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Despite the substantial advancement in developing various hydrogel microparticle (HMP) synthesis methods, emulsification through porous medium to synthesize functional hybrid protein-polymer HMPs has yet to be addressed. Here, the aided porous medium emulsification for hydrogel microparticle synthesis (APME-HMS) system, an innovative approach drawing inspiration from porous medium emulsification is introduced. This method capitalizes on emulsifying immiscible phases within a 3D porous structure for optimal HMP production. Using the APME-HMS system, synthesized responsive bovine serum albumin (BSA) and polyethylene glycol diacrylate (PEGDA) HMPs of various sizes are successfully synthesized. Preserving protein structural integrity and functionality enable the formation of cytochrome c (cyt c) - PEGDA HMPs for hydrogen peroxide (H2O2) detection at various concentrations. The flexibility of the APME-HMS system is demonstrated by its ability to efficiently synthesize HMPs using low volumes (≈50 µL) and concentrations (100 µm) of proteins within minutes while preserving proteins' structural and functional properties. Additionally, the capability of the APME-HMS method to produce a diverse array of HMP types enriches the palette of HMP fabrication techniques, presenting it as a cost-effective, biocompatible, and scalable alternative for various biomedical applications, such as controlled drug delivery, 3D printing bio-inks, biosensing devices, with potential implications even in culinary applications.
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Separation of equally sized particles distinguished solely by material properties remains still a very challenging task. Here a simple separation of differently charged, thermo-responsive polymeric particles (for example microgels) but equal in size, via the combination of pressure-driven microfluidic flow and precise temperature control is proposed. The separation principle relies on forcing thermo-responsive microgels to undergo the volume phase transition during heating and therefore changing its size and correspondingly the change in drift along a pressure driven shear flow. Different thermo-responsive particle types such as different grades of ionizable groups inside the polymer matrix have different temperature regions of volume phase transition temperature (VPTT). This enables selective control of collapsed versus swollen microgels, and accordingly, this physical principle provides a simple method for fractioning a binary mixture with at least one thermo-responsive particle, which is achieved by elution times in the sense of particle chromatography. The concepts are visualized in experimental studies, with an intend to improve the purification strategy of the broad distribution of charged microgels into fractioning to more narrow distribution microgels distinguished solely by slight differences in net charge.
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In the context of advanced nanomaterials research, nanogels (NGs) have recently gained broad attention for their versatility and promising biomedical applications. To date, a significant number of NGs have been developed to meet the growing demands in various fields of biomedical research. Summarizing preparation methods, physicochemical and biological properties, and recent applications of NGs may be useful to help explore new directions for their development. This article presents a comprehensive overview of the latest NG synthesis methodologies, highlighting advances in formulation with different types of hydrophilic or amphiphilic polymers. It also underlines recent biomedical applications of NGs in drug delivery and imaging, with a short section dedicated to biosafety considerations of these innovative nanomaterials. In conclusion, this article summarizes recent innovations in NG synthesis and their numerous applications, highlighting their considerable potential in the biomedical field.
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This study aims to investigate the effects of interfacial layer composition and structure on the formation, physicochemical properties and stability of Pickering emulsions. Interfacial layers were formed using pea protein isolate (PPI), PPI microgel particles (PPIMP), a mixture of PPIMP and sodium alginate (PPIMP-SA), or PPIMP-SA conjugate. The encapsulation and protective effects on different hydrophobic bioactives were then evaluated within these Pickering emulsions. The results demonstrated that the PPIMP-SA conjugate formed thick and robust interfacial layers around the oil droplet surfaces, which increased the resistance of the emulsion to coalescence, creaming, and environmental stresses, including heating, light exposure, and freezing-thawing cycle. Additionally, the emulsion stabilized by the PPIMP-SA conjugate significantly improved the photothermal stability of hydrophobic bioactives, retaining a higher percentage of their original content compared to those in non-encapsulated forms. Overall, the novel protein microgels and the conjugate developed in this study have great potential for improving the physicochemical stability of emulsified foods.
