells (MSCs) through the presence of active nanoparticles such as graphene oxide (GO). Here, biomimetic hydrogels were developed by cross-linking alginate, gelatin, and chondroitin sulfate biopolymers in the presence of GO as a bioactive filler, with excellent processability for developing bioactive 3D printed scaffolds and for the bioprinting process. A novel bioink based on our hydrogel with embedded human MSCs presented a cell survival rate near 100% after the 3D bioprinting process. The effects of processing and filler concentration on cell differentiation were further quantitatively evaluated. The nanocomposited hydrogels render high MSC proliferation and viability, exhibiting intrinsic chondroinductive capacity without any exogenous factor when used to print scaffolds or bioprint constructs. The bioactivity depended on the GO concentration, with the best performance at 0.1 mg mL-1. These results were explained by the rational combination of the three biopolymers, with GO nanoparticles having carboxylate and sulfate groups in their structures, therefore, biomimicking the highly negatively charged ECM of cartilage. The bioactivity of this biomaterial and its good processability for 3D printing scaffolds and 3D bioprinting techniques open up a new approach to developing novel biomimetic materials for cartilage repair.

Berberine-fluconazole microparticle-based combination therapy to treat candidiasis infections.

AIM: This study aims to incorporate alginate microparticles containing berberine and fluconazole into two different types of pharmaceutical formulations, to subsequently evaluate the antifungal activity against Candida albicans. METHODS AND RESULTS: Alginate microparticles containing BBR (berberine) and FLU (fluconazole) were produced by the spray-drying technique, characterized and incorporated in two pharmaceutical formulations, a vaginal cream and artificial saliva. Broth microdilution, checkerboard, time-kill curve, and scanning electron microscopy were carried out to determine the antifungal effects of BBR and FLU against C. albicans. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values of free BBR were 125 µg ml-1. Synergism between BBR and FLU was demonstrated by a fractional inhibitory concentration index (FICI) = 0.0762. The time-kill curve for the combination BBR + FLU showed a more pronounced decrease in fungal growth in comparison to free drugs, and an antibiofilm effect of BBR occurred in the formation and preformed biofilm. CONCLUSION: Alginate microparticles containing BBR and FLU were obtained and incorporated in a vaginal cream and artificial saliva. Both formulations showed good stability, antifungal effects, and organoleptic characteristics, which suggest that BBR-FLU microparticles in formulations have potential as antifungal therapy.

Effect of slow-release urea on intake, ingestive behavior, digestibility, nitrogen metabolism, microbial protein production, blood and ruminal parameters of sheep.

We conducted two experiments. The first aimed to obtain and characterize microparticles of slow-release urea (SRU) using calcium alginate as the encapsulating agent. The second experiment evaluated their inclusion in sheep diets. In the first experiment, four treatments from a completely randomized design were employed to develop an SRU through the ionic gelification technique testing two drying methods (oven and lyophilizer) and addition or no of sulfur (S): SRU oven-dried with sulfur (MUSO) and without sulfur (MUO), SRU freeze-dried/lyophilized with (MUSL), and without sulfur (MUL). MUO exhibited better yield and encapsulation efficiency among these formulations than the others. Therefore, the second experiment was conducted to compare free urea (U) as control and three proportions (1%, 1.5%, and 2% of total dry matter) of MUO in the diet of sheep. Twenty-four non-castrated male Santa Ines lambs, with an average body weight of 22 ± 3.0 kg, were used and distributed in a completely randomized design with four treatments and six replications. The inclusion of 1% alginate-encapsulated urea (MUO1%) resulted in higher dry matter (DM) intake than free urea (p ≤ 0.05). MUO2% inclusion promoted higher NDF digestibility than U and MUO1%. MUO1% showed higher DM than MUO2% and higher NFC digestibility than U and MUO2% (p ≤ 0.05). Sheep fed MUO1.5% and MUO2% exhibited similar nutrient intake and digestibility. Sheep receiving MUO1% had higher N-intake, N-urinary, N-excretion total, N-digested, and N-retained compared to U. Sheep fed MUO1% showed greater N-retained (as % ingested and digested), microbial protein production, and efficiency when compared to other treatments (p ≤ 0.05). MUO2% addition (SRU) promoted the lowest microbial protein production and efficiency in sheep. MUO dietary inclusion increased feeding time and reduced idleness time compared to U, regardless of the MUO level (p ≤ 0.05). Adding MUO1% improved the intake efficiency of DM and NDF and resulted in more feed boli than the other MUO levels (p ≤ 0.05). Sheep receiving U had (4 h after fending) higher NH3-N, pH, and blood urea nitrogen (BUN) and lower TGL serum compared to sheep fed MUO (p ≤ 0.05), without significant difference among MUO levels (p > 0.05), except NH3-N was higher in MUO1.5% and MUO2% compared to MUO1.0%. The external ionic gelation technique proved suitable for urea microencapsulation in calcium alginate (3%), demonstrating high quality, efficiency, and yield. MUO represents a promising slow-release urea for ruminants and is recommended for sheep diets at an inclusion level of 1.0%. This inclusion level improves intake efficiency and nutrient digestibility, increases rumen nitrogen retention, and reduces BUN without compromising sheep health.

