Search Results (141)

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

Spinal cord injuries (SCIs) present a major clinical challenge, often resulting in permanent loss of function and limited treatment options. Traditional approaches, including surgery, drugs, and rehabilitation, have had modest success in restoring neural connectivity due to the complex pathophysiology of SCI. In recent years, bioactive hydrogels have gained attention as a versatile platform for neural repair. Their ability to mimic the extracellular matrix, deliver therapeutic agents, and support cell survival makes them promising tools in regenerative medicine. This narrative review highlights the latest advances in hydrogel-based therapies for SCI, with a focus on innovations such as self-healing, conductive, and anti-inflammatory hydrogels. We also explore hybrid approaches that integrate nanomaterials, stem cells, and bioelectronics to address both primary and secondary injury mechanisms. While various hydrogel systems have been investigated, we place particular emphasis on gelatin-based hydrogels, especially gelatin methacryloyl (GelMA), due to their emerging clinical relevance. GelMA stands out for its bioactivity, tunable mechanics, and compatibility with 3D printing, making it a strong candidate for personalized therapies and scalable production. Unlike previous reviews that broadly summarize hydrogel use, this work specifically contextualizes gelatin-based platforms within the wider landscape of SCI repair, underscoring their translational potential. We also address current challenges, such as immune response, long-term integration, and clinical validation, and suggest future directions for bridging the gap from bench to bedside. Full article

Glioblastoma (GBM, isocitrate dehydrogenase wild-type) is the most common primary malignant brain tumor in adults and is associated with a severely low survival rate. Treatments offer mere palliation and are ineffective, due, in part, to a lack of understanding of the intricate mechanisms underlying the disease, including the contribution of the tumor microenvironment (TME). Current GBM models continue to face challenges as they lack the critical components and properties required. To address this limitation, we developed innovative and practical three-dimensional (3D) GBM models with structural and mechanical biomimicry and tunability. These models allowed for more accurate emulation of the extracellular matrix (ECM) and vasculature characteristics of the native GBM TME. Additionally, 3D bioprinting was utilized to integrate these complexities, employing a hydrogel composite to mimic the native environment that is known to contribute to tumor cell growth. First, we examined the changes in physical properties that resulted from adjoining hydrogels at diverse concentrations using Fourier-Transform Infrared Spectroscopy (FTIR), compression testing, scanning electron microscopy (SEM), rheological analysis, and degradation analysis. Subsequently, we refined and optimized the embedded bioprinting processes. The resulting 3D GBM models were structurally reliable and reproducible, featuring integrated inner channels and possessing tunable properties to emulate the characteristics of the GBM ECM. Biocompatibility testing was performed via live/dead and AlamarBlue analyses using GBM cells (both commercial cell lines and patient-derived cell lines) encapsulated in the constructs, along with immunohistochemistry staining to understand how ECM properties altered the functions of GBM cells. The observed behavior of GBM cells indicated greater functionality in softer matrices, while the incorporation of hyaluronic acid (HA) into the gelatin methacryloyl (gelMA) matrix enhanced its biomimicry of the native GBM TME. The findings underscore the critical role of TME components, particularly ECM properties, in influencing GBM survival, proliferation, and molecular expression, laying the groundwork for further mechanistic studies. Additionally, the outcomes validate the potential of leveraging 3D bioprinting for GBM modeling, providing a fully controllable environment to explore specific pathways and therapeutic targets that are challenging to study in conventional model systems. Full article

Regenerative Endodontic Therapies (RETs) offer transformative potential by leveraging polymer-based scaffolds, stem cells, and growth factors to regenerate damaged dental pulp tissue, thereby restoring tooth vitality and prolonging tooth function. While conventional treatments focus on infection control, they often compromise the structural and biological integrity of the tooth. RETs, in contrast, aim to restore the natural function of the pulp–dentin complex by promoting cellular regeneration and immune modulation. In this context, biodegradable polymers—such as collagen, gelatin methacryloyl (GelMA), and synthetic alternatives—serve as scaffolding materials that mimic the extracellular matrix, support cell attachment and proliferation, and enable localized delivery of bioactive factors. Together, the tissue engineering triad—polymer-based scaffolds, stem cells, and signaling molecules—facilitates root development, apical closure, and increased fracture resistance. Recent innovations in polymeric scaffold design, including injectable hydrogels and 3D bioprinting technologies, have enhanced clinical translation by enabling minimally invasive and patient-specific RETs. Despite progress, challenges such as immune compatibility, scaffold degradation rates, and the standardization of clinical protocols remain. RETs, thus, represent a paradigm shift in dental care, aligning with the body’s intrinsic healing capacity and offering improved long-term outcomes for patients. Full article

