An In†Situ Depot for Continuous Evolution of Gaseous H2 Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis.

Inflammation is involved in many human pathologies, including osteoarthritis (OA). Hydrogen (H2 ) is known to have anti-inflammatory effects; however, the bioavailability of directly administered H2 gas is typically poor. Herein, a local delivery system that can provide a high therapeutic concentration of gaseous H2 at inflamed tissues is proposed. The delivery system comprises poly(lactic-co-glycolic acid) microparticles that contain magnesium powder (Mg@PLGA MPs). Mg@PLGA MPs that are intra-muscularly injected close to the OA knee in a mouse model can act as an in situ depot that can evolve gaseous H2 continuously, mediated by the cycle of passivation/activation of Mg in body fluids, at a concentration that exceeds its therapeutic threshold. The analytical data that are obtained in the biochemical and histological studies indicate that the proposed Mg@PLGA MPs can effectively mitigate tissue inflammation and prevent cartilage from destruction, arresting the progression of OA changes.

A compartmentalized culture device for studying the axons of CNS neurons.

We report here the development of a compartmentalized culture device that allows the spatial separation of the somatodendrites and axons of central nervous system (CNS) neurons. The device consists of two compartments separated by a septum constructed by attaching a porous polycarbonate track etch (PCTE) filter on top of a microchannel-filled polydimethylsiloxane (PDMS) membrane. The surface and microchannels of the septum are coated and filled, respectively, with materials that support neuron growth and neurite migration. When rat hippocampal neurons are cultured in the top compartment, axons are the only processes that can migrate through the septum to the bottom compartment. The axons in the bottom compartment can be studied directly in real-time or through immunofluorescence staining after fixation. Axons containing ∼3 µg protein can be isolated from each device for biochemical analyses. In addition, the septum also impedes the movement of small molecules between the top and bottom compartments. This feature allows the somatodendrites and axons of neurons, which occupy the top and bottom compartments of the device, respectively, to be manipulated independently. The potential applications of the device as a tool in diverse studies concerning neuronal axons and in screening reagents that regulate axonal functions have also been discussed.

Preliminary study of acoustic analysis for evaluating speech-aid oral prostheses: Characteristic dips in octave spectrum for comparison of nasality.

BACKGROUND/PURPOSE: Acoustic analysis is often used in speech evaluation but seldom for the evaluation of oral prostheses designed for reconstruction of surgical defect. This study aimed to introduce the application of acoustic analysis for patients with velopharyngeal insufficiency (VPI) due to oral surgery and rehabilitated with oral speech-aid prostheses. METHODS: The pre- and postprosthetic rehabilitation acoustic features of sustained vowel sounds from two patients with VPI were analyzed and compared with the acoustic analysis software Praat. RESULTS: There were significant differences in the octave spectrum of sustained vowel speech sound between the pre- and postprosthetic rehabilitation. Acoustic measurements of sustained vowels for patients before and after prosthetic treatment showed no significant differences for all parameters of fundamental frequency, jitter, shimmer, noise-to-harmonics ratio, formant frequency, F1 bandwidth, and band energy difference. The decrease in objective nasality perceptions correlated very well with the decrease in dips of the spectra for the male patient with a higher speech bulb height. CONCLUSION: Acoustic analysis may be a potential technique for evaluating the functions of oral speech-aid prostheses, which eliminates dysfunctions due to the surgical defect and contributes to a high percentage of intelligible speech. Octave spectrum analysis may also be a valuable tool for detecting changes in nasality characteristics of the voice during prosthetic treatment of VPI.

Examination of ceramic restoration adhesive coverage in cusp-replacement premolar using acoustic emission under fatigue testing.

