Hydrogel Microspheres Research Articles

Incorporation of carboxymethyl chitosan (CMCS) for the modulation of physio-chemical characteristics and cell proliferation environment of the composite hydrogel microspheres

Hydrogels have excellent swelling properties and have been widely applied in tissue engineering because of their similarity to the extracellular matrix (ECM). Sodium alginate (SA) and carboxymethyl chitosan (CMCS) were prepared into hydrogel microspheres with Ca2+crosslinking in our study. The morphology, inner structure, mechanical properties, water content, swelling rate and BMP-2 loading and releasing properties were characterized. Our results showed that the composite SA /CMCS hydrogel microspheres were translucent and spherical in shape with uniform particle size. The incorporation of CMCS further increased the diameters of the microspheres, internal pore structure, water content, and mechanical properties of the SA/CMCS hydrogel microspheres. At the same SA concentration, with the increase of CMSC concentration, the diameter of microspheres could be increased by about 0.4 mm, the water content can be increased about 1%-2%. As for the mechanical properties, the compressive strength can be increased by 0.04-0.1 MPa, and the modulus of elasticity can be increased by 0.1-0.15 MPa. BMP-2 was chosen as a model agent and it could be loaded into SA/CMCS microspheres, and the incorporation of CMCS increased BMP-2 loading. The encapsulated BMP-2 was sustainably releasedin vitro. The leaching solutions of the SA/CMCS hydrogel microspheres exhibited good cytocompatibility and could increase ALP activity, ALP expression, and biomineralization on MC3T3-E1 cells. After 7 d of co-culture, ALP activities in S2.5C2 and S2.5C3 groups was increased by 50% and 45% compared with that of the control group. When embedded in the SA/CMCS microspheres, the MC3T3-E1 cells were evenly distributed inside the hydrogel microspheres and remained viable. Transcriptomic studies showed that incorporation of CMCS induced upregulation of 1141 differentially expressed genes (DEGs) and downregulation of 1614 DEGs compared with SA microspheres. The most significantly enriched pathways were the Wnt and MAPK signaling pathways induced by the incorporation of CMCS and BMP-2. In conclusion, our results indicated that the physiochemical characteristics of the SA hydrogel microspheres could be greatly modulated by CMCS to better mimic the ECM microenvironment and induce osteo-inductive activities of MC3T3-E1 cells.

Colonic long-term retention and colonization of probiotics by double-layer chitosan/tannic acid coating and microsphere embedding for treatment of ulcerative colitis and radiation enteritis

Oral probiotics can alleviate enteric inflammations but their rapid transit through the gut limits their retention and colonization in the colon. Here, a novel strategy integrating the bacterial double-layer coating and hydrogel microsphere embedding techniques was used to highly enhance the colonic retention and colonization efficiency of Lactobacillus rhamnosus GG (LGG). LGG was coated by the double layers of chitosan (CS) and tannic acid (TA), and then embedded in calcium alginate (CA) hydrogel microspheres to form LGG@CT@CA. The microspheres resisted gastric liquids, improving LGG safe transit through the stomach to reach the colon. LGG@CT was rapidly released in the colon due to the good swelling of hydrogel microspheres. More importantly, LGG exhibited long-term retention up to 7 days in the colon and colonized the deep site of the colonic mucosa. LGG@CT@CA had a high therapeutic efficiency of ulcer colitis with the long colon and the low intestinal permeability of colonic tissues. LGG@CT@CA also alleviated the small intestinal damage induced by irradiation and the survival rates were improved. The mechanisms included local ROS decrease, IL-10 increase, and ferroptosis reduction in the small intestine. The oral colon-targeted system holds promise for oral probiotic therapy by the long-term retention and colonization in the colon.

