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Bioprinted breast tumor microenvironment (TME) models with spatial heterogeneity recaptured a well-defined cancer cell-rich stroma structure. Heterogeneity in angiogenesis and extracellular matrix (ECM) stiffness was found in bioprinted TME models. Intercellular crosstalk was identified in bioprinted TME models, which was associated with tumor angiogenesis and ECM remodeling. Bioprinted TME models demonstrated spatially heterogeneous drug resistance in breast cancer. Cellular, extracellular matrix (ECM), and spatial heterogeneity of tumor microenvironments (TMEs) regulate disease progression and treatment efficacy. Developing in vitro models that recapitulate the TME promises to accelerate studies of tumor biology and identify new targets for therapy. Here, we used extrusion-based, multi-nozzle 3D bioprinting to spatially pattern triple-negative MDA-MB-231 breast cancer cells, endothelial cells (ECs), and human mammary cancer-associated fibroblasts (HMCAFs) with biomimetic ECM inks. Bioprinted models captured key features of the spatial architecture of human breast tumors, including varying-sized dense regions of cancer cells and surrounding microvessel-rich stroma. Angiogenesis and ECM stiffening occurred in the stromal area but not the cancer cell-rich (CCR) regions, mimicking pathological changes in patient samples. Transcriptomic analyses revealed upregulation of angiogenesis-related and ECM remodeling-related signatures in the stroma region and identified potential ligand–receptor (LR) mediators of these processes. Breast cancer cells in distinct parts of the bioprinted TME showed differing sensitivities to chemotherapy, highlighting environmentally mediated drug resistance. In summary, our 3D-bioprinted tumor model will act as a platform to discover integrated functions of the TME in cancer biology and therapy. Graphical abstract [Display omitted] This study demonstrates a proof of concept for an in vitro 3D-bioprinted tumor model that recapitulates the spatial heterogeneity of the breast tumor microenvironment. The model mimics key physiological features of patient samples, such as localized vasculature and mechanical stiffness variations, and identifies potential intercellular interactions involved in pathological processes, validating its biological relevance. It also exhibits spatially distinct chemotherapeutic sensitivities, highlighting its potential for studying microenvironment-mediated drug resistance and discovering novel therapies. To advance this technology, optimizing and standardizing the bioprinting process are essential for reproducibility and scalability. Functional assays and preclinical testing are required to validate predictive accuracy. Collaboration with clinical researchers and regulatory bodies is crucial for validation and scale-up, enhancing cancer research and improving therapeutic strategies. Applied bioprinted vascularized breast tumor models recapturing tumor–stroma structures of human breast tumors to study intratumoral heterogeneity and drug resistance. Bioprinted tumor models recapitulated spatially distinct pathological features and identified potential intercellular interactions regulating these pathological changes. Bioprinted tumor models also demonstrated microenvironmentally mediated drug resistance. [ABSTRACT FROM AUTHOR]

Cardiovascular disease has emerged as the leading cause of death worldwide. Since coronary arteries, carotid arteries, and other blood vessels are prone to narrowing, small‐diameter artificial blood channels offer a crucial solution for restoring blood flow. Ideal grafts must emulate the structure of natural blood vessels, possess adequate mechanical strength, ensure long‐term patency, and incorporate functional cells with minimal immunogenicity. Enhanced cell sources and engineering methods are vital for the creation of functional small‐diameter blood vessels (SDBVs). Among potential cell sources, stem cells stand out due to their ability to differentiate into multiple cell types, self‐renew, and exhibit low immunogenicity. Additionally, three‐dimensionally (3D) printed vascular stents have attracted widespread attention for their precision and controllable bioink application. The need for tissue‐engineered blood vessels is currently rising, and innovative design concepts integrating stem cells and 3D printing present promising solutions. Herein, the construction requirements of vascular grafts are reviewed, current status of using stem cells as a cell source and 3D printing as an engineering strategy is described, and prospects and challenges for the development of SDBVs in the medical field are discussed. [ABSTRACT FROM AUTHOR]

Tissue-engineered skin substitutes (TESS) emerged as a new therapeutic option to improve skin transplantation. However, establishing an adequate and rapid vascularization in TESS is a critical factor for their clinical application and successful engraftment in patients. Therefore, several methods have been applied to improve the vascularization of skin substitutes including (i) modifying the structural and physicochemical properties of dermal scaffolds; (ii) activating biological scaffolds with growth factor-releasing systems or gene vectors; and (iii) developing prevascularized skin substitutes by loading scaffolds with capillary-forming cells. This review provides a detailed overview of the most recent and important developments in the vascularization strategies for skin substitutes. On the one hand, we present cell-based approaches using stem cells, microvascular fragments, adipose tissue derived stromal vascular fraction, endothelial cells derived from blood and skin as well as other pro-angiogenic stimulation methods. On the other hand, we discuss how distinct 3D bioprinting techniques and microfluidics, miRNA manipulation, cell sheet engineering and photosynthetic scaffolds like GelMA, can enhance skin vascularization for clinical applications. Finally, we summarize and discuss the challenges and prospects of the currently available vascularization techniques that may serve as a steppingstone to a mainstream application of skin tissue engineering. [ABSTRACT FROM AUTHOR]