BACKGROUND: This study investigates CAD/CAM ceramic cusp-replacing restoration resistance with and without buccal cusp replacement under static and dynamic cyclic loads, monitored using the acoustic emission (AE) technique. METHOD: The cavity was designed in a typical MODP (mesial-occlusal-distal-palatal) restoration failure shape when the palatal cusp has been lost. Two ceramic restorations [without coverage (WOC) and with (WC) buccal cuspal coverage with 2.0 mm reduction in cuspal height] were prepared to perform the fracture and fatigue tests with normal (200 N) and high (600 N) occlusal forces. The load versus AE signals in the fracture and fatigue tests were recorded to evaluate the restored tooth failure resistance. RESULTS: The results showed that non-significant differences in load value in the fracture test and the accumulated number of AE signals under normal occlusal force (200 N) in the fatigue test were found between with and without buccal cuspal coverage restorations. The first AE activity occurring for the WOC restoration was lower than that for the WC restoration in the fracture test. The number of AE signals increased with the cyclic load number. The accumulated number of AE signals for the WOC restoration was 187, higher than that (85) for the WC restoration under 600 N in the fatigue test. CONCLUSION: The AE technique and fatigue tests employed in this study were used as an assessment tool to evaluate the resistances in large CAD/CAM ceramic restorations. Non-significant differences in the tested fracture loads and accumulated number of AE signals under normal occlusal force (200 N) between different restorations indicated that aggressive treatment (with coverage preparation) in palatal cusp-replacing ceramic premolars require more attention for preserving and protecting the remaining tooth.

The gamification and development of a chatbot to promote oral self-care by adopting behavior change wheel for Taiwanese children.

Background: Oral health is closely related to general health and quality of life. School-aged children are at a critical stage for developing their self-care ability in oral health. Digital interventions can encourage and facilitate oral self-care in children. Objective: This study aims to present the development of an educational chatbot for school-aged children to address their oral self-care and evaluate its usability. Methods: The development and evaluation of the chatbot for oral self-care consisted of four stages: target behavior analysis, intervention design, system development, and the chatbot evaluation. The target behavior analysis identified barriers to children's engagement in oral self-care based on dentists' clinical observations; hence, the requirements for achieving the desired behavior were categorized according to the capability-opportunity-motivation behavior model. Interventional functions were created following the behavior change wheel. A menu-driven chatbot was created and evaluated for usability as well as likeability. Results: The barriers and requirements for achieving good behavior in school-aged children's oral self-care were identified by the dental professionals. Intervention strategy incorporated specific functions enriched with gamification features to support school-aged children in developing their abilities for engaging in oral self-care. The intervention functions consist of capability establishment, motivation enhancement, and opportunity creation, which were designed to support children in their oral self-care practices. The designed chatbot was piloted with a convenient sample of 30 school-aged children and their accompanying parents at the pediatric dental clinic. The results indicated good usability, with a mean usability score of 79.91, and high likeability with a mean score of 4.32 out of 5 for the designed chatbot. Conclusions: The educational chatbot incorporated a combination of clinical dentistry practice and guidelines, aiming to promote oral self-care behavior in school-aged children. The designed chatbot achieved high scores for its usability and user likability.

A novel biodegradable magnesium skin staple: A safety and functional evaluation.

BACKGROUND: The potential of biodegradable magnesium (Mg) skin staple has recently garnered widespread attention due to their biodegradability and biocompatibility rather than traditional stainless steel staples, the most commonly used in current clinical practice. The aim of this study is to evaluate the safety and mechanical properties of a novel biodegradable Mg skin staple. METHODS: A prototype of Mg skin staple was designed using a novel ZK60 Mg alloy. The mechanical properties of the staple were evaluated using a universal testing machine. The cytotoxicity of the staple was examined in vitro and the efficacy of the staple in wound closure was assessed in New Zealand rabbits for one and three weeks, respectively. RESULTS: The tensile strength of this Mg alloy is 258.4 MPa with 6.9% elongation. The treatment of HaCaT and L929 cells with the staple extract resulted in over 95% cell viability, indicating no cytotoxicity. In vivo, no tissue irritation was observed. No difference was found in wound healing between the Mg skin staple and the stainless steel staple after one and three weeks in the cutting wound on the back of rabbits. Some Mg skin staples spontaneously dislodged from the skin within three weeks, while others were easily removed. CONCLUSION: Our results confirm the safety, biocompatibility, and functionality of the novel Mg skin staple in wound closure. The efficacy of the staple in wound closure was demonstrated to be as effectively as conventional staples, with the added benefit of decreased long-term retention of skin staples in the wounds.

Xeno-free culture and proliferation of hPSCs on 2D biomaterials.

