Natural rubber latex-based biomaterials for drug delivery and regenerative medicine: Trends and directions.

Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.

Is the carotenoid production from Phaffia rhodozyma yeast genuinely sustainable? a comprehensive analysis of biocompatibility, environmental assessment, and techno-economic constraints.

Microorganisms, such as yeasts, filamentous fungi, bacteria, and microalgae, have gained significant attention due to their potential in producing commercially valuable natural carotenoids. In recent years, Phaffia rhodozyma yeasts have emerged as intriguing non-conventional sources of carotenoids, particularly astaxanthin and ß-carotene. However, the shift from academic exploration to effective industrial implementation has been challenging to achieve. This study aims to bridge this gap by assessing various scenarios for carotenoid production and recovery. It explores the use of ionic liquids (ILs) and bio-based solvents (ethanol) to ensure safe extraction. The evaluation includes a comprehensive analysis involving Life Cycle Assessment (LCA), biocompatibility assessment, and Techno-Economic Analysis (TEA) of two integrated technologies that utilize choline-based ILs and ethanol (EtOH) for astaxanthin (+ß-carotene) recovery from P. rhodozyma cells. This work evaluates the potential sustainability of integrating these alternative solvents within a yeast-based bioeconomy.

Comparing the wound healing potential of natural rubber latex serum and F1-protein: An in vivo approach.

Chronic wounds pose significant health concerns. Current treatment options include natural compounds like natural rubber latex (NRL) from Hevea brasiliensis. NRL, particularly the F1 protein fraction, has demonstrated bioactivity, biocompatibility, and angiogenic effects. So far, there is no study comparing F1 protein with total NRL serum, and the necessity of downstream processing remains unknown. Here, we evaluated the angiogenic potential of F1 protein compared to total NRL serum and the need for downstream processing. For that, ion exchange chromatography (DEAE-Sepharose), antioxidant activity, physicochemical characterization, cell culture in McCoy fibroblasts, and wound healing in Balb-C mice were performed. Also, the evaluation of histology and collagen content and the levels of inflammatory mediators were quantified. McCoy fibroblast cell assay showed that F1 protein (0.01 %) and total NRL serum (0.01 %) significantly increased cell proliferation by 47.1 ± 11.3 % and 25.5 ± 2.5 %, respectively. However, the AA of F1 protein (78.9 ± 0.8 %) did not show a significant difference compared to NRL serum (77.0 ± 1.1 %). F1 protein and NRL serum were more effective in wound management in rodents. Histopathological analysis confirmed accelerated healing and advanced tissue repair. Similarly, the F1 protein (0.01 %) increased collagen, showing that this fraction can stimulate the synthesis of collagen by fibroblastic cells. Regarding cytokines production (IL-10, TNF-α, IFN-γ), F1 protein and NRL serum did not exert an impact on the synthesis of these cytokines. Furthermore, we did not observe statistically significant changes in dosages of enzymes (MPO and EPO) among the groups. Nevertheless, Nitric Oxide dosage was reduced drastically when the F1 protein (0.01 %) protein was applied topically. These findings contribute to the understanding of F1 protein and NRL serum properties and provide insights into cost-effectiveness and practical applications in medicine and biotechnology. Therefore, further research is needed to assess the economic feasibility of downstream processing for NRL-based herbal medicine derived from Hevea brasiliensis.

Amphotericin B-loaded natural latex dressing for treating Candida albicans wound infections using Galleria mellonella model.