Bone pathologies are still among the most challenging issues for orthopedics. Over the past decade, different methods are developed for bone repair. In addition to advanced surgical and graft techniques, polymer‐based biomaterials, bioactive glass, chitosan, hydrogels, nanoparticles, and cell‐derived exosomes are used for bone healing strategies. Owing to their variation and promising advantages, most of these methods are not translated into clinical practice. Three dimensonal (3D) bioprinting is an additive manufacturing technique that has become a next‐generation biomaterial technique adapted for anatomic modeling, artificial tissue or organs, grafting, and bridging tissues. Polymer‐based biomaterials are mostly used for the controlled release of various drugs, therapeutic agents, mesenchymal stem cells, ions, and growth factors. Polymers are now among the most preferable materials for 3D bioprinting. Melatonin is a well‐known antioxidant with many osteoinductive properties and is one of the key hormones in the brain–bone axis. 3D bioprinted melatonin‐loaded polymers with unique lipophilic, anti‐inflammatory, antioxidant, and osteoinductive properties for filling large bone gaps following fractures or congenital bone deformities may be developed in the future. This study summarized the benefits of 3D bioprinted and polymeric materials integrated with melatonin for sustained release in bone regeneration approaches. [ABSTRACT FROM AUTHOR]

Cartilage defect is one of the common tissue defect clinical diseases and may finally lead to osteoarthritis (OA) which threat patients' physical and psychological health. Polysaccharide is the main component of extracellular matrix (ECM) in cartilage tissue. In the past decades, polysaccharide-based hydrogels have shown great potential for cartilage regeneration considering unique qualities such as biocompatibility, enhanced cell proliferation, drug delivery, low toxicity, and many others. Structures such as chain length and chain branching make polysaccharides have different physical and chemical properties. In this review, cartilage diseases and current treatment options of polysaccharidebased hydrogels for cartilage defection repair were illustrated. We focus on how components and structures of recently developed materials affect the performance. The challenges and perspectives for polysaccharide-based hydrogels in cartilage repair and regeneration were also discussed in depth. [ABSTRACT FROM AUTHOR]

The liver coordinates over 500 biochemical processes crucial for maintaining homeostasis, detoxification, and metabolism. Its specialized cells, arranged in hexagonal lobules, enable it to function as a highly efficient metabolic engine. However, diseases such as cirrhosis, fatty liver disease, and hepatitis present significant global health challenges. Traditional drug development is expensive and often ineffective at predicting human responses, driving interest in advanced in vitro liver models utilizing 3D bioprinting and microfluidics. These models strive to mimic the liver's complex microenvironment, improving drug screening and disease research. Despite its resilience, the liver is vulnerable to chronic illnesses, injuries, and cancers, leading to millions of deaths annually. Organ shortages hinder liver transplantation, highlighting the need for alternative treatments. Tissue engineering, employing polymer-based scaffolds and 3D bioprinting, shows promise. This review examines these innovative strategies, including liver organoids and liver tissue-on-chip technologies, to address the challenges of liver diseases. [ABSTRACT FROM AUTHOR]

Engineering functional, thick tissues with integrated vascular architectures is crucial for advancing regenerative medicine. This study applied a novel 3D bioprinting strategy to construct thick adipose tissues featuring complex, hierarchical vascular networks. Mature adipocytes and endothelial cells are encapsulated within a collagen matrix, with structural integrity and vascular functionality ensured through a combination of bioinks. An innovative approach is utilized to establish millimetric vascular channels that connect to microvascular networks, forming a fully perfusable, hierarchical vasculature throughout the 3D bioprinted tissue. The structural stability and endothelial functionality of the vascularized constructs are assessed under continuous flow. In‐vitro analyses confirmed the integrity of the vascular networks and demonstrated the functional characteristics of the printed mature adipose cells. Direct anastomosis of the bioprinted tissue to a rat femoral artery resulted in effective vascular integration and tissue viability, as evidenced by efficient blood perfusion and significant host vascular ingrowth within the implanted tissues. The findings highlighted the potential of the presented bioprinting technique in the development of fully functional, vascularized adipose tissues suitable for surgical reconstruction and regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Gelatin methacryloyl (GelMA), typically derived from mammalian sources, has recently emerged as an ideal bio-ink for three-dimensional (3D) bioprinting. Herein, we developed a fish skin-based GelMA bio-ink for the fabrication of a 3D GelMA skin substitute with a 3D bioprinter. Several concentrations of methacrylic acid anhydride were used to fabricate GelMA, in which their physical-mechanical properties were assessed. This fish skin-based GelMA bio-ink was loaded with human adipose tissue-derived mesenchymal stromal cells (ASCs) and human platelet lysate (HPL) and then printed to obtain 3D ASCs + HPL-loaded GelMA scaffolds. Cell viability test and a preliminary investigation of its effectiveness in promoting wound closure were evaluated in a critical-sized full thickness skin defect in a rat model. The cell viability results showed that the number of ASCs increased significantly within the 3D GelMA hydrogel scaffold, indicating its biocompatibility property. In vivo results demonstrated that ASCs + HPL-loaded GelMA scaffolds could delay wound contraction, markedly enhanced collagen deposition, and promoted the formation of new blood vessels, especially at the wound edge, compared to the untreated group. Therefore, this newly fish skin-based GelMA bio-ink developed in this study has the potential to be utilized for the printing of 3D GelMA skin substitutes. [ABSTRACT FROM AUTHOR]