Nanozyme microspheres with structural color-coding labels for synergistic therapy of psoriasis

Psoriasis is an immune system-mediated skin disease identified by the appearance of erythematous as a central symptom. As a recurrent and chronic inflammatory disease, psoriasis is influenced by both genetic and environmental factors and is known to be with no effective cure. Considering a multifaceted etiology of psoriasis, synergistic therapy exhibits great benefits over monotherapy, which becomes common for the treatment of various diseases. Herein, we present the nanozyme microspheres with structural color-coding labels for synergistic therapy of psoriasis. In particular, microsphere hydrogel is fabricated by the edible hydroxypropyl cellulose (HPC), which can generate a photonic liquid crystalline mesophase under lyotropic conditions in solution. Through adjustment of hydrogel components, microspheres endow with different functions, including moisturizing (paraffin), cfDNA scavenging (chitosan), and anti-inflammation (cerium oxide nanozyme). To improve patient convenience, hydrogel drops with different properties are tailored with different vivid structural colors by exploiting the lyotropic behavior of HPC. Of particular note, both in vitro and in vivo experiments have demonstrated the significant therapeutic effects of the encoded structural color microspheres. Green moisturizing microspheres facilitate to relieve dry, flaky skin patches; blue cfDNA scavenging and red anti-inflammatory microspheres significantly reduce skin inflammation. More importantly, combination therapy with encoded microspheres exerted the synergistic effects, including the increased body weight, thicker epidermal layer, and reduced immune activation. Overall, this synergistic treatment offers a promising platform for personalized management of psoriasis and various inflammatory skin diseases.

Injectable GelMA Hydrogel Microspheres with Sustained Release of Platelet-Rich Plasma for the Treatment of Thin Endometrium.

Platelet-rich plasma (PRP) intrauterine infusion has been demonstrated to be effective in treating thin endometrium and achieving pregnancy. However, the rapid release of growth factors limits its effectiveness in clinical applications, and thus, multiple intrauterine infusions are often required to achieve therapeutic efficacy. In this study, a GelMA hydrogel microsphere biomaterial is developed using droplet microfluidics to modify the delivery mode of PRP and thus prolong its duration of action. Its biocompatibility is confirmed through both in vivo and in vitro studies. Cell experiments show that PRP-loaded microspheres significantly enhance cell proliferation, migration, and angiogenesis. In vivo experiments show that the effects of PRP-loaded microspheres on repairing the endometrium and restoring fertility in mice could achieve the impact of triple PRP intrauterine infusions. Further mechanistic investigations reveal that PRP could facilitate endometrial repair by regulating the expression of E2Fs, a group of transcription factors. This study demonstrates that hydrogel microspheres could modify the delivery of PRP and prolong its duration of action, enabling endometrial repair and functional reconstruction. This design avoids repeated intrauterine injections of PRP in the clinic, reduces the number of patient visits, and provides a new avenue for clinical treatment of thin endometrium.

Spatio-temporally controlled all-in-one hydrogel microspheres for ulcerative colitis treatment based on cocktail strategy

Due to the complex pathogenesis of ulcerative colitis (UC), particularly excessive reactive oxygen species (ROS), gut microbiota dysbiosis, and hyperpolarization of M1 macrophages, the cocktail strategy is urgently needed to obtain a sufficient therapeutic outcome. Meanwhile, the accurate lesion location targeting of these combined therapeutic agents is still crucial. Herein, based on NPs-in-MPs approach, a novel integrated “all-in-one” oral delivery system (BMM/MPs), containing the natural gut microbiota regulator berberine, MnO2 nanoenzymes, and cell penetrating peptides-decorated magnolol liposomes to regulate macrophage polarization, was constructed to address these above issues in sequence. BMM/MPs could non-destructively cross the gastrointestinal tract, enduringly detain, and dissociate in the colon site due to the pH-sensitive properties. Conceivably, the released MnO2 nanoenzymes depleted the excess ROS at the colitis location into O2, sequentially promoting the acceleration of hydrogel microspheres rupture and oxidative damage remission. Accordingly, the oral administration of BMM/MPs exhibited remarkably satisfactory therapeutic effects against DSS-induced UC mice, by ameliorating the representative symptoms, scavenging ROS, relieving inflammation, and inhibiting M1 macrophage polarization at colon sites. Meanwhile, the dysbiosis of microbes was effectively regulated by facilitating SCFAs production. This study provides a feasible strategy for administration in the treatment of UC.

