Tunable Release Research Articles

Synthetic molecular motor activates drug delivery from polymersomes.

The design of stimuli-responsive systems in nanomedicine arises from the challenges associated with the unsolved needs of current molecular drug delivery. Here, we present a delivery system with high spatiotemporal control and tunable release profiles. The design is based on the combination of an hydrophobic synthetic molecular rotary motor and a PDMS-b-PMOXA diblock copolymer to create a responsive self-assembled system. The successful incorporation and selective activation by low-power visible light (λ = 430 nm, 6.9 mW) allowed to trigger the delivery of a fluorescent dye with high efficiencies (up to 75%). Moreover, we proved the ability to turn on and off the responsive behavior on demand over sequential cycles. Low concentrations of photoresponsive units (down to 1 mol% of molecular motor) are shown to effectively promote release. Our system was also tested under relevant physiological conditions using a lung cancer cell line and the encapsulation of an Food and Drug Administration (FDA)-approved drug. Similar levels of cell viability are observed compared to the free given drug showing the potential of our platform to deliver functional drugs on request with high efficiency. This work provides an important step for the application of synthetic molecular machines in the next generation of smart delivery systems.

Investigations of hybrid infill pattern in additive manufactured tablets: A novel approach towards tunable drug release.

The significance of 3D printing has risen exponentially in biomedical and pharmaceutical applications. Its potential in the field of fabricating drug delivery systems, by virtue of processing biocompatible polymers, has been very lucrative. This work aims to tap the interstitial drug delivery kinetics that are often inaccessible through machine-specific infill patterns in additive manufactured tablets fabricated using PVA biopolymer as an excipient. In this regard, a myo-inositol containing tablet has been printed using Fused Deposition Modeling preceded by Hot Melt Extrusion drug loading route. Two machine-specific infill patterns were taken, namely straight and grid. Later, these two distinct patterns were juxtaposed to obtain novel hybrid infill patterns in the tablets. Then, these tablets and their filament were subjected to various thermal, mechanical, imaging and pharmaceutical characterization tests to assess the feasibility of the research attempt. Finally, dissolution tests were conducted to evaluate their dissolution behavior over a time period. The characterization tests proved the scientific viability of this attempt along with amorphous existence of drug in the polymeric filament. The dissolution results showed favorable drug release by achieving interstitial dissolution timings with surface area/volume (SA/V) ratio being found to be the principal factor.

Reversible cross-linking of gelatin by a disulphide-containing bis-succinimide for tunable degradation and release.

Generally, gelatin was irreversibly cross-linked by chemical reagents to improve its water-resistance. However, few chemical reagents meet both the requirements of high cross-inking efficiency and tunable degradation. Here a reversible cross-linker, disulphide-containing bis-succinimide, was synthesized and used to control the cross-linking and degradation of edible gelatin film. Mixture of the gelatin and cross-linker for 120min generated gelatin films that could preserve their morphology in 37 ℃ warm water for above 40days. The gelatin film changed its microstructure from net to tightness after the cross-linking, thus facilitating the embedding of the targeted molecule into the gelatin material. The degradation of the cross-linked gelatin film and the release of its inclusion could be controlled by biocompatible glutathione. This work provides a good method for preparing modified gelatin with promising water-resistance, good biocompatibility, and tunable degradation for food/biomedical engineering applications.

Tunable catalytic release of nitric oxide via copper‐loaded coatings on titanium nanotubes for regulating biological performance

AbstractSevere lesions in vessels need to be treated with implantable interventional devices such as vascular stents, which should be anti‐coagulantion, anti‐proliferation and promoting endothelialisation. Nitric oxide (NO), as a physiological gas signalling molecule, play an important role in revascularisation. Catalysing the release of NO from endogenous donors has already been widely favoured to treatment strategy for lesioned vessels. In this work, a series of copper‐loaded coatings (titanium nanotube (TNT)/PDA‐Cu) was fabricated by TNTs combined with polydopamine and ions, which achieve controlled in situ catalytic release of NO. This strategy could effectively immobilised copper ions on TNTs, and promoted the proliferation of endothelial cells and inhibited growth of smooth muscle cells (SMCs) via the performance of NO, as well as restrain the platelet adhesion. With the multiple function, TNT/PDA‐Cu provides a promise approach for promoting endothelialisation, anti‐coagulation and inhibition of SMC proliferation via copper‐loaded coatings on TNTs.