Agaricus blazei Murill extract-loaded in alginate/poly(vinyl alcohol) films prepared by Ca2+ cross-linking for wound healing applications.

This work aimed the development and evaluation of the wound healing activity of films based on sodium alginate, polyvinyl alcohol (PVA) and Ca2+ loaded with Agaricus blazei Murill hydroalcoholic extract (AbE). Firstly, AbE was prepared using a previously standardized methodology. The films were prepared by casting technique and cross-linked with Ca2+ using CaCl2 as cross-linking agent. The physicochemical, morphological and water vapor barrier properties of the films were analyzed and the pre-clinical efficacy was investigated against the cutaneous wound model in mice. The films showed barrier properties to water vapor promising for wound healing. AbE showed physical and chemical interactions between both polymers, noticed by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and thermal analysis. The delivery of AbE in alginate/PVA films enhanced the antioxidant and wound healing properties of these polymers. Consequently, a reduction of malondialdehyde levels was observed, as well as an increase of the epidermis/dermis thickness and enhancement in collagen I deposition. Thus, these formulations are promising biomaterials for wound care and tissue repairing.

Development of a photosynthetic hydrogel as potential wound dressing for the local delivery of oxygen and bioactive molecules.

The development of biomaterials to improve wound healing is a critical clinical challenge and an active field of research. As it is well described that oxygen plays a critical role in almost each step of the wound healing process, in this work, an oxygen producing photosynthetic biomaterial was generated, characterized, and further modified to additionally release other bioactive molecules. Here, alginate hydrogels were loaded with the photosynthetic microalgae Chlamydomonas reinhardtii, showing high integration as well as immediate oxygen release upon illumination. Moreover, the photosynthetic hydrogel showed high biocompatibility in vitro and in vivo, and the capacity to sustain the metabolic oxygen requirements of zebrafish larvae and skin explants. In addition, the photosynthetic dressings were evaluated in 20 healthy human volunteers following the ISO-10993-10-2010 showing no skin irritation, mechanical stability of the dressings, and survival of the photosynthetic microalgae. Finally, hydrogels were also loaded with genetically engineered microalgae to release human VEGF, or pre-loaded with antibiotics, showing sustained release of both bioactive molecules. Overall, this work shows that photosynthetic hydrogels represent a feasible approach for the local delivery of oxygen and other bioactive molecules to promote wound healing. STATEMENT OF SIGNIFICANCE: As oxygen plays a key role in almost every step of the tissue regeneration process, the development of oxygen delivering therapies represents an active field of research, where photosynthetic biomaterials have risen as a promising approach for wound healing. Therefore, in this work a photosynthetic alginate hydrogel-based wound dressing containing C. reinhardtii microalgae was developed and validated in healthy skin of human volunteers. Moreover, hydrogels were modified to additionally release other bioactive molecules such as recombinant VEGF or antibiotics. The present study provides key scientific data to support the use of photosynthetic hydrogels as customizable dressings to promote wound healing.

Ionic complexation improves wound healing in deep second-degree burns and reduces in-vitro ciprofloxacin cytotoxicity in fibroblasts.

The development of new treatments capable of controlling infections and pain related to burns continues to be a challenge. Antimicrobials are necessary tools, but these can be cytotoxic for regenerating cells. In this study, antibiotic-anesthetic (AA) smart systems obtained by ionic complexation of polyelectrolytes with ciprofloxacin and lidocaine were obtained as films and hydrogels. Ionic complexation with sodium alginate and hyaluronate decreased cytotoxicity of ciprofloxacin above 70% in a primary culture of isolated fibroblasts (p < 0.05). In addition, the relative levels of the proteins involved in cell migration, integrin ß1 and p-FAK, increased above 1.5 times (p < 0.05) with no significant differences in cell mobility. Evaluation of the systems in a deep second-degree burn model revealed that reepithelization rate was AA-films = AA-hydrogels > control films > no treated > reference cream (silver sulfadiazine cream). In addition, appendage conservation and complete dermis organization were achieved in AA-films and AA-hydrogels. Encouragingly, both the films and the hydrogels showed a significantly superior performance compared to the reference treatment. This work highlights the great potential of this smart system as an attractive dressing for burns, which surpasses currently available treatments.