Porous sodium alginate/cellulose nanofiber composite hydrogel microspheres for heavy metal removal in wastewater

High adsorption capacity, high adsorption rate and reusable adsorbents are urgent needed for removing heavy metals from wastewater. In this study, porous sodium alginate/cellulose nanofiber (SA/CNF) composite hydrogel microspheres were prepared by combining sodium alginate with cellulose nanofibers by microfluidics technology and adding polyethylene glycol (PEG) as pore making agent. The SA/CNF composite hydrogel microspheres could efficiently adsorb heavy metals (Pb2+, Cu2+ and Cd2+) in wastewater. The influencing factors of adsorption process, including pH, temperature, initial concentration, coexisting ions and aquatic environments, were systematically discussed. The adsorption process was more consistent with Langmuir isotherm model and pseudo-second-order model in batch system, indicating the adsorption process was mainly chemical adsorption. The adsorption capacity to Pb2+ obtained by Langmuir model was as high as 544.66 mg/g at 20 °C. Fixed-bed column adsorption experiments demonstrated the excellent performance of the as-prepared SA/CNF microspheres for treatment of the flowing wastewater in a column system. Overall, a highly practical adsorption process based on hydrogel adsorbents was developed for the removal of heavy metals from actual wastewater.

Design and preparation of hydrogel microspheres for spinal cord injury repair.

A severe disorder known as spinal cord damage causes both motor and sensory impairment in the limbs, significantly reducing the patients' quality of life. After a spinal cord injury, functional recovery and therapy have emerged as critical concerns. Hydrogel microspheres have garnered a lot of interest lately because of their enormous promise in the field of spinal cord injury rehabilitation. The material classification of hydrogel microspheres (natural and synthetic macromolecule polymers) and their synthesis methods are examined in this work. This work also covers the introduction of several kinds of hydrogel microspheres and their use as carriers in the realm of treating spinal cord injuries. Lastly, the study reviews the future prospects for hydrogel microspheres and highlights their limitations and problems. This paper can offer feasible ideas for researchers to advance the application of hydrogel microspheres in the field of spinal cord injury.

A Novel Cellulose-Based Composite Hydrogel Microsphere Material: for Efficient Adsorption of Co(II) and Ni(II) Ions in Water

A Novel Cellulose-Based Composite Hydrogel Microsphere Material: for Efficient Adsorption of Co(II) and Ni(II) Ions in Water

Precise Lubrication and Protection of Cartilage Damage by Targeting Hydrogel Microsphere.

Osteoarthritis (OA) is a degenerative bone and joint disease characterized by decreased cartilage lubrication, leading to continuous wear and ultimately irreversible damage. This situation is particularly challenging for early-stage OA, as current bio-lubricants lack precise targeting for small inflammatory lesions. In this work, an antibody-mediated targeting hydrogel microspheres (HMS) is developed to precisely lubricate the local injury site of cartilage and prevent the progression of early OA. Anti-Collagen type I (Anti-Col1) is an antibody that targets cartilage injury sites in early OA stages. It is anchored on a HMS matrix made of Gelatin methacrylate (GelMA) and poly (sulfobetaine methacrylate) (PSBMA) to create targeted HMS (T-G/S HMS). The T-G/S HMS's high hydrophilicity, along with the dynamic interaction between its surficial Anti-Col1 and the Col1 on cartilage injury site, ensures its precise and effective lubrication of early OA lesions. Consequently, injecting T-G/S HMS into rats with early OA significantly slows disease progression and reduces symptoms. In conclusion, the developed injectable targeted lubricating HMS and the precisely targeted lubrication strategy represent a promising, convenient technique for treating OA, particularly for slowing the early-stage OA progression.

Targeting Osteoblast-Osteoclast Cross-Talk Bone Homeostasis Repair Microcarriers Promotes Intervertebral Fusion in Osteoporotic Rats.