Human pluripotent stem cells (human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs)) have unlimited proliferative potential, whereas adult stem cells such as bone marrow-derived stem cells and adipose-derived stem cells have problems with aging. When hPSCs are intended to be cultured on feeder-free or xeno-free conditions without utilizing mouse embryonic fibroblasts or human fibroblasts, they cannot be cultured on conventional tissue culture polystyrene dishes, as adult stem cells can be cultured but should be cultivated on material surfaces grafted or coated with (a) natural or recombinant extracellular matrix (ECM) proteins, (b) ECM protein-derived peptides and specific synthetic polymer surfaces in xeno-free and/or chemically defined conditions. This review describes current developing cell culture biomaterials for the proliferation of hPSCs while maintaining the pluripotency and differentiation potential of the cells into 3 germ layers. Biomaterials for the cultivation of hPSCs without utilizing a feeder layer are essential to decrease the risk of xenogenic molecules, which contributes to the potential clinical usage of hPSCs. ECM proteins such as human recombinant vitronectin, laminin-511 and laminin-521 have been utilized instead of Matrigel for the feeder-free cultivation of hPSCs. The following biomaterials are also discussed for hPSC cultivation: (a) decellularized ECM, (b) peptide-grafted biomaterials derived from ECM proteins, (c) recombinant E-cadherin-coated surface, (d) polysaccharide-immobilized surface, (e) synthetic polymer surfaces with and without bioactive sites, (f) thermoresponsive polymer surfaces with and without bioactive sites, and (g) synthetic microfibrous scaffolds.

Preparation and characterization of ferulic acid-modified water soluble chitosan and poly (γ-glutamic acid) polyelectrolyte films through layer-by-layer assembly towards protein adsorption.

In this study, ferulic acid-modified water soluble chitosan and poly (γ-glutamic acid) polyelectrolyte multilayers films were constructed through the layer-by-layer (LBL) self-assembly technique. Chitosan (CS) or ferulic acid modified chitosan (MCS) and Poly (γ-glutamic acid) (PGA) was alternately deposited on the surface of glass substrate for the enhancement of surface modification. The obtained films were characterized by Fourier transform spectroscopy (FTIR), X-ray diffractometry (XRD), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), UV-vis spectroscopy and water contact angle to study its physico-chemical properties including protein absorption. The (PGA/MCS) films showed intense deposition of multilayers built upon the surface roughness and an increase in the exponential growth of multilayer films by UV-vis spectroscopy. Water contact angle indicated that the (PGA/MCS) films performed well with good wettability due to the increase in the number of layers. The LBL multilayer coatings of (PGA/MCS) films surface possessed a reduced amount of protein adsorption. These results indicated that it can resist the protein adsorption and can enhance the biocompatibility towards the biomedical application through the protein interaction. The (PGA/MCS) films has the potential to utilization as a good biomaterial for biomedical purposes to intensify the bio-active surface.

Effect of toothbrush/dentifrice abrasion on weight variation, surface roughness, surface morphology and hardness of conventional and CAD/CAM denture base materials.

We evaluated the effect of toothbrush/dentifrice brushing on the weight variation and surface properties of different denture bases. Four denture base materials (conventional heat cure, high impact, CAD/CAM, and polyamide resins) were subjected to toothbrushing abrasion (50,000 strokes). The weight value, surface roughness, and topography of each group were determined before and after toothbrushing. The hardness was measured by the Vickers hardness test. Data were analyzed using ANOVA and Bonferroni tests. After toothbrushing, the weight of the polyamide resin had significantly increased; significant weight losses were observed for conventional heat cure and high impact resins, but none for the CAD/CAM resin. The surface roughness of each group increased significantly owing to the wear caused by toothbrushing. The weight variation and surface roughness were not affected by the hardness. Our results suggested that denture base materials deteriorate after brushing with toothpaste, in which the polyamide resin exhibited lower levels of abrasion.

Conductive Materials for Healing Wounds: Their Incorporation in Electroactive Wound Dressings, Characterization, and Perspectives.

The use of conductive materials to promote the activity of electrically responsive cells is an effective means of accelerating wound healing. This article focuses on recent advancements in conductive materials, with emphasis on overviewing their incorporation with non-conducting polymers to fabricate electroactive wound dressings. The characteristics of these electroactive dressings are deliberated, and the mechanisms on how they accelerate the wound healing process are discussed. Potential directions for the future development of electroactive wound dressings and their potential in monitoring the course of wound healing in vivo concomitantly are also proposed.