We herein demonstrate the utility of gelatin methacryloyl (GelMA)/poly(ethylene glycol) diacrylate (PEGDA)–cerium oxide (CeO₂) hydrogel inks for manufacturing hydrogel scaffolds with antimicrobial efficacy by vat photopolymerization. For uniform blending with GelMA/PEGDA hydrogels, CeO₂ nanoparticles with a round shape were synthesized by the precipitation method coupled with calculation at 600 °C. In addition, they had highly crystalline phases and the desired chemical structures (oxidation states of Ce³⁺ and Ce⁴⁺) required for outstanding antimicrobial efficacy. A range of GelMA/PEGDA-CeO₂ hydrogel scaffolds with different CeO₂ contents (0% w/v, 0.1% w/v, 0.5% w/v, 1% w/v, and 5% w/v with respect to distilled water content) were manufactured. The photopolymerization behavior, mechanical properties, and biological properties (swelling and biodegradation behaviors) of hydrogel scaffolds were characterized to optimize the CeO₂ content. GelMA/PEGDA-CeO₂ hydrogel scaffolds produced with the highest CeO₂ content (5% w/v) showed reasonable mechanical properties (compressive strength = 0.56 ± 0.09 MPa and compressive modulus = 0.19 ± 0.03 MPa), a high swelling ratio (1063.3 ± 10.9%), and the desired biodegradation rate (remaining weight after 28 days = 39.6 ± 2.3%). Furthermore, they showed outstanding antimicrobial efficacy (the number of colony-forming units = 76 ± 44.6 (×10³)). In addition, macroporous GelMA/PEGDA-CeO₂ hydrogel scaffolds with tightly controlled porous structures could be manufactured by vat photopolymerization. Full article

The side effects associated with the chemotherapy of triple-negative breast cancer (TNBC), such as nucleotide-binding oligomerization domain (NOD)-like receptor family (NLR), pyrin domain containing 3 (NLRP3) inflammasome activity, are responsible for the treatment failure and high mortality rates. Therefore, advanced delivery systems have been developed to improve the transport and targeted administration of anti-tumor agents at the tumor sites using tissue engineering approaches. Implantable delivery systems based on biodegradable polymers are an effective alternative due high biocompatibility, porosity, and mechanical strength. Moreover, the use of paclitaxel (PTX)-cyclodextrin complexes increases the solubility and permeability of PTX, enhancing the bioavailability and efficacy of the drug. All of these properties contribute to the efficient encapsulation and controlled release of drugs, preventing the damage of healthy tissues. In the current study, we detailed the synthesis process and evaluation of 3D scaffolds based on gelatin functionalized with methacryloyl groups (GelMA) and pectin loaded with PTX–cyclodextrin inclusion complexes on TNBC pathogenesis in vitro and in vivo. Bio-physio-chemical analysis of the proposed scaffolds revealed favorable mechanical and biological properties for the cellular component. To improve the drug solubility, a host–guest interaction was performed by the complexation of PTX with a cyclodextrin derivative prior to scaffold synthesis. The presence of PTX suppressed the growth of breast tumor cells and promoted caspase-1 activity, the release of interleukin (IL)-1β, and the production of reactive oxygen species (ROS), conditioning the expression levels of the genes and proteins associated with breast tumorigenesis and NLRP3 inflammasome. The in vivo experiments suggested the activation of pyroptosis tumor cell death, confirming the in vitro experiments. In conclusion, the bio-mechanical properties of the GelMA and pectin-based scaffolds as well as the addition of the PTX–cyclodextrin complexes allow for the targeted and efficient delivery of PTX, suppressing the viability of the breast tumor cells via pyroptosis cell death initiation. Full article

Objectives: Treatment of osteochondral defects is hindered by several challenges, including the failure of traditional scaffolds with a predefined cylindrical or cuboid shape to comprehensively match the natural osteochondral tissue. Herein, we employed reverse modeling and three-dimensional (3D) printing technologies to prepare subchondral bone and cartilage. Methods: The osteochondral scaffold was prepared by bonding the subchondral bone and cartilage layers, and the curvature distribution and biomechanical behavior were compared with those of the native tissue. Biocompatibility and osteochondral regeneration performance were further evaluated using cell adhesion and proliferation assays, as well as animal osteochondral defect repair tests. Results: We found that increasing the printing temperature or decreasing the layer height improved the dimensional accuracy of printed subchondral bones, whereas increasing the exposure time or decreasing the layer height enhanced the dimensional accuracy of the printed cartilage. Biomimetic scaffolds exhibited curvature distribution and biomechanical behavior more similar to native tissues than traditional cylindrical scaffolds. Incorporating gelatin methacryloyl into poly (ethylene glycol) diacrylate markedly improved the biocompatibility, and correspondingly prepared osteochondral scaffolds had better osteochondral regeneration ability than the traditional scaffolds. Conclusions: Osteochondral scaffolds exhibiting biomimetic morphology and an internal structure could be prepared based on reverse modeling and 3D printing, facilitating personalized osteochondral injury treatment. Full article