Balancing osteoblast-osteoclast (OB-OC) cross-talk is crucial for restoring bone tissue structure and function. Current clinical drugs targeting either osteogenesis or osteoclastogenesis fail to effectively regulate cross-talk, impeding efficient bone repair in osteoporosis patients. Ubiquitin-specific protease 26 (USP26) is shown to coordinate OB-OC cross-talk by independently regulating β-catenin and Iκb-α. However, effective drugs for activating USP26 are still lacking. Here, they constructed bone homeostasis repair microcarriers (BHRC) that encapsulate Usp26 mRNA-loaded lipid nanoparticles (mRNA@LNP) within MMPs-responsive GelMA hydrogel microspheres. These microcarriers target the osteoporotic microenvironment and regulate OB-OC cross-talk, thereby facilitating intervertebral fusion in osteoporotic rats. Results demonstrate that mRNA@LNP exhibits uniform particle size and high transfection efficiency, while GelMA hydrogel microspheres possess excellent biocompatibility and MMP responsiveness, providing favorable cell survival space and controllable release of mRNA@LNP. The released LNP upregulates USP26 protein expression, effectively promoting osteogenesis while suppressing osteoclast formation. In vivo experiments show that injecting BHRC into the defect site of intervertebral discs in osteoporotic rats significantly promotes tail vertebrae fusion by responding to the microenvironment and regulating cell-to-cell cross-talk. Thus, the BHRC holds great potential in regulating osteoporotic homeostasis, particularly in challenging bone defects such as intervertebral fusion in osteoporotic environments.

Surface- modified preparation of CuFe2O4/sodium alginate hydrogel catalysts for the long-lasting degradation of tetracycline

Copper ferrate spinel (CuFe2O4) catalysts are widely used in advanced oxidation processes for environmental wastewater treatment due to their advantages of low price, mild reaction conditions and ease of operation. Therefore, it is crucial to investigate the factors influence the surface properties of catalysts on their catalytic activity. In this research, the effects of process parameters on the surface properties of CuFe2O4 were investigated, and the relationship between the surface properties of CuFe2O4 and its catalytic activity was clarified. The optimised CuFe2O4 exhibited 92.4 % degradation of tetracycline (TC) and 55 % mineralisation of total organic carbon (TOC) within 30 min, the pseudo-first-order reaction rate was 0.0315 min−1, which was 2.2 times higher than that of the unoptimised CuFe2O4. The mechanism of action for enhancing catalyst performance and the degradation mechanism of tetracycline were clarified through a combination of characterization analysis. To further solve the problems of secondary pollution caused by ion leaching and the difficulty of practical application of powder catalysts, novel hydrogel microspheres composed of sodium alginate and CuFe2O4 were prepared by using the property of metal ions and sodium alginate to form a solid gel (SA/Ort-6). SA/Ort-6 was characterized by low ion leaching, excellent performance and excellent stability. The mass ratio of catalyst to treated water could be up to 1:22,000, and the mass ratio of catalyst to treated water can reach up to 1:22000, the removal rate of TOC was stable above 35 %. This study provides valuable insights into the relationship between surface properties and catalytic performance of CuFe2O4, offers a new approach to effectively solve leaching of metal ions, and opens up a new avenue for practical application of powder catalysts.

Microfluidic Engineering of Addressable Multicompartmental Microspheres for Multicellular Systems.

With the advantages of high-throughput manufacturing and customizability, on-microsphere construction of in vitro multicellular analytical systems has garnered significant attention. However, achieving a precise, biocompatible cell arrangement and spatial signal analysis in hydrogel microspheres remains challenging. In this work, a microfluidic method is reported for the biocompatible generation of addressable supersegmented multicompartmental microspheres. Additionally, these microspheres are developed as novel label-free multicellular systems. In the microfluidic approach, controllable microfluidics is used to finely tune the internal microstructure of the microspheres, and the gas ejector ensures the biocompatibility of the preparation process. As a proof of concept, six- and twenty-compartment microspheres were obtained without the addition of any biohazardous reagents. For microsphere decoding, the visualization of two basic compartments can provide clues for identifying label-free cells due to the structural regularity of the microspheres. Finally, by encapsulating cells of different types, these microspheres as multicellular systems were successfully used for cell coculture and drug testing. These biocompatible, scalable, and analyzable microspheres will open up new prospects for biomedical analysis.

