Search Results (293)

In recent years, significant progress has been made in breast reconstructive surgery, particularly with the use of three-dimensional (3D) disassemblable scaffolds. Reconstructive plastic surgery aimed at restoring the shape and size of the mammary gland offers medical, psychological, and social benefits. Using autologous tissues allows surgeons to recreate the appearance of the mammary gland and achieve tactile sensations similar to those of a healthy organ while minimizing the risks associated with implants; 3D disassemblable scaffolds are a promising solution that overcomes the limitations of traditional methods. These constructs offer the potential for patient-specific anatomical adaptation and can provide both temporary and long-term structural support for regenerating tissues. One of the most promising approaches in post-mastectomy breast reconstruction involves the use of autologous cellular and tissue components integrated into either synthetic scaffolds—such as polylactic acid (PLA), polyglycolic acid (PGA), poly(lactic-co-glycolic acid) (PLGA), and polycaprolactone (PCL)—or naturally derived biopolymer-based matrices, including alginate, chitosan, hyaluronic acid derivatives, collagen, fibrin, gelatin, and silk fibroin. In this context, two complementary research directions are gaining increasing significance: (1) the development of novel hybrid biomaterials that combine the favorable characteristics of both synthetic and natural polymers while maintaining biocompatibility and biodegradability; and (2) the advancement of three-dimensional bioprinting technologies for the fabrication of patient-specific scaffolds capable of incorporating cellular therapies. Such therapies typically involve mesenchymal stromal cells (MSCs) and bioactive signaling molecules, such as growth factors, aimed at promoting angiogenesis, cellular proliferation, and lineage-specific differentiation. In our review, we analyze existing developments in this area and discuss the advantages and disadvantages of 3D disassemblable scaffolds for mammary gland reconstruction, as well as prospects for their further research and clinical use. Full article

The cryopreservation of three-dimensional (3D) biofabricated constructs is a key enabler for their clinical application in regenerative medicine. Unlike two-dimensional (2D) cultures, 3D systems such as encapsulated cell spheroids, molded hydrogels, and bioprinted tissues present specific challenges related to cryoprotectant (CPA) diffusion, thermal gradients, and ice formation during freezing and thawing. This review examines the current strategies for preserving 3D constructs, focusing on the role of biomaterials as cryoprotective matrices. Natural polymers (e.g., hyaluronic acid, alginate, chitosan), protein-based scaffolds (e.g., silk fibroin, sericin), and synthetic polymers (e.g., polyethylene glycol (PEG), polyvinyl alcohol (PVA)) are evaluated for their ability to support cell viability, structural integrity, and CPA transport. Special attention is given to cryoprotectant systems that are free of dimethyl sulfoxide (DMSO), and to the influence of hydrogel architecture on freezing outcomes. We have compared the efficacy and limitations of slow freezing and vitrification protocols and review innovative approaches such as temperature-controlled cryoprinting, nano-warming, and hybrid scaffolds with improved cryocompatibility. Additionally, we address the regulatory and manufacturing challenges associated with developing Good Manufacturing Practice (GMP)-compliant cryopreservation workflows. Overall, this review provides an integrated perspective on material-based strategies for 3D cryopreservation and identifies future directions to enable the long-term storage and clinical translation of engineered tissues. Full article

Three-dimensional (3D) spheroid models have revolutionized in vitro cancer research by offering more physiologically relevant alternatives to traditional two-dimensional (2D) cultures. A systematic search identifies English-language studies on patient-derived cancer spheroids for drug screening, using defined inclusion and exclusion criteria, with data extracted on cancer type, culture methods, spheroid characteristics, and therapeutic responses. This manuscript evaluates the methods for spheroid formation and the cellular sources used, highlighting the diverse applications and preferences in this field. The five most investigated cancer origins for spheroid seeding are breast, colon, lung, ovary, and brain cancers, reflecting their clinical importance and research focus. Among seeding methodologies, forced-floating and scaffold-based methods predominate, demonstrating reliability and versatility in spheroid generation. Other techniques, including microfluidics, bioprinting, hanging drop, and suspension culture also play significant roles, each with distinct advantages and limitations. This review underscores the increasing use of spheroid models and the need for standardization in methodologies to enhance the reproducibility and translational potential in cancer research. Full article

Three-dimensional (3D) bioprinting has emerged as a highly promising technology within the realms of tissue engineering and regenerative medicine. The assessment of printability is essential for ensuring the quality of bio-printed constructs and the functionality of the resultant tissues. Polymer materials, extensively utilized as bioink materials in extrusion-based bioprinting, have garnered significant attention from researchers due to the critical need for evaluating and optimizing their printability. Machine learning, a powerful data-driven technology, has attracted increasing attention in the evaluation and optimization of 3D bioprinting printability in recent years. This review provides an overview of the application of machine learning in the printability research of polymers for 3D bioprinting, encompassing the analysis of factors influencing printability (such as material and printing parameters), the development of predictive models, and the formulation of optimization strategies. Additionally, the review briefly explores the utilization of machine learning in predicting cell viability, evaluates the advanced nature and developmental potential of machine learning in 3D bioprinting, and examines the current challenges and future trends. Full article

