Emulsion Method Research Articles

Characterization of GABA-loaded nanoliposomes and its health benefits

γ-Aminobutyric acid (GABA), a non-protein amino acid widely distributed in animals and plants, strongly affected the early stage of sleep. Nevertheless, exogenous GABA was easily decomposed by GABA transaminase (GABA-T) in body. Therefore, in this study, GABA-loaded nanoliposomes (GN) were constructed by the freeze-drying double emulsion (FDE) method. The average size, encapsulation efficiency and loading efficiency of GN was 171.9 nm, 89.9 % and 7.7 %, respectively, and GN were able to be stored at 4 °C for at least 30 days. GN showed sustained release effect, and significantly increased the effective content of GABA by 16 % in vivo than free-GABA treatment. On the one hand, the sleep quality of Caenorhabditis elegans was effectively enhanced by GN, including the improvement of sleep duration and frequency, the increase of the contents of inhibitory neurotransmitters, and the reduction of heat-stress-induced neurons damages. On the other hand, GN improved the health benefits of worms by enhancing the locomotion ability, promoting the growth and alleviating mitochondrial structure disorders. Overall, this study had improved the stability and bioavailability of GABA by embedding GABA in liposome.

3D printed scaffolds with quercetin and vitamin D3 nanocarriers: In vitro cellular evaluation.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

Phosphatidylcholine-depleted lecithin as low-HLB emulsifier in double emulsions: A sensitivity analysis

Phosphatidylcholine-depleted (PC-depleted) lecithin is characterized by a lower phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio, favoring the formation of water-in-oil (W/O) emulsions, and thus can be applied in water-in-oil-in-water (W/O/W) double emulsions (DEs). However, up to now, only a limited number of studies have described the use of PC-depleted lecithin in double emulsions. In this study, the influence of the formulation and processing conditions on the formation and stability of PC-depleted lecithin stabilized-DEs was investigated. The characterizations of DEs involved morphology, droplet size, viscosity, and entrapped water yield. The experimental results indicated that the incorporation of glucose in the water phase instead of potassium chloride (KCl) increased both the droplet size and the entrapped water yield in DEs, whereby the latter was increased by around 65% as compared to DEs containing 100 mM KCl. Reducing the salt content also facilitated the formation of DEs. Moreover, a correlation between the oil type and the 1st homogenization method was found: whereas DEs formulated with high oleic sunflower oil were always unstable irrespective of the emulsification method used, stable DEs were produced by the combination of medium-chain triglyceride oil and a rotor-stator system whereby microfluidization caused phase inversion. In addition, PC-depleted lecithin could stabilize up to 60% of water in oil. Meanwhile, stable DEs with a maximum internal water fraction of 24.1% were obtained by adjusting the original W/O/W ratio to 25/25/50. Finally, DEs stabilized by PC-depleted lecithin showed a comparable stability to those stabilized by polyglycerol polyricinoleate (PGPR) during 28 days of storage. To sum up, this work provides a better understanding of the sensitivity of PC-depleted lecithin-stabilized W/O/W emulsions towards the applied formulation conditions.

Several common methods of making vesicles (except an emulsion method) capture intended lipid ratios.

Small changes to the amounts and types of lipids in membranes can drastically affect the membrane's behavior. Unfortunately, it is unknown whether (or to what extent) different methods of making vesicles alter the ratios of lipids in membranes, even when identical stock solutions are used. This presents challenges for researchers when comparing data with colleagues who use different methods. Here, we measure ratios of lipid types in vesicle membranes produced by five methods. We assess each method's reproducibility and compare resulting vesicle compositions across methods. In doing so, we provide a quantitative basis that the scientific community can use to estimate whether differences between their results can be simply attributed to differences between methods or to sample-to-sample variations.

Preparation of Monodisperse Silica Mesoporous Microspheres with Narrow Pore Size Distribution.