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The inclusion of hollow channels in tissue-engineered hydrogels is crucial for mimicking the natural physiological conditions and facilitating the delivery of nutrients and oxygen to cells. Although bio-fabrication techniques provide diverse strategies to create these channels, many require sophisticated equipment and time-consuming protocols. Herein, collagenase, a degrading agent for methacrylated gelatin hydrogels, and magnetic nanoparticles (MNPs) are combined and processed into enzymatically active spherical structures using a straightforward oil bath emulsion methodology. The generated microgels are then used to microfabricate channels within biomimetic hydrogels via a novel sculpturing approach that relied on the precise coupling of protein-enzyme pairs (for controlled local degradation) and magnetic actuation (for directional control). Results show that the sculpting velocity can be tailored by adjusting the magnetic field intensity or concentration of MNPs within the microgels. Additionally, varying the magnetic field position or microgel size generated diverse trajectories and channels of different widths. This innovative technology improves the viability of encapsulated cells through enhanced medium transport, outperforming non-sculpted hydrogels and offering new perspectives for hydrogel vascularization and drug/biomolecule administration. Ultimately, this novel concept can help design fully controlled channels in hydrogels or soft materials, even those with complex tortuosity, in a single wireless top-down biocompatible step.
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The pericellular matrix (PCM) surrounding chondrocytes is essential for articular cartilage tissue engineering. As the current isolation methods to obtain chondrocytes with their PCM (chondrons) result in a heterogeneous mixture of chondrocytes and chondrons, regenerating the PCM using a tissue engineering approach could prove beneficial. In this study, we aimed to discern the behavior of articular chondrocytes (ACs) in regenerating the PCM in such an approach and whether this would also be true for articular cartilage-derived progenitor cells (ACPCs), as an alternative cell source. Bovine ACs and ACPCs were encapsulated in agarose microgels using droplet-based microfluidics. ACs were stimulated with TGF-ß1 and dexamethasone and ACPCs were sequentially stimulated with BMP-9 followed by TGF-ß1 and dexamethasone. After 0, 3, 5, and 10 days of culture, PCM components, type-VI collagen and perlecan, and ECM component, type-II collagen, were assessed using flow cytometry and fluorescence microscopy. Both ACs and ACPCs synthesized the PCM before the ECM. It was seen for the first time that synthesis of type-VI collagen always preceded perlecan. While the PCM synthesized by ACs resembled native chondrons after only 5 days of culture, ACPCs often made less well-structured PCMs. Both cell types showed variations between individual cells and donors. On one hand, this was more prominent in ACPCs, but also a subset of ACPCs showed superior PCM and ECM regeneration, suggesting that isolating these cells may potentially improve cartilage repair strategies.
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A distinct feature of pancreatic ductal adenocarcinoma (PDAC) is a prominent tumor microenvironment (TME) with remarkable cellular and spatial heterogeneity that meaningfully impacts disease biology and treatment resistance. The dynamic crosstalk between cancer cells and the dense stromal compartment leads to spatially and temporally heterogeneous metabolic alterations, such as acidic pH that contributes to drug resistance in PDAC. Thus, monitoring the extracellular pH metabolic fluctuations within the TME is crucial to predict and to quantify anticancer drug efficacy. Here, a simple and reliable alginate-based 3D PDAC model embedding ratiometric optical pH sensors and cocultures of tumor (AsPC-1) and stromal cells for simultaneously monitoring metabolic pH variations and quantify drug response is presented. By means of time-lapse confocal laser scanning microscopy (CLSM) coupled with a fully automated computational analysis, the extracellular pH metabolic variations are monitored and quantified over time during drug testing with gemcitabine, folfirinox, and paclitaxel, commonly used in PDAC therapy. In particular, the extracellular acidification is more pronounced after drugs treatment, resulting in increased antitumor effect correlated with apoptotic cell death. These findings highlight the importance of studying the influence of cellular metabolic mechanisms on tumor response to therapy in 3D tumor models, this being crucial for the development of personalized medicine approaches.
