Search Results (519)

Chronic wounds represent a significant global healthcare challenge, affecting millions of patients and imposing substantial economic burdens on healthcare systems. Traditional wound management approaches often fail to address the complex pathophysiology underlying chronic wounds, including persistent inflammation, impaired angiogenesis, and disrupted extracellular matrix remodeling. Three-dimensional (3D) bioprinting has emerged as a transformative technology that enables the fabrication of patient-specific, biomimetic tissue constructs capable of addressing these intricate challenges. This comprehensive review synthesizes recent advances in 3D bioprinting for chronic wound treatment, examining bioprinting technologies, biomaterial innovations, mechanisms of wound healing, and clinical applications. Recent studies demonstrate that bioprinted constructs incorporating living cells, growth factors, and bioactive molecules can significantly accelerate wound closure, enhance vascularization, and restore functional skin architecture. Notable innovations include in situ bioprinting systems, photosynthetic scaffolds for oxygen delivery, and immunomodulatory bioinks. While significant technical challenges remain—including vascularization, scalability, and regulatory approval—the integration of advanced bioprinting techniques with regenerative medicine principles offers unprecedented opportunities for personalized chronic wound care and improved patient outcomes. Full article

Radiotherapy is essential for treating head and neck cancer but frequently leads to radiation-induced fibrosis (RIF) in salivary glands (SGs). RIF develops through a cascade of radiation-triggered events, including DNA damage, excessive oxidative stress, and epithelial cell death. Persistent injury can cause cells to become senescent and release inflammatory signals, fueling chronic inflammation. These processes activate pathways, particularly TGF-β/SMAD, resulting in fibroblast activation, myofibroblast differentiation, and extracellular matrix accumulation. Potential treatments include drugs, mesenchymal stem/stromal cell (MSC) therapy, and gene-transfer approaches. In which, MSC therapy is particularly promising as MSCs can migrate to injured tissue and support epithelial regeneration. Yet progress is limited by the difficulty of expanding human acinar cells (ACs) in vitro. To address this gap, tunable alginate–gelatin–hyaluronic acid (AGHA) bioink hydrogels have emerged as a suitable system as gelatin provides adhesion sites for AC attachment and 3D organoid formation, alginate offers tunable mechanical support through ionic crosslinking, and hyaluronic acid contributes essential cues for cell adhesion, migration, and morphogenesis. The aim of this review is to synthesize current understanding of the mechanisms driving RIF, evaluate available therapeutic strategies, and highlight the role of AGHA in generating engineered SG constructs to test MSC therapies for RIF. Full article

Shear stress is a significant consideration in 3D bioprinting systems, with implications for cell viability and behaviour. This study hypothesised that relevant levels of shear stress would be generated during the process of 3D bioprinting human nasoseptal chondrocytes in a nanocellulose alginate bioink, with implications for cell viability and chondrogenic gene expression. Through a combined approach of in silico modelling and in vitro testing, we assessed chondrocyte viability and gene expression immediately within the first 72 h post-printing. Cell viability was determined using live–dead, alamarBlue and lactate dehydrogenase assays immediately and 24 h post-printing compared to cell-only and unprinted cell–biomaterial controls. Gene expression analysis of Type 2 collagen, SOX9, aggrecan and alkaline phosphatase gene expression was performed 4 h and 72 h post-printing. Computational fluid dynamics predicted a shear stress of 292 Pa and maximum fluid velocity of 19 mm/s during the bioprinting process. No statistically significant cell death or cell lysis was detected between groups immediately post-printing; however, statistically significant chondrocyte cell death was observed at 24 h in the printed group (p = 0.047). Moreover, the bioprinting process evoked a transient initial rise in both chondrogenic (SOX9, aggrecan) and osteogenic gene expression (ALP) with a marked suppression in type 2 collagen expression at 72 h (0.05, p = 0.0005), indicating biological effects evoked by shear stress during printing. This study highlights the importance of optimising the bioprinting process to facilitate low shear stress conditions for durable cartilage tissue engineering. Full article

Anionic polysaccharides are sugars with a negative charge. Common examples include alginic acid, hyaluronic acid, pectin, chondroitin sulfate, and heparin. These molecules are bioactive and widely used in medicine, food, and cosmetics. On their own, they usually do not bind to cells. However, they can serve as bioinks or as parts of bioink mixtures. In 3D bioprinting, anionic polysaccharides are often combined with natural polymers like collagen or with synthetic materials to form hydrogels. These hydrogels act as scaffolds that give cells a three-dimensional space to grow and form tissue. The properties of these hydrogels can be tuned to match specific needs. Together, anionic polysaccharides and 3D bioprinting offer strong potential for tissue engineering, making it possible to build complex, custom tissue structures that may help solve problems in organ repair and replacement. This review summarizes the sources, structures, and key properties of Common anionic polysaccharides, with a comparative analysis of their chemical, biological, and mechanical characteristics and recent 3D printing strategies. It highlights the advantages of anionic polysaccharide bioinks, particularly their compatibility with enzymatic, photo-, and ionic crosslinking, and presents representative examples demonstrating their suitability for diverse tissue engineering applications and printing requirements. Full article