Chitosan nanoparticles containing the insecticide dimethoate: A new approach in the reduction of harmful ecotoxicological effects.

Organophosphate insecticides such as dimethoate (DMT) are widely used in agriculture. As a side effect, however, these insecticides contaminate bodies of water, resulting in damage to aquatic organisms. The development of nanopesticides may be an innovative alternative in the control of agricultural pests, increasing effectiveness and reducing their toxicological effects. Based upon this, the present study has investigated encapsulated DMT in alginate chitosan nanoparticles (nanoDMT) and evaluated its toxicological effects on non-target organisms. The nanoparticles were characterized by DLS, NTA and AFM, as well as being evaluated by the release profile. Nanoparticle toxicity was also evaluated in comparison with DMT, empty nanoparticles and DMT (NP + DMT), and commercial formulations (cDMT), in the embryos and larvae of Danio rerio (zebrafish) according to lethality, morphology, and behavior. The nanoparticle control (NP) showed hydrodynamic size values of 283 ± 4 nm, a PDI of 0.5 ± 0.05 and a zeta potential of -31 ± 0.4 mV. For nanoparticles containing dimethoate, the nanoparticles showed 301 ± 7 nm size values, a PDI of 0.45 ± 0.02, a zeta potential of -27.9 ± 0.2 mV, and an encapsulation of 75 ± 0.32%, with slow-release overtime (52% after 48 h). The AFM images showed that both types of nanoparticles showed spherical morphology. Major toxic effects on embryo larval development were observed in commercial dimethoate exposure followed by the technical pesticide, predominantly in the highest tested concentrations. With regard to the toxic effects of sodium alginate/chitosan, although there was an increase for LC50-96 h concerning the technical dimethoate, the behavior of the larvae was not affected. The data obtained demonstrate that nanoencapsulated dimethoate reduces the toxicity of insecticides on zebrafish larvae, suggesting that nanoencapsulation may be safer for non-target species, by eliminating collateral effects and thus promoting sustainable agriculture.

UVA as environmental signal for alginate production in Pseudomonas aeruginosa: role of this polysaccharide in the protection of planktonic cells and biofilms against lethal UVA doses.

Pseudomonas aeruginosa is an extremely versatile microorganism that survives in a wide variety of niches. It is capable to respond rapidly to changes in the environment by producing secondary metabolites and virulence factors, including alginate. Alginate is an extracellular polysaccharide that protects the bacteria from antibiotics and oxidative agents, and enhances cell adhesion to solid surfaces in the process of biofilm formation. In the present study, we analyzed the role of alginate in the response of P. aeruginosa to lethal doses of ultraviolet-A (UVA) radiation, the major fraction of solar UV radiation reaching the Earth's surface. We also studied the role of alginate in the context of the adaptive responses generated when P. aeruginosa is exposed to sublethal doses of UVA radiation. The survival studies demonstrated that alginate has a key role in the resistance of P. aeruginosa to the oxidative stress generated by lethal UVA doses, both in planktonic cells and in static biofilms. In addition, the presence of alginate proved to be essential in the occurrence of adaptive responses such as induction of biofilm formation and cross-protection against hydrogen peroxide and sodium hypochlorite, both generated by exposure to low UVA doses. Finally, we demonstrated that the increase of biofilm formation is accompanied by an increase in alginate concentration in the biofilm matrix, possibly through the ppGpp-dependent induction of genes related to alginate regulation (algR and algU) and biosynthesis (algD operon). Given the importance of alginate in biofilm formation and its protective roles, better understanding of the mechanisms associated to its functions and synthesis is relevant, given the normal exposure of P. aeruginosa to UVA radiation and other types of oxidative stresses.

Potential Alendronate Sodium drug carrier by preparation and characterization of sodium alginate cross-linked Montmorillonite

Abstract In drug therapy, it is important to provide therapeutic levels of drug to the site of action and maintain them during the treatment. This work describes the in vitro release of alendronate from sodium alginate cross-linked Montmorillonite (MMT) composite beads. Effect of crosslinking cation, concentration of montmorillonite and media on encapsulation efficiencies, and release profiles of alendronate were studied. Beads were characterized using equilibrium swelling ability study, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Energy-dispersive x-ray spectroscopy (EDX) and scanning electron microscopy (SEM). Results indicate that addition of montmorillonite increases the encapsulation efficiencies and slows down the release rates significantly.