Fabrication of Pulsatile Polymeric Microparticles Encapsulating Rabies Antigen.

The current guidelines for rabies post-exposure prophylaxis require multiple injections administered over several weeks. This can be disproportionately burdensome to those living in low- and middle-income countries (LMICs), where the majority of deadly exposures to rabies occur. Different drug delivery strategies have been explored to condense vaccine regimens to a single injection by encapsulating antigens into polymeric particles. However, harsh stressors during the encapsulation process can cause denaturation of the encapsulated antigen. This article describes a method for encapsulating the rabies virus (RABV) antigen into polymeric microparticles that exhibit tunable pulsatile release. This method, termed Particles Uniformly Liquified and Sealed to Encapsulate Drugs (PULSED), generates microparticles using soft lithography to create inverse polydimethylsiloxane (PDMS) molds from a multi-photon, 3D-printed master mold. Poly(lactic-co-glycolic acid) (PLGA) films are then compression-molded into the PDMS molds to generate open-faced cylinders that are filled with concentrated RABV using a piezoelectric dispensing robot. These microstructures are then sealed by heating the top of the particles, allowing the material to flow and form a continuous, nonporous polymeric barrier. Post-fabrication, an enzyme-linked immunosorbent assay (ELISA) specific to the detection of intact trimeric rabies virus glycoprotein is used to confirm the high recovery of immunogenic antigen from the microparticles.

Monodisperse Hyperbranched Polytriazoles as Unimolecular Nanocontainers for Encapsulation of Functional Payloads.

In this work, a series of polytriazole-based unimolecular nanocontainers (UNs) with good water solubility, uniformity, and colloidal stability via a bottom-up chain-growth copper-catalyzed azide-alkyne cycloaddition (co)polymerization that features tunable size, degree of branching (DB), and functionality of the UNs is developed. A broad selection of hydrophobic payload molecules, including Nile red (NR), camptothecin, pyrene, 1-pyrenemethanol, and IR676, are successfully encapsulated to demonstrate the high versatility of these polymers as UNs. Using NR as a probe guest, the relationship between the encapsulation performance and the structural properties of UNs, including size and DB, is investigated. Furthermore, the localization and dispersity of encapsulated NR are explored and the dependence of payload's dispersity on the DB of UNs is revealed. The payload encapsulated in UNs exhibits tunable release kinetics, determined by either adjusting release conditions or including pH-responsive structural units in the UNs. Meanwhile, the dyes encapsulated in UNs exhibit improved photostability and stronger resistance to photobleaching. It is expected that these explorations address the size and stability issues widely encounter in current drug/dye nanocarriers and provide a versatile platform of polytriazole-based UNs for suitable payloads in various applications, including drug delivery and bio-imaging.

D55. A Tunable Nanoparticle-based Botulinum Toxin Formulation for Extended Duration of Therapeutic Effect

PURPOSE: Botulinum toxins (BoNT) are increasingly popular neuromodulators with an array of aesthetic and neurological indications. However, these agents are limited by their duration of effect, necessitating frequent redosing. We aim to develop a nanoparticle-based delivery system to extend BoNT release and characterize its release profile. METHODS: Botulinum toxin A (BoNTa) neuromodulators were encapsulated within polymeric nanoparticles (NPs) using a kinetically controlled microfluidic assembly method. Dynamic light scattering was used to measure particle size and uniformity. ELISA was used to quantify the protein release profile. RESULTS: Particle sizes were uniform with most particles centered at 100nm and nearly all particles between 50-200nm. A tunable release profile was achieved, in which BoNTa could be released linearly or with an initial bolus followed by sustained release at the desired rate. Reproducibility of NP performance was demonstrated in 3 independent trials. Our early in-vivo and mechanistic studies have demonstrated preservation of toxin bioactivity and extended therapeutic effect in a rat model. CONCLUSION: We developed a novel nanoparticle-based Botox formulation capable of providing long-acting release of neuromodulator with tunable kinetics at designated dosage. This sustained release delivery modality enables superior therapeutic outcomes with less frequent re-dosing.

