Composite Microgels Loaded with Doxorubicin-Conjugated Amine-Functionalized Zinc Ferrite Nanoparticles for Stimuli-Responsive Sustained Drug Release.

Purpose: The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development. Methods: We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 oC, with the drug release kinetics being analyzed using various models. Results: The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion. Conclusion: Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation.

BACKGROUND: Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. RESULTS: In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-ß/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. CONCLUSION: In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation.

Novel Pickering bigels stabilized by whey protein microgels: Interfacial properties, oral sensation and gastrointestinal digestive profiles.

In the ongoing quest to formulate sensory-rich, low-fat products that maintain structural integrity, this work investigated the potential of bigels, especially those created using innovative Pickering techniques. By harnessing the unique properties of whey protein isolate (WPI) and whey protein microgel (WPM) as interfacial stabilizers, WPM-based Pickering bigels exhibited a remarkable particle localization at the interface due to specific intermolecular interactions. The rise in protein concentration not only intensified particle coverage and interface stabilization but also amplified attributes like storage modulus, yield stress, and adhesiveness, owing to enhanced intermolecular forces and a compact gel matrix. Impressively, WPM-based Pickering bigels outshone in practical applications, showcasing exceptional oil retention during freeze-thaw cycles and extended flavor release-a promising indication for frozen food product applications. Furthermore, these bigels underwent a sensory evolution from a lubricious texture at lower concentrations to a stable plateau at higher ones, offering an enriched consumer experience. In a comparative digestibility assessment, WPM-based Pickering bigels demonstrated superior prowess in decelerating the release of free fatty acids, indicating slowed lipid digestion. This study demonstrates the potential to fine-tune oral sensations and digestive profiles in bigels by modulating Pickering particle concentrations.

Photocrosslinkable microgels derived from human platelet lysates: injectable biomaterials for cardiac cell culture.

Cardiovascular diseases are a major global cause of morbidity and mortality, and they are often characterized by cardiomyocytes dead that ultimately leads to myocardial ischemia (MI). This condition replaces functional cardiac tissue with fibrotic scar tissue compromising heart function. Injectable systems for the in situ delivery of cells or molecules to assist during tissue repair have emerged as promising approaches for tissue engineering, particularly for myocardial repair. Methacryloyl platelet lysates (PLMA) have been employed for constructing full human-based 3D cell culture matrices and demonstrated potential for xeno-free applications. In this study, we propose using PLMA to produce microparticles (MPs) serving as anchors for cardiac and endothelial cells and ultimately as injectable systems for cardiac tissue repair. The herein reported PLMA MPs were produced by droplet microfluidics and showed great properties for cell attachment. More importantly, it is possible to show the capacity of PLMA MPs to serve as cell microcarriers even in the absence of animal-derived serum supplementation in the culture media.

MicroLOCK: Highly stable microgel biosensor using locked nucleic acids as bioreceptors for sensitive and selective detection of let-7a.

Chemically modified oligonucleotides can solve biosensing issues for the development of capture probes, antisense, CRISPR/Cas, and siRNA, by enhancing their duplex-forming ability, their stability against enzymatic degradation, and their specificity for targets with high sequence similarity as microRNA families. However, the use of modified oligonucleotides such as locked nucleic acids (LNA) for biosensors is still limited by hurdles in design and from performances on the material interface. Here we developed a fluorogenic biosensor for non-coding RNAs, represented by polymeric PEG microgels conjugated with molecular beacons (MB) modified with locked nucleic acids (MicroLOCK). By 3D modeling and computational analysis, we designed molecular beacons (MB) inserting spot-on LNAs for high specificity among targets with high sequence similarity (95%). MicroLOCK can reversibly detect microRNA targets in a tiny amount of biological sample (2 µL) at 25 °C with a higher sensitivity (LOD 1.3 fM) without any reverse transcription or amplification. MicroLOCK can hybridize the target with fast kinetic (about 30 min), high duplex stability without interferences from the polymer interface, showing high signal-to-noise ratio (up to S/N = 7.3). MicroLOCK also demonstrated excellent resistance to highly nuclease-rich environments, in real samples. These findings represent a great breakthrough for using the LNA in developing low-cost biosensing approaches and can be applied not only for nucleic acids and protein detection but also for real-time imaging and quantitative assessment of gene targeting both in vitro and in vivo.