Biotissues represent a new technology in tissue regeneration in otolaryngology. Various biomaterials functioning in different combinations are used as bioinks for 3D bioprinting of tissues/tissue fragments. The scaffolds can be populated with several cell categories, each offering distinct advantages and disadvantages, depending on the targeted pathology. Results from in vitro and in vivo studies on animal models are promising, with superior therapeutic potential. The combination of these elements provides promising results, enabling their potential application in personalized medicine. Based on these findings, their application in ENT (ear, nose, and throat) pathology is starting to gain traction. Despite being an emerging field, 3D/4D bioprinting in otolaryngology is rapidly evolving, increasingly replacing conventional inert materials with more sophisticated, bio-integrated alternatives. These alternatives are based on novel bioink formulation involving cells capable of proliferating and integrating the new neo-fragment organ into the host’s endogenous tissues. In this context, this review outlines novel applications that could enhance traditional procedures in ENT reconstructive medicine. Furthermore, biomimetic scaffolds for otolaryngology can be tailored to address factors influencing implant fate during the procedure and in the early and late postoperative periods. Full article

Dental tissue regeneration, particularly alveolar bone and gingival repair, remains a major challenge in regenerative medicine. 3D bioprinting offers patient-specific and anatomically precise constructs, representing an advanced alternative to conventional grafting. In this study, nanohydroxyapatite (nHA), chitosan (CS), and collagen (CoL) were combined to fabricate and characterize 3D bioprinted dental grafts. SEM revealed a highly porous, interconnected architecture favorable for cell infiltration and nutrient exchange. EDS confirmed Ca/P ratios of 2.06 for nHA/CoL and 1.83 for nHA/CS/CoL, both of which are above the stoichiometric 1.67, indicating the presence of additional mineral phases and ion substitutions. FTIR and XRD verified characteristic functional groups and crystalline phases, including B-type HA with carbonate substitution. Mechanical testing showed that pure nHA exhibited the lowest compressive strength, whereas CoL incorporation improved stiffness. The nHA/CS/CoL composite achieved the highest compressive strength, elastic modulus, and toughness, demonstrating superior mechanical resilience. DSC analysis indicated endothermic peaks at 106.49 °C and 351.91 °C, with enthalpy values (264.91 J/g and 15.09 J/g) surpassing those of nHA alone. TGA revealed ~28.8% weight loss across three degradation stages, confirming enhanced thermal stability. In vitro cytocompatibility testing using L929 fibroblasts validated the biocompatibility of the composites. Collectively, the synergy between bioceramics and biopolymers markedly improved both mechanical and thermal performance. These findings position the nHA/CS/CoL scaffold as a promising candidate for clinical applications in dental tissue regeneration. Unlike conventional grafting materials, this study introduces a synergistically optimized nHA/CS/CoL bio-ink formulation specifically designed for extrusion-based 3D bioprinting of patient-specific dental constructs. The core innovation lies in the precise integration of nHA within a dual-polymer matrix (CS/CoL), which bridges the gap between mechanical resilience and biological signaling, achieving a compressive strength that mimics native alveolar bone while maintaining high cytocompatibility. Full article

In regenerative medicine, three-dimensional (3D) printing provides precise spatial control over the fabrication of complex, biomimetic tissue constructs, enabling the production of architecturally defined and functionally tailored scaffolds. By enabling precise layer-by-layer deposition of cells, biomaterials, and bioactive compounds, 3D printing overcomes many limitations associated with conventional scaffold fabrication methods. This approach facilitates the development of tailored structures that mimic the mechanical, biological, and structural characteristics of native tissues, thereby enhancing cellular organization, proliferation, and differentiation. Extensive research in tissue engineering has led to the development of 3D-printed scaffolds for the regeneration of vascular, skin, bone, cartilage, and soft tissues. Advances in bioink formulations—including growth factor-loaded systems, decellularized extracellular matrix components, and natural and synthetic polymers—have further improved tissue-specific functionality. Moreover, multimaterial and multiscale printing strategies enable the fabrication of heterogeneous constructs with controlled porosity, mechanical gradients, and spatially regulated biological cues. Although vascularized tissue constructs remain a major challenge for clinical translation, recent bioprinting advancements have significantly accelerated progress in this area. Integration of computer-aided design with patient-specific imaging data has further strengthened the potential of 3D printing for personalized regenerative therapies. Despite these advances, challenges related to scalability, regulatory approval, and long-term functionality persist. Nevertheless, continued progress in printing technologies, biomaterials, and regulatory and standards frameworks is expected to drive the clinical adoption of 3D printing. Ultimately, 3D printing represents a transformative approach in tissue engineering, redefining strategies for functional tissue regeneration and translational regenerative medicine. Full article

