Delivery Of Bioactive Molecules Research Articles

Chitosan alchemy: transforming tissue engineering and wound healing.

Chitosan, a biopolymer acquired from chitin, has emerged as a versatile and favorable material in the domain of tissue engineering and wound healing. Its biocompatibility, biodegradability, and antimicrobial characteristics make it a suitable candidate for these applications. In tissue engineering, chitosan-based formulations have garnered substantial attention as they have the ability to mimic the extracellular matrix, furnishing an optimal microenvironment for cell adhesion, proliferation, and differentiation. In the realm of wound healing, chitosan-based dressings have revealed exceptional characteristics. They maintain a moist wound environment, expedite wound closure, and prevent infections. These formulations provide controlled release mechanisms, assuring sustained delivery of bioactive molecules to the wound area. Chitosan's immunomodulatory properties have also been investigated to govern the inflammatory reaction during wound healing, fostering a balanced healing procedure. In summary, recent progress in chitosan-based formulations portrays a substantial stride in tissue engineering and wound healing. These innovative approaches hold great promise for enhancing patient outcomes, diminishing healing times, and minimizing complications in clinical settings. Continued research and development in this field are anticipated to lead to even more sophisticated chitosan-based formulations for tissue repair and wound management. The integration of chitosan with emergent technologies emphasizes its potential as a cornerstone in the future of regenerative medicine and wound care. Initially, this review provides an outline of sources and unique properties of chitosan, followed by recent signs of progress in chitosan-based formulations for tissue engineering and wound healing, underscoring their potential and innovative strategies.

Polymeric biomaterials for periodontal tissue engineering and periodontitis

Biomaterials made of polymers has shown significant progress for periodontal regeneration and the treatment of periodontitis due to their superior properties such as controlled bioactive molecule delivery and 3D bioprintability.

Hydrogel Microparticles for Bone Regeneration.

Hydrogel microparticles (HMPs) stand out as promising entities in the realm of bone tissue regeneration, primarily due to their versatile capabilities in delivering cells and bioactive molecules/drugs. Their significance is underscored by distinct attributes such as injectability, biodegradability, high porosity, and mechanical tunability. These characteristics play a pivotal role in fostering vasculature formation, facilitating mineral deposition, and contributing to the overall regeneration of bone tissue. Fabricated through diverse techniques (batch emulsion, microfluidics, lithography, and electrohydrodynamic spraying), HMPs exhibit multifunctionality, serving as vehicles for drug and cell delivery, providing structural scaffolding, and functioning as bioinks for advanced 3D-printing applications. Distinguishing themselves from other scaffolds like bulk hydrogels, cryogels, foams, meshes, and fibers, HMPs provide a higher surface-area-to-volume ratio, promoting improved interactions with the surrounding tissues and facilitating the efficient delivery of cells and bioactive molecules. Notably, their minimally invasive injectability and modular properties, offering various designs and configurations, contribute to their attractiveness for biomedical applications. This comprehensive review aims to delve into the progressive advancements in HMPs, specifically for bone regeneration. The exploration encompasses synthesis and functionalization techniques, providing an understanding of their diverse applications, as documented in the existing literature. The overarching goal is to shed light on the advantages and potential of HMPs within the field of engineering bone tissue.

Application of inulin for the formulation and delivery of bioactive molecules and live cells

Inulin is a fructan biosynthesized mainly in plants of the Asteraceae family. It is also found in edible vegetables and fruits such as onion, garlic, leek, and banana. For the industrial production of inulin, chicory and Jerusalem artichoke are the main raw material. Inulin is used in the food, pharmaceutical, cosmetic as well biotechnological industries. It has a GRAS status and exhibits prebiotic properties. Inulin can be used as a wall material in the encapsulation process of drugs and other bioactive compounds and the development of their delivery systems. In the review, the use of inulin for the encapsulation of probiotics, essential and fatty oils, antioxidant compounds, natural colorant and other bioactive compounds is presented. The encapsulation techniques, materials and the properties of final products suitable for the delivery into food are discussed. Research limitations are also highlighted.