Synthesis and characterization of ion-induced sodium alginate/soy protein isolate microgels for the controlled release.

In this study, sodium alginate/ soy protein isolate (SPI) microgels cross-linked by various divalent cations including Cu2+, Ba2+, Ca2+, and Zn2+ were fabricated. Cryo-scanning electron microscopy observations revealed distinctive structural variations among the microgels. In the context of gastric pH conditions, the degree of shrinkage of the microgels followed the sequence of Ca2+ > Ba2+ > Cu2+ > Zn2+. Meanwhile, under intestinal pH conditions, the degree of swelling was ranked as Zn2+ > Ca2+ > Ba2+ > Cu2+. The impact of these variations was investigated through in vitro digestion studies, revealing that all microgels successfully delayed the release of ß-carotene within the stomach. Within the simulated intestinal fluid, the microgel cross-linked with Zn2+ exhibited an initial burst release, while those cross-linked with Cu2+, Ba2+, or Ca2+ displayed a sustained release pattern. This research underscores the potential of sodium alginate/SPI microgels cross-linked with different divalent cations as efficient controlled-release delivery systems.

Microgels with Immobilized Glycosyltransferases for Enzymatic Glycan Synthesis.

Glycans, composed of linked monosaccharides, play crucial roles in biology and find diverse applications. Enhancing their enzymatic synthesis can be achieved by immobilizing enzymes on materials such as microgels. Here, we present microgels with immobilized glycosyltransferases, synthesized through droplet microfluidics, immobilizing enzymes either via encapsulation or postattachment. SpyTag-SpyCatcher interaction was used for enzyme binding, among others. Fluorescamine and permeability assays confirmed enzyme immobilization and microgel porosity, while enzymatic activities were determined using HPLC. The potential application of microgels in cascade reactions involving multiple enzymes was demonstrated by combining ß4GalT and α3GalT in an enzymatic reaction with high yields. Moreover, a cascade of ß4GalT and ß3GlcNAcT was successfully implemented. These results pave the way toward a modular membrane bioreactor for automated glycan synthesis containing the presented biocatalytic microgels.

Embedded Bioprinting of Tissue-like Structures Using κ-Carrageenan Sub-Microgel Medium.

Embedded three-dimensional (3D) bioprinting utilizing a granular hydrogel supporting bath has emerged as a critical technique for creating biomimetic scaffolds. However, engineering a suitable gel suspension medium that balances precise bioink deposition with cell viability and function presents multiple challenges, particularly in achieving the desired viscoelastic properties. Here, a novel κ-carrageenan gel supporting bath is fabricated through an easy-to-operate mechanical grinding process, producing homogeneous sub-microscale particles. These sub-microgels exhibit typical Bingham flow behavior with small yield stress and rapid shear-thinning properties, which facilitate the smooth deposition of bioinks. Moreover, the reversible gel-sol transition and self-healing capabilities of the κ-carrageenan microgel network ensure the structural integrity of printed constructs, enabling the creation of complex, multi-layered tissue structures with defined architectural features. Post-printing, the κ-carrageenan sub-microgels can be easily removed by a simple phosphate-buffered saline wash. Further bioprinting with cell-laden bioinks demonstrates that cells within the biomimetic constructs have a high viability of 92% and quickly extend pseudopodia, as well as maintain robust proliferation, indicating the potential of this bioprinting strategy for tissue and organ fabrication. In summary, this novel κ-carrageenan sub-microgel medium emerges as a promising avenue for embedded bioprinting of exceptional quality, bearing profound implications for the in vitro development of engineered tissues and organs.

Taking SCFAs produced by Lactobacillus reuteri orally reshapes gut microbiota and elicits antitumor responses.