The purpose of this study is to prepare monodisperse silica mesoporous microspheres with narrow pore size distribution to promote their application in the field of liquid chromatography. An improved emulsion method was used to prepare silica mesoporous microspheres, and the rotary evaporation temperature, emulsification speed, dosage of porogen DMF, and dosage of the catalyst NH3·H2O were optimized. Subsequently, these microspheres were respectively treated by alkali-heating, calcination, and sieving. The D50 (particle size at the cumulative particle size distribution percentage of 50%) of as-prepared silica mesoporous microspheres is 26.3 μm, and the D90/D10 (the ratio of particle size at a cumulative particle size distribution percentage of 90% to a cumulative particle size distribution percentage of 10%) is 1.94. The resultant silica mesoporous microspheres have distinctive pore structures, with a pore volume of more than 1.0 cm3/g, an average pore size of 11.35 nm, and a median pore size of 13.4 nm. The silica mesoporous microspheres with a large particle size, uniform particle size distribution, large average pore size and pore volume, and narrow mesopore size distribution can basically meet the requirements of preparative liquid chromatographic columns.

Doxycycline monohydrate and azelaic acid Co-loaded nanoemulgel for the treatment of facial rosacea: In vitro and In vivo evaluation

Nanoemulgel have gained importance as topical delivery systems because of their potential to incorporate hydrophilic and lipophilic drugs simultaneously like emulsions and improved stability and spreadability like gels. Therefore, the current research was aimed to prepare, optimize, and evaluate the combined therapeutic efficacy of doxycycline monohydrate (DOX.H2O) and azelaic acid (AZL) loaded into a nanoemulgel (NE) against facial rosacea. The nanoemulsion was prepared via phase inversion low energy emulsification method by solubilizing DOX.H2O in peppermint oil and AZL in deionized water. The formulation was optimized using Design Expert 13. The optimized nanoemulsion has a particle size of 210.6 nm, a PDI of 0.234 and a zeta potential of −15.1 mV. SEM observations revealed the spherical morphology of oil globules, whereas FTIR results confirmed that no chemical interaction among the ingredients took place. The in vitro release study showed the burst release of 82.1 % AZL and 48.1 % release of DOX.H2O from the optimized DOX-AZL co-loaded NE in 6 h. The ex vivo permeation profile showed a minimum permeation of DOX.H2O and AZL across rat skin. Croton oil induced inflammation in mice ear confirmed the therapeutic efficacy of the prepared NE against facial rosacea. Considering the results obtained herein, the developed NE could enhance the safety and efficacy of the combination therapy against facial rosacea.

Janus and Amphiphilic MoS2 2D Sheets for Surface-Directed Orientational Assemblies toward Ex Vivo Dual Substrate Release.

The two-dimensional (2-D) Janus and amphiphilic molybdenum disulfide (MoS2) nanosheet with opposite optical activities on each side (amphichiral) is synthesized by modifying sandwich-like bulk MoS2 with tannic acid and cholesterol through biphasic emulsion method. This new type of amphichiral Janus MoS2 nanosheet consists of a hydrophilic and positive optical activity tannic acid side as well as a hydrophobic and negative optical activity cholesterol side thereby characterized by circular dichroism. Surface-directed orientational differentiation assemblies are performed for the as-synthesized 2D material and are characterized by contact angle, infrared spectroscopy, X-ray photoelectron, and circular dichroism spectroscopies. The amphiphilic nature of the materials is demonstrated by the pre-organization of the nanosheets on either hydrophobic or hydrophilic surfaces, providing unprecedented properties of circular dichroism signal enhancement and wettability. Selective detachment of the surface organic groups (cholesterol and tannic acid fragments) is realized by matrix-assisted laser desorption/ionisation - time-of-flight(MALDI-TOF) mass spectrometry, and the dual substrate release in tissue is detected by ex vivo mass spectrometry imaging.

Effects of MARDI Nano-Fertilizer Application Frequency on the Growth of Rock Melon

For many years, fertilizers have been utilized in agriculture to increase the fruit yield and quality of various crops, which in turn will increase the nutritive content of products. Recently, MARDI has developed a nano-fertilizer based on nanoemulsions to increase the productivity of rock melon. The development of nanoemulsion-based fertilizer was carried out using the high-energy emulsification method which has significant advantages, such as enhancing the solubilization of active constituents while preserving biological activity. In this work, the effects of the vegetative growth of rock melon on different application frequencies (T1=0, T2=2, T3=4, T4=6, and T5=8 times) of MARDI nano-fertilizer through foliar treatment were studied. The results showed that the vegetative growth of the rock melon including plant height, stem diameter, relative chlorophyll content, and leaf area of rock melon were significantly (p≤0.05) increased by 15.07%, 7.8%, 41.5% and 41.5%, respectively at T3, photosynthetic pigments of Chlorophyll a by 21.1% at T5, Chlorophyll b and carotenoid by 24.99% at T4 treatment. The dry weight biomass did not vary significantly in all treatments but showed an increase in dry biomass over the nano-fertilizers treatment compared to the control. These findings indicate that adding the foliar application of MARDI nano-fertilizer produces optimal growth in rock melon plants.

Gelatin/PLGA Microspheres as a 3D Scaffold for Chondrocytes

Background: Osteoarthritis (OA) degrades cartilage and bone. Osteochondral autograft, allograft, and total replacement knee surgery have limitations, such as prompt immune responses, lack of cartilage tissue obtainability, invasiveness, and a loosening implant that may require further correction. Tissue engineering, which involves injecting chondrocytes into 3D porous scaffold carriers in the joint, seems promising for tissue repair and growth. Objective: To develop gelatin/poly DL-lactide-co-glycolide (PLGA) microspheres as a porous scaffold for chondrocyte carriers. Methods: The double emulsion method is one of the most popular and best methods for forming microspheres. In summary, in the PLGA oil phase, we emulsified a gelatin solution representing the inner aqueous phase. Next, in an external aqueous phase of polyvinyl alcohol (PVA), we emulsified the resultant first emulsion. The double emulsion was stirred to evaporate organic solvent and centrifuged to collect gelatin and PLGA microspheres. Results: The Mastersizer result showed polydispersed particles with 23.53% of the desirable cell injection size range between 1-300 µm. Scanning electronic microscope (SEM) images revealed spherical and porous microspheres with smooth surfaces. The average absolute zeta potential value was -30.7±4.895, indicating stable preparation. Conclusions: Gelatin and PLAGA polymers worked together to make 3D scaffold microspheres that were the right size, had the right number of holes, and were strong.

Shock attenuation of silicone rubber composites with shear thickening fluid

This study investigated the enhancement of shock attenuation in silicone rubber (SR) matrix composites through the incorporation of shear thickening fluid (STF) microdroplets. A series of SR-STF composites with various STF mass fractions (0 to 50 wt. %) were fabricated using an efficient emulsification method. The primary focus was on assessing the shock attenuation capabilities of SR-STF through laser-induced shock experiments. The results indicate a significant improvement in shock wave attenuation in the composites due to the addition of STF microdroplets. Notably, the SR-STF composite containing 30 wt. % STF exhibited a maximum 60 % reduction in shock pressure attenuation compared to SR of the same thickness. This enhancement is attributed to multiple mechanisms, including viscosity-induced dissipation, the initiation and propagation of cracks within both the SR matrix and the STF microdroplets, and interface-induced effects like interface separation, shock wave reflection and scattering, along with the thickening behavior of STF. An intriguing observation was the interplay of these mechanisms at different STF concentrations, leading to the identification of an optimal STF content for maximizing the shock attenuation. This research's findings highlight the crucial role of STF microdroplets in shock wave attenuation and offer a strategic approach for developing SR matrix composites with enhanced shock attenuation capacities.

Surface decoration of PLGA nanoparticles enables efficient transport of floxuridine oligomers into mammalian cells

2′-deoxy-5-fluorouridine (Floxuridine, FdU) oligomers are repeated FdU residues linked to each other through phosphate groups exhibiting anticancer properties. One of the major hurdles exhibited by natural oligomers is their reduced stability and limited ability to impart cellular uptake. To overcome these drawbacks, electrostatic and covalent strategies have been used to combine oligomers with nanoparticles (NPs) to enhance stability and cellular internalization. Polymeric NPs, prepared from oil-in-water (O/W) PLGA nano-emulsions (NEs) using low-energy emulsification methods, have shown potential in many biomedical applications owing to their ability to transport drugs across cellular membranes. Carbodiimide-mediated amine coupling reaction and thiol-based Michael-type addition were used to attach FdU oligomers formed by five FdU residues (FdU5) to PLGA NPs. Colloidally stable dispersions of FdU5-decorated PLGA NPs were obtained and characterized in terms of size, surface charge, and morphology in physiological medium. Additionally, synthetic strategies were envisaged to functionalize the surface of FdU5-decorated polymeric NPs with folic acid (FA). Cell culture experiments showed that FdU5-decorated PLGA NPs were able to internalize efficiently inducing cytotoxic effect and inhibiting cell proliferation in tumor cells. These outcomes suggest the feasibility of grafting oligomeric FdU produgs in a covalent fashion into nanoscale platforms as a potential approach for cancer therapy.

Facile Synthesis of Surface-Modified Hollow-Silica (SiO2) Aerogel Particles via Oil-Water-Oil Double Emulsion Method.

Due to their high surface area and low weight, silica aerogels are ideally suited for several uses, including drug delivery, catalysis, and insulation. Oil-water-oil (OWO) double emulsion is a simple and regulated technique for encasing a volatile oil phase in a silica shell to produce hollow silica (SiO2) aerogel particles by using hydrophilic and hydrophobic emulsifiers. In this study, the oil-water-oil (OWO) double emulsion method was implemented to synthesize surface-modified hollow silica (SiO2) aerogel particles in a facile and effective way. This investigation mainly focused on the influence of the N-hexane-to-water glass (OW) ratio (r) in the first emulsion, silica (water glass) content concentration (x), and surfactant concentration (s) variations. Furthermore, surface modification techniques were utilized to customize the aerogel's characteristics. The X-ray diffraction (XRD) patterns showed no imprints of impurities except SiO2. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images highlight the hollow microstructure of silica particles. Zeta potential was used to determine particle size analysis of hollow silica aerogel particles. The oil-water-oil (OWO) double emulsion approach was successfully employed to synthesize surface-modified hollow silica (SiO2) aerogel particles, providing precise control over the particle characteristics. By the influence of the optimization condition, this approach improves the aerogel's potential applications in drug delivery, catalysis, and insulation by enabling surface modifications.

Evaluation of Doxorubicin-loaded Echogenic Macroemulsion for Targeted Drug Delivery.

The latest technology trend in targeted drug delivery highlights stimuliresponsive particles that can release an anticancer drug in a solid tumor by responding to external stimuli. This study aims to design, fabricate, and evaluate an ultrasound-responsive drug delivery vehicle for an ultrasound-mediated drug delivery system. The drug-containing echogenic macroemulsion (eME) was fabricated by an emulsification method using the three phases (aqueous lipid solution as a shell, doxorubicin (DOX) contained oil, and perfluorohexane (PFH) as an ultrasound-responsive agent). The morphological structure of eMEs was investigated using fluorescence microscopy, and the size distribution was analyzed by using DLS. The echogenicity of eME was measured using a contrast-enhanced ultrasound device. The cytotoxicity was evaluated using a breast cancer cell (MDA-MB-231) via an in vitro cell experiment. The obtained eME showed an ideal morphological structure that contained both DOX and PFH in a single particle and indicated a suitable size for enhancing ultrasound response and avoiding complications in the blood vessel. The echogenicity of eME was demonstrated via an in vitro experiment, with results showcasing the potential for targeted drug delivery. Compared to free DOX, enhanced cytotoxicity and improved drug delivery efficiency in a cancer cell were proven by using DOX-loaded eMEs and ultrasound. This study established a platform technology to fabricate the ultrasound-responsive vehicle. The designed drug-loaded eME could be a promising platform with ultrasound technology for targeted drug delivery.

PDMS microspheres as rheological additives for PDMS-based DIW inks

Direct Ink Writing holds vast potential for additive manufacturing with broad material compatibility as long as appropriate rheological properties are exhibited by the material of choice. Additives are often included to attain the desired rheological properties for printing, but these same additives can yield products with undesirable mechanical properties. For example, silica fillers are used to create silicone inks appropriate for printing but yield cured structures that are too stiff. In this work, we investigate the applicability of PDMS microspheres as a rheological and thixotropic additive for PDMS based DIW inks. We utilize a facile oil-in-water emulsion method to reproducibly obtain small (∼5 μm) PDMS microspheres, which are then incorporated into PDMS-based inks. More traditional inks with fumed silica and thixotropic additive were compared with inks containing PDMS microspheres at equal volume loadings to determine whether the PDMS microspheres could impart the desired rheological properties for DIW. Inks including PDMS microspheres exhibited surprising thixotropic effects, which enabled prints with fidelity analogous to traditional ink employing silica filler, while producing mechanically softer prints.

Preservation of chilled beef using active films based on bacterial cellulose and polyvinyl alcohol with the incorporation of Perilla essential oil Pickering emulsion

In this study, Perilla essential oil (PEO) Pickering emulsions, prepared using soybean protein isolate-chitosan nanoparticles (SPI-CSNPs) as emulsifiers (SCEO), were used to improve the performance of bacterial cellulose/polyvinyl alcohol (BC/PVA) films for application in chilled beef preservation. The SCEO has a smaller particle size (185 nm), higher viscosity, a more uniform dispersion and was more stable at an oil phase volume fraction of 80 %. An increase in the films' surface roughness and in the hydrogen bonding between SCEO and the films' matrix was also observed, resulting in a lower tensile strength (TS, 94.75–62.02 MPa) and higher elongation at break (EAB, 26.78–55.62 %). Moreover, the thermal stability, water vapor permeability, antioxidant and antibacterial properties of the composite films improved as the SCEO content increased. Furthermore, the Pickering emulsion method was effective in preventing the loss of PEO during storage. Overall, one particular composite film, BP/SCEO3, could prolong the shelf life of chilled beef by up to 14 days, and hence was promising for food preservation.

Intranasal Immunization for Zika in a Pre-Clinical Model.

Humans continue to be at risk from the Zika virus. Although there have been significant research advancements regarding Zika, the absence of a vaccine or approved treatment poses further challenges for healthcare providers. In this study, we developed a microparticulate Zika vaccine using an inactivated whole Zika virus as the antigen that can be administered pain-free via intranasal (IN) immunization. These microparticles (MP) were formulated using a double emulsion method developed by our lab. We explored a prime dose and two-booster-dose vaccination strategy using MPL-A® and Alhydrogel® as adjuvants to further stimulate the immune response. MPL-A® induces a Th1-mediated immune response and Alhydrogel® (alum) induces a Th2-mediated immune response. There was a high recovery yield of MPs, less than 5 µm in size, and particle charge of -19.42 ± 0.66 mV. IN immunization of Zika MP vaccine and the adjuvanted Zika MP vaccine showed a robust humoral response as indicated by several antibodies (IgA, IgM, and IgG) and several IgG subtypes (IgG1, IgG2a, and IgG3). Vaccine MP elicited a balance Th1- and Th2-mediated immune response. Immune organs, such as the spleen and lymph nodes, exhibited a significant increase in CD4+ helper and CD8+ cytotoxic T-cell cellular response in both vaccine groups. Zika MP vaccine and adjuvanted Zika MP vaccine displayed a robust memory response (CD27 and CD45R) in the spleen and lymph nodes. Adjuvanted vaccine-induced higher Zika-specific intracellular cytokines than the unadjuvanted vaccine. Our results suggest that more than one dose or multiple doses may be necessary to achieve necessary immunological responses. Compared to unvaccinated mice, the Zika vaccine MP and adjuvanted MP vaccine when administered via intranasal route demonstrated robust humoral, cellular, and memory responses. In this pre-clinical study, we established a pain-free microparticulate Zika vaccine that produced a significant immune response when administered intranasally.

Controlled delivery of nikkomycin by PEG coated PLGA nanoparticles inhibits chitin synthase to prevent growth of Aspergillus flavus and Aspergillus fumigatus.

Aspergillosis is one of the most common fungal infections that can threaten individuals with immune compromised condition. Due to the increasing resistance of pathogens to the existing antifungal drugs, it is difficult to tackle such disease conditions. Whereas, nikkomycin is an emerging safe and effective antifungal drug which causes fungal cell wall disruption by inhibiting chitin synthase. Hence, the study aims at the development of nikkomycin loaded PEG coated PLGA nanoparticles for its increased antifungal efficiency and inhibiting Aspergillus infections. The P-PLGA-Nik NPs were synthesized by w/o/w double emulsification method which resulted in a particle size of 208.3±15 nm with a drug loading of 52.97 %. The NPs showed first order diffusion-controlled drug release which was sustained for 24 h. These nanoparticle's antifungal efficacy was tested using the CLSI- M61 guidelines and the MIC50 defined against Aspergillus flavus and Aspergillus fumigatus was found to be >32 μg/ml which was similar to the nikkomycin MIC. The hyphal tip bursting showed the fungal cellwall disruption. The non-cytotoxic and non-haemolytic nature highlights the drug safety profile.

Piezoelectric-synchronized step emulsification for facile generation of microdroplet library with fluid-independent drop size regulation regime

Microdroplets play a crucial role in various applications based on microfluidics, including biomedicine, materials synthesis, and analytical chemistry. However, there is still an urgent need for a microdroplet preparation method that is simple in design, precise in droplet size control and meanwhile independent of the properties of the fluid. Here, we present a piezoelectric-synchronized step emulsification method. The drop formation process can be synchronized by the introduced periodic vibration via the piezoelectric element, which occurs in a specific frequency range determined by a dimensionless parameter. The competing between the step emulsification regime and the piezoelectric-triggered local flow rate fluctuation leads to various microscopic flow behavior. A novel instantaneous jetting regime is found to be responsible for the extended achievable drop size range. By combining the piezoelectric step emulsification and the XY stage control, we achieve facile production of microdroplet and hydrogel microsphere library in well plates, which is promising to be integrated as a low-cost drop-generating technique into bioassay instruments.

Non-covalent interaction induces controlled reinforcement of thermoplastic elastomer composites homologously incorporated with hydrophobized cellulose nanocrystals

Surface hydrophobization of cellulose nanocrystal (CNC) is developed through Pickering emulsion method and esterification-grafting, consequentially enhancing its thermal properties and hydrophobicity, and tensile modulus in thermoplastic elastomer composites. n-Tetradecenylsuccinic anhydride (TDSA) provides a high level of compatibility owing to the structural homology by non-covalent interactions between CNC-graft-TDSA and poly(styrene)-block-poly(isoprene)-block-poly(styrene) (SIS). Theoretical calculations supports the molecular-level insight on how the nanofiller and SIS interacts. Density functional theory calculations and the energy decomposition analysis reveal the stabilization free energy of −2.59 kcal mol−1 gained through hydrophobic and OH–π interactions, which is assigned as the key component for the superior mechanical properties. At the filler contents of 0.6–2.5 vol %, the moduli of the TPE nanocomposites gradually strengthen while retaining thermoplasticity, without sacrificing the ultimate tensile characteristics of SIS, although it is below the calculated φc of 5.9 vol % (critical percolation threshold) for filler-filler interactions. Origin of the controlled boost in filler-matrix binding is rationalized by pronounced hydrophobic interactions in isoprene-rich rubbery phase (86 wt % in SIS). Interestingly, at 5.1 vol % near to filler-filler interactions, even though reinforcements in storage/initial modulus, and toughness increase by up to 14/4.0-, and 1.2-fold, the tensile stress at break only decreases by 27 %.

Promoting tissue repair using deferoxamine nanoparticles loaded biomimetic gelatin/HA composite hydrogel

To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferation in vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.