Amphotericin B (AmB) is the gold standard for antifungal drugs. However, AmB systemic administration is restricted because of its side effects. Here, we report AmB loaded in natural rubber latex (NRL), a sustained delivery system with low toxicity, which stimulates angiogenesis, cell adhesion and accelerates wound healing. Physicochemical characterizations showed that AmB did not bind chemically to the polymeric matrix. Electronic and topographical images showed small crystalline aggregates from AmB crystals on the polymer surface. About 56.6% of AmB was released by the NRL in 120 h. However, 33.6% of this antifungal was delivered in the first 24 h due to the presence of AmB on the polymer surface. The biomaterial's excellent hemo- and cytocompatibility with erythrocytes and human dermal fibroblasts (HDF) confirmed its safety for dermal wound application. Antifungal assay against Candida albicans showed that AmB-NRL presented a dose-dependent behavior with an inhibition halo of 30.0 ± 1.0 mm. Galleria mellonella was employed as an in vivo model for C. albicans infection. Survival rates of 60% were observed following the injection of AmB (0.5 mg.mL-1) in G. mellonella larvae infected by C. albicans. Likewise, AmB-NRL (0.5 mg.mL-1) presented survival rates of 40%, inferring antifungal activity against fungus. Thus, NRL adequately acts as an AmB-sustained release matrix, which is an exciting approach, since this antifungal is toxic at high concentrations. Our findings suggest that AmB-NRL is an efficient, safe, and reasonably priced ($0.15) dressing for the treatment of cutaneous fungal infections.

Role of dietary food intake patterns, anthropometric measures, and multiple biochemical markers in the development of pregnancy-specific urinary incontinence in gestational diabetes mellitus.

OBJECTIVES: The aim of this study was to assess maternal dietary food intake patterns, anthropometric measures, and multiple biochemical markers in women with gestational diabetes mellitus and pregnancy-specific urinary incontinence and to explore whether antedating gestational diabetes mellitus environment affects the pregnancy-specific urinary incontinence development in a cohort of pregnant women with gestational diabetes mellitus and pregnancy-specific urinary incontinence. METHODS: Maternal dietary information and anthropometric measurements were collected. At 24 wk of gestation, with a fasting venipuncture sample, current blood samples for biochemical markers of hormones, vitamins, and minerals were analyzed. The groups were compared in terms of numerical variables using analysis of variance for independent samples followed by multiple comparisons. RESULTS: Of the 900 pregnant women with complete data, pregnant women in the gestational diabetes mellitus pregnancy-specific urinary incontinence group had higher body mass index during pregnancy, arm circumference, and triceps skinfold than the non-gestational diabetes mellitus continent and non-gestational diabetes mellitus pregnancy-specific urinary incontinence groups, characterizing an obesogenic maternal environment. Regarding dietary food intake, significant increases in aromatic amino acids, branched-chain amino acids, dietary fiber, magnesium, zinc, and water were observed in pregnancy-specific urinary incontinence group compared with the non-gestational diabetes mellitus continent group. Serum vitamin C was reduced in the gestational diabetes mellitus pregnancy-specific urinary incontinence group compared with the non-gestational diabetes mellitus pregnancy-specific urinary incontinence group. CONCLUSIONS: This study emphasizes the necessity for a comprehensive strategy for gestational diabetes mellitus women with pregnancy-specific urinary incontinence in terms of deviation in maternal adaptation trending toward obesity and maternal micronutrients deficiencies.

Recent advances and perspectives on natural latex serum and its fractions for biomedical applications.

Advances and the discovery of new biomaterials have opened new frontiers in regenerative medicine. These biomaterials play a key role in current medicine by improving the life quality or even saving the lives of millions of people. Since the 2000s, Natural Rubber Latex (NRL) has been employed as wound dressings, mechanical barrier for Guided Bone Regeneration (GBR), matrix for drug delivery, and grafting. NRL is a natural polymer that can stimulate cell proliferation, neoangiogenesis, and extracellular matrix (ECM) formation. Furthermore, it is well established that proteins and other biologically active molecules present in the Natural Latex Serum (NLS) are responsible for the biological properties of NRL. NLS can be obtained from NRL by three main methods, namely (i) Centrifugation (fractionation of NRL in distinct fractions), (ii) Coagulation and sedimentation (coagulating NRL to separate the NLS from rubber particles), and (iii) Alternative extraction process (elution from NRL membrane). In this review, the chemical composition, physicochemical properties, toxicity, and other biological information such as osteogenesis, vasculogenesis, adhesion, proliferation, antimicrobial behavior, and antitumoral activity of NLS, as well as some of its medical instruments and devices are discussed. The progress in NLS applications in the biomedical field, more specifically in cell cultures, alternative animals, regular animals, and clinical trials are also discussed. An overview of the challenges and future directions of the applications of NLS and its derivatives in tissue engineering for hard and soft tissue regeneration is also given.

Eco-sustainable coatings based on chitosan, pectin, and lemon essential oil nanoemulsion and their effect on strawberry preservation.

Films and coatings manufactured with bio-based renewable materials, such as biopolymers and essential oils, could be a sustainable and eco-friendly alternative for protecting and preserving agricultural products. In this work, we developed films and coatings from pectin and chitosan to protect strawberries (Fragaria x ananassa Duch.) from spoilage and microbial contamination. We developed three coatings containing equal amounts of glycerol and Sicilian lemon essential oil (LEO) nanoemulsion. We identified seventeen chemicals from LEO by GC-MS chromatogram, including d-limonene, α-Pinene, ß-Pinene, and γ-Terpinene. The pectin and chitosan coatings were further characterized using different physicochemical, mechanical, and biological methods. The films demonstrated satisfactory results in strength and elongation at the perforation as fruit packaging. In addition, the coatings did not influence the weight and firmness of the strawberry pulps. We observed that 100 % essential oil was released in 1440 min resulting from the erosion process. Also, the oil preserved the chemical stability of the films. Antioxidant activity (AA), measured by Electron Paramagnetic Resonance (EPR), showed that the coatings loaded with 2 % LEO nanoemulsion (PC + oil) showed that almost 50 % of AA from LEO nanoemulsion was preserved. The chitosan and the pectin-chitosan coatings (PC + oil) inhibited filamentous fungi and yeast contaminations in strawberries for at least 14 days, showing a relationship between the AA and antimicrobial results.

Aloe vera-loaded natural rubber latex dressing as a potential complementary treatment for psoriasis.

Psoriasis is a disease that causes keratinocytes to proliferate ten times faster than normal, resulting in chronic inflammation and immune cell infiltration in the skin. Aloe vera (A. vera) creams have been used topically for treating psoriasis because they contain several antioxidant species; however, they have several limitations. Natural rubber latex (NRL) has been used as occlusive dressings to promote wound healing by stimulating cell proliferation, neoangiogenesis, and extracellular matrix formation. In this work, we developed a new A. vera-releasing NRL dressing by a solvent casting method to load A. vera into NRL. FTIR and rheological analyzes revealed no covalent interactions between A. vera and NRL in the dressing. We observed that 58.8 % of the loaded A. vera, present on the surface and inside the dressing, was released after 4 days. Biocompatibility and hemocompatibility were validated in vitro using human dermal fibroblasts and sheep blood, respectively. We observed that ~70 % of the free antioxidant properties of A. vera were preserved, and the total phenolic content was 2.31-fold higher than NRL alone. In summary, we combined the antipsoriatic properties of A. vera with the healing activity of NRL to generate a novel occlusive dressing that may be indicated for the management and/or treatment of psoriasis symptoms simply and economically.

Biocompatible anti-aging face mask prepared with curcumin and natural rubber with antioxidant properties.

Natural rubber latex (NRL) is a biopolymer widely used in biomedical applications. In this work, we propose an innovative cosmetic face mask, combining the NRL's biological properties with curcumin (CURC), which has a high level of antioxidant activity (AA) to provide anti-aging benefits. Chemical, mechanical and morphological characterizations were performed. The CURC released by the NRL was evaluated by permeation in Franz cells. Cytotoxicity and hemolytic activity assays were performed to assess safety. The findings showed that the biological properties of CURC were preserved after loading in the NRL. About 44.2 % of CURC was released within the first six hours, and in vitro permeation showed that 9.36 % ± 0.65 was permeated over 24h. CURC-NRL was associated with a metabolic activity higher than 70 % in 3 T3 fibroblasts, cell viability ≥95 % in human dermal fibroblasts, and a hemolytic rate ≤ 2.24 % after 24 h. Furthermore, CURC-NRL maintained the mechanical characteristics (range suitable) for human skin application. We observed that CURC-NRL preserved ~20 % antioxidant activity from curcumin-free after loading in the NRL. Our results suggest that CURC-NRL has the potential to be used in the cosmetics industry, and the experimental methodology utilized in this study can be applied to different kinds of face masks.