BACKGROUND: Colorectal cancer (CRC) incidence is increasing in recent years due to intestinal flora imbalance, making oral probiotics a hotspot for research. However, numerous studies related to intestinal flora regulation ignore its internal mechanisms without in-depth research. RESULTS: Here, we developed a probiotic microgel delivery system (L.r@(SA-CS)2) through the layer-by-layer encapsulation technology of alginate (SA) and chitosan (CS) to improve gut microbiota dysbiosis and enhance anti-tumor therapeutic effect. Short chain fatty acids (SCFAs) produced by L.r have direct anti-tumor effects. Additionally, it reduces harmful bacteria such as Proteobacteria and Fusobacteriota, and through bacteria mutualophy increases beneficial bacteria such as Bacteroidota and Firmicutes which produce butyric acid. By binding to the G protein-coupled receptor 109A (GPR109A) on the surface of colonic epithelial cells, butyric acid can induce apoptosis in abnormal cells. Due to the low expression of GPR109A in colon cancer cells, MK-6892 (MK) can be used to stimulate GPR109A. With increased production of butyrate, activated GPR109A is able to bind more butyrate, which further promotes apoptosis of cancer cells and triggers an antitumor response. CONCLUSION: It appears that the oral administration of L.r@(SA-CS)2 microgels may provide a treatment option for CRC by modifying the gut microbiota.

A Pump-Free Strategy for the Controllable Generation of Alginate Microgels as Cellular Microcarriers.

Microgels are advanced scaffolds for tissue engineering due to their proper biodegradability, good biocompatibility, and high specific surface area for effective oxygen and nutrient transfer. However, most of the current monodispersed microgel fabrication systems rely heavily on various precision pumps, which highly increase the cost and complexity of their downstream application. In this work, we developed a simple and facile system for the controllable generation of uniform alginate microgels by integrating a gas-shearing strategy into a glass microfluidic device. Importantly, the cell-laden microgels can be rapidly prepared in a pump-free manner under an all-aqueous environment. The three-dimensional cultured green fluorescent protein-human A549 cells in alginate microgels exhibited enhanced stemness and drug resistance compared to those under two-dimensional conditions. The pancreatic cancer organoids in alginate microgels exhibited some of the key features of pancreatic cancer. The proposed microgels showed decent monodispersity, biocompatibility, and versatility, providing great opportunities in various biomedical applications such as microcarrier fabricating, organoid engineering, and high-throughput drug screening.

Dual growth factor methacrylic alginate microgels combined with chitosan-based conduits facilitate peripheral nerve repair.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

Bioactive microgel-coated electrospun membrane with cell-instructive interfaces and topology for abdominal wall defect repair.

Current mesh materials used for the clinical treatment of abdominal defects struggle to balance mechanical properties and bioactivity to support tissue remodeling. Therefore, a bioactive microgel-coated electrospinning membrane was designed with the superiority of cell-instructive topology in guiding cell behavior and function for abdominal wall defect reconstruction. The electrostatic spinning technique was employed to prepare a bioabsorbable PLCL fiber membrane with an effective mechanical support. Additionally, decellularized matrix (dECM)-derived bioactive microgels were further coated on the fiber membrane through co-precipitation with dopamine, which was expected to endow cell-instructive hydrophilic interfaces and topological morphologies for cell adhesion. Moreover, the introduction of the dECM into the microgel promoted the myogenic proliferation and differentiation of C2C12 cells. Subsequently, in vivo experiments using a rat abdominal wall defect model demonstrated that the bioactive microgel coating significantly contributed to the reconstruction of intact abdominal wall structures, highlighting its potential for clinical application in promoting the repair of soft tissue defects associated with abdominal wall damage. This study presented an effective mesh material for facilitating the reconstruction of abdominal wall defects and contributed novel design concepts for the surface modification of scaffolds with cell-instructive interfaces and topology.

Enzyme-loaded rod-like microgel shapes: a step towards the creation of shape-specific microreactors for blood detoxification purposes.