Fabrication and characterization of bioprints with Lactobacillus crispatus for vaginal application

Bacterial vaginosis (BV) is characterized by low levels of lactobacilli and overgrowth of potential pathogens in the female genital tract. Current antibiotic treatments often fail to treat BV in a sustained manner, and > 50% of women experience recurrence within 6 months post-treatment. Recently, lactobacilli have shown promise for acting as probiotics by offering health benefits in BV. However, as with other active agents, probiotics often require intensive administration schedules incurring difficult user adherence. Three-dimensional (3D)-bioprinting enables fabrication of well-defined architectures with tunable release of active agents, including live mammalian cells, offering the potential for long-acting probiotic delivery. One promising bioink, gelatin alginate has been previously shown to provide structural stability, host compatibility, viable probiotic incorporation, and cellular nutrient diffusion. This study formulates and characterizes 3D-bioprinted Lactobacillus crispatus-containing gelatin alginate scaffolds for gynecologic applications. Different weight to volume (w/v) ratios of gelatin alginate were bioprinted to determine formulations with highest printing resolution, and different crosslinking reagents were evaluated for effect on scaffold integrity via mass loss and swelling measurements. Post-print viability, sustained-release, and vaginal keratinocyte cytotoxicity assays were conducted. A 10:2 (w/v) gelatin alginate formulation was selected based on line continuity and resolution, while degradation and swelling experiments demonstrated greatest structural stability with dual genipin and calcium crosslinking, showing minimal mass loss and swelling over 28 days. 3D-bioprinted L. crispatus-containing scaffolds demonstrated sustained release and proliferation of live bacteria over 28 days, without impacting viability of vaginal epithelial cells. This study provides in vitro evidence for 3D-bioprinted scaffolds as a novel strategy to sustain probiotic delivery with the ultimate goal of restoring vaginal lactobacilli following microbiological disturbances.

Magnetoelectricity-Mediated Tunable Absorption and Release of Peroxide Dianions

Peroxide dianion (O22-) has strong oxidizing activity and ease of proton abstraction and is extremely unstable. Direct and controllable adsorption and release of O22- has large application implication and is a large challenge so far. Here, we use a unique metal (Ni)-organic (diphenylalanine, DPA) framework (MOF), Ni(DPA)2, as adsorbents for absorption and release of O22-. This MOF structure has room-temperature magnetoelectricity via distortion of the Ni-centered octahedron {NiN2O4} and thus possesses a tunable ferroelectric polarization under applied electric/magnetic fields. Controllable adsorption and release of O22- are realized in such a MOF system via electrochemical redox measurements. Structural/spectroscopic characterization and calculations reveal that a number of NH active sites in the nanopores of MOF can effectively adsorb O22- by hydrogen bonds and then tunable ferroelectric polarization induces controllable release of O22- under applied magnetic fields. This work presents a constructive way for controllable adsorption and release of reactive oxygen species.

Tunable release of poly(butylenes adipate-co-terephthalate)/poly(lactic acid) blend-based antibacterial bionanocomposites: comparative study of modified montmorillonite and graphene nanopletelets

Tunable release of poly(butylenes adipate-co-terephthalate)/poly(lactic acid) blend-based antibacterial bionanocomposites: comparative study of modified montmorillonite and graphene nanopletelets

Nanosilicate-hydrogel microspheres formed by aqueous two-phase separation for sustained release of small molecules

Introduction: Hydrogel microspheres are an attractive option for drug delivery applications due to their ease of injection and potential for tunable controlled delivery. However, their utility is limited due to high initial burst release and rapid overall release, which is especially pronounced for small molecules or small size microspheres. We and others have shown that the addition of two-dimensional nanosilicate (NS) particles to hydrogels can significantly prolong release kinetics from hydrogels while minimizing burst release.Materials and Methods: Here we explored whether NS could modulate release kinetics of small molecules from small size injectable microspheres. Polyethylene glycol (PEG)-based hydrogel microspheres were fabricated via polymer/salt aqueous two-phase separation (ATPS), which is facile, high yield, and scalable, without the need for organic solvents or oils.Results and Discussion: Importantly, NS and acridine orange (AO), a model cationic small molecule, were shown to phase separate into the PEG-rich phase, allowing for successful encapsulation within hydrogel microspheres. The fabricated microspheres were stable, similar in size to red blood cells, and easily injectable. The effect of various fabrication parameters, including the addition of NS and AO, on microsphere size and polydispersity were explored. Release of AO was significantly slowed from PEG-NS microspheres compared to PEG-only microspheres and correlated with NS concentration. Two additional small molecules, the chemotherapeutic doxorubicin (positive charge), and the model small molecule Brilliant Blue FCF (negative charge), were shown to exhibit prolonged release, underscoring the broad utility of the system. The dependence of release kinetics on encapsulated NS concentration allows for tunable and prolonged release of small molecules from an injectable hydrogel delivery device.