A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer

Oral ulcer can be treated with diverse biomaterials loading drugs or cytokines. However, most patients do not benefit from these materials because of poor adhesion, short-time retention in oral cavity and low drug therapeutic efficacy. Here we report a self-stabilized and water-responsive deliverable coenzyme salt polymer poly(sodium α-lipoate) (PolyLA-Na)/coenzyme polymer poly(α-lipoic acid) (PolyLA) binary synergistic elastomer adhesive patch, where hydrogen bonding cross-links between PolyLA and PolyLA-Na prevents PolyLA depolymerization and slow down the dissociation of PolyLA-Na, thus allowing water-responsive sustainable delivery of bioactive LA-based small molecules and durable adhesion to oral mucosal wound due to the adhesive action of PolyLA. In the model of mice and mini-pig oral ulcer, the adhesive patch accelerates the healing of the ulcer by regulating the damaged tissue inflammatory environment, maintaining the stability of oral microbiota, and promoting faster re-epithelialization and angiogenesis. This binary synergistic patch provided a therapeutic strategy to treat oral ulcer.

Targeted Delivery of IL-12 Via CD19-Modified Extracellular Vesicles Enhances CAR-T Cell Efficacy Against Lymphoma

Introduction Chimeric Antigen Receptor T-Cell (CAR-T cell) Therapy faces challenges related to low potency and poor in vivo persistence. Incorporating cytokine signals, such as interleukin-12 (IL-12), has emerged as a promising strategy to enhance CAR-T cell functionality due to its potent immunostimulatory effects. However, clinical application of IL-12 is hindered by pleiotropic toxicity and limited bioavailability. Therefore, alternative agents or delivery systems are desired to exploit the benefits of IL-12 safely. This study investigated the therapeutic potential of a novel IL-12 delivery system utilizing extracellular vesicles (EVs) modified with the target antigen CD19 to specifically deliver IL-12 to CD19 CAR-T cells, thus augmenting their anti-tumor effects. Method IL-12-anchored extracellular vesicles (IL-12 EVs) were generated from engineered 293T cells expressing IL-12 on the cell membrane via GPI structure. Additionally, EVs co-expressing IL-12 and CD19 (CD19/IL-12 EVs) were produced from 293T cells co-expressing CD19 and IL-12. The physicochemical characteristics of the EVs were analyzed using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot (WB). Binding and uptake efficiency of the EVs with CD19 CAR-T cells were validated using flow cytometry and imaging flow cytometry. In vitro experiments were conducted to investigate the effects of the EVs on the cytotoxic function, degranulation, cytokine secretion, and proliferation of CD19 CAR-T cells. Furthermore, the therapeutic efficacy and safety of CD19 CAR-T cells combined with intratumoral injection of IL-12 EVs were evaluated in a mouse model of Raji lymphoma xenograft. Result HEK293T cell-derived, IL-12-bearing EVs were successfully prepared. IL-12 on the surface of EVs was quantified by enzyme-linked immunosorbent assay. IL-12 EVs promoted interferon-γ secretion of co-cultured CAR-T cells in a dose-dependent manner, reaching a peak at a concentration of about 1 ng/mL of IL-12 EVs. At this concentration, IL-12 EVs significantly enhanced CAR-T cell cytotoxicity while recombinant human interleukin-12 not. Co-expressing CD19 and IL-12 EVs were prepared and visualized by imaging flow cytometry, showing the presence of both IL-12 and CD19 on the surface of each individual EV. CD19/IL-12 EVs exhibited stronger tropism towards anti-CD19 CAR-T cells than IL-12 EVs (Figure 1). Similarly, CD19/IL-12 EVs could promote CAR-T cells with increased cytokine secretion and improved tumor-killing ability. In a Raji subcutaneous lymphoma xenograft mouse model, intratumoral injection of CD19/IL-12 EVs observably promoted CAR-T cell function, achieved superior proliferation and enhanced anti-tumor effects without systemic toxicity (Figure 2). Conclusion This study demonstrated that surface modification of EVs with target antigens empowers EVs with improved CAR-T cell targeting, creating an effective delivery platform for targeted delivery of bioactive molecules, such as IL-12, to CAR-T cells, thereby enhancing immunotherapeutic efficacy.

Functionalizing Dendrimers for Targeted Delivery of Bioactive Molecules to Macrophages: A Potential Treatment for Mycobacterium tuberculosis Infection-A Review.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.