Lung cancer continues to have one of the highest morbidity and mortality rates of any cancer. Although radiochemotherapy, in combination with immunotherapy, has significantly improved overall survival, new treatment options are urgently needed. However, preclinical radiotherapy testing is often performed in animal models, which has several drawbacks, including species-specific differences and ethical concerns. To replace animal models, this study used a micro-extrusion bioprinting approach to generate a three-dimensional (3D) human lung cancer model consisting of lung tumor cells embedded in human primary lung fibroblasts for radiotherapy research. The models were placed in a mouse phantom, i.e., a 3D-printed mouse model made of materials that mimic the X-ray radiation attenuation rates found in mice. In radiotherapy experiments, the model demonstrated a selective cytotoxic effect of X-rays on tumor cells, consistent with findings in 2D cells. Furthermore, the analysis of metabolic activity, cell death, apoptosis, and DNA damage-induced γH2AX foci formation revealed different results in the 3D model inside the phantom compared to those observed in irradiated models without phantom and 2D cells. The proposed setup of the bioprinted 3D lung model inside the mouse phantom provides a physiologically relevant model system to study radiation effects. [ABSTRACT FROM AUTHOR]

Recently application of 3D bioprinting to bioengineering has gained interest for the availability of advanced biomaterials with promising properties for regenerative medicine and drug delivery. In particular, extrusion-based bioprinting has the possibility to use a wide range of hydrogels of natural and synthetic origin. One of the most critical weaknesses of bioprinting is the poor post-printing shape fidelity of 3D scaffold possibly due to the porous-viscoelastic nature and swelling behavior of extruded polymers through the printing head. In this work, a quantitative index, termed shape fidelity index, is proposed to evaluate the discrepancy between ideal and real printed scaffolds. Scaffolds were printed with natural polysaccharides, such as alginate and cellulose (Xplore®), and synthetic polymers, such as polyethylene glycol (START®). Four process parameters on 2 levels were selected for the study according to a DOE analysis: inlet pressure, printing speed, temperature and type of biomaterial. 16 experiments were performed with an extrusion-based bioprinter to produce 3D porous scaffolds, the shape and surface areas of which were characterized with optical microscopy and image analysis. Shape fidelity indices were characterized to guide the optimization of the bioprinting process. The proposed approach permits also to determine the process parameter influencing the most the printing outcome and to rank the parameter importance for optimizing the shape fidelity of the bioprinted manufacts with soft biomaterials. [ABSTRACT FROM AUTHOR]

In vitro liver models are pivotal in early drug development as they serve in assessing drug toxicity. Currently, most of the liver models include static cultures of liver derived cell spheroids. Mimicking dynamic conditions (similar to native liver – such as blood flow, glucose gradients etc.) in in vitro liver models would be essential for studying drug induced liver injury (DILI). The current work investigated and developed a simple bioink composed of gelatin and alginate blends (GA) that can be used to 3D bioprint hepatocyte laden scaffolds, serving as an in vitro liver model for drug toxicity assays. Rheological evaluation (using a rotary rheometer) of various compositions of GA blends was performed to assess their printability with an extrusion bioprinter. Suitable GA compositions with human liver carcinoma cells (HepG2) were 3D bioprinted. The scaffolds were stabilized by crosslinking the alginate (using calcium chloride) and gelatin (using microbial transglutaminase). Cell viability and proliferation of HepG2 in bioprinted scaffolds was assessed for 28 days. Further work includes fabrication of HepG2 laden hollow tubes and colonization of inner lumen with human umbilical vein endothelial cells (HUVEC), followed by DILI studies in long-term perfusion culture. [ABSTRACT FROM AUTHOR]