Broad-temperature-range mechanically tunable hydrogel microcapsules for controlled active release.

Here, we report PNIPAm-co-PEGDA hydrogel shelled microcapsules with a thin oil layer to achieve tunable thermo-responsive release of the encapsulated small hydrophilic actives. We use a microfluidic device integrated with a temperature-controlled chamber for consistent and reliable production of the microcapsules by utilizing triple emulsion drops (W/O/W/O) with a thin oil layer as capsule templates. The interstitial oil layer between the aqueous core and the PNIPAm-co-PEGDA shell provides a diffusion barrier for the encapsulated active until the temperature reaches a critical point above which the destabilization of interstitial oil layer occurs. We find that the destabilization of the oil layer with temperature increase is caused by outward expansion of the aqueous core due to volume increase and the radial inward compression from the deswelling of the thermo-responsive hydrogel shell. The copolymerization of NIPAm with PEGDA increases the biocompatibility of the resulting microcapsule while offering the ability to alter the compressive modulus in broad ranges by simply varying crosslinker concentrations thereby to precisely tune the onset release temperature. Based on this concept, we further demonstrate that the release temperature can be enhanced up to 62°C by adjusting the shell thickness even without varying the chemical composition of the hydrogel shell. Moreover, we incorporate gold nanorods within the hydrogel shell to spatiotemporally regulate the active release from the microcapsules by illuminating with non-invasive near infrared (NIR) light.

Fibro-Gel: An All-Aqueous Hydrogel Consisting of Microfibers with Tunable Release Profile and its Application in Wound Healing.

Injectable hydrogels are valuable tools in tissue engineering and regenerative medicine due to their unique advantages of injectability with minimal invasiveness and usability for irregularly shaped sites. However, it remains challenging to achieve scalable manufacturing together with matching physicochemical properties and on-demand drug release for a high level of control over biophysical and biomedical cues to direct endogenous cells. Here, the use of an injectable fibro-gel is demonstrated, a water-filled network of entangled hydrogel microfibers, whose physicochemical properties and drug release profiles can be tailored to overcome these shortcomings. This fibro-gel exhibits favorable in vitro biocompatibility and the capability to aid vascularization. The potential use of the fibro-gel for advancing tissue regeneration is explored with a mice excision skin model. Preliminary in vivo tests indicate that the fibro-gel promotes wound healing and new healthy tissue regeneration at a faster rate than a commercial gel. Moreover, it is demonstrated that the release of distinct drugs at different rates can further accelerate wound healing with higher efficiency, by using a two-layer fibro-gel model. The combination of injectability and tailorable properties of this fibro-gel offers a promising approach in biomedical fields such as therapeutic delivery, medical dressings, and 3D tissue scaffolds for tissue engineering.

3D bioprinting of gene delivery scaffolds with controlled release

Localized gene delivery via engineered scaffolds offers spatiotemporal control of the gene vector release. Here, we explored the capability of digital light processing based bioprinting to fabricate 3D scaffolds in hydrogels for controlled gene delivery. We demonstrated the compatibility of the method with three representative hydrogel biomaterials for gene delivery. We further investigated the highly tunable release profile with these scaffolds by creating and combining distinct release mechanisms of diffusion and ion exchange. The efficacy of gene delivery of these scaffolds was validated in vitro using 293T cells. Results from this work could potentially facilitate the development of synergistic and personalized gene therapies.

Antibacterial-Anti-Inflammatory-Bone Restoration Procedure Achieved by MIN-Loaded PLGA Microsphere for Efficient Treatment of Periodontitis.