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. The tumor microenvironment plays a crucial role in multiple myeloma pathogenesis, progression, and drug resistance. Traditional two-dimensional cell culture models have been instrumental in multiple myeloma research. However, they fail to recapitulate the complex in vivo bone marrow microenvironment, leading to limited predictive value for clinical outcomes. Three-dimensional cell culture models emerged as more physiologically relevant systems, offering enhanced insights into multiple myeloma biology. Scaffold-based systems (e.g., hydrogels, collagen, and Matrigel), scaffold-free spheroids, and bioprinted models have been developed to simulate the bone marrow microenvironment, incorporating key components like mesenchymal stromal cells, osteoblasts, endothelial cells, and immune cells. These models enable the functional assessment of cell adhesion-mediated drug resistance, cytokine signaling networks, and hypoxia-induced adaptations, which are often lost in 2D cultures. Moreover, 3D platforms demonstrated improved predictive value in preclinical drug screening, facilitating the evaluation of novel agents and combination therapies in a setting that better mimics the in vivo tumor context. Hence, 3D cultures represent a pivotal step toward bridging the gap between basic myeloma research and translational applications, supporting the development of more effective and patient-specific therapies. Full article

In the last years, considerable innovation has been made regarding bioprinting, particularly in the development of cell-loaded hydrogels. The specific properties of the bioinks are crucial for printing an adequate cell-laden hydrogel structure. In this research, we aimed to develop a 3D-printable hydrogel using a natural biocompatible polymer. The process is based on the use of sodium alginate subjected to calcium ion cross-linking for immediate stiffness after printing. Using the Cellink INKREDIBLE+ printer (Cellink Inc., Goteborg, Sweden), 3D structures were successfully produced. The developed bioink exhibited a viscosity suitable for extrusion printing while ensuring its structural integrity at the same time. Next, 3D spheroids developed by using bioinks were morphologically characterized by using light, a fluorescent microscope, and field emission scanning electron microscopy (FESEM). In conclusion, the properties of the construct obtained using the lab-formulated biocompatible polymer hydrogel suggest its potential use as a framework for three-dimensional cell culture, with possible applications in both fields of research and regenerative medicine. Full article

Large segmental bone defects present significant challenges due to the insufficient vascularization of implanted grafts, necessitating advances in vascularized bone tissue engineering. Recent innovations focus primarily on enhancing graft vascularization through advanced biomaterial scaffolds, precise three-dimensional (3D) bioprinting technologies, biochemical interventions, and co-culture techniques. Biomaterial scaffolds featuring microchannels and high-surface-area architectures facilitate endothelial cell infiltration and subsequent vessel formation. Concurrently, sophisticated 3D-bioprinting methods, including inkjet, extrusion, and laser-assisted approaches, enable the precise placement of endothelial and osteogenic cells, promoting anatomically accurate vascular networks. Biochemical strategies that utilize the simultaneous delivery of angiogenic factors (e.g., vascular endothelial growth factor) and osteogenic factors (e.g., bone morphogenetic protein-2) effectively couple angiogenesis and osteogenesis. Additionally, co-culturing mesenchymal stem cells and endothelial progenitors accelerates the development of functional capillary networks. Preclinical studies consistently demonstrate superior outcomes for prevascularized grafts, as evidenced by enhanced vascular inosculation, increased bone formation, and improved mechanical stability compared to non-vascularized controls. These technological advancements collectively represent significant progress toward the clinical translation of engineered vascularized bone grafts capable of addressing complex and previously intractable bone defects. Full article