Tumor whole-cell vaccines are designed to introduce a wide range of tumor-associated antigens into the body to counteract the immunosuppression caused by tumors. In cases of lymphoma of which the specific antigen is not yet determined, the tumor whole-cell vaccine offers distinct advantages. However, there is still a lack of research on an effective preparation method for the lymphoma whole-cell vaccine. To solve this challenge, we prepared a whole-cell vaccine derived from non-Hodgkin B-cell lymphoma (A20) via the photothermal effect mediated by Prussian blue nanoparticles (PBNPs). The immune activation effect of this vaccine against lymphoma was verified at the cellular level. The PBNPs-treated A20 cells underwent immunogenic cell death (ICD), causing the loss of their ability to form tumors while retaining their ability to trigger an immune response. A20 cells that experienced ICD were further ultrasonically crushed to prepare the A20 whole-cell vaccine with exposed antigens and enhanced immunogenicity. The A20 whole-cell vaccine was able to activate the dendritic cells (DCs) to present antigens to T cells and trigger specific immune responses against lymphoma. Whole-cell vaccines are primarily administered through direct injection, a method that often results in low delivery efficiency and poor patient compliance. Comparatively, the microneedle patch system provides intradermal delivery, offering enhanced lymphatic absorption and improved patient adherence due to its minimally invasive approach. Thus, we developed a porous microneedle patch system for whole-cell vaccine delivery using Gelatin Methacryloyl (GelMA) hydrogel and n-arm-poly(lactic-co-glycolic acid) (n-arm-PLGA). This whole-cell vaccine combined with porous gel microneedle patch delivery system has the potential to become a simple immunotherapy method with controllable production and represents a promising new direction for the treatment of lymphoma. Full article

Background: Wound management is a critical component of clinical practice. Promoting timely healing of wounds is essential for patient recovery. Traditional treatments have limited efficacy due to prolonged healing times, excessive inflammatory responses, and susceptibility to infection. Methods: In this research, we created an injectable hydrogel wound dressing formulated from gelatin methacryloyl (GelMA) that encapsulates quercetin-loaded zeolitic imidazolate framework-8 (Qu@ZIF-8) nanoparticles. Next, its ability to promote skin wound healing was validated through in vitro experiments and animal studies. Results: Research conducted both in vitro and in vivo indicated that this hydrogel dressing effectively mitigates inflammation, inhibits bacterial growth, and promotes angiogenesis and collagen synthesis, thus facilitating a safe and efficient healing process for wounds. Conclusions: This cutting-edge scaffold system provides a novel strategy for wound repair and demonstrates significant potential for clinical applications. Full article

To date, severe bone defects remain a significant challenge to the quality of life. All clinically used bone grafts have their limitations. Bone tissue engineering offers the promise of novel bone graft substitutes. Various biomaterial scaffolds are fabricated by mimicking the natural bone structure, mechanical properties, and biological properties. Among them, gelatin methacryloyl (GelMA), as a modified natural biomaterial, possesses a controllable chemical network, high cellular stability and viability, good biocompatibility and degradability, and holds the prospect of a wide range of applications. However, because they are hindered by their mechanical properties, degradation rate, and lack of osteogenic activity, GelMA hydrogels need to be combined with other materials to improve the properties of the composites and endow them with the ability for osteogenesis, vascularization, and neurogenesis. In this paper, we systematically review and summarize the research progress of GelMA composite hydrogel scaffolds in the field of bone defect repair, and discuss ways to improve the properties, which will provide ideas for the design and application of bionic bone substitutes. Full article

This study investigates the synthesis, characterization, and antimicrobial properties of hydrogels synthesized through the UV-pulsed laser photopolymerization of a polymer–photoinitiator–chlorpromazine mixture. Chlorpromazine was used for its known enhanced antimicrobial properties when exposed to UV laser radiation. The hydrogel was formed from a mixture containing 0.05% Irgacure 2959, 10% gelatin methacryloyl, and various concentrations of chlorpromazine (1, 2, and 4 mg/mL). Laser-induced fluorescence spectroscopy was employed to monitor the photoinduced changes of chlorpromazine and Irgacure 2959 during hydrogel formation, providing insight into the photodegradation dynamics. FTIR spectroscopy confirmed the incorporation of irradiated chlorpromazine within the hydrogel matrix, while the release profiles of chlorpromazine showed sustained release only in hydrogels containing 1 mg/mL of CPZ. The hydrogel showed significant antimicrobial activity against MRSA bacteria when compared to that of penicillin. These findings highlight the potential of CPZ loaded during the photopolymerization process into hydrogels as effective antimicrobial agents with sustained release properties, making them suitable for combating resistant bacterial strains. Full article