Alginate-amphotericin B nanocomplexes covered by nanocrystals from bacterial cellulose: physico-chemical characterization and in vitro toxicity.

Nanocomplexes systems made up natural poylymers have pharmacotechnical advantages such as increase of water solubility and a decrease of drugs toxicity. Amphotericin B (AmB) is a drug apply as anti-leishmanial and anti-fungal, however it has low water solubility and high toxicity, limiting its therapeutic application. With this in mind, the present study aimed to produce nanocomplexes composed by alginate (Alg), a natural polymer, with AmB covered by nanocrystals from bacterial cellulose (CNC). For this reason, the nanocomplexes were produced utilizing sodium alginate, amphotericin B in a borate buffer (pH 11.0). The CNC was obtained by enzymatic hydrolysis of the bacterial cellulose. To CNC cover the nanocomplexes 1 ml of the nanocomplexes was added into 1 ml of 0.01% CNC suspension. The results showed an ionic adsorption of the CNC into the Alg-AmB nanocomplexes surface. This phenomena was confirmed by an increase in the particle size and PDI decrease. Besides, nanocomplexes samples covered by CNC showed uniformity. The amorphous inclusion of AmB complex into the polysaccharide chain network in both formulations. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic compared to the free-drug. The in vitro toxicity results indicated the Alg-AmB nanocomplexes can be considered a non-toxic alternative to improve the AmB therapeutic effect. All process to obtain nanocomplexes and it coat was conduce without organic solvents, can be considered a green process, and allowed to obtain water soluble particles. Furthermore, CNC covering the nanocomplexes brought additional protection to the system can contribut advancement in the pharmaceutical.

Influence of the macromolecular crowder alginate in the fibrillar organization of the functional amyloid FapC from Pseudomonas aeruginosa.

Bacterial biofilms are an alternative lifestyle in which communities of bacteria are embedded in an extracellular matrix manly composed by polysaccharides, nucleic acids and proteins, being the hallmark of bacterial survival in a variety of ecological niches. Amyloid fibrils are one of the proteinaceous components of such extracellular crowded environments. FapC is the main component of the functional amyloid recently discovered in Pseudomonas species, including the opportunistic pathogen P. aeruginosa, which is a major cause of nosocomial infections and contamination of medical devices. Considering that several functional roles have been attributed to this bacterial amyloid, FapC emerged as a novel target to control Pseudomonas biofilm formation and to design new treatments against chronic infections. In this study, we used complementary biophysical techniques to evaluate conformational signatures of FapC amyloids formed in the presence of alginate, the major exopolysaccharide associated with the mucoid phenotype of P. aeruginosa strains isolated from cystic fibrosis patients. We found that the this naturally occurring macromolecular crowder leads to morphological similar yet polymorphic FapC fibrils, highlighting the importance of considering the complexity of the extracellular matrix in order to improve our understanding of microbial functional amyloids.

Alginate-chitosan microcapsules improve vaccine potential of gamma-irradiated Listeria monocytogenes against listeriosis in murine model.

Listeria monocytogenes is a cause of infectious food-borne disease in humans, characterized by neurological manifestations, abortion, and neonatal septicemia. It is intracellular bacterium, which limits the development of protective inactivated vacines. Adjuvants capable of stimulating cellular immune response are important tools for developing novel vaccines against intracellular bacteria. The aim of this study was to evaluate the vaccine potential of L. monocytogenes inactivated by gamma irradiation (KLM-γ) encapsulated in alginate microcapsules associated or not with chitosan against listeriosis in the murine model. At the fourth day after challenge there was a reduction in bacterial recovery in mice vaccinated with KLM-γ encapsulated with alginate or alginate-chitosan, with lower bacterial loads in the spleen (10 fold) and liver (100 fold) when compared to non-vaccinated mice. In vitro stimulation of splenocytes from mice vaccinated with alginate-chitosan-encapsulated KLM-γ resulted in lymphocyte proliferation, increase of proportion of memory CD4+ and CD8+ T cell and production of IL-10 and IFN-γ. Interestingly, the group vaccinated with alginate-chitosan-encapsulated KLM-γ had increased survival to lethal infection with lower L. monocytogenes-induced hepatic inflammation and necrosis. Therefore, KLM-γ encapsulation with alginate-chitosan proved to have potential for development of novel and safe inactivated vaccine formulations against listeriosis.