Advances in pharmaceutical technology have positioned 3D printing and bioprinting as promising tools for developing personalized drug therapies. These innovations may redefine compounding practices by enabling precise, patient-specific drug formulations. Evaluating pharmacists’ readiness to adopt such technologies is therefore becoming increasingly important. Aim: The aim of this study is to investigate pharmacists’ knowledge, attitudes, and perceived barriers regarding the application of 3D printing and bioprinting technologies, as well as their perspectives on the regulation and implementation of these technologies in the context of personalized pharmacy. Materials and Methods: A custom-designed questionnaire was developed for the purposes of this pilot study, based on a review of the existing literature and informed by expert consultation to ensure conceptual relevance and clarity. The survey was conducted between September and December 2024. The data collection instrument comprises three main sections: (1) sociodemographic and professional characteristics, (2) knowledge regarding the applications of 3D printing and bioprinting in pharmacy, and (3) attitudes toward the regulatory framework and implementation of these technologies. Results: A total of 353 respondents participated, and 65.5% of them (n = 231) correctly distinguished between the concepts of “3D printing” and “bioprinting.” More than 25% (n = 88) were uncertain, and 8.5% (n = 30) were unable to differentiate between the two. Regarding the perceived benefits of personalized pharmacy, 83% (n = 293) of participants identified “the creation of personalized medications tailored to individual needs” as the main advantage, while 66% (n = 233) highlighted the “optimization of drug concentration to enhance therapeutic efficacy and minimize toxicity and adverse effects.” Approximately 60% (n = 210) of the pharmacists surveyed believed that the introduction of 3D-bioprinted pharmaceuticals would have a positive impact on the on-site preparation of customized drug formulations in community and hospital pharmacies. Lack of regulatory guidance and unresolved ethical concerns were identified as primary barriers. Notably, over 40% (n = 142) of respondents expressed concern that patients could be subjected to treatment approaches resembling “laboratory experimentation.” Nearly 90% (n = 317) of participants recognized the need for specialized training and expressed a willingness to engage in such educational initiatives. Conclusions: Three-dimensional printing and bioprinting technologies are considered cutting-edge instruments that may contribute to the advancement of pharmaceutical practice and industry, particularly in the field of personalized medicine. However, respondents’ views suggest that successful integration may require improved pharmacist awareness and targeted educational initiatives, along with the development and adaptation of appropriate regulatory frameworks to accommodate these novel technologies in drug design and compounding. Full article

Background: Nasal reconstruction requires a balance between aesthetic and functional restoration. Recent advances in three-dimensional (3D) printing have introduced new approaches to this field, enabling precise, patient-specific interventions. This review explores the applications, benefits, and challenges of integrating 3D printing in nasal reconstruction. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science to identify studies on 3D printing in nasal reconstruction. Peer-reviewed articles and clinical trials were analyzed to assess the impact of 3D-printed models, implants, and bioengineered scaffolds. Results: 3D printing facilitates the creation of anatomical models, surgical guides, and implants, enhancing surgical precision and patient outcomes. Techniques such as stereolithography (SLA) and selective laser sintering (SLS) enable high-resolution, biocompatible constructs using materials like polylactic acid, titanium, and hydroxyapatite. Computational fluid dynamics (CFD) tools improve surgical planning by optimizing nasal airflow. Studies show that 3D-printed guides reduce operative time and improve symmetry. Emerging bioprinting techniques integrating autologous cells offer promise for tissue regeneration. Challenges and Future Directions: Challenges include high costs, imaging limitations, regulatory hurdles, and limited vascularization in bioprinted constructs. Future research should focus on integrating bioactive materials, artificial intelligence-assisted design, and regulatory standardization. Conclusions: 3D printing offers specific advantages in nasal reconstruction, improving precision and outcomes in selected cases. Addressing current limitations through technological and regulatory advancements will further its clinical integration, potentially enhancing reconstructive surgery techniques. Full article

Viral lung infections are a never-ending threat to public health due to the emergence of new variants and their seasonal nature. While vaccines offer some protection, the need for effective antiviral drugs remains high. The existing research methods using 2D cell culture and animal models have their limitations. Human cell-based tissue engineering approaches hold great promise for bridging this gap. Here, we describe a microextrusion bioprinting approach to generate three-dimensional (3D) lung models composed of four cell types: endothelial cells, primary fibroblasts, macrophage cells, and epithelial cells. A549 and Calu-3 cells were selected as epithelial cells to simulate the cells of the lower and upper respiratory tract, respectively. Cells were bioprinted in a hydrogel consisting of alginate, gelatin, hyaluronic acid, collagen, and laminin-521. The models were cultured under air–liquid interface (ALI) conditions to further enhance their physiological relevance as lung cells. Their viability, metabolic activity, and expression of specific cell markers were analyzed during long-term culture for 21 days. The constructs were successfully infected with both a seasonal influenza A virus (IAV) and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, demonstrating their potential for studying diverse viral infections. 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

Background: Three-dimensional (3D) cell models may bridge the gap between two-dimensional (2D) cell cultures and animal models. Technical advances have led to the development of 3D-bioprinted cell models, characterized by greater reproducibility and the ability to mimic in vivo conditions. Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with poor clinical outcomes due to its heterogeneity, angiogenic activity, and invasiveness. Src family kinases (SFKs) play a crucial role in GBM progression, making them attractive targets for drug development. Here, we show results about the pharmacological profile of a new prodrug synthesized from a Src inhibitor, SI306. Methods: Three-dimensional-bioprinted GBM cell models were used in predicting the antitumor activity of the prodrug SI306-PD2 with respect to its precursor, SI306. Results: Since the prodrug releases the active inhibitor through the cleavage by specific enzymes, SI306-PD2 was analyzed for stability and release kinetics in various media, including fetal bovine serum (FBS), which is normally used in cell culture. In comparison to SI306, SI306-PD2 demonstrated higher solubility in water, higher permeability across gastrointestinal and blood–brain barrier membranes, and the ability to release the drug in the presence of FBS progressively. In the 2D GBM cell model, using U87 and U251 cell lines, both compounds similarly reduced tumor cell viability. In 3D-bioprinted cell models, in the presence of an FBS-free medium, SI306-PD2 exhibited a more effective antitumor activity compared to SI306, reducing the proliferation and diameter of U251 spheroids grown within the bioprinted scaffold in a statistically significant manner. The analysis of proteins extracted from 3D scaffolds confirmed that SI306-PD2 inhibited Src activation more efficiently than SI306. Conclusions: Our study suggests that, when tissue permeability represents a discriminating characteristic, bioprinted cell models can provide a valid alternative for studying the cytotoxicity of new antitumor compounds. This approach has permitted us to ascertain the potential of the prodrug SI306-PD2 as a therapeutic agent for GBM, demonstrating better tissue penetration and antiproliferative efficacy compared to the precursor compound SI306. Full article

Polyvinyl alcohol cryogels (PVA-C) are promising materials for vascular tissue engineering due to their biocompatibility, hydrophilicity, and tuneable mechanical properties. This study investigates the mechanical performance of multi-layered PVA-C constructs fabricated via sub-zero extrusion-based three-dimensional (3D) bioprinting. Samples with two, four, and six alternating layers were evaluated to assess the effect of layered architecture on elastic and viscoelastic behaviour. Uniaxial tensile testing revealed that increasing the number of layers led to a moderate reduction in stiffness; for instance, at 20% strain, six-layered constructs showed a significantly lower (p < 0.05) Young’s modulus (36.7 ± 2.5 kPa) compared to two-layered ones (47.3 ± 3.1 kPa). Stress–strain curves exhibited nonlinear characteristics, better captured by quadratic (as opposed to linear) fitting, within the tested strain range (≤40%). Dynamic mechanical analysis demonstrated a frequency-independent storage modulus (E′) across 1–10 Hz, with subtle variations in viscoelastic response linked to the number of layers. Visual inspection confirmed improved print fidelity and hydration retention in thicker constructs. These findings demonstrate that a multi-layered design influences the mechanical profile of PVA-C and suggests potential for functionally graded design strategies to enhance compliance matching and mimic the biomechanics of native vessels in small-diameter vascular grafts. Full article

Skin is composed of three layers: the epidermis, dermis, and hypodermis. It is enriched with skin appendages, including hair follicles, sweat glands, and sebaceous glands, which play essential roles in regulating fluid exchange, controlling body temperature, and providing protection against pathogens. Currently, skin regeneration treatments rely on transplantations. However, this approach has several disadvantages, including hemostasis at the recipient site, limitations in donor area closure, increased graft contraction, and hypertrophic scarring. Recent advancements in three-dimensional (3D) bioprinting technologies have enabled the fabrication of structures that closely mimic native tissues, with the aim of enhancing tissue regeneration. Bioprinting offers several advantages, such as high reproducibility, precision, and the ability to create complex geometries. The most promising bioinks combine excellent biocompatibility and biodegradability, with mechanical and rheological stability. This review highlights the most recent and innovative studies on 3D-printed bioinks in the field of skin tissue engineering. In particular, considering the growing interest in the regenerative potential of exosomes, we discuss cutting-edge research involving exosome-loaded bioinks and their potential to support skin regeneration and repair. Full article

Cardiovascular diseases (CVD) are the primary cause of death and disability around the world. Over the past decades, several conventional model systems based on two-dimensional (3D) monolayer cultures or experimental animals have been adopted to dissect and understand heart diseases in order to develop treatment modalities. However, traditional models exhibit several limitations in recapitulating human-specific key physiological and pathological characteristics, which highlights the necessity of developing physiologically relevant models. In recent years, tissue engineering approaches have been extensively employed to generate revolutionary three-dimensional (3D) cardiac models. In particular, the combined use of various bioengineering strategies and cellular reprogramming approaches has facilitated the development of various models. This review presents an overview of different approaches (bioprinting, scaffolding, and electrospinning) for creating bioengineered cardiac tissue models. Next, a broad survey of recent research related to the modeling of various cardiac diseases is presented. Finally, current challenges and future directions are proposed to foster further developments in the field of cardiac tissue engineering. Full article