Finite element and Weibull analyses to estimate failure risks in the ceramic endocrown and classical crown for endodontically treated maxillary premolar.

The present study evaluated the failure risks of an endodontically treated premolar with severely damaged coronal hard tissue and restored with either a computer-aided design/computer-aided manufacturing (CAD/CAM) ceramic endocrown or a classical crown configuration. Two, three-dimensional finite element maxillary premolar models were designed with endodontic treatment and restored with either a chairside economic reconstruction of esthetic ceramic (CEREC) ceramic endocrown or a classical crown. The Weibull function was incorporated with finite element analysis to calculate the long-term failure probability relative to different load conditions. Additionally, an in vitro fatigue-load fracture experiment was performed to validate the numerical simulation results. The results indicated that the stress values on the dentin and luting cement for the endocrown restoration were lower than those for the crown configuration. Weibull analysis revealed that the individual failure probability in the endocrown dentin and luting cement diminished more than those for the crown restoration. While the overall failure probabilities for the endocrown and the classical crown were similar, fatigue fracture testing revealed that the endocrown restoration had higher fracture resistance than the classical crown configuration (1,446 vs. 1,163 MPa). This investigation implies that the endocrown can be considered as a conservative, aesthetic, and clinically feasible restorative approach for endodontically treated maxillary premolars.

Complete unilateral maxillary sinus opacity in computed tomography.

BACKGROUND/PURPOSE: Unilateral maxillary sinus opacity can be caused by many diseases, but an exact diagnosis is difficult to make. The aim of this study was to describe the pathological conditions and clinical features of patients with unilateral maxillary sinus opacity. METHODS: From 2004 to 2008, 830 consecutive patients underwent sinus surgery or endonasal endoscopic biopsy at an academic tertiary care center. The preoperative computed tomography (CT) images for these patients were reviewed, and 11 6 patients were identified with complete unilateral maxillary sinus opacification. We then analyzed presenting symptoms, physical examinations, specific CT findings, and pathology. RESULTS: The most frequent diagnoses were as follows: chronic rhinosinusitis (52.6%), fungus ball (29.3%), antrochoanal polyp (2.6%), benign tumor (10.4%), and malignancy (5.1%). Fungus ball was the most common diagnosis (10/18, 55.6%) in the subgroup of patients with isolated maxillary sinus opacity without disease in the other sinuses. Nasal discharge and foul-smelling breath were more common in inflammatory disease than in neoplastic disease. Neoplastic disease was more likely to present as epistaxis; a polyp or mass revealed by nasal endoscopy; mass effect in the cheek, palate, or gingiva; and bony erosion on CT. Erosion of the maxillary posterolateral wall and extra-sinus extension suggested malignancy. CONCLUSION: Although unilateral maxillary sinus opacity is usually inflammatory in origin, fungal sinusitis and neoplastic disorder are also likely. A careful history-taking, a thorough head and neck examination including nasal endoscopy, and CT evaluation are all imperative for reaching a correct diagnosis.

Effect of Ti2Cu precipitation on antibacterial property of Ti-5Cu alloy.

To instill pure Ti with an antibacterial effect, Cu was added by metallurgical alloying to produce Ti-5 wt% Cu alloy (Ti-5Cu alloy). The precipitation of the likes of Ti2Cu in a Ti-Cu alloy is one of the factors that influences its antibacterial property. However, in the present study, Ti-5Cu alloy precipitates with different microstructures were obtained by applying heat treatment at different temperatures and for different durations. After the heat treatment, metallographic, microstructure, and element analyses were performed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) combined with energy dispersive X-ray spectroscopy (EDS). The antibacterial property of the Ti-5Cu alloy was assessed by the plated-count method using Escherichia coli (E. coli). The microstructure analysis revealed that the solution-treated alloy had no precipitation, while the aged alloy contained precipitations of intermetallic Ti2Cu compound. The aged alloy exhibited better antibacterial performance as the duration of the aging treatment increased. The optimal heat treatment for Ti-5Cu was found to be aging at 700 °C for 4 h, at which point the nucleation formation of the Ti2Cu particles would assume an acicular morphology. These acicular precipitates exhibit a high Cu content which, in turn, influences the antibacterial performance.