Rapid removal of toxic substances is crucial to restore the normal functions of our body and ensure survival. Due to their high substrate specificity and catalytic efficiency, enzymes are unique candidates to deplete toxic compounds. While enzymes display several limitations including low stability and high immunogenicity, these can be overcome by entrapping them in a diverse range of carriers. The resulting micro/nanoreactors shield the enzymes from their surroundings, preventing their misfolding or denaturation thus allowing them to conduct their function. The micro/nanoreactors must circulate in the blood stream for extended periods of time to ensure complete depletion of the toxic agents. Surprisingly, while it is widely acknowledged that non-spherical carriers exhibit longer residence time in the bloodstream than their spherical counterparts, so far, all the reported micro/nanoreactors have been assembled with a spherical architecture. Herein, we address this important issue by pioneering the first shape-specific microreactors. We use UV-assisted punching to create rod-like microgel shapes with dimensions of 8 µm × 1 µm × 2 µm and demonstrate their biocompatibility by conducting hemolysis and cell viability assays with a macrophage and an endothelial cell line. Upon encapsulation of the model enzyme ß-lactamase, the successful fabrication of rod-shaped microreactors is demonstrated by their ability to convert the yellow nitrocefin substrate into its hydrolyzed product.

Construction of Fu brick tea polysaccharide-cold plasma modified alginate microgels for probiotic delivery: Enhancing viability and colonization.

Emerging food processing technologies provide broader avenues for enhancing probiotic delivery systems. In this study, the new Fu brick tea polysaccharide (FBTP) was extracted and combined with cold plasma-modified alginate nano-montmorillonite (AMT) to prepare microgels by ionic gelation to improve the viability of encapsulated Lactobacillus kefiranofaciens JKSP109. Results showed that cold plasma treatment for 3 min changed the surface charge of AMT biopolymer solution, and FBTP addition reduced the particle size to the lowest of 223 ± 5.50 nm. Morphological analysis showed that the AMT treated with cold plasma for 3 min and FBTP (C3AMT + FBTP) formed a dense microgel through electrostatic interaction, and the probiotics were randomly distributed in their internal polysaccharide network, as well as the interlayer and surrounding of nanoparticles. The probiotics immobilized in C3AMT + FBTP microgel exhibited the highest viability (8.48 ± 0.03 log CFU/g) and colonic colonization after exposure to simulated gastrointestinal conditions. In addition, the good antioxidant activity of FBTP reduced the loss of probiotic viability during storage, with only 2.58 log CFU/g decreased after 4 weeks. Therefore, such probiotic products enriched with natural bioactive ingredients can be developed as a potential functional food additive.

Characteristics of Pickering emulsions stabilized by microgel particles of five different plant proteins and their application.

Pickering emulsions stabilized by protein particles are of great interest for use in real food systems. This study was to investigate the properties of microgel particles prepared from different plant proteins, i.e., soybean protein isolate (SPI), pea protein isolate (PPI), mung bean protein isolate (MPI), chia seed protein isolate (CSPI), and chickpea protein isolate (CPI). MPI protein particles had most desirable Pickering emulsion forming ability. The particles of SPI and PPI had similar particle size (316.23 nm and 294.80 nm) and surface hydrophobicity (2238.40 and 2001.13) and emulsion forming ability, while the CSPI and CPI particle stabilized emulsions had the least desirable properties. The MPI and PPI particle stabilized Pickering emulsions produced better quality ice cream than the one produced by SPI particle-stabilized emulsions. These findings provide insight into the properties of Pickering emulsions stabilized by different plant protein particles and help expand their application in emulsions and ice cream.

DBD-FISH Using Specific Chromosomal Region Probes for the Study of Cervical Carcinoma Progression.

Genomic instability is an important biomarker in the progression of cervical carcinoma. DBD-FISH (DNA breakage detection-fluorescence in situ hybridization) is a sensitive method that detects strand breaks, alkali-labile sites, and incomplete DNA excision repair in cells of the cervical epithelium. This technique integrates the microgel immersion of cells from a vaginal lesion scraping and the DNA unwinding treatment with the capacity of FISH integrated into digital image analysis. Cells captured within an agarose matrix are lysed and submerged in an alkaline unwinding solution that generates single-stranded DNA motifs at the ends of internal DNA strand breaks. After neutralization, the microgel is dehydrated and the cells are incubated with DNA-labeled probes. The quantity of a hybridized probe at a target sequence corresponds to the measure of the single-stranded DNA produced during the unwinding step, which is equivalent to the degree of local DNA breakage. DNA damage does not show uniformly throughout the entire DNA of a cell; rather, it is confined to specific chromosomal sites. In this chapter, an overview of the technique is supplied, focusing on its ability for assessing the association between DNA damage in specific sequences and in the progressive stages of cervical carcinoma.