Articular cartilage degeneration poses a significant public health challenge; techniques such as 3D bioprinting are being explored for its regeneration in vitro. Gelatin-based hydrogels represent one of the most promising biopolymers used in cartilage tissue engineering, especially for its collagen composition and tunable mechanical properties. However, there are no standard protocols that define process parameters such as the crosslinking method to apply. To this aim, a reproducible study was conducted for exploring the influence of different crosslinking methods on 3D bioprinted gelatin structures. This study assessed mechanical properties and cell viability in relation to various crosslinking techniques, revealing promising results particularly for dual (photo + ionic) crosslinking methods, which achieved high cell viability and tunable stiffness. These findings offer new insights into the effects of crosslinking methods on 3D bioprinted gelatin for cartilage applications. For example, ionic and photo-crosslinking methods provide softer materials, with photo-crosslinking supporting cell stretching and diffusion, while ionic crosslinking preserves a spherical stem cell morphology. On the other hand, dual crosslinking provides a stiffer, optimized solution for creating stable cartilage-like constructs. The results of this study offer a new perspective on the standardization of gelatin for cartilage bioprinting, bridging the gap between research and clinical applications. Full article

This study investigated gelatin methacryloyl (GelMA) and polycaprolactone (PCL) blend scaffolds incorporating cerium oxide (CeO) nanoparticles at concentrations of 0%, 5%, and 10% w/w via electrospinning for periodontal tissue engineering. The impact of photocrosslinking on these scaffolds was evaluated by comparing crosslinked (C) and non-crosslinked (NC) versions. Methods included Fourier transform infrared spectroscopy (FTIR) for chemical analysis, scanning electron microscopy (SEM) for fiber morphology/diameters, and assessments of swelling capacity, degradation profile, and biomechanical properties. Biological evaluations with alveolar bone-derived mesenchymal stem cells (aBMSCs) and human gingival fibroblasts (HGFs) encompassed tests for cell viability, mineralized nodule deposition (MND), and collagen production (CP). Statistical analysis was performed using Kruskal–Wallis or ANOVA/post-hoc tests (α = 5%). Results indicate that C scaffolds had larger fiber diameters (~250 nm) compared with NC scaffolds (~150 nm). NC scaffolds exhibited higher swelling capacities than C scaffolds, while both types demonstrated significant mass loss (~50%) after 60 days (p < 0.05). C scaffolds containing CeO showed increased Young’s modulus and tensile strength than NC scaffolds. Cells cultured on C scaffolds with 10% CeO exhibited significantly higher metabolic activity (>400%, p < 0.05) after 7 days among all groups. Furthermore, CeO-containing scaffolds promoted enhanced MND by aBMSCs (>120%, p < 0.05) and increased CP in 5% CeO scaffolds for both variants (>180%, p < 0.05). These findings underscore the promising biomechanical properties, biodegradability, cytocompatibility, and enhanced tissue regenerative potential of CeO-loaded GelMA/PCL scaffolds for periodontal applications. Full article

Ischemia/reperfusion (I/R) injury following myocardial infarction is a major cause of cardiomyocyte death and impaired cardiac function. Although clinical data show that metformin is effective in repairing cardiac I/R injury, its efficacy is hindered by non-specific targeting during administration, a short half-life, frequent dosing, and potential adverse effects on the liver and kidneys. In recent years, injectable hydrogels have shown substantial potential in overcoming drug delivery challenges and treating myocardial infarction. To this end, we developed a natural polymer hydrogel system comprising methacryloylated chitosan and methacryloylated gelatin modified with polyaniline conductive derivatives. In vitro studies demonstrated that the optimized hydrogel exhibited excellent injectability, biocompatibility, biodegradability, suitable mechanical properties, and electrical conductivity. Incorporating metformin into this hydrogel significantly extended the administration cycle, mitigated mitochondrial damage, decreased abnormal ROS production, and enhanced cardiomyocyte function. Animal experiments indicated that the metformin/hydrogel system reduced arrhythmia incidence, infarct size, and improved cardiac mitochondrial and overall cardiac function, promoting myocardial repair in I/R injury. Overall, the metformin-loaded conductive hydrogel system effectively mitigates mitochondrial oxidative damage and improves cardiomyocyte function, thereby offering a theoretical foundation for the potential application of metformin in cardioprotection. Full article

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. Full article