A conductive cell-delivery construct as a bioengineered patch that can improve electrical propagation and synchronize cardiomyocyte contraction for heart repair.

Cardiac tissue engineering is of particular importance in the combination of contracting cells with a biomaterial scaffold, which serves as a cell-delivery construct, to replace cardiomyocytes (CMs) that are lost as a result of an infarction, to restore heart function. However, most biomaterial scaffolds are nonconductive and may delay regional conduction, potentially causing arrhythmias. In this study, a conductive CM-delivery construct that consists of a gelatin-based gelfoam that is conjugated with a self-doped conductive polymer (poly-3-amino-4-methoxybenzoic acid, PAMB) is proposed as a cardiac patch (PAMB-Gel patch) to repair an infarcted heart. A nonconductive plain gelfoam (Gel patch) is used as a control. The electrical conductivity of the PAMB-Gel patch is approximately 30 times higher than that of the Gel patch; as a result, the conductive PAMB-Gel patch can substantially increase electrical conduction between distinct clusters of beating CMs, facilitating their synchronous contraction. In vivo epicardial implantation of the PAMB-Gel patch that is seeded with CMs (the bioengineered patch) in infarcted rat hearts can significantly enhance electrical activity in the fibrotic tissue, improving electrical impulse propagation and synchronizing CM contraction across the scar region, markedly reducing its susceptibility to cardiac arrhythmias. Echocardiography shows that the bioengineered conductive patch has an important role in the restoration of cardiac function, perhaps owing to the synergistic effects of its conductive construct and the synchronously beating CMs. These experimental results reveal that the as-proposed bioengineered conductive patch has great potential for repairing injured cardiac tissues.

Photosynthesis-inspired H2 generation using a chlorophyll-loaded liposomal nanoplatform to detect and scavenge excess ROS.

A disturbance of reactive oxygen species (ROS) homeostasis may cause the pathogenesis of many diseases. Inspired by natural photosynthesis, this work proposes a photo-driven H2-evolving liposomal nanoplatform (Lip NP) that comprises an upconversion nanoparticle (UCNP) that is conjugated with gold nanoparticles (AuNPs) via a ROS-responsive linker, which is encapsulated inside the liposomal system in which the lipid bilayer embeds chlorophyll a (Chla). The UCNP functions as a transducer, converting NIR light into upconversion luminescence for simultaneous imaging and therapy in situ. Functioning as light-harvesting antennas, AuNPs are used to detect the local concentration of ROS for FRET biosensing, while the Chla activates the photosynthesis of H2 gas to scavenge local excess ROS. The results thus obtained indicate the potential of using the Lip NPs in the analysis of biological tissues, restoring their ROS homeostasis, possibly preventing the initiation and progression of diseases.

Enrichment of cancer-initiating cells from colon cancer cells through porous polymeric membranes by a membrane filtration method.

Cancer-initiating cells (CICs) or cancer stem cells (CSCs) are primarily responsible for tumor initiation, growth, and metastasis and represent a few percent of the total tumor cell population. We designed a membrane filtration protocol to enrich CICs (CSCs) from the LoVo colon cancer cell line via nylon mesh filter membranes with 11 and 20 µm pore sizes and poly(lactide-co-glycolic acid)/silk screen (PLGA/silk screen) porous membranes (pore sizes of 20-30 µm). The colon cancer cell solution was filtered through the membranes to obtain a permeate solution. Subsequently, the cell culture medium was filtered through the membranes to collect the recovery solution where the cells attached to the membranes were rinsed off into the recovery solution. Then, the membranes were cultivated in the cultivation medium to collect the migrated cells from the membranes. The cells migrated from any membrane had higher expression of the CSC surface markers CD44 and CD133, had higher colony formation levels, and produced more carcinoembryonic antigen (CEA) than the colon cancer cells cultivated on conventional tissue culture plates (control). We established a method to enrich the CICs (CSCs) of colon cancer cells from migrated cells through porous polymeric membranes by the membrane filtration protocol developed in this study.