Exploration of Curvature and Stiffness Dual-Regulated Breast Cancer Cell Motility by a Motor-Clutch Model and Cell Traction Force Characterization.

The migration of breast cancer cells is the main cause of death and significantly regulated by physical factors of the extracellular matrix (ECM). To be specific, the curvature and stiffness of the ECM were discovered to effectively guide cell migration in velocity and direction. However, it is not clear what the extent of effect is when these dual-physical factors regulate cell migration. Moreover, the mechanobiology mechanism of breast cancer cell migration in the molecular level and analysis of cell traction force (CTF) are also important, but there is a lack of systematic investigation. Therefore, we employed a microfluidic platform to construct hydrogel microspheres with an independently adjustable curvature and stiffness as a three-dimensional substrate for breast cancer cell migration. We found that the cell migration velocity was negatively correlated to curvature and positively correlated to stiffness. In addition, curvature was investigated to influence the focal adhesion expression as well as the assignment of F-actin at the molecular level. Further, with the help of a motor-clutch mathematical model and hydrogel microsphere stress sensors, it was concluded that cells perceived physical factors (curvature and stiffness) to cause changes in CTF, which ultimately regulated cell motility. In summary, we employed a theoretical model (motor-clutch) and experimental strategy (stress sensors) to understand the mechanism of curvature and stiffness regulating breast cancer cell motility. These results provide evidence of force driven cancer cell migration by ECM physical factors and explain the mechanism from the perspective of mechanobiology.

Preparation and Characterization of Responsive Cellulose-Based Gel Microspheres for Enhanced Oil Recovery.

As an important means to enhance oil recovery, ternary composite flooding (ASP flooding for short) technology has achieved remarkable results in Daqing Oilfield. Alkalis, surfactants and polymers are mixed in specific proportions and injected into the reservoir to give full play to the synergistic effect of each component, which can effectively enhance the fluidity of crude oil and greatly improve the oil recovery. At present, the technology for further improving oil recovery after ternary composite flooding is not mature and belongs to the stage of technical exploration. The presence of alkaline substances significantly alters the reservoir's physical properties and causes considerable corrosion to the equipment used in its development. This is detrimental to both the environment and production. Therefore, it is necessary to develop green displacement control agents. In the reservoir environment post-ASP flooding, 2-(methylamino)ethyl methacrylate and glycidyl methacrylate were chosen as monomers to synthesize a polymer responsive to alkali, and then grafted with cellulose nanocrystals to form microspheres of alkali-resistant swelling hydrogel. Cellulose nanocrystals (CNCs) modified with functional groups and other materials were utilized to fabricate hydrogel microspheres. The product's structure was characterized and validated using Fourier transform infrared spectroscopy and X-ray diffraction. The infrared spectrum revealed characteristic absorption peaks of CNCs at 1165 cm-1, 1577 cm-1, 1746 cm-1, and 3342 cm-1. The diffraction spectrum corroborated the findings of the infrared analysis, indicating that the functional modification occurred on the CNC surface. After evaluating the swelling and erosion resistance of the hydrogel microspheres under various alkaline conditions, the optimal particle size for compatibility with the target reservoir was determined to be 6 μm. The potential of cellulose-based gel microspheres to enhance oil recovery was assessed through the evaluation of Zeta potential and laboratory physical simulations of oil displacement. The study revealed that the absolute value of the Zeta potential for gel microspheres exceeds 30 in an alkaline environment with pH values ranging from 7 to 14, exhibiting a phenomenon where stronger alkalinity correlates with a greater absolute value of Zeta potential. The dispersion stability spans from good to excellent. The laboratory oil displacement simulation experiment was conducted using a cellulose-based gel microsphere system following weak alkali ASP flooding within the pH value range from 7 to 10. The experimental interventions yielded recovery rates of 2.98%, 3.20%, 3.31%, and 3.38%, respectively. The study indicates that cellulose-based gel microspheres exhibit good adaptability in alkaline reservoirs. This research offers a theoretical foundation and experimental approaches to enhance oil recovery techniques post-ASP flooding.