Marine algae, microalgae, and Cyanophyceae emerge as sustainable and versatile sources of biomacromolecules for the fabrication of hydrogels with broad biomedical potential. Their phycocolloids, such as alginate, agar, carrageenan, ulvan, and extracellular polysaccharides (EPS), exhibit intrinsic biocompatibility, tunable gelation behavior, and bioactive sulfated structures that support cell viability, tissue regeneration, and therapeutic delivery. This review provides a comprehensive overview of hydrogel fabrication strategies, including physical, chemical, and hybrid crosslinking approaches, and highlights recent advances in composite systems incorporating proteins, glycosaminoglycans, and functional nanomaterials. Applications in skin repair, cartilage and bone regeneration, neural and cardiovascular engineering, and controlled drug delivery are examined, alongside the expanding role of marine-derived hydrogels as bioinks for 3D and 4D bioprinting. Despite their promise, challenges remain related to extract variability, purification complexity, mechanical limitations, and the need for standardized characterization. Future perspectives emphasize genetic engineering of algae and cyanobacteria, development of multifunctional hybrid hydrogels, sustainable large-scale production, and pathways toward clinical translation. Together, these insights position marine-derived hydrogels as next-generation biomaterials with significant potential for regenerative medicine and therapeutic innovation. Full article

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology—from embryogenesis and cell–matrix interactions to molecular and neural regulation—and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration. Full article

Current in vitro tissue models struggle to recapitulate the structural, vascular, and mechanical complexity of human tissues, limiting their physiological relevance for disease modelling and preclinical testing. Self-organising three-dimensional cultures such as spheroids and organoids capture key aspects of cellular organisation and differentiation, but they commonly lack controlled geometry, perfusable vasculature, and reproducible mechanical microenvironments. Conversely, biofabrication strategies, such as three-dimensional (3D) bioprinting and organ-on-chip (OoC) microfluidic devices, offer spatial control, integrated perfusion, and dynamic mechanical stimulation, yet often fall short in recapitulating the full cellular diversity and self-organisation of native tissues. Notably, emerging hybrid approaches that embed self-organising biological units (e.g., organoids and spheroids) into engineered scaffolds or microfluidic platforms combine biological relevance, architectural fidelity, and functional control. Advances in bioink chemistry, sacrificial-printing vascularisation, and chip–organoid interfaces now enable perfusable, multicompartment tissues suitable for disease modelling and preclinical testing. This review highlights the most recent (2020–2025) progress in organoid vascularisation, bioprinting strategies for prevascularised constructs, and OoC integration, outlining remaining challenges and emphasising priorities for next-generation hybrid cellular and tissue models. Full article

Three-dimensional (3D) bioprinting is an advanced additive manufacturing technology that utilizes bioinks composed of living cells and biomaterials to construct tissue-like structures for a wide range of medical applications. This paper reviews key applications, including tissue engineering, organ modeling and printing, drug testing and development, disease modeling, cosmetics and chemical testing, regenerative medicine, and personalized medicine. In parallel, biomimicry of natural plant architectures offers powerful opportunities for innovation in biomedical material design. Among these, the rose stands out for its intricate hierarchical geometry, which provides not only aesthetic appeal but also exceptional mechanical resilience. Incorporating rose-inspired structural elements into 3D-bioprinted medical constructs can significantly enhance mechanical strength, flexibility, and surface adaptability. This review also highlights plant- and rose-inspired approaches in medical applications and outlines the potential of rose-inspired 3D bioprinting to advance the design of functional and biomimetic tissue models. Nature provides a rich source of inspiration for biomimetic design, and translating biological principles into engineering solutions can contribute to sustainable technological development aligned with the Sustainable Development Goals (SDGs). In this regard, roses and other plant systems offer valuable structural and functional inspiration for advancing 3D bioprinting in medical applications. Full article