Numerical investigation of macro- and micro-mechanics of a ceramic veneer bonded with various cement thicknesses using the typical and submodeling finite element approaches.

OBJECTIVES: This study investigates the influence of cement thickness on the macro- and micro-mechanical responses in a ceramic veneer adjacent to an incisal overlapped incisor. METHODS: Seven finite element (FE) ceramic veneer macro-models with different cement thicknesses (10-180mum) were generated. A 10N load was applied with an angulation of 60 degrees to the longitudinal tooth axis. Seven FE micro-models corresponding to the macro-models were constructed at an enamel-adhesive interface where the stress concentration was found. Based on an interfacial scanning electron microscope (SEM) micrograph, morphology of resin tags in the micro-models was generated. The micro-model boundary conditions were determined from the macro-model results. The principal stress on each node in the macro- and micro-models was calculated to investigate interfacial mechanics. A tensile test was performed to obtain an ultimate cement tensile strength to determine the material failure parameters. RESULTS: The highest stress concentration within the cement was found at the resin tag base of the enamel-adhesive interface in lingual side. Maximum stress values from 10.6 to 14.7MPa for the micro-models were higher (44-48%) than that from 7.2 to 10.0MPa for the macro-models when the cement layers increased. Based on the ultimate tensile strength (11.8MPa), bonding failure could found when the micro-models with the cement layers presented more than about 50mum. This seems to correspond with data from previous studies. CONCLUSIONS: Higher stresses develop in the adhesive as the cement thickness increases. Cement thicknesses less than 50mum might reduce the adhesive bonding failure.

Damage accumulation simulations in the adhesive of enamel/ceramic interface using the FE submodelling and the element deactivation approaches.

PURPOSE: To investigate the micromechanics and damage accumulation of the enamel/adhesive interface using sub-modelling and element deactivation methods. MATERIALS AND METHODS: A finite element (FE) macromodel of the enamel/adhesive/ceramic interface subjected to shear bond testing was generated for mechanical analysis. The FE micromodel was constructed at the upper enamel/adhesive interface where stress concentration was found. The morphology of the micromechanical interlockings at the bonded interface was assigned based on a scanning electron micrograph. Boundary conditions of the micromodel were determined from the macromodel's results. Furthermore, an iterative code with the element deactivation method was used to calculate the microdamage accumulation. Parallel experiments were performed to validate the simulation. RESULTS: The micromodel results demonstrated that stress concentration within the adhesive mainly occurred at the upper corner near the enamel/adhesive interface and the base of the resin tags. A simulated fracture path was found at the base of the resin tags along the enamel/adhesive interface. The morphological observation of fracture patterns obtained from in vitro testing corresponded with the simulation results. CONCLUSION: This study showed that the FE submodelling and the element deactivation approaches could better simulate the micromechanical responses and the microdamage accumulation noted at the enamel/adhesive interface.

[Study on fatigue and fracture resistance of metal ceramic crowns with CAD/CAM-fabricated titanium copings].

PURPOSE: To compare the fatigue and fracture resistance of metal ceramic crowns (MCCs) with nickel-chromium and CAD/CAM-fabricated titanium copings. METHODS: Twelve premolar MCCs were fabricated with cast nickel-chromium alloy (Ni group) and CAD/CAM-fabricated titanium (Ti group) copings, respectively. To minimize the differences among specimens, the geometric dimensions of the MCCs were tested with a laboratory scanner and digital measurement software and then adjusted. After cemented to identically milled titanium dies, each specimen was subjected to thermocycling (5-55℃, 5000 cycles) and cyclic loading (75000 cycles) test, followed by a static load-to-fracture test to measure the fracture loads(F). The fractures were characterized using stereomicroscope. SPSS13.0 software package was used for statistical analysis. RESULTS: The mean fracture loads were (1645±356)N for Ni group and (1555±331)N for Ti group. No significant difference was observed (P=0.525). Most of the fractures were confined to the palatal third. The chief failure mode for all specimens from Ni group and most of the specimens from Ti groups was mixed failure. Adhesive failure was noted in 3 specimens from Ti group. CONCLUSIONS: The fracture resistance of MCCs with CAD/CAM-fabricated titanium copings is similar to that of MCCs with nickel-chromium copings.

Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses.

Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.