Amphiphilic Copolymer-based Pesticide Nanoformulations for Better Crop Protection: Advances and Future Need

Abstract: Amphiphilic copolymers (ACPs) are widely recognized due to their self-organizing micellar characteristics in an aqueous medium and their extensive application potential in bioactive molecule delivery. However, their use in agriculture is still limited with some scattered research studies, especially on the delivery of pesticides for crop protection. Hence, the present study comprehensively summarizes these research findings mainly focusing on synthesis, selfassembly, and release properties of pesticide nanoformulations prepared using poly(ethylene glycol) (PEG)-based ACPs. PEG-based ACPs are synthesized using linker molecules through a simple esterification reaction in the presence of an acid catalyst or an enzyme. However, multistep reactions are noticed in the synthesis of ACPs employing biopolymers, like chitosan-based ACPs. On spontaneous emulsification, ACPs develop nanomicelles (~10-300 nm), and their micellar characteristics are highly dependent on the nature of the blocks. The polymeric micellar barrier of ACPs also leads to the slow release of entrapped pesticide molecules from these nanomicelles with diffusion as the dominant release mechanism. Hence, the field appraisal of these ACPs-based pesticide nanoformulations has shown reduced pesticide doses as compared to the conventional formulations. However, despite these stated advantages, ACPs-based pesticide nanoformulations are yet to reach their full potential, which might be due to several key researchable gaps, like a lack of ACPs with high pesticide loading capacity, lack of biosafety data, environmental fate details, etc. The use of ACPs is still gaining pace in formulating pesticides and being proven as a smart material for targeted pesticide delivery to attain sustainable agriculture with a promise to reduce environmental hazards due to pesticide application.

Cancer Therapy Empowered by Extracellular Vesicle-Mediated Targeted Delivery.

Extracellular vesicles (EVs) are a class of nanoparticles that mediate signaling molecules delivery between donor and recipient cells. Heterogeneity in the content of EVs and their membrane surface proteins determines their unique targetability. Their low immunogenicity, capability to cross various biological barriers, and superior biocompatibility enable engineering-modified EVs to be ideal drug delivery carriers. In addition, the engineered EVs that emerge in recent years have become a powerful tool for cancer treatment through the selective delivery of bioactive molecules to therapeutic targets, such as tumor cells and stroma. Our review focuses on the various types of EV modifications and their promoting therapeutic capabilities, which provide an innovative means for cancer precision therapy.

Rational design of surface engineered albumin nanoparticles of asiatic acid for EGFR targeted delivery to lung cancer: Formulation development and pharmacokinetics

Targeted delivery of natural bioactive molecules has the potential to reduce toxicity while increasing anticancer therapeutic efficacy. Nanoparticles (NPs) conjugated with targeting ligands are widely explored because they offer better drug release profiles, biocompatibility, and tunability in particle size. The goal of this research was to create targeted nanoparticles comprised of bovine serum albumin (ALB) and asiatic acid (ASA) conjugated with cetuximab antibodies, which bind specifically to cells overexpressing the EGFR (epidermal growth factor receptor). Physicochemical characterization of the formulations revealed stable particles with the typical size range of approximately 200 nm. In vitro drug release tests show that the drug is released slowly over time. An in vitro MTT assay was performed on A549 and HEK-293 cells to determine the cytotoxicity of formulations. Furthermore, cellular uptake studies were conducted. Moreover, apoptosis studies and cell cycle analyses were performed on A549 cells. A concentration equivalent to the IC50 value of CTX-ASA-ALB-NPs resulted in greater apoptosis in A-549 cells compared to ASA and also led to G0/G1 phase cell cycle arrest. However, the extent of cytotoxicity of CTX-ASA-ALB-NPs in HEK-293 cells (control cells) was lower, which demonstrates the specific targeting efficiency in cancerous cells. Subsequently, in vivo investigations were conducted on Wistar rats to evaluate pharmacokinetic properties and acute toxicity. These findings suggest that ASA-ALB-NPs conjugated with an anti-EGF receptor ligand (Cetuximab) hold promise as a viable nanomedicine for specific lung cancer therapy.

Magnetic Nanoemulsions for the Intra-Articular Delivery of Ascorbic Acid and Dexamethasone.