On-chip fabrication and in-flow 3D-printing of microgel constructs: from chip to scaffold materials in one integral process.

Bioprinting has evolved into a thriving technology for the fabrication of cell-laden scaffolds. Bioinks are the most critical component for bioprinting. Recently, microgels have been introduced as a very promising bioink, enabling cell protection and the control of the cellular microenvironment. However, the fabrication of the bioinks involves the microfluidic production of the microgels, with a subsequent multistep process to obtain the bioink, which so far has limited its application potential. Here we introduce a direct coupling of microfluidics and 3D-printing for the continuous microfluidic production of microgels with direct in-flow printing into stable scaffolds. The 3D-channel design of the microfluidic chip provides access to different hydrodynamic microdroplet formation regimes to cover a broad range of droplet and microgel diameters. After exiting a microtubing the produced microgels are hydrodynamically jammed into thin microgel filaments for direct 3D-printing into two- and three-dimensional scaffolds. The methodology enables the continuous on-chip encapsulation of cells into monodisperse microdroplets with subsequent in-flow cross-linking to produce cell-laden microgels. The method is demonstrated for different cross-linking methods and cell lines. This advancement will enable a direct coupling of microfluidics and 3D-bioprinting for scaffold fabrication.

Porous Anisometric PNIPAM Microgels: Tailored Porous Structure and Thermal Response.

The porous structure of microgels significantly influences their properties and, thus, their suitability for various applications, in particular as building blocks for tissue scaffolds. Porosity is one of the crucial features for microgel-cell interactions and significantly increases the cells' accumulation and proliferation. Consequently, tailoring the porosity of microgels in an effortless way is important but still challenging, especially for nonspherical microgels. This work presents a straightforward procedure to fabricate complex-shaped poly(N-isopropyl acrylamide) (PNIPAM) microgels with tuned porous structures using the so-called cononsolvency effect during microgel polymerization. Therefore, the classical solvent in the reaction solution is exchanged from water to water-methanol mixtures in a stop-flow lithography process. For cylindrical microgels with a higher methanol content during fabrication, a greater degree of collapsing is observed, and their aspect ratio increases. Furthermore, the collapsing and swelling velocities change with the methanol content, indicating a modified porous structure, which is confirmed by electron microscopy micrographs. Furthermore, swelling patterns of the microgel variants occur during cooling, revealing their thermal response as a highly heterogeneous process. These results show a novel procedure to fabricate PNIPAM microgels of any elongated 2D shape with tailored porous structure and thermoresponsiveness by introducing the cononsolvency effect during stop-flow lithography polymerization.

In vitro development and optimization of cell-laden injectable bioprinted gelatin methacryloyl (GelMA) microgels mineralized on the nanoscale.

Bone defects may occur in different sizes and shapes due to trauma, infections, and cancer resection. Autografts are still considered the primary treatment choice for bone regeneration. However, they are hard to source and often create donor-site morbidity. Injectable microgels have attracted much attention in tissue engineering and regenerative medicine due to their ability to replace inert implants with a minimally invasive delivery. Here, we developed novel cell-laden bioprinted gelatin methacrylate (GelMA) injectable microgels, with controllable shapes and sizes that can be controllably mineralized on the nanoscale, while stimulating the response of cells embedded within the matrix. The injectable microgels were mineralized using a calcium and phosphate-rich medium that resulted in nanoscale crystalline hydroxyapatite deposition and increased stiffness within the crosslinked matrix of bioprinted GelMA microparticles. Next, we studied the effect of mineralization in osteocytes, a key bone homeostasis regulator. Viability stains showed that osteocytes were maintained at 98 % viability after mineralization with elevated expression of sclerostin in mineralized compared to non-mineralized microgels, showing that mineralization can effectively enhances osteocyte maturation. Based on our findings, bioprinted mineralized GelMA microgels appear to be an efficient material to approximate the bone microarchitecture and composition with desirable control of sample injectability and polymerization. These bone-like bioprinted mineralized biomaterials are exciting platforms for potential minimally invasive translational methods in bone regenerative therapies.

ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction.

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 µm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.