Scaffold‐based tissue engineering provides an efficient approach for repairing uterine tissue defects and restoring fertility. In the current study, a novel trilayer tissue engineering scaffold with high similarity to the uterine tissue in structure was designed and fabricated via 4D printing, electrospinning and 3D bioprinting for uterine regeneration. Highly stretchable poly(l‐lactide‐co‐trimethylene carbonate) (PLLA‐co‐TMC, "PTMC" in short)/thermoplastic polyurethane (TPU) polymer blend scaffolds were firstly made via 4D printing. To improve the biocompatibility, porous poly(lactic acid‐co‐glycolic acid) (PLGA)/gelatin methacryloyl (GelMA) fibers incorporated with polydopamine (PDA) particles were produced on PTMC/TPU scaffolds via electrospinning. Importantly, estradiol (E2) was encapsulated in PDA particles. The bilayer scaffolds thus produced could provide controlled and sustained release of E2. Subsequently, bone marrow derived mesenchymal stem cells (BMSCs) were mixed with gelatin methacryloyl (GelMA)‐based inks and the formulated bioinks were used to fabricate a cell‐laden hydrogel layer on the bilayer scaffolds via 3D bioprinting, forming ultimately biomimicking trilayer scaffolds for uterine tissue regeneration. The trilayer tissue engineering scaffolds thus formed exhibited a shape morphing ability by transforming from the planar shape to tubular structures when immersed in the culture medium at 37°C. The trilayer tissue engineering scaffolds under development would provide new insights for uterine tissue regeneration. [ABSTRACT FROM AUTHOR]

Constructing tissue/organ analogs with natural structures and cell types in vitro offers a valuable strategy for the in situ repair of damaged tissues/organs. Three-dimensional (3D) bioprinting is a flexible method for fabricating these analogs. However, extrusion-based 3D bioprinting faces the challenge of balancing the use of soft bioinks with the need for high-fidelity geometric shapes. To address these challenges, recent advancements have introduced various suspension mediums based on gelatin, agarose, and gellan gum microgels. The emergence of these gel-based suspension mediums has significantly advanced the fabrication of tissue/organ constructs using 3D bioprinting. They effectively stabilize and support soft bioinks, enabling the formation of complex spatial geometries. Moreover, they provide a stable, cell-friendly environment that maximizes cell viability during the printing process. This minireview will summarize the properties, preparation methods, and potential applications of gel-based suspension mediums in constructing tissue/organ analogs, while also addressing current challenges and providing an outlook on the future of 3D bioprinting. [ABSTRACT FROM AUTHOR]

Droplet‐based bioprinting has shown remarkable potential in tissue engineering and regenerative medicine. However, it requires bioinks with low viscosities, which makes it challenging to create complex 3D structures and spatially pattern them with different materials. This study introduces a novel approach to bioprinting sophisticated volumetric objects by merging droplet‐based bioprinting and cryobioprinting techniques. By leveraging the benefits of cryopreservation, we fabricated, for the first time, intricate, self‐supporting cell‐free or cell‐laden structures with single or multiple materials in a simple droplet‐based bioprinting process that is facilitated by depositing the droplets onto a cryoplate followed by crosslinking during revival. The feasibility of this approach is demonstrated by bioprinting several cell types, with cell viability increasing to 80%–90% after up to 2 or 3 weeks of culture. Furthermore, the applicational capabilities of this approach are showcased by bioprinting an endothelialized breast cancer model. The results indicate that merging droplet and cryogenic bioprinting complements current droplet‐based bioprinting techniques and opens new avenues for the fabrication of volumetric objects with enhanced complexity and functionality, presenting exciting potential for biomedical applications. [ABSTRACT FROM AUTHOR]

The common use of hydrogel materials in 3D bioprinting techniques is dictated by the unique properties of hydrogel bioinks, among which some of the most important in terms of sustaining vital cell functions in vitro in 3D cultures are the ability to retain large amounts of liquid and the ability to modify rigidity and mechanical properties to reproduce the structure of the natural extracellular matrix. Due to their high biocompatibility, non-immunogenicity, and the possibility of optimizing rheological properties and bioactivity at the same time, one of the most commonly used hydrogel bioink compositions are polymer solutions based on sodium alginate and gelatin. In 3D bioprinting techniques, it is necessary for hydrogel printouts to feature an appropriate geometry to ensure proper metabolic activity of the cells contained inside the printouts. The desired solution is to obtain a thin-walled printout geometry, ensuring uniform nutrient availability and gas exchange during cultivation. Within this study's framework, tubular bioprinted structures were developed based on sodium alginate and gelatin, containing cells of the immortalized fibroblast line NIH/3T3 in their structure. Directly after the 3D printing process, such structures are characterized by extremely low mechanical strength. The purpose of this study was to perform a comparative analysis of the viability and spreading ability of the biological material contained in the printouts during their incubation for a period of 8 weeks while monitoring the effect of cellular growth on changes in the mechanical properties of the tubular structures. The observations demonstrated that the cells contained in the 3D printouts reach the ability to grow and spread in the polymer matrix after 4 weeks of cultivation, leading to obtaining a homogeneous, interconnected cell network inside the hydrogel after 6 weeks of incubation. Analysis of the mechanical properties of the printouts indicates that with the increasing time of cultivation of the structures, the degree of their overgrowth by the biological material contained inside, and the progressive degradation of the polymer matrix process, the tensile strength of tubular 3D printouts varies. [ABSTRACT FROM AUTHOR]