(1) Osteoarthritis (OA) is a progressive joint degenerative disease that currently has no cure. Limitations in the development of innovative disease modifying therapies are related to the complexity of the underlying pathogenic mechanisms. In addition, there is the unmet need for efficient drug delivery methods. Magnetic nanoparticles (MNPs) have been proposed as an efficient modality for the delivery of bioactive molecules within OA joints, limiting the side effects associated with systemic delivery. We previously demonstrated MNP's role in increasing cell proliferation and chondrogenesis. In the design of intra-articular therapies for OA, the combined NE-MNP delivery system could provide increased stability and biological effect. (2) Proprietary Fe3O4 MNPs formulated as oil-in-water (O/W) magneto nanoemulsions (MNEs) containing ascorbic acid and dexamethasone were tested for size, stability, magnetic properties, and in vitro biocompatibility with human primary adipose mesenchymal cells (ADSC), cell mobility, and chondrogenesis. In vivo biocompatibility was tested after systemic administration in mice. (3) We report high MNE colloidal stability, magnetic properties, and excellent in vitro and in vivo biocompatibility. By increasing ADSC migration potential and chondrogenesis, MNE carrying dexamethasone and ascorbic acid could reduce OA symptoms while protecting the cartilage layer.

Therapeutic Applications of Plant-Derived Extracellular Vesicles as Antioxidants for Oxidative Stress-Related Diseases.

Extracellular vesicles (EVs) composed of a lipid bilayer are released from various cell types, including animals, plants, and microorganisms, and serve as important mediators of cell-to-cell communication. EVs can perform a variety of biological functions through the delivery of bioactive molecules, such as nucleic acids, lipids, and proteins, and can also be utilized as carriers for drug delivery. However, the low productivity and high cost of mammalian-derived EVs (MDEVs) are major barriers to their practical clinical application where large-scale production is essential. Recently, there has been growing interest in plant-derived EVs (PDEVs) that can produce large amounts of electricity at a low cost. In particular, PDEVs contain plant-derived bioactive molecules such as antioxidants, which are used as therapeutic agents to treat various diseases. In this review, we discuss the composition and characteristics of PDEVs and the appropriate methods for their isolation. We also discuss the potential use of PDEVs containing various plant-derived antioxidants as replacements for conventional antioxidants.

Novel microemulsions formulated from sodium N-Lauroyl sarcosinate as nanocarrier for encapsulation of α-Tocopherol

Oil-in-water (o/w) microemulsions (MEs) are gaining increasing attention as nanocarriers for the encapsulation and delivery of hydrophobic bioactive molecules which has huge applications in cosmetic, pharmacological, food and beverage industries. However, the major challenge is to formulate these MEs from biodegradable and biocompatible components in low concentration to form stable formulations. In the current work, physiochemical characterization of blank and α-tocopherol loaded o/w MEs formulated using the biodegradable amino-acid based sodium N-lauroyl sarcosinate (SNLS) as surfactant was performed. These MEs were utilized as potential nanocarriers to solubilize and encapsulate an antioxidant α-tocopherol. The utilization of o/w MEs increased the solubility of α-tocopherol from 0.1% in 10% SNLS solution to 0.2% and 0.8% in MEs without and with cosurfactant respectively. The effect of cosurfactant, concentration of Smix (SNLS:butanol = 1:1) and oil was evaluated using conductivity, viscosity studies and encapsulation efficiency to select the optimum composition for encapsulation. The Z-average size of blank MEs without and with cosurfactant was 304 nm and 199 nm respectively with low PDI and negative zeta potential values determine the enhanced stability of these MEs. The HRTEM images revealed the spherical shape of o/w MEs with darker oily core and were utilized to study the effect of cosurfactant and encapsulation of α-tocopherol on the size and morphology of o/w ME droplets. Further, FTIR studies showed the molecular interactions in α-tocopherol and in the optimized ME. In addition to this, the in-vitro antioxidant study of α-tocopherol loaded MEs was determined by the DPPH free radical scavenging activity and the IC50 value was 9 mg/mL for the optimized ME containing 0.5% α-tocopherol. The contact angle studies revealed excellent wetting and spreading ability of MEs on the hydrophobic surface. Thus, SNLS based o/w MEs could be utilized as potential nanocarriers for the encapsulation and delivery of α-tocopherol.