Hydrogel microspheres for stem cell recruitment and induction of directed differentiation in osteoarthritis therapy

The utilization of stem cell biotechnology for osteoarthritis (OA) treatment is hindered by high operational costs, difficulties in maintaining stem cell viability, and limited efficacy of unguided stem cell differentiation. Magnesium ions (Mg2+), crucial for tissue regeneration and repair, hold significant potential in OA treatment. However, further investigation is required to elucidate the precise mechanisms of Mg2+ in OA treatment. Here, we investigated the optimal concentration of Mg2+ to induce directed differentiation of stem cells and synthesized bioactive hydrogel microspheres (MDGM-Ps) capable of precisely releasing this concentration using microfluidic technology. Synthesized via polymerization of dopamine methacrylamide (DMA) and methacrylated gelatin (GelMA), these microspheres could chelate Mg2+ and incorporate platelet-derived growth factor-BB into the hydrogel matrix for sustained release. In vitro, MDGM-Ps showed excellent biocompatibility and promoted stem cell recruitment. Importantly, Mg2+ released from MDGM-Ps could guide stem cell differentiation through the PI3K-AKT pathway. Moreover, in vivo experiments suggested that MDGM-Ps could maintain the cartilage matrix and mitigate the progression of OA. In summary, MDGM-Ps not only harnessed the advantages of stem cell therapy, but also expanded the therapeutic applications of metal ions, thereby presenting a promising candidate for OA therapy.

Comparing embolic particles for prostatic artery embolization to treat lower urinary tract symptoms in patients with benign prostatic hyperplasia.

Compare the safety and efficacy of polyvinyl alcohol particles (PVA) versus trisacryl gelatin microspheres (Embospheres) versus hydrogel microspheres coated with polyzene-F (Embozenes) for prostatic artery embolization (PAE) to treat patients with benign prostatic hyperplasia (BPH). A single-center prospective cohort study from 2019 to 2023, including patients with international prostate symptom score (IPSS) ≥ 15 and/or quality of life score (QoL) ≥ 4. Allocation to embolic agents was performed chronologically: 100-300 µm PVA (n = 53), followed by 300-500 µm Embospheres (n = 50), and finally, 400 µm Embozenes (n = 50). All patients were evaluated at baseline and at 1 and 6 months after PAE with IPSS/QoL; peak urinary flow rate, post-void residual volume, and prostate volume with ultrasound and prostate-specific antigen. Adverse events and the need for prostatic re-interventions were assessed. There were no significant baseline differences between the three groups except for patient age (62.5 years PVA; 66.1 years Embospheres and 66.6 years Embozenes; p = 0.019). There were no major adverse events and no differences between groups regarding minor adverse events. All outcome measures improved significantly from baseline, with no significant differences between groups. Mean ± standard deviation IPSS/QoL improvement at 6 months: -10.7 ± 7.9/-2.2 ± 1.7 PVA; -10.4 ± 7.3/-2.0 ± 1.5 Embospheres; -10.4 ± 7.0/-2.2 ± 1.6 Embozenes (p = 0.987). Re-intervention rates after 6 months: 9% (n = 5/53) PVA; 14% (n = 7/50) Embospheres; 8% (n = 4/50) Embozenes (p = 0.591). PAE with PVA particles, Embospheres, and Embozenes is equally safe and effective in treating BPH-related lower urinary tract symptoms. This is the first prospective study showing equivalence between the most frequently used embolic agents for prostatic artery embolization. Different particles can be used interchangeably for prostatic artery embolization. The improvements in measured metrics were the same between groups, with no differences in adverse events. The need for prostatic medication and re-intervention rates were the same at 1 and 6 months after embolization.