We describe the development of a bioink to bioprint human induced pluripotent stem cells (hiPSCs) for possible cardiac tissue engineering using a gelatin methacrylate (GelMA)-based hydrogel. While previous studies have shown that GelMA at a low concentration (5% w/v) allows for the growth of diverse cells, its 3D printability has been found to be limited by its low viscosity. To overcome that drawback, making the hydrogel both compatible with hiPSCs and 3D-printable, we developed an extrudable GelMA-based bioink by adding xanthan gum (XG). The GelMA-XG composite hydrogel had an elastic modulus (~9 kPa) comparable to that of cardiac tissue, and enabled 3D printing with high values of printing accuracy (83%) and printability (0.98). Tests with hiPSCs showed the hydrogel's ability to promote their proliferation within both 2D and 3D cell cultures. The tests also showed that hiPSCs inside hemispheres of the hydrogel were able to differentiate into cardiomyocytes, capable of spontaneous contractions (average frequency of ~0.5 Hz and amplitude of ~2%). Furthermore, bioprinting tests proved the possibility of fabricating 3D constructs of the hiPSC-laden hydrogel, with well-defined line widths (~800 μm). [ABSTRACT FROM AUTHOR]

Central composite design (CCD) is a statistical experimental design technique that utilizes a combination of factorial and axial points to study the effects of multiple variables on a response. This study focused on optimizing hydrogel formulations for 3D printing using CCD. Three biopolymers were selected: sodium alginate (SA), gelatin (GEL), and carboxymethyl cellulose (CMC). The maximum and minimum concentrations of each polymer were established using a Google Scholar search, and CCD was employed to generate various combinations for hydrogel preparation. The hydrogels were characterized in accordance with their swelling degree (SD) in phosphate-buffered saline (PBS) and Dulbecco's Modified Eagle Medium (DMEM), as well as their printability in 2D and 3D assays. The formulation consisting of 7.5% SA, 7.5% GEL, and 2.5% CMC exhibited the best swelling properties and exceptional printability, surpassing all other tested formulations. This study highlights the effectiveness of design of experiment methodologies in accelerating the development of optimized hydrogel formulations for various applications in 3D printing and suggests avenues for future research to explore their performance in specific biological contexts. [ABSTRACT FROM AUTHOR]

Introduction: Since 3D printing can be used to design implants according to the specific conditions of patients, it has become an emerging technology in tissue engineering and regenerative medicine. How to improve the mechanical, elastic and adhesion properties of 3D-printed photocrosslinked hydrogels is the focus of cartilage tissue repair and reconstruction research. Materials and Methods: We established a strategy for toughening hydrogels by mixing GelMA-DOPA (GD), which is prepared by coupling dopamine (DA) with GelMA, with HAMA, bacterial cellulose (BC) to produce composite hydrogels (HB–GD). HB–GD hydrogel scaffolds were characterized in vitro by scanning electron microscopy (SEM), Young's modulus, swelling property and rheological property tests. And biocompatibility and chondrogenic ability were tested by live/dead staining, DNA quantitative analysis and immunofluorescence staining. Combined with 3D bioprinting technology, mouse chondrocytes (ADTC5) were added to form a biological chain to construct an in vitro model, and the feasibility of the model for nasal cartilage regeneration was verified by cytology evaluation. Results: With the increase of GD concentration, the toughness of the composite hydrogel increased (47.0 ± 2.7 kPa (HB–5GD)–158 ± 3.2 kPa (HB–20GD)), and it had excellent swelling properties, rheological properties and printing properties. The HB–GD composite hydrogel promoted the proliferation and differentiation of ATDC5. Cells in 3D printed scaffolds had higher survival rates (> 95%) and better protein expression than the encapsulated cultures. Conclusion: The HB–10GD hydrogel can be made into a porous scaffold with precise shape, good internal pore structure, high mechanical strength and good swelling rate through extrusion 3D printing. No Level Assigned: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 [ABSTRACT FROM AUTHOR]

The high-throughput method based on the micron-level structure that 3D bioprinting technology offers for various environmental microbiological engineering applications is made possible by its several printing paths and precision programming control. This versatility makes it an on-demand manufacturing technology. A novel 3D manufacturing technique called 3D bioprinting may be used to precisely uptake and disperse bacteria to create microbial active substances with a variety of intricate functionalities for environmental applications. The technological challenges that the current 3D bioprinting technology must face include the mechanical properties of materials, the creation of specific bioinks to adapt to different strains, and the exploration of 4D bioprinting for intelligent applications. Therefore, this analysis delves deeply into the core technological ideas of 3D bioprinting, bioink materials, and their environmental applications. It also offers recommendations about the challenges and opportunities associated with 3D bioprinting. Combined with the present advancements in microbe enhancement technology, 3D bioprinting will provide an enabling platform for multifunctional microorganisms and facilitate the management of in situ directional responses in the environmental domain. This review highlights the applications of 3D bioprinting in the environmental monitoring and bioremediation. 3D printing in solid waste management is also discussed in detail. [ABSTRACT FROM AUTHOR]