Evaluation of wound healing effect of alginate film containing Aloe vera gel and cross-linked with zinc chloride.

PURPOSE: To develop a new wound dressing composed of alginate and Aloe vera gel and cross-linked with zinc ions. METHODS: The aloe-alginate film was characterized using scanning electron microscopy (SEM), swelling profile, mechanical properties, polysaccharide content and X-ray diffraction (XRD). Thirty Wistar rats were divided in two groups a) treated with aloe-alginate film and b) control (treated with sterile gauze). Wound contraction measurements and hystological analysis were performed on 7th, 14th and 21st days after wound surgery. RESULTS: The aloe-alginate film presented adequated mechanical resistance and malleability for application as wound dressing. There was no statistical difference in wound contraction between two groups. Histological assay demonstrated that aloe-alginate film presented anti-inflammatory activity, stimulated angiogenesis on proliferative phase and a more significant increased in collagen type I fibers and decreased type III fibers which promoted a mature scar formation when compared to control. CONCLUSIONS: The aloe-alginate film showed adequate physicochemical characteristics for wound dressing applications. The in vivo assay demonstrated that aloe-alginate film enhanced the healing process of incisional skin wounds.

Effects of Hydrogel With Enriched Sodium Alginate in Wounds of Diabetic Patients.

Objective of this study was to evaluate the efficacy of the autolytic debridement promoted by hydrogel with sodium alginate enriched with fatty acids and vitamins A and E in the healing of foot wounds in diabetic patients. A clinical study was conducted at an outpatient clinic of medical specialties. The sample comprised 8 patients supervised for a 3-month period, from April to July 2017, by means of a clinical history, photographic record, planimetry, and classification of the wound severity by the Pressure Ulcer Scale for Healing (PUSH) system. Of the 8 patients supervised, 1 dropped out and 7 were followed up for 12 weeks. Only 2 had complete wound healing, but all presented a reduction of the lesion area of approximately 22.2% and PUSH score of 9.8 to 6.6. This study found that hydrogel showed good results for the treatment of diabetic feet, reducing the area and overall PUSH score of the wounds.

Injectable in situ forming nanogel: A hybrid Alginate-NLC formulation extends bupivacaine anesthetic effect.

Finding an ideal anesthetic agent for postoperative pain control, with long action and low side effects, is still a challenge. Local anesthetics have potential for such application if their time of action is improved. This work introduces a new hybrid formulation formed by the association of a nanostructured lipid carrier with a biopolymeric system to encapsulate bupivacaine (BVC). The hybrid formulation was physicochemical and structurally characterized by DLS, TEM, DSC, XRD and FTIR-ATR, and it remained stable for 12 months at room temperature. In vivo analgesia and imaging tests showed that the hybrid system was able to modulate the release, and to increase the concentration of BVC at the site of action, by forming a nanogel in situ. Such nanogel improved over 5 times (>24 h) the anesthesia duration, when compared to free BVC at clinical (0.5%) doses. Therefore, this novel in situ-forming nanogel shows great potential to be used in postsurgical pain control, improving the action of BVC, without losing its versatility of (infiltrative) application.

Biological evaluation of zinc-containing calcium alginate-hydroxyapatite composite microspheres for bone regeneration.

Zinc is an important element for bone structure and metabolism. Its interaction with hydroxyapatite has been investigated for the improvement of bone repair. The objective of this study was to evaluate the in vitro and in vivo biological response to nanostructured calcium alginate-hydroxyapatite (HA) and zinc-containing HA (ZnHA). Cytocompatibility was evaluated by applying PrestoBlue reagent after exposing murine pre-osteoblast cells to extracts of each biomaterial microspheres. After physical and chemical characterization, the biomaterial microspheres were implanted in a critical size calvaria defect (8 mm) in Wistar rats (n = 30) that were randomly divided into the HA and ZnHA groups. Tissue samples were evaluated through histological and histomorphometric analyses after 1, 3, and 6 months (n = 5). The results showed cellular viability for both groups compared to the negative control, and no differences in metabolic activity were observed. The HA group presented a significant reduction of biomaterial compared with the ZnHA group in all experimental periods; however, a considerable amount of new bone formation was observed surrounding the ZnHA spheres at the 6-month time point compared with the HA group (p < .05). Both biomaterials were biocompatible, and the combination of zinc with hydroxyapatite was shown to improve bone repair.