Efficient removal of direct dyes by SA-Er biopolymer gel spheres: Equilibrium isotherms, kinetics and regeneration performance study

Biomass-based adsorbent materials are characterized by their low cost, environmental friendliness, and ease of design and operation. In this study, biomass-based hydrogel microspheres erbium alginate (SA/Er) with high stability and adsorption properties were prepared by a one-step synthesis method. The prepared materials were characterized and analyzed by SEM-EDS, XRD, TGA, FT-IR, UV–Vis, BET-BJH and XPS, and the adsorption performance of SA/Er was investigated for high concentrations of azo dyes in water. The results showed that the adsorption performance of SA/Er on the azo dyes of direct violet N (DV 1) and direct dark green NB (DG 6) with concentrations of 850 mg/L and 1100 mg/L under the optimal conditions was very high, and the adsorption amount could be up to 692 mg/g and 864 mg/g, respectively. The adsorption process was in accordance with the quasi-secondary kinetic model, which was accomplished by physical and chemical adsorption; the Langmuir isothermal model was able to better respond to the adsorption equilibrium, and the adsorption was dominated by the adsorption of surface monolayers; after seven desorption cycles, the removal of both azo dyes by the adsorbent material could reach >79.7 %. Combined with the results of FT-IR, UV–vis and XPS analysis before and after the adsorption, it was revealed that the adsorption of SA/Er with the dye molecules mainly consisted of hydrogen bonding, electrostatic adsorption and surface complexation, which resulted in the significant adsorption effect on the two azo dyes, and the above results can provide a reference for the treatment of dye wastewater.

Homogeneously complexed alginate-chitosan hydrogel microspheres for the viability enhancement of entrapped hepatocytes

The future deployment of biomedicine fields will require a new generation of biodegradable, biocompatible, and non-toxic hydrogels. Alginate and chitosan, naturally occurring polymers, have gained significant interest for hydrogel applications. However, integrating chitosan within alginate-based hydrogels to form microspheres with homogeneous distribution and a tailored surface charge remains challenging. Herein, we report the design and fabrication of homogeneously complexed alginate-chitosan hydrogel microspheres, demonstrating their ability to enhance the viability and liver-specific functionalities of entrapped hepatocytes. By exploring and optimizing the pH and ratio of alginate and chitosan solutions, we achieved well-controlled physicochemical properties, including the degree of sphericity, hydrophilicity, charge property, and surface roughness. Unlike traditional alginate-based hydrogel microspheres, hepatocytes entrapped in homogeneous alginate-chitosan microspheres displayed enhanced viability and liver-specific functions, including albumin secretion, urea synthesis, and cytochrome P-450 enzymatic activity. This work illustrates a potential pathway for manufacturing functionalized microspheres with tunable mechanical properties and functionalities based on biocompatible alginate and chitosan for hepatocyte applications.

Nanoclay Hydrogel Microspheres with a Sandwich‐Like Structure for Complex Tissue Infection Treatment

Nanoclay Hydrogel Microspheres with a Sandwich‐Like Structure for Complex Tissue Infection Treatment

Synthesis of Gelatin Methacryloyl Analogs and Their Use in the Fabrication of pH-Responsive Microspheres.

pH-responsive hydrogels have numerous applications in tissue engineering, drug delivery systems, and diagnostics. Gelatin methacryloyl (GelMA) is a biocompatible, semi-synthetic polymer prepared from gelatin. When combined with aqueous solvents, GelMA forms hydrogels that have extensive applications in biomedical engineering. GelMA can be produced with different degrees of methacryloyl substitution; however, the synthesis of this polymer has not been tuned towards producing selectively modified materials for single-component pH-responsive hydrogels. In this work, we have explored two different synthetic routes targeting different gelatin functional groups (amine, hydroxyl, and/or carboxyl) to produce two GelMA analogs: gelatin A methacryloyl glycerylester (polymer A) and gelatin B methacrylamide (polymer B). Polymers A and B were used to fabricate pH-responsive hydrogel microspheres in a flow-focusing microfluidic device. At neutral pH, polymer A and B microspheres displayed an average diameter of ~40 µm. At pH 6, microspheres from polymer A showed a swelling ratio of 159.1 ± 11.5%, while at pH 10, a 288.6 ± 11.6% swelling ratio was recorded for polymer B particles.