Direct ink writing is especially relevant to the biomedical field due to the customizable extrusion and the possibility of creating pre‐designed architectures. Abundant natural polymers are sustainable and biocompatible alternatives to synthetic and persistent polymers. The printing of pure nanocellulose suspensions proves difficult due to low solid loadings, high shrinkage, as well as non‐fitting rheology. Emulsion gels (emulgel) alternatives gain attention in the field owing to their favorable viscoelastic properties and the possibility of creating multiphase systems. The authors’ sulfur‐free cationic cellulose nanocrystals (CNC) of low degree of substitution enable straightforward deployment in Pickering emulsions. An emulgel ink co‐stabilized by cationic CNC and α‐cyclodextrin is introduced as an interfacial inclusion complex. All ink components are natural and biodegradable compounds. The produced emulgel inks allow for high fidelity printing and minimum shrinkage upon drying that relaxes the need for supports, even in complex overhanging structures. A low yield stress (230–270 Pa) facilitates the inclusion of cells for biomedical applications into the formulation. The emulgel can be tuned to the desired rheological properties and be equipped with both polar and apolar compounds due to the biphasic system, making it a promising platform for biocompatible additive manufacturing. [ABSTRACT FROM AUTHOR]

Decellularized small intestine submucosa (dSIS) is a promising biomaterial for promoting tissue regeneration. Isolated from the submucosal layer of animal jejunum, SIS is rich in extracellular matrix (ECM) proteins, including collagen, laminin, and fibronectin. Following mild decellularization, dSIS becomes an acellular matrix that supports cell adhesion, proliferation, and differentiation. Conventional dSIS matrix is usually obtained by thermal crosslinking, which yields a soft scaffold with low stability. To address these challenges, dSIS is modified with methacrylate groups for photocrosslinking into stable hydrogels. However, dSIS has not been modified with clickable handles for orthogonal crosslinking. Here, the development of norbornene‐modified dSIS, named dSIS‐NB, via reacting amine groups of dSIS with carbic anhydride in acidic aqueous reaction conditions is reported. Using triethylamine (TEA) as a mild base catalyst, high degrees of NB substitution on dSIS are obtained. In addition to describing the synthesis of dSIS‐NB, its adaptability in orthogonal hydrogel crosslinking for cancer and vascular tissue engineering is explored. Impressively, compared with physically crosslinked dSIS and collagen matrices, orthogonally crosslinked dSIS‐NB hydrogels supported rapid dissemination of cancer cells and superior vasculogenic and angiogenic properties. dSIS‐NB is also exploited as a versatile bioink for 3D bioprinting. [ABSTRACT FROM AUTHOR]

In recent years, 3D bioprinting technology has developed rapidly, becoming an essential tool in the fields of cancer research, tissue engineering, disease modeling and mechanistic studies. This paper reviewed the fundamental principles of bioprinting technology and its current applications in cancer research and tissue engineering. Bioprinting is an additive manufacturing technology that constructs complex three-dimensional tissue structures by digitally controlling the layer-by-layer deposition of biomaterials and living cells. The core steps of bioprinting include designing a 3D model, selecting appropriate bioprinting techniques and materials, printing layer by layer, followed by post-processing involving cell culture and functionalization. In cancer research, 3D bioprinting can create complex tumor models that simulate the tumor microenvironment, revealing new mechanisms of tumor initiation and progression. Traditional in vitro models, such as 2D cell cultures or animal models, often fail to accurately replicate the complexity of human tumors. However, 3D bioprinted tumor models, which mimic the dynamic interactions between tumor cells and their environment such as immune cells, stroma and blood vessels, offer a more biomimetic platform for studying tumor growth, invasion and metastasis. These models provide a research platform that closely mirrors actual tumor behavior. Additionally, Bioprinted models and scaffolds can be leveraged in personalized precision therapies by efficiently constructing patient-specific 3D models from their own cells. These models enable the prediction of patient’s sensitivity to drugs and radiotherapy. Additionally, localized scaffolds can be developed to meet individual patient needs, allowing for the formulation of appropriate drug types and dosages. Furthermore, 3D-printed scaffolds can support drug delivery by targeting specific areas, reducing drug-related side effects. They can also be used to facilitate local immunotherapy, cytokine therapy, cancer vaccines, and chimeric antigen receptor cell therapy, enhancing therapeutic outcomes. In tissue engineering, traditional tissue repair methods often struggle to address the complex requirements of constructing intricate tissue structures. 3D bioprinting offers a novel solution by enabling the creation of complex tissue architectures and promoting tissue regeneration. Basic tissues, such as bone, cartilage and skin, which have higher regenerative capacities, are gradually being incorporated into clinical practice. Significant progress has also been made in the repair and reconstruction of more complex organs like the liver and heart, though considerable challenges remain before these advancements can be fully translated into clinical applications. Finally, this paper discussed the current challenges and future directions of 3D bioprinting in these fields, aiming to provide reference for researchers. [ABSTRACT FROM AUTHOR]

The technology of 3D bioprinting has sparked interest in improving tendon repair and regeneration, promoting quality of life. To perform this procedure, surgical intervention is often necessary to restore functional capacity. In this way, 3D bioprinting offers a scaffold design, producing tendons with precise microarchitectures, promoting the growth of new tissues. Furthermore, it may incorporate bioactive compounds that can further stimulate repair. This review elucidates how 3D bioprinting holds promise for tendon repair and regeneration, detailing the steps involved and the various approaches employed. They demonstrate future challenges and perspectives and provide valuable information on the concept, bioprinting design, and 3D bioprinting techniques for the repair of tendon injuries. [ABSTRACT FROM AUTHOR]

Skin aging is influenced by intrinsic and extrinsic factors that progressively impair skin functionality over time. Investigating the skin aging process requires thorough research using innovative technologies. This review explores the use of in vitro human 3D culture models, serving as valuable alternatives to animal ones, in skin aging research. The aim is to highlight the benefits and necessity of improving the methodology in analyzing the molecular mechanisms underlying human skin aging. Traditional 2D models, including monolayers of keratinocytes, fibroblasts, or melanocytes, even if providing cost-effective and straightforward methods to study critical processes such as extracellular matrix degradation, pigmentation, and the effects of secretome on skin cells, fail to replicate the complex tissue architecture with its intricated interactions. Advanced 3D models (organoid cultures, "skin-on-chip" technologies, reconstructed human skin, and 3D bioprinting) considerably enhance the physiological relevance, enabling a more accurate representation of skin aging and its peculiar features. By reporting the advantages and limitations of 3D models, this review highlights the importance of using advanced in vitro systems to develop practical anti-aging preventive and reparative approaches and improve human translational research in this field. Further exploration of these technologies will provide new opportunities for previously unexplored knowledge on skin aging. [ABSTRACT FROM AUTHOR]

Tumor behavior, including its response to treatments, is influenced by interactions between mesenchymal and malignant cells, as well as their spatial arrangement. To study tumor biology and evaluate anticancer drugs, accurate 3D tumor models are essential. Here, we developed an in vitro biomimetic hepatoma microenvironment model by combining an extracellular matrix (3DM-7721). Initially, the internal grid structure, composed of 10/6 % GelMA/gelatin loaded with SMMC-7721 cells, was printed using 3D bioprinting. The external component consisted of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. A control model (3DP-7721) lacked external cell loading. GelMA/gelatin hydrogels provided robust structural support and biocompatibility. The SMMC-7721 cells in the 3DM-7721 model exhibit superior tumor-associated gene expression and proliferation characteristics when compared to the 3DP-7721 model. Furthermore, the 3DM-7721 type exhibited increased resistance to anticancer agents. SMMC-7721 cells in the 3DM-7721 model exhibit significant tumorigenicity in nude mice. The 3DM-7721 model group showed pathological characteristics of malignant tumors, with a high degree of deterioration, and a significant positive correlation between malignant tumor-related gene pathways. This high-fidelity 3DM-7721 tumor microenvironment model is invaluable for studying tumor progression, devising effective treatment strategies, and discovering drugs. 1. A hepatoma microenvironment model (3DM-7721) incorporating an extracellular matrix that is designed to establish solid tumor models in vitro. 2. This model contains a 3D-printed internal tumor component of liver cancer cells loaded with 10/6 % gelatin methacrylate (GelMA)/gelatin (the 3DP-7721 model) and an external extracellular-matrix component of fibroblasts and human umbilical vein endothelial cells loaded with 10/3 % GelMA/gelatin. 3. The 3DM-7721 model outperforms the 3DP-7721 model in terms of the SMMC-7721 cell proliferation characteristics and tumorigenicity, tumor-related gene expression, anticancer drug resistance, and malignant tumor characteristics. [Display omitted] [ABSTRACT FROM AUTHOR]

Subcutaneous delivery of cell therapy is an appealing minimally-invasive strategy for the treatment of various diseases. However, the subdermal site is poorly vascularized making it inadequate for supporting engraftment, viability, and function of exogenous cells. In this study, we developed a 3D bioprinted scaffold composed of alginate/gelatin (Alg/Gel) embedded with mesenchymal stem cells (MSCs) to enhance vascularization and tissue ingrowth in a subcutaneous microenvironment. We identified bio-ink crosslinking conditions that optimally recapitulated the mechanical properties of subcutaneous tissue. We achieved controlled degradation of the Alg/Gel scaffold synchronous with host tissue ingrowth and remodeling. Further, in a rat model, the Alg/Gel scaffold was superior to MSC-embedded Pluronic hydrogel in supporting tissue development and vascularization of a subcutaneous site. While the scaffold alone promoted vascular tissue formation, the inclusion of MSCs in the bio-ink further enhanced angiogenesis. Our findings highlight the use of simple cell-laden degradable bioprinted structures to generate a supportive microenvironment for cell delivery. [ABSTRACT FROM AUTHOR]

Recent advancements in 3D-bioprinting technology have sparked a growing interest in its application for brain repair, encompassing tissue regeneration, drug delivery, and disease modeling. This literature review examines studies conducted over the past five years to assess the current state of research in this field. Common bioprinting methods and key parameters influencing their selection are explored, alongside an analysis of the diverse types of bioink utilized and their associated parameters. The extrusion-based 3D-bioprinting method emerged as the most widely studied and popular topic, followed by inkjet-based and laser-based bioprinting and stereolithography. Regarding bioinks, fibrin-based and collagen-based bioinks are predominantly utilized. Furthermore, this review elucidates how 3D bioprinting holds promise for neural tissue repair, regeneration, and drug screening, detailing the steps involved and various approaches employed. Neurovascular 3D printing and bioscaffold 3D printing stand out as the top two preferred methods for brain repair. The recent studies' shortcomings and potential solutions to address them are also examined and discussed. Overall, by synthesizing recent findings, this review provides valuable insights into the potential of 3D bioprinting for advancing brain repairment strategies. [ABSTRACT FROM AUTHOR]

3D bioprinting holds transformative potential for the field of regenerative medicine, offering unprecedented opportunities for the fabrication of complex, living tissues. Central to this technological innovation is the development of suitable bioinks that can accurately replicate the native cellular environment. Decellularized extracellular matrix (dECM) has emerged as a promising candidate due to its inherent biocompatibility, bioactivity, and structural resemblance to native tissues. Decellularization is a crucial process in tissue engineering that involves the removal of cellular components from the extracellular matrix (ECM) to create scaffolds suitable for tissue regeneration. This article provides a review of some decellularization methods, categorizing them into physical, chemical, and biological approaches. The article discusses the advantages and limitations of each method, highlighting the need to balance effective decellularization with the preservation of the ECM's functional properties. Understanding these methods is critical for developing optimized scaffolds for various tissue engineering applications. [ABSTRACT FROM AUTHOR]

Xiaobo Zhang,1,* Xidan Gao,1,* Xuefang Zhang,1 Xin Yao,1 Xin Kang2 1Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’An, Shaanxi, P.R. China; 2Department of Sports Medicine, Honghui Hospital, Xi’an Jiao Tong University, Xi’An, Shaanxi, P.R. China*These authors contributed equally to this workCorrespondence: Xin Kang, Email honghuikangxin@163.comAbstract: Hydrogels are multifunctional platforms. Through reasonable structure and function design, they use material engineering to adjust their physical and chemical properties, such as pore size, microstructure, degradability, stimulus-response characteristics, etc. and have a variety of biomedical applications. Hydrogel three-dimensional (3D) printing has emerged as a promising technique for the precise deposition of cell-laden biomaterials, enabling the fabrication of intricate 3D structures such as artificial vertebrae and intervertebral discs (IVDs). Despite being in the early stages, 3D printing techniques have shown great potential in the field of regenerative medicine for the fabrication of various transplantable tissues within the human body. Currently, the utilization of engineered hydrogels as carriers or scaffolds for treating intervertebral disc degeneration (IVDD) presents numerous challenges. However, it remains an indispensable multifunctional manufacturing technology that is imperative in addressing the escalating issue of IVDD. Moreover, it holds the potential to serve as a micron-scale platform for a diverse range of applications. This review primarily concentrates on emerging treatment strategies for IVDD, providing an in-depth analysis of their merits and drawbacks, as well as the challenges that need to be addressed. Furthermore, it extensively explores the biological properties of hydrogels and various nanoscale biomaterial inks, compares different prevalent manufacturing processes utilized in 3D printing, and thoroughly examines the potential clinical applications and prospects of integrating 3D printing technology with hydrogels.Keywords: intervertebral disc degeneration, 3D bioprinting, hydrogel, novel therapy, challenges

Abstract Gelatin methacryloyl (GelMA), typically derived from mammalian sources, has recently emerged as an ideal bio-ink for three-dimensional (3D) bioprinting. Herein, we developed a fish skin-based GelMA bio-ink for the fabrication of a 3D GelMA skin substitute with a 3D bioprinter. Several concentrations of methacrylic acid anhydride were used to fabricate GelMA, in which their physical-mechanical properties were assessed. This fish skin-based GelMA bio-ink was loaded with human adipose tissue-derived mesenchymal stromal cells (ASCs) and human platelet lysate (HPL) and then printed to obtain 3D ASCs + HPL-loaded GelMA scaffolds. Cell viability test and a preliminary investigation of its effectiveness in promoting wound closure were evaluated in a critical-sized full thickness skin defect in a rat model. The cell viability results showed that the number of ASCs increased significantly within the 3D GