New approaches to second-degree burn healing: Polyvinyl alcohol membrane loaded to arnica combined to laser therapy.

Second-degree burns require greater care, as the damage is more extensive and worrisome and the use of a biomaterial can help in the cell repair process, with better planning, low cost, and better accessibility. Arnica has anti-inflammatory and analgesic properties in skin lesions treatments and laser therapy is another therapeutic alternative for burns. Evaluate the effects of arnica incorporated into PVA associated or not with low intensity laser on burns in rats. PVA and PVA with arnica (PVA+A) were obtained and characterized physicochemically. Through in vivo studies, the effects of PVA and PVA+A with or without the application of laser on the lesions allowed histological and immunohistochemical analyzes. PVA+A was biocompatible and with sustained release of the active, being a promising pharmacological tool and confirmed that laser therapy was effective in accelerating the healing process, due to its potential biomodulator, improving inflammatory aspects, promoting rapid healing in skin lesions.

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24 weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

Synthesis of epoxidized natural rubber grafted with hyaluronic acid for the development of biomaterials.

Natural Rubber (NR), extracted from Hevea brasiliensis rubber trees, is a biocompatible biopolymer with properties that support in the tissue repair process. However, its biomedical applications are limited due to the presence of allergenic proteins, hydrophobicity, and unsaturated bonds. To overcome these limitations and contribute to the development of new biomaterials, this study aims to deproteinize, epoxidize, and subject NR to copolymerization by grafting with hyaluronic acid (HA), which is widely recognized for its bioactive properties in the medical field. The deproteinization, epoxidation, and graft copolymerization through the esterification reaction were confirmed by Fourier Transform Infrared Spectroscopy and Hydrogen Nuclear Magnetic Resonance Spectroscopy analysis. Thermogravimetry and Differential Scanning Calorimetry demonstrated that the grafted sample exhibited a lower degradation rate and a higher glass transition temperature, indicating strong intermolecular interactions. Moreover, contact angle measurement revealed that the grafted NR exhibited a high hydrophilic character. The results obtained suggest the formation of a novel material with great potential for application in biomaterials involved in tissue repair processes.

Electrospun Membrane Based on Poly(L-co-D,L lactic acid) and Natural Rubber Containing Copaiba Oil Designed as a Dressing with Antimicrobial Properties.

Drug delivery systems of natural antimicrobial compounds, such as copaiba oil (CO), have become relevant in the scientific community due to the recent prevalence of the public health complications related to antibiotic resistance. Electrospun devices act as an efficient drug delivery system for these bioactive compounds, reducing systemic side effects and increasing the effectiveness of the treatment. In this way, the present study aimed to evaluate the synergistic and antimicrobial effect of the direct incorporation of different concentrations of CO in a poly(L-co-D,L lactic acid) and natural rubber (NR) electrospun membrane. It was observed that CO showed bacteriostatic and antibacterial effects against S. aureus in antibiogram assays. The prevention of biofilm formation was confirmed via scanning electron microscopy. The test with crystal violet demonstrated strong bacteria inhibition in membranes with 75% CO. A decrease in hydrophilicity, observed in the swelling test, presented that the addition of CO promotes a safe environment for the recovery of injured tissue while acting as an antimicrobial agent. In this way, the study showed strong bacteriostatic effects of the CO incorporation in combination with electrospun membranes, a suitable feature desired in wound dressings in order to promote a physical barrier with prophylactic antimicrobial properties to avoid infections during tissue healing.

The impact of non-deproteinization on physicochemical and biological properties of natural rubber latex for biomedical applications.

Latex is a colloidal suspension derived from the Hevea brasiliensis tree, derived from natural rubber, poly(isoprene), and assorted constituents including proteins and phospholipids. These constituents are inherent to both natural rubber and latex serum. This investigation was undertaken to examine the impact of the deproteinization process on chemical and biological dynamics of natural rubber latex. Natural Rubber (NR) extracted from the pure latex (LNCP) was obtained through centrifugation, followed by six rounds of solvent purification (LP6). The structure was characterized using Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), swelling test, surface zeta potential (ζ), scanning electron microscopy (SEM) and in vitro assay. The results revealed that the LP6 group presented decreased swelling kinetics, reduced cell adhesion and proliferation, and a smoother surface with decreased negative surface charge. Conversely, the LNCP group shown accelerated swelling, heightened adhesion and cellular growth, and a more negatively charged and rougher surface. As such, the attributes of latex serum and proteins have potential usage across numerous biomedical applications.

In Vitro Cell Behavior and Antibiotic Activity under Sustained Release of Doxycycline-Loaded Poly(lactic-co-glycolic acid) Microspheres.

The state-of-the-art sustained drug delivery systems are related to features to improve pharmacological transport through a controlled ratio between drug release and the desired therapeutic effect. Microspheres of biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), play an important role in these approaches, directing the release in a specific region of interest. In this way, the encapsulation of doxycycline (DOX) as a microbial agent turns the PLGA microspheres into a potential device for the treatment of topic oral diseases. Thus, this work aimed to produce DOX-loaded PLGA microspheres and see how they interfered with mesenchymal stem cell viability and in the sustained release in antimicrobial assays. Scanning electron microscopy showed the spherical microstructured pattern, revealing assorted sized distribution, with major diameters ranging 1-3 µm. The encapsulation efficiency presented a mean of 80% in both methods to obtain the microspheres (sonication and magnetic rotation). The DOX release test revealed a gradual and continuous profile of 30-40% between 120 and 168 h. Mesenchymal stem cells cultured in PLGA with or without DOX at several concentrations revealed no effect on the cell metabolic activity. Striking morphology changes were observed by confocal microscopy after 1 to 3 days under culture. The live/dead assay indicated that when microsphere densities were increased (from 10 to 100 µg/mL) cultured cells presented an internalized pattern of microspheres in both groups of PLGA containing DOX or not, while slight cell death signals were identified nearby microsphere clusters. Microbiological assays performed by the agar diffusion test pointed out that an inhibition zone was identified in Staphylococcus aureus (S. aureus) cultures at earlier times of DOX release. Despite the well-known use of PLGA as a drug delivery vehicle, when synthesized with DOX, it presents both characteristics of the desired treatment to prevent healthy tissue damage while avoiding bacterial growth in a microenvironment with anatomical features, such as grooves, projections, and other tough conditions that favor the development of oral diseases.

Poly(L-co-D,L lactic acid-co-Trimethylene Carbonate) 3D printed scaffold cultivated with mesenchymal stem cells directed to bone reconstruction: In vitro and in vivo studies.

A recent and quite promising technique for bone tissue engineering is the 3D printing, peculiarly regarding the production of high-quality scaffolds. The 3D printed scaffold strictly provides suitable characteristics for living cells, in order to induce treatment, reconstruction and substitution of injured tissue. The purpose of this work was to evaluate the behavior of the 3D scaffold based on Poly(L-co-D,L lactic acid-co-Trimethylene Carbonate) (PLDLA-TMC), which was designed in Solidworks™ software, projected in 3D Slicer™, 3D printed in filament extrusion, cultured with mesenchymal stem cells (MSCs) and tested in vitro and in vivo models. For in vitro study, the MSCs were seeded in a PLDLA-TMC 3D scaffold with 600 µm pore size and submitted to proliferation and osteogenic differentiation. The in vivo assays implanted the PLDLA-TMC scaffolds with or without MSCs in the calvaria of Wistar rats submitted to 8 mm cranial bone defect, in periods of 8-12 weeks. The results showed that PLDLA-TMC 3D scaffolds favored adherence and cell growth, and suggests an osteoinductive activity, which means that the material itself augmented cellular differentiation. The implanted PLDLA-TMC containing MSCs, showed better results after 12 weeks prior grafting, due the absence of inflammatory processes, enlarged regeneration of bone tissue and facilitated angiogenesis. Notwithstanding, the 3D PLDLA-TMC itself implanted enriched tissue repair; the addition of cells known to upregulate tissue healing reinforce the perspectives for the PLDLA-TMC applications in the field of bone tissue engineering in clinical trials.

A New Dermal Substitute Containing Polyvinyl Alcohol with Silver Nanoparticles and Collagen with Hyaluronic Acid: In Vitro and In Vivo Approaches.

The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match for PVA as a dressing, as it focuses on creating a physical barrier to avoid wound dehydration. When associated with extracellular components, such as the collagen matrix, the device obtained can create the desired biological conditions to act as a skin substitute. This study aimed to analyze the anti-microbiological activity and the in vitro and in vivo responses of a bilaminar device of PVA containing AgNPs associated with a membrane of collagen-hyaluronic acid (col-HA). Additionally, mesenchymal stem cells were cultured in the device to evaluate in vitro responses and in vivo immunomodulatory and healing behavior. The device morphology revealed a porous pattern that favored water retention and in vitro cell adhesion. Controlled wounds in the dorsal back of rat skins revealed a striking skin remodeling with new epidermis fulfilling all previously injured areas after 14 and 28 days. No infections or significant inflammations were observed, despite increased angiogenesis, and no fibrosis-markers were identified as compared to controls. Although few antibacterial activities were obtained, the addition of AgNPs prevented fungal growth. All results demonstrated that the combination of the components used here as a dermal device, chosen according to previous miscellany studies of low/mid-cost biomaterials, can promote skin protection avoiding infections and dehydration, minimize the typical wound inflammatory responses, and favor the cellular healing responses, features that give rise to further clinical trials of the device here developed.