Highly stable emulsion gels with micellar casein based on the jamming transition, for bioactive molecule delivery

Emulsion gels have numerous practical applications in the pharmaceutical and food industries, the preparation of which involves multiple processing steps including the production of emulsions and transition of emulsions into gels. Improving the stability of emulsion gels and simplifying their preparation process are key issues. By exploiting the properties of micellar casein (MC), pectin (P) and sodium alginate (SA), a highly stable emulsion gel with 70% oil was created through one-pot homogenization based on the jamming transition. Emulsion gels prepared with an SA-MC ratio of 3:7 exhibited high stability during acidification, heating and with addition of Ca2+, maintained their stability after more than 810 days of storage. It also prolonged the release rate of caffeic acid phenethyl (CAPE) while protecting proanthocyanidin (PC) from degradation during simulated gastrointestinal digestion. Interestingly, P/SA-MC (3:7) emulsion gels containing PC and CAPE prevented the cytotoxic effects of PC and CAPE on human colon epithelial NCM-460 cells, but still allowed PC and CAPE to exert a strong anticancer effect on Caco-2 colon cancer cells. Our approach not only eliminates additional pre- and/or post-treatments used to prepare or stabilize the emulsion gel, but also provides a promising carrier for bioactive molecules.

Preparation of high internal phase Pickering emulsion by centrifugation for 3D printing and astaxanthin delivery

Oil in water high internal phase Pickering emulsion (HIPEs) stabilized by edible colloid particles have attracted considerable attention for three-dimensional (3D) printing and delivery of a hydrophobic bioactive. In this paper, a facile route for preparing oil in water HIPEs was demonstrated, only requiring centrifuging gliadin/gelatinized starch nanocomposites (G/SNPs) stabilized pre-emulsions. The surface properties of G/SNPs were engineered which helped prevent oil coalescence during centrifugation, while obtaining HIPEs with oil phase fractions up to 77.3%, simultaneously. The resultant HIPEs exhibited shear-thinning behavior with high solid viscoelasticity. Furthermore, HIPEs with internal phase fraction above 80% were successfully prepared simply by adjusting the ionic strength. The HIPEs with suitable rheology properties for 3D printing were obtained, and the enhanced viscoelasticity and thixotropic recovery could be attributed to the electrostatic shielding under higher ionic strength. In addition, the light stability and bioaccessibility of astaxanthin were significantly improved by HIPEs, and more than 90% astaxanthin was retained after heating at 95 °C for 30 min. These results proved a new route for producing HIPEs with improved performance, opening new possibilities for manufacturing future food and delivery of hydrophobic bioactive molecules.

Comparative study of encapsulated cannabidiol ternary solid dispersions prepared by different techniques: The application of a novel technique jet milling

Jet milling is a common technique in ultrafine powder preparation field. It has never been used to design delivery systems. Cannabidiol (CBD) is an important cannabinoid of hemp but poor aqueous solubility limited its applications. In this study, solid dispersion (SD) technique was combined with cyclodextrin complexation technique, and jet milling was used for the first time to prepare SDs for improving CBD solubility. Different characterizations demonstrated that the dispersion effect and complexation structure of CBD SD3 prepared by jet milling were comparable to that of CBD SD2 prepared by spray drying (a common solution-based method), and were better than that of CBD SD1 prepared by cogrinding. The water solubility of CBD was increased to 20.902 μg/mL (909-fold) in CBD SD3. Besides, the antioxidant activity and cytotoxicity to tumor cells of CBD were enhanced by dispersion. This work indicated that jet milling, as a new technique with low cost and excellent applicability, could be further developed for the delivery of food functional factors or bioactive molecules.