Maternal care of the whole litter improves the success rate of diabetes in pregnancy in rats.

Induction of diabetes mellitus by streptozotocin (STZ) in rats at birth is of high mortality and low success rate when male puppies are separated from females, prioritizing females breastfeeding. Cross-parental care of the entire litter and SZT-induced diabetes up to 12 h post-birth become with high success rate, low animal death, and females with glycaemia >140 mg/dL on the 90 postnatal day. Cross-parental care is more effective in STZ-induction of diabetes, which is maintained during pregnancy (diabetes in pregnancy), than the conventional protocol of male separation at birth.

Transcriptomic Profiling of Rectus Abdominis Muscle in Women with Gestational Diabetes-Induced Myopathy: Characterization of Pathophysiology and Potential Muscle Biomarkers of Pregnancy-Specific Urinary Incontinence.

Gestational diabetes mellitus (GDM) is recognized as a "window of opportunity" for the future prediction of such complications as type 2 diabetes mellitus and pelvic floor muscle disorders, including urinary incontinence and genitourinary dysfunction. Translational studies have reported that pelvic floor muscle disorders are due to a GDM-induced-myopathy (GDiM) of the pelvic floor muscle and rectus abdominis muscle (RAM). We now describe the transcriptome profiling of the RAM obtained by Cesarean section from GDM and non-GDM women with and without pregnancy-specific urinary incontinence (PSUI). We identified 650 genes in total, and the differentially expressed genes were defined by comparing three control groups to the GDM with PSUI group (GDiM). Enrichment analysis showed that GDM with PSUI was associated with decreased gene expression related to muscle structure and muscle protein synthesis, the reduced ability of muscle fibers to ameliorate muscle damage, and the altered the maintenance and generation of energy through glycogenesis. Potential genetic muscle biomarkers were validated by RT-PCR, and their relationship to the pathophysiology of the disease was verified. These findings help elucidate the molecular mechanisms of GDiM and will promote the development of innovative interventions to prevent and treat complications such as post-GDM urinary incontinence.

Pro-angiogenic approach for skeletal muscle regeneration.

The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed.

Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus.

Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women's quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting.

Hancornia speciosa latex for biomedical applications: physical and chemical properties, biocompatibility assessment and angiogenic activity.

The latex obtained from Hancornia speciosa is used in folk medicine for treatment of several diseases, such as acne, warts, diabetes, gastritis and inflammation. In this work, we describe the biocompatibility assessment and angiogenic properties of H. speciosa latex and its potential application in medicine. The physical-chemical characterization was carried out following different methodologies (CHN elemental analyses; thermogravimetric analyses and Fourier transform infrared spectroscopy). The biocompatibility was evaluated through cytotoxicity and genotoxicity tests in fibroblast mouse cells and the angiogenic properties were evaluated using the chick chorioallantoic membrane (CAM) assay model. The physical-chemical results showed that the structure of Hancornia speciosa latex biomembrane is very similar to that of Hevea brasiliensis (commercially available product). Moreover, the cytotoxicity and genotoxicity assays showed that H. speciosa latex is biocompatible with life systems and can be a good biomaterial for medical applications. The CAM test showed the efficient ability of H. speciosa latex in neovascularization of tissues. The histological analysis was in accordance with the results obtained in the CAM assay. Our data indicate that the latex obtained from H. speciosa and eluted in water showed significant angiogenic activity without any cytotoxic or genotoxic effects on life systems. The same did not occur with H. speciosa latex stabilized with ammonia. Addition of ammonia does not have significant effects on the structure of biomembranes, but showed a smaller cell survival and a significant genotoxicity effect. This study contributes to the understanding of the potentialities of H. speciosa latex as a source of new phytomedicines.

Biocompatibility studies of natural rubber latex from different tree clones and collection methods.