Alternative Cutaneous Substitutes Based on Poly(l-co-d,l-lactic acid-co-trimethylene carbonate) with Schinus terebinthifolius Raddi Extract Designed for Skin Healing.

The search for new therapies and drugs that act as topical agents to relieve pain and control the inflammatory processes in burns always attracted interest in clinical trials. As an alternative to synthetic drugs, natural extracts are useful in the development of new strategies and formulations for improving the quality of life. The aim of this study was to develop a wound dressing using poly(l-co-d,l-lactic acid-co-trimethylene carbonate) (PLDLA-TMC) containing Schinus terebinthifolius Raddi (S.T.R.). S.T.R. is a native Brazilian plant known for its strong anti-inflammatory responses. The membrane of PLDLA-TMC + S. terebinthifolius Raddi was prepared at different concentrations of S.T.R. (5, 10, 15, and 50%). The Fourier transform infrared results showed no change in the PLDLA-TMC spectrum after S.T.R. addition, whereas the swelling test showed changes only in PLDLA-TMC + S.T.R. at 50%. The wettability measurements showed a mass loss due to the decrease in the contact angle in all samples after the S.T.R. addition in the polymer, whereas the S.T.R. release test showed a linear delivery pattern. The scanning electron microscopy analysis showed that S.T.R. was homogeneously distributed at only 5 and 10%. Tensile tests demonstrated an increase in Young's modulus and a reduction in the elongation till rupture of PLDLA-TMC after the addition of S.T.R. The biocompatibility in vitro evaluation with rat fibroblast cells seeded in the membranes of PLDLA-TMC + S.T.R. showed that although S.T.R. interfered in cell morphology, all concentrations tested showed that cells were able to adhere and proliferate during 7 days. Thus, S.T.R. at 50% was chosen to be tested for in vivo trials. The histological and immunohistochemistry results revealed an accelerated skin healing at 7 days after controlled secondary burns were introduced in the dorsal skin, with a striking total recovery of the epidermis and high rates of molecular activation of cell proliferation. Due to the known biocompatibility properties of PLDLA-TMC and its stable release of S.T.R., we strongly recommend S.T.R.-containing PLDLA-TMC as a curative device to favor skin healing.

Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release of Curcumin.

AIMS AND BACKGROUND: The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801). MATERIALS AND METHODS: SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR. RESULTS: The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. CONCLUSION: Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties.

Development of a membrane of poly (L-co-D,L lactic acid-co-trimethylene carbonate) with aloe vera: An alternative biomaterial designed to improve skin healing.

The search for new therapies and drugs that act as topical agents to relieve pain and control the infectious processes in burns always attracted interest in clinical trials. As an alternative to synthetic drugs, the use of natural extracts is useful in the development of new strategies and formulations for improving the life quality. The aim of this study was to develop a wound dressing using Poly(L-co-D,L lactic acid-co-TMC) (PLDLA-co-TMC) containing aloe vera (AV). This natural plant extract is known for its modulatory effects under healing process. The membrane of PLDLA-co-TMC+aloe vera was prepared at different concentrations of AV (5, 10, 15 and 50%). The FTIR showed no change in the PLDLA-co-TMC spectrum after AV addition, while the swelling test showed changes only in PLDLA-co-TMC+AV at 50%. The wettability measurements showed decrease in the contact angle in all samples after the AV addition in the polymer, while the AV release test showed that PLDLA-co-TMC+50%AV sample has higher AV release rate than the sample with other AV concentrations. The SEM analysis showed that AV was homogeneously distributed at 5% only. Tensile tests demonstrated an increase in the Young's modulus and a reduction in the elongation till rupture of the PLDLA-co-TMC after the addition of AV. Biocompatibility in vitro evaluation with fibroblast cells seeded in the membranes of PLDLA-co-TMC+AV showed that the cells were able to adhere, proliferate and maintain mitochondrial activity in all AV concentrations tested. Due to the known skin medicinal properties attributed to AV and the results here obtained, we suggest that after in vivo trials, the PLDLA-co-TMC+AV should be a promising biomaterial for application as a device for skin curative and healing agent.