The main development process of periodontitis involves periodontal pathogenic bacteria as the initiating factor causing the onset of destructive inflammation, which in turn stimulates the destruction of periodontal tissue. It is difficult to achieve the eradication of periodontitis due to the complex interaction among antibacterial, anti-inflammatory, and bone restoration. Herein, we propose an antibacterial-anti-inflammatory-bone restoration procedural treatment strategy with minocycline (MIN) for the efficient treatment of periodontitis. In brief, MIN was prepared into PLGA microspheres with tunable release behavior using different species of PLGA, respectively. The optimally selected PLGA microspheres (LA:GA with 50:50, 10kDa, and carboxyl group) had a drug loading of 16.91%, an in vitro release of approximately 30days, which also had a particle size of approximately 11.8µm with a smooth appearance and a rounded morphology. The DSC and XRD results showed that the MIN was completely encapsulated in the microspheres as an amorphous state. Cytotoxicity tests demonstrated the safety and biocompatibility of the microspheres (cell viabilities at a concentration of 1-200μg/mL were greater than 97%), and in vitro bacterial inhibition tests showed that the selected microspheres could achieve effective bacterial inhibition at the initial stage after administration. The favorable anti-inflammatory (low TNF-α and IL-10 levels) and bone restoration effects (BV/TV: 71.8869%; BMD: 0.9782g/cm3; TB.Th: 0.1366mm; Tb.N: 6.9318mm-1; Tb.Sp: 0.0735mm) were achieved in a SD rat periodontitis model after administering once a week for four weeks. The MIN-loaded PLGA microspheres were proved to be an efficient and safe treatment for periodontitis by procedural antibacterial, anti-inflammatory, and bone restoration.

Abstract OT3-28-01: A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects with Metastatic Breast Cancer NCT05261269

Abstract Clinical Study: This clinical study is designed to evaluate DAN-222 as a monotherapy and in combination with a PARP inhibitor which is expected to increase efficacy without significant increase in toxicity. DAN-222 is a novel therapeutic nanoparticle with a complimentary mechanism for combination with a PARP inhibitor anticipated for patients with HRD+ and HRD- tumors, and not restricted to BRCAm. This is an ongoing phase 1/2 study to evaluate the safety and pharmacology of DAN-222 in patients with metastatic breast cancer and initial evaluation of efficacy. Here we report on the initial pharmacology. The results in the patients show the expected characteristics of the designed product, including consistency with preclinical models (e.g. T1/2= 28 hours), which is a feature of this platform given the non-enzymatic release mechanism of the payload that allows for improved translation from preclinical species to clinical patients as well low variability between patients (e.g. CV%=16.5). Study Rationale: DAN-222 is a topoisomerase-1 inhibitor (Camptothecin) nanoparticle therapeutic that has been optimized for tumor biodistribution and pharmacokinetics. DAN-222 has a broad therapeutic index in preclinical evaluation and the complementary mechanism of action with PARP inhibitors provides significantly enhanced efficacy while also sparing bone marrow. Importantly, the complementary enhanced efficacy is independent of tumor homologous repair deficiency (HRD) status, including BRCA status. The efficacy of DAN-222 was evaluated alone and in combination with a PARP inhibitor (niraparib) in HRD+ breast cancer (MDA-MB-436) and HRD- ovarian cancer (OVCAR-3) xenograft models. Table 1 highlights the endpoints of the study as measured by partial response, complete response, tumor free survival and median tumor volume at end of study (Day 60). DAN-222 alone had PR effects and reduced median tumor volume compared to niraparib alone. The combination demonstrated enhancement of response as evidenced by an increase in partial response, a shift from partial to complete response, an increase in tumor-free survivors, and significant further reduction in median tumor volume. Conclusion: The clinical pharmacology will be presented and demonstrates the designed behavior of the nanoparticle. A design feature of the nanoparticle is that the payload and linker are sequestered in the core, protecting them from circulatory components. Moreover, the covalent attachment of the payload allows for tunable release kinetics via a hydrolytic linker, preventing burst release and associated toxicities common to physical encapsulation-based nanoparticle systems (e.g., liposomes, micelles). The preliminary PK profile in patients supports the translatability across species and consistency of exposure across patients. Table 1: Efficacy of DAN-222 Alone or Combination with Niraparib Citation Format: Ashley P. Wright, Emily A. Wyatt, Timothy Hagerty. A Dose-escalation Study of the Safety and Pharmacology of DAN-222 in Subjects with Metastatic Breast Cancer NCT05261269 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-28-01.

Modular Metal-Quinone Networks with Tunable Architecture and Functionality.

Nanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones through metal-acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, hydrophilic, and pH-degradable materials. A library of metal-quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to the assembly of particles, tubes, capsules, and films. Importantly, MQNs show bidirectional pH-responsive disassembly in acidic and alkaline solutions, where the quinone ligands mediate the disassembly kinetics, enabling temporal and spatial control over the release of multiple components using multilayered MQNs. Leveraging this tunable release and the inherent medicinal properties of quinones, MQN prodrugs with a high drug loading (>89 wt %) are engineered using doxorubicin for anti-cancer therapy and shikonin for the inhibition of the main protease in the SARS-CoV-2 virus.

Modular Metal‐Quinone Networks with Tunable Architecture and Functionality

AbstractNanostructured materials with tunable structures and functionality are of interest in diverse areas. Herein, metal ions are coordinated with quinones through metal‐acetylacetone coordination bonds to generate a class of structurally tunable, universally adhesive, hydrophilic, and pH‐degradable materials. A library of metal‐quinone networks (MQNs) is produced from five model quinone ligands paired with nine metal ions, leading to the assembly of particles, tubes, capsules, and films. Importantly, MQNs show bidirectional pH‐responsive disassembly in acidic and alkaline solutions, where the quinone ligands mediate the disassembly kinetics, enabling temporal and spatial control over the release of multiple components using multilayered MQNs. Leveraging this tunable release and the inherent medicinal properties of quinones, MQN prodrugs with a high drug loading (>89 wt %) are engineered using doxorubicin for anti‐cancer therapy and shikonin for the inhibition of the main protease in the SARS‐CoV‐2 virus.

Low-Cost, High-Pressure-Synthesized Oxygen-Entrapping Materials to Improve Treatment of Solid Tumors.

Tumor hypoxia drives resistance to many cancer therapies, including radiotherapy and chemotherapy. Methods that increase tumor oxygen pressures, such as hyperbaric oxygen therapy and microbubble infusion, are utilized to improve the responses to current standard-of-care therapies. However, key obstacles remain, in particular delivery of oxygen at the appropriate dose and with optimal pharmacokinetics. Toward overcoming these hurdles, gas-entrapping materials (GeMs) that are capable of tunable oxygen release are formulated. It is shown that injection or implantation of these materials into tumors can mitigate tumor hypoxia by delivering oxygen locally and that these GeMs enhance responsiveness to radiation and chemotherapy in multiple tumor types. This paper also demonstrates, by comparing an oxygen (O2 )-GeM to a sham GeM, that the former generates an antitumorigenic and immunogenic tumor microenvironment in malignant peripheral nerve sheath tumors. Collectively the results indicate that the use of O2 -GeMs is promising as an adjunctive strategy for the treatment of solid tumors.

Nanogel-based scaffolds for tissue engineering and regenerative medicine

Nanogels are an emerging class of nanomaterials that have shown great potential for biomedical applications, particularly in the field of tissue engineering and regenerative medicine. Nanogel-based scaffolds are promising due to their unique properties, such as high water content, biocompatibility, and tunable drug release. This review article provides an overview of the current state-of-the-art in nanogel-based scaffolds, including their synthesis and characterization, properties, applications in tissue engineering and regenerative medicine, challenges and limitations, and future directions. The synthesis of nanogels is discussed, along with the various methods used for their characterization, such as size and zeta potential measurements, microscopy, and spectroscopy. The unique properties of nanogel-based scaffolds, such as their high water content and tunable drug release, are also discussed in detail. The review article highlights the applications of nanogel-based scaffolds in tissue engineering and regenerative medicine, including their use in wound healing, bone regeneration, and drug delivery. Additionally, the challenges and limitations of nanogel-based scaffolds are discussed, along with future directions for research in this exciting field. Overall, this review article provides a comprehensive overview of the current state-of-the-art in nanogel-based scaffolds, highlighting their potential for future biomedical applications.