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In this study, the novel 3D-printed pressure chamber for encapsulated single-cell stimulation (3D-PRESS) platform is introduced for the mechanical stimulation of single stem cells in 3D microgels. The custom-designed 3D-PRESS, allows precise pressure application up to 400 kPa at the single-cell level. Microfluidics is employed to encapsulate single mesenchymal stem cells within ionically cross-linked alginate microgels with cell adhesion RGD peptides. Rigorous testing affirms the leak-proof performance of the 3D-PRESS device up to 400 kPa, which is fully biocompatible. 3D-PRESS is implemented on mesenchymal stem cells for mechanotransduction studies, by specifically targeting intracellular calcium signaling and the nuclear translocation of a mechanically sensitive transcription factor. Applying 200 kPa pressure on individually encapsulated stem cells reveals heightened calcium signaling in 3D microgels compared to conventional 2D culture. Similarly, Yes-associated protein (YAP) translocation into the nucleus occurs at 200 kPa in 3D microgels with cell-binding RGD peptides unveiling the involvement of integrin-mediated mechanotransduction in singly encapsulated stem cells in 3D microgels. Combining live-cell imaging with precise mechanical control, the 3D-PRESS platform emerges as a versatile tool for exploring cellular responses to pressure stimuli, applicable to various cell types, providing novel insights into single-cell mechanobiology.
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Enzymes play a vital role in synthesizing complex biological molecules like hyaluronic acid (HA). Immobilizing enzymes on support materials is essential for their efficient use and reuse in multiple cycles. Microgels, composed of cross-linked, highly swollen polymer networks, are ideal for enzyme uptake owing to their high porosity. This study demonstrates the immobilization of His6-tagged hyaluronan synthase from Pasteurella multocida (PmHAS) onto nitrilotriacetic acid functionalized microgels using different bivalent ions (Ni2+, Co2+, Mn2+, Mg2+, and Fe2+) via metal affinity binding. The results indicate that using Ni2+ yields the microgels with the highest enzyme uptake and HA formation. The immobilized PmHAS enables repetitive enzymatic production, producing high molecular weight HAs with decreasing dispersities in each step. Furthermore, the highest reported yield of HA with high molecular weight for immobilized PmHAS is achieved. This system establishes a foundation for continuous HA formation, with future works potentially enhancing PmHAS stability through protein engineering.
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In this work, the effect of sonication on the molecular characteristics of polyacrylic acid (Carbopol® Ultrez 10), as well as on its rheological behavior in aqueous dispersions and microgels, was analyzed for the first time by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels containing 0.25 wt.% of Ultrez 10 were sonicated in a commercial ultrasound bath at constant power and at different times. The main rheological properties of the microgel, namely, shear modulus, yield stress and viscosity, all decreased with increasing sonication time, while the microgel's Herschel-Bulkley (H-B) behavior, without thixotropy, was preserved. Also, Mw of Ultrez 10 decreased up to almost one-third (109,212 g/mol) of its original value (300,860 g/mol) after 180 min of sonication. These results evidence a softening of the gel microstructure, which results from the reduction in the Mw of polyacrylic acid with sonication time. Separately, FTIR measurements show that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy observations revealed a diminution of the size of the microsponge domains and more free solvent with sonication time, which is reflected in a less compact and softer microstructure. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids, in general, may be manipulated or tailored by systematic high-power ultrasonication.
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Stimuli-responsive microgels have attracted great interest in recent years as building blocks for fabricating smart surfaces with many technological applications. In particular, PNIPAM microgels are promising candidates for creating thermo-responsive scaffolds to control cell growth and detachment via temperature stimuli. In this framework, understanding the influence of the solid substrate is critical for tailoring microgel coatings to specific applications. The surface modification of the substrate is a winning strategy used to manage microgel-substrate interactions. To control the spreading of microgel particles on a solid surface, glass substrates are coated with a PEI or an APTES layer to improve surface hydrophobicity and add positive charges on the interface. A systematic investigation of PNIPAM microgels spin-coated through a double-step deposition protocol on pristine glass and on functionalised glasses was performed by combining wettability measurements and Atomic Force Microscopy. The greater flattening of microgel particles on less hydrophilic substrates can be explained as a consequence of the reduced shielding of the water-substrate interactions that favors electrostatic interactions between microgels and the substrate. This approach allows the yielding of effective control on microgel coatings that will help to unlock new possibilities for their application in biomedical devices, sensors, or responsive surfaces.
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Shape-anisotropic hydrogel microparticles have attracted considerable attention for drug-delivery applications. Particularly, nonspherical hydrogel microcarriers with enhanced adhesive and circulatory abilities have demonstrated value in gastrointestinal drug administration. Herein, inspired by the structures of natural suckers, we demonstrate an ionic polymerization-based production of calcium (Ca)-alginate microparticles with tunable shapes from Janus emulsion for the first time. Monodispersed Janus droplets composed of sodium alginate and nongelable segments were generated using a coflow droplet generator. The interfacial curvatures, sizes, and production frequencies of Janus droplets can be flexibly controlled by varying the flow conditions and surfactant concentrations in the multiphase system. Janus droplets were ionically solidified on a chip, and hydrogel beads of different shapes were obtained. The in vitro and in vivo adhesion abilities of the hydrogel beads to the mouse colon were investigated. The anisotropic beads showed prominent adhesive properties compared with the spherical particles owing to their sticky hydrogel components and unique shapes. Finally, a novel computational fluid dynamics and discrete element method (CFD-DEM) coupling simulation was used to evaluate particle migration and contact forces theoretically. This review presents a simple strategy to synthesize Ca-alginate particles with tunable structures that could be ideal materials for constructing gastrointestinal drug delivery systems.
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The proficient handling of diabetic wounds, a rising issue coinciding with the global escalation of diabetes cases, poses significant clinical difficulties. A range of biofunctional dressings have been engineered and produced to expedite the healing process of diabetic wounds. This study proposes a multifunctional hydrogel dressing for diabetic wound healing, which is composed of Polyvinyl Alcohol (PVA) and N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1, N1, N3, N3-teramethylpropane-1, 3-diaminium (TSPBA), and a dual-drug loaded Gelatin methacryloyl (GM) microgel. The GM microgel is loaded with sodium fusidate (SF) and nanoliposomes (LP) that contain metformin hydrochloride (MH). Notably, adhesive and self-healing properties the hydrogel enhance their therapeutic potential and ease of application. In vitro assessments indicate that SF-infused hydrogel can eliminate more than 98% of bacteria within 24 h and maintain a sustained release over 15 days. Additionally, MH incorporated within the hydrogel has demonstrated effective glucose level regulation for a duration exceeding 15 days. The hydrogel demonstrates a sustained ability to neutralize ROS throughout the entire healing process, predominantly by electron donation and sequestration. This multifunctional hydrogel dressing, which integrated biological functions of efficient bactericidal activity against both MSSA and MRSA strains, blood glucose modulation, and control of active oxygen levels, has successfully promoted the healing of diabetic wounds in rats in 14 days. The hydrogel dressing exhibited significant effectiveness in facilitating the healing process of diabetic wounds, highlighting its considerable promise for clinical translation.
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Antibacterianos , Bandagens , Hidrogéis , Álcool de Polivinil , Espécies Reativas de Oxigênio , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Álcool de Polivinil/química , Masculino , Hiperglicemia/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Ratos Sprague-Dawley , Gelatina/química , Metformina/farmacologia , Metformina/química , Lipossomos/química , Staphylococcus aureus/efeitos dos fármacos , Metacrilatos/química , Metacrilatos/farmacologia , Adesivos/química , Adesivos/farmacologia , InjeçõesRESUMO
Conversion of toxic nitroarenes into less toxic aryl amines, which are the most suitable precursors for different types of compounds, is done with various materials which are costly or take more time for this conversion. In this regards, a silica@poly(chitosan-N-isopropylacrylamide-methacrylic acid) Si@P(CS-NIPAM-MAA) Si@P(CNM) core-shell microgel system was synthesized through free radical precipitation polymerization (FRPP) and then fabricated with palladium nanoparticles (Pd NPs) by in situ-reduction method to form Si@Pd-P(CNM) and characterized with XRD, TEM, FTIR, SEM, and EDX. The catalytic efficiency of Si@Pd-P(CNM) hybrid microgels was studied for reduction of 4-nitroaniline (4NiA) under diverse conditions. Different nitroarenes were successfully transformed into their corresponding aryl amines with high yields using the Si@Pd-P(CNM) system as catalyst and NaBH4 as reductant. The Si@Pd-P(CNM) catalyst exhibited remarkable catalytic efficiency and recyclability as well as maintaining its catalytic effectiveness over multiple cycles.