Chitosan-coated and thymol-loaded polymeric semi-interpenetrating hydrogels: An effective platform for bioactive molecule delivery and bone regeneration in vivo

Thymol (2-isopropyl-5-methylphenol; Thy) is a monoterpene phenolic phytocompound with medicinal properties; however, its impact on osteogenesis is yet to be thoroughly investigated. Its distribution is often hampered because of its intricate hydrophobic structure, which reduces its bioavailability. In this study, we synthesized a drug delivery vehicle using semi-interpenetrating polymer network (SIPN) hydrogels containing sodium alginate and poly(2-ethyl-2-oxazoline) (SA/Pox) loaded with Thy at varying concentrations (100, 150, and 200 μM). Subsequently, they were coated with chitosan (CS) to increase bioactivity and for sustained and prolonged release of Thy. Thy-loaded CS-coated SIPN hydrogels (SA/Pox/CS-Thy) were developed using ionic gelation and polyelectrolyte-complexation techniques. The addition of CS to hydrogels enhanced their physicochemical and material properties. These hydrogels were cytofriendly toward mouse mesenchymal stem cells (mMSCs). When mMSCs were cultured on hydrogels, Thy stimulated osteoblastic differentiation, as evidenced by calcium deposits at the cellular level. The expression of RUNX2, a key bone transcriptional factor, and other differentiation biomarkers was significantly enhanced in mMSCs cultured on SA/Pox/CS-Thy hydrogels. Notably, Thy in the SA/Pox/CS hydrogels significantly activated the TGF-β/BMP signaling pathway, which is involved in osteogenesis. A rat tibial bone defect model system revealed that the incorporation of Thy into SA/Pox/CS hydrogels augmented bone regeneration. Thus, sustained and prolonged release of Thy from the SA/Pox/CS hydrogels promoted osteoblast differentiation in vitro and bone formation in vivo. These findings shed light on the effect of Thy bioavailability in fostering osteoblast differentiation and its prospective application in bone rejuvenation.

A dynamic DNA tetrahedron framework for active targeting.

An active targeting strategy-enabled DNA tetrahedron delivery vehicle could facilitate stable drug encapsulation and stimuli-responsive on-demand release, building a universal platform for different drug delivery requirements. Owing to the excellent biocompatible nature, programmability and remarkable cell and tissue permeability, the tetrahedral DNA nanostructure (TDN) has proven its value in the delivery of various bioactive molecules. We previously described this as a static multifunctional complex in our earlier protocol. However, static structures and passive targeting behavior might introduce off-target effects under complicated biological conditions. Therefore, in this Protocol Extension, we present a major update of the TDN delivery vehicle enabling an active targeting strategy to be used for stimuli-sensitive conformation changes and on-site cargo release, which could avoid drawbacks, including complex and time-consuming fabrication processes and undetermined cell penetration ability of other DNA-based delivery vehicles. Upon exquisite design of TDN size based on cargo type, one-pot annealing is applied to fabricate the Tiamat-designed TDN exoskeleton. Then the design of the dynamic DNA apparatus can be based on the target and environmental stimuli, including DNA strand hybridization-based and pH-sensitive DNA apparatus, and careful titration of strand lengths and mismatches is achieved using polyacrylamide and agarose gel electrophoresis, or fluorophore modifications. Finally, cargo loading strategies are designed, including site and stand titration and cargo encapsulation verification. The dynamic structures show promising targetability and effectiveness in antitumor and anti-inflammatory treatment in vitro and in vivo. Assembly and characterization in the lab takes ~5 d, and the timing for the verification of biostability and biological applications depends on the uses.

Foliar applications to vines of methyl jasmonate and nanoparticles doped with methyl jasmonate: impact on grape and wine polysaccharide composition

Polysaccharides in wine play important roles in the stabilization and in the sensory properties of wines. Elicitor application constitutes an interesting field of research since it is indirectly involved in the accumulation in grape cell walls of molecules like callose, lignin, phenolic compounds and glycoproteins. Currently, biomimetic calcium phosphate (ACP) nanoparticles are successfully used in viticulture for the controlled delivery of bioactive molecules, such as elicitors. The aim of this study was to compare the effect of the application of two different elicitors on both grape and wine of Tempranillo polysaccharide composition. Methyl jasmonate (MeJ) and nanoparticles doped with MeJ were applied to the canopy at veraison and one week later in two vintages. In the grape extracts, the foliar treatments did not increase the content of monosaccharides or that of the main pectin families; therefore, the elicitors did not reinforce the cell walls of the Tempranillo grape. The extractability and solubility of the pectic families of the grape cell walls into the wine depended on the type of family and the climate of the vintages.

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 containingC. reinhardtiimicroalgae 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.