Natural rubber latex (NRL) has several features that make it an excellent biomaterial to promote the growth and repair of tissues, skin and bones. Most of the research with NRL membranes uses a mixture of different clones and chemical preservatives in the collection process. In this study, we compared five clones that produce NRL, seeking to identify their differences in biocompatibility. The clones studied were RRIM 600, PB 235, GT1, PR 255 and IAN 873 commonly found in plantations in Brazil. We did also study the effect of ammonia used during latex collection. NRL membranes were prepared aseptically and sterilized. In the in vitro tests, the membranes remained in direct contact with mouse fibroblasts cells for three periods, 24, 48 and 72 h. In the in vivo tests, the membranes were implanted subcutaneously in rabbits. The results indicated the biocompatibility of the membranes obtained from all clones. Membranes from the clones RRIM 600 and IAN 873 induced greater cell proliferation, suggesting greater bioactivity. It was found that the membranes made from latex that was in contact with ammonia during collection, showed cytotoxic and genotoxic effects in cultures, as well as necrosis, and increased inflammatory cells in the rabbit's tissues close to the implant.

Estudo comparativo do desempenho de diferentes membranas oclusivas de látex em natural no reparo ósseo / A comparative study on the performance of different occlusive natural latex membranes in bone repair

Introdução: Na odontologia, a reabsorção óssea alveolar é fator limitante no bem estar dos indivíduos interferindo diretamente no sistema estomatognático, acarretando problemas no âmbito de saúde em geral. Com o objetivo de promover modalidades biológicas que possam estimular a regeneração óssea, várias estratégias biomiméticas têm sido desenvolvidas recorrendo à utilização dos mais diversos materiais possíveis à matriz óssea, culminando com o desenvolvimento de técnicas que promovam tal reparo. Objetivo: Este trabalho consiste no estudo comparativo do desempenho de filmes confeccionados com látex como membrana oclusiva em procedimento de Regeneração Óssea Guiada (ROG) em 3 preparações: Látex preservado em amônia, Látex produzidos por seringueiras dos clones IAN873 e PR255 polimerizados logo após a coleta e sem uso de amônia como conservante. Métodos: Foram utilizados 60 ratos Wistar, divididos randomicamente em 4 grupos de 15 animais, nos quais defeitos ósseos de tamanho crítico (8mm de diâmetro) foram confeccionados cirurgicamente na calvária. O grupo A foi tratado por ROG através da membrana de látex preservada em amônia, o grupo B recebeu a membrana do clone IAN873, o grupo C, a membrana do clone PR255 e o grupo D, não foi tratado por ROG. Após o período de 7, 15 e 50 dias, 5 animais de cada grupo foram eutanasiados, e as peças contendo o defeito ósseo coletadas para análise microscópica (histológica descritiva e histomorfometria). Resultados: Os resultados demonstraram que após 50 dias, houve formação óssea em maiores proporções no grupo D (p<0.05, ANOVA seguido de Tukey), sugerindo que novos experimentos devem ser realizados para se concluir a respeito da presença da amônia e a influência da espécie de seringueira.

Introduction: In dentistry, alveolar bone resorption is a limiting factor in the well being of individuals directly interfering in the stomatognathic system, causing problems in the context of overall health. Aiming to promote biological methods that can stimulate bone regeneration, several biomimetic strategies have been developed by the use of diverse materials possible to the bone matrix, culminating in the development of techniques that promote such repair. Objective: This work is a comparative study of the performance of films made with latex as occlusive membrane for Guided Bone Regeneration (GBR) procedure in three preparations: Latex preserved in ammonia, produced by Latex rubber clones IAN873 and PR255 polymerized immediately after collection and without use ammonia as a preservative. Methods: Sixty Wistar rats were randomly divided into 4 groups of 15 animals in which bone defects of critical size (8mm diameter) were made surgically in the skull. Group A was treated by GBR through the membrane látex preserved with ammonia, Group B received the membrane made of latex from IAN873, Group C, the membrane clone PR255 and group D was not treated by GBR. After a period of 7, 15 and 50 days, 5 animals from each group were euthanized, and specimens containing bone defect collected for microscopic examination (descriptive histology and histomorphometry). Results: The results showed that after 50 days there was bone formation in higher proportions in group D (p <0.05, ANOVA followed by Tukey), suggesting that further experiments should be conducted to conclude about the presence of ammonia and the influence of kind of rubber.