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Acrilamidas , Quitosana , Nanopartículas Metálicas , Paládio , Dióxido de Silício , Paládio/química , Catálise , Dióxido de Silício/química , Quitosana/química , Nanopartículas Metálicas/química , Acrilamidas/química , Microgéis/química , Oxirredução , Metacrilatos/químicaRESUMO
Intravesical instillation is an efficient therapeutic technique based on targeted administration of a drug directly into the lesion for the treatment of bladder diseases. This is an alternative to traditional systemic administration of drugs. However, this technique requires repeated procedures, which can lead to even greater inflammation and infection of the urethra. To date, novel systems that allow prolonged drug retention in the bladder cavity are actively being developed. We recently reported a targeted drug delivery system based on the mucoadhesive emulsion microgels consisting of the natural component whey protein isolate. Such micron-sized carriers possess high loading capacity, a prolonged drug release profile, and efficient mucoadhesive properties to the bladder urothelium. As a continuation of this work, we present a protocol for the synthesis of mucoadhesive emulsion microgels. Detailed procedures for preparing precursor solutions as well as studying the physico-chemical parameters of microgels (including loading capacity and drug release rate) and the mucoadhesive properties using the model of porcine bladder urothelium are discussed. Precautionary measures and nuances that are worth paying attention to during each experimental stage are given as well. Key features ⢠The protocol for the synthesis of mucoadhesive emulsion microgels based on whey protein isolate is presented. The experimental conditions of emulsion microgels synthesis are discussed. ⢠Methods for studying the physico-chemical properties of mucoadhesive emulsion microgels (size of emulsion microgels particles, loading capacity, release kinetics) are described. ⢠The method for assessing mucoadhesive properties of emulsion microgels is demonstrated using the porcine bladder tissue model ex vivo.
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A sodium alginate (Alg) based REDOX (reduction and oxidation)-responsive and fluorescent active microgel was prepared via water in oil (w/o) mini-emulsion polymerization technique. Here, we initially synthesized sodium alginate-based disulfide cross linked microgels and after that those microgels were tagged with rhodamine amine derivative (RhB-NH2) by ionic interaction to get the pH-responsive fluorescent property. Functionalized microgels were characterized using 1H NMR, FTIR, DLS, HRTEM, FESEM, UV-vis, and fluorescence spectroscopy analyses. Presence of the REDOX-responsive disulfide-containing crosslinkers in the microgels enhances the release of doxorubicin (DOX), an anti-cancer drug in the reducing environment of the cancer-cells (simulated). Existence of the rhodamine-amine derivative in the microgels triggers the pH-dependent fluorescence property by showing fluorescence emission at 560-580 nm at pH 5.5 (cancer cell pH). The cytotoxicity of the biopolymer based microgel was assessed over both cancerous HeLa (IC50 100 µg/mL) and non-cancerous MDCK (IC50 200 µg/mL) cells by MTT assay which showed the synthesized microgel is non-toxic whereas DOX-loaded microgels showed significant toxicity. FACS and cell uptake (in vitro) analyses were conducted to understand the cell apoptosis cycle and behavior of the cancer cells in presence of the DOX-loaded microgels. This pH-responsive fluorescent active alginate-based biomaterial could be a promising material for the anti-cancer drug delivery and other medical fields.
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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.
