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.

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.

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.

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.

Natural latex serum: characterization and biocompatibility assessment using Galleria mellonella as an alternative in vivo model.

Natural latex serum (NLS) is one of the natural rubber latex fractions from Hevea brasiliensis tree, which is formed by centrifuged serum and is composed of proteins, acids, nucleotides, salts and carbohydrates. The proteins present in NLS have demonstrated several interesting biological properties, including angiogenic, healing, osteogenic, anti-inflammatory, antimicrobial, in addition to inducing neovascularization, bone formation and osseointegration. Thus, we proposed to characterize NLS by physicochemical techniques and to investigate the biocompatibility by toxicological assays and safety test in Galleria mellonella. Infrared spectrum showed vibrational bands characteristic of amide I, II and III that are linked to the protein content, which was confirmed by the High Performance Liquid Chromatography profile and by the Electrophoresis analysis. This material did not exhibit hemolytic (rate <0.5%) and cytotoxic effects (viability >70%) and was able to enhance the proliferation of fibroblasts (>600%) after 3 days. The pronounced proliferative effect observed in fibroblast cells can be explained by the presence of the fibroblast growth factor (FGF) like protein revealed by the Western blot test. Moreover, NLS did not provoke toxic effects (survival ∼ 80%) on the G. mellonella model, indicating that it is a biocompatible and safe material.

Implant osseointegration in circumferential bone defects treated with latex-derived proteins or autogenous bone in dog's mandible.

BACKGROUND: In sites with diminished bone volume, the osseointegration of dental implants can be compromised. Innovative biomaterials have been developed to aid successful osseointegration outcomes. PURPOSE: The aim of this study was to evaluate the osteogenic potential of angiogenic latex proteins for improved bone formation and osseointegration of dental implants. MATERIALS AND METHODS: Ten dogs were submitted to bilateral circumferential defects (5.0 × 6.3 mm) in the mandible. Dental implant (3.3 × 10.0 mm, TiUnite MK3™, Nobel Biocare AB, Göteborg, Sweden) was installed in the center of the defects. The gap was filled either with coagulum (Cg), autogenous bone graft (BG), or latex angiogenic proteins pool (LPP). Five animals were sacrificed after 4 weeks and 12 weeks, respectively. Implant stability was evaluated using resonance frequency analysis (Osstell Mentor, Osstell AB, Göteborg, Sweden), and bone formation was analyzed by histological and histometric analysis. RESULTS: LPP showed bone regeneration similar to BG and Cg at 4 weeks and 12 weeks, respectively (p ≥ .05). Bone formation, osseointegration, and implant stability improved significantly from 4 to 12 weeks (p ≤ .05). CONCLUSION: Based on methodological limitations of this study, Cg alone delivers higher bone formation in the defect as compared with BG at 12 weeks; compared with Cg and BG, the treatment with LPP exhibits no advantage in terms of osteogenic potential in this experimental model, although overall osseointegration was not affected by the treatments employed in this study.