Background and Objectives: Hypocalcemia due to hypoparathyroidism (HypoPTH) is the most common complication following thyroid surgery, typically resulting from iatrogenic removal, tissue damage, or compromised vascularization of the parathyroid glands. Patients with persistent HypoPTH are at risk for long-term complications such as osteoporosis, cardiac dysfunction, and renal impairment. Lifelong regulation of calcium levels is therefore essential to prevent morbidity and mortality associated with these complications. In this study, we aimed to evaluate the functional engraftment efficacy of 3D bioprinted human parathyroid tissue constructs in a xenograft model in vivo. Materials and Methods: Primary cells obtained from freshly excised human parathyroid tissue specimens were isolated and 3D bioprinted using alginate-based bioink. The bioprinted tissue constructs were implanted into CD1 athymic mice. Histopathological evaluation of the grafted constructs was performed at different time points. In addition, surface calcium-sensing receptor (CaSR) expression was assessed by immunofluorescence as an indicator of functional parathyroid tissue engraftment. Results: The presence of CaSR on parathyroid cells within the 3D-printed scaffolds confirmed the persistence of functional parathyroid cells following implantation. In tissue samples obtained during the first, second, and third weeks after implantation, CaSR positivity was consistently observed in the parathyroid cells. However, at the three-month follow-up, the pores within the scaffolds were found to be filled with calcified material and replaced by fibrotic tissue. At this stage, the absence of parathyroid hormone (PTH) expression indicated a loss of functional activity in the grafted biomaterial. Conclusions: Human primary parathyroid cells were successfully isolated, and a functional, hormone-active parathyroid tissue substitute was developed ex vivo using 3D-bioprinted hydrogel scaffolds combined with autologous cells. Although short-term functional engraftment was achieved, long-term graft viability and hormonal activity were limited due to scaffold degradation and fibrosis. These findings indicate the necessity for further improvement in scaffold biocompatibility to enhance the therapeutic potential of 3D-bioprinted parathyroid tissue constructs for in vivo applications. Full article

In this work, we report the synthesis and evaluation of a bioink based on marine collagen, chitosan, and silica-doped hydroxyapatite (HA–SiO₂) for extrusion-based 3D bioprinting. FTIR spectroscopy confirmed amide (I–III) and phosphate/siloxane signals, TGA showed initial dehydration and degradation stages compatible with the process’s thermal handling, and SEM revealed an interconnected porous microstructure. Rheologically, the ink exhibited elastic dominance (G′ > G″) within the linear range and pseudoplastic, shear-thinning behavior—consistent with pneumatic extrusion. Process evaluation on a BIO X printer (14 G nozzle, low print speeds, moderate pressure, cartridge at 37 °C to 45 °C, and a cooled build platform) enabled deposition of strands with local shape retention. However, filament continuity was limited and line width varied, indicating only preliminary printability and a narrow operating window. Overall, physicochemical, microstructural, and rheological evidence supports the formulation’s viability as a starting point for scaffold fabrication. Full article

Three-dimensional (3D) bioprinting has rapidly emerged as a transformative technology at the interface of biomedical engineering and regenerative medicine. By enabling the spatially controlled deposition of living cells, biomaterials, and bioactive molecules, it offers an unprecedented potential to fabricate functional tissues and potentially whole organs in the future. This review explores recent advances in bioprinting materials, processes, and applications, emphasizing the integration of bioinks, printing methods, and mechanical design principles that underpin tissue functionality. Natural and synthetic biomaterials such as hydrogels (e.g., collagen, alginate), polyethylene glycol (PEG), and polyesters like PLGA are evaluated in terms of biocompatibility, printability, and degradation behavior. Key bioprinting modalities, including extrusion, inkjet, and laser-assisted bioprinting, are compared based on printing resolution, cell viability, and scalability. Structural considerations such as scaffold architecture, mechanical stability, and biomimetic design are discussed in relation to native tissue mechanics and requirements. The review also surveys emerging applications in tissue engineering (e.g., bone, cartilage, skin replacements), organ-on-a-chip systems for drug testing, and patient-specific implants, while addressing persistent challenges such as standardization of biofabrication, regulatory and ethical considerations, and manufacturing scale-up. Finally, future trends, including the integration of artificial intelligence (AI) and robotic automation, multi-material and four-dimensional (4D) bioprinting, and the maturation of personalized bioprinting strategies, are highlighted as pathways toward more autonomous and clinically relevant bioprinting systems. Collectively, these developments signify a paradigm shift in how biological constructs are designed and manufactured, bridging the gap between laboratory research and clinical translation. Full article

Extrusion-based 3D bioprinting enables the fabrication of complex tissue structures, yet achieving both high structural fidelity and cell viability remains challenging due to complex bioink rheology and parameter interplay. This review presents a quantitative framework linking hydrogel properties to printing outcomes. Key rheological features—shear-thinning, yield stress, reversible gel-sol transition, self-healing, and creep resistance—are examined for their roles in extrusion and shape retention. We also evaluate printing accuracy using metrics such as filament uniformity and multilayer stability. Advanced models, including Herschel-Bulkley and extrusion pressure models, correlate material parameters with flow dynamics and predict critical factors like wall shear stress. Finally, we propose an integrated assessment system combining material properties, process parameters, and structural fidelity to guide bioink design and printing optimization, advancing the field of hydrogel bioprinting. Full article