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Preparações de Ação Retardada , Doxorrubicina , Portadores de Fármacos , Liberação Controlada de Fármacos , Compostos Férricos , Microgéis , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Doxorrubicina/administração & dosagem , Humanos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células MCF-7 , Compostos Férricos/química , Concentração de Íons de Hidrogênio , Microgéis/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Alginatos/química , Aminas/química , Carboximetilcelulose Sódica/química , Nanopartículas/química , Zinco/química , Compostos de Zinco/química , Sobrevivência Celular/efeitos dos fármacosRESUMO
Hydrogels are ideal for antifouling materials due to their high hydrophilicity and low adhesion properties. Herein, poly(ionic liquid) hydrogels integrated with zwitterionic copolymer-functionalized gallium-based liquid metal (PMPC-GLM) microgels were successfully prepared by a one-pot reaction. Poly(ionic liquid) hydrogels (IL-Gel) were obtained by chemical cross-linking the copolymer of ionic liquid, acrylic acid, and acrylamide, and the introduction of ionic liquid (IL) significantly increased the cross-linking density; this approach consequently enhanced the mechanical and antiswelling properties of the hydrogels. The swelling ratio of IL-Gel decreased eight times compared to the original hydrogels. PMPC-GLM microgels were prepared through grafting the zwitterionic polymer PMPC onto the GLM nanodroplet surface, which exhibited efficient antifouling performance attributed to the bactericidal effect of Ga3+ and the antibacterial effect of the zwitterionic polymer layer PMPC. Based on the synergistic effect of PMPC-GLM microgels and IL, the composite hydrogels PMPC-GLM@IL-Gel not only exhibited excellent mechanical and antiswelling properties but also showed outstanding antibacterial and antifouling properties. Consequently, PMPC-GLM@IL-Gel hydrogels achieved inhibition rates of over 90% against bacteria and more than 85% against microalgae.
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Physically crosslinked microgels (PCMs) offer a biocompatible platform for various biomedical applications. However, current PCM fabrication methods suffer from their complexity and poor controllability, due to their reliance on altering physical conditions to initiate gelation and their dependence on specific materials. To address this issue, a novel PCM fabrication method is devised, which employs water transport-induced liquid-liquid phase separation (LLPS) to trigger the intermolecular interaction-supported sol-gel transition within aqueous emulsion droplets. This method enables the controllable and facile generation of PCMs through a single emulsification step, allowing for the facile production of PCMs with various materials and sizes, as well as controllable structures and mechanical properties. Moreover, this PCM fabrication method holds great promise for diverse biomedical applications. The interior of the PCM not only supports the encapsulation and proliferation of bacteria but also facilitates the encapsulation of eukaryotic cells after transforming the system into an all-aqueous emulsion. Furthermore, through appropriate surface functionalization, the PCMs effectively activate T cells in vitro upon coculturing. This work represents an advancement in PCM fabrication and offers new insights and perspectives for microgel engineering.
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HYPOTHESIS: Particle surface chemistry and internal softness are two fundamental parameters in governing the mechanical properties of dense colloidal suspensions, dictating structure and flow, therefore of interest from materials fabrication to processing. EXPERIMENTS: Here, we modulate softness by tuning the crosslinker content of poly(N-isopropylacrylamide) microgels, and we adjust their surface properties by co-polymerization with polyethylene glycol chains, controlling adhesion, friction and fuzziness. We investigate the distinct effects of these parameters on the entire mechanical response from restructuring to complete fluidization of jammed samples at varying packing fractions under large-amplitude oscillatory shear experiments, and we complement rheological data with colloidal-probe atomic force microscopy to unravel variations in the particles' surface properties. FINDINGS: Our results indicate that surface properties play a fundamental role at smaller packings; decreasing adhesion and friction at contact causes the samples to yield and fluidify in a lower deformation range. Instead, increasing softness or fuzziness has a similar effect at ultra-high densities, making suspensions able to better adapt to the applied shear and reach complete fluidization over a larger deformation range. These findings shed new light on the single-particle parameters governing the mechanical response of dense suspensions subjected to deformation, offering synthetic approaches to design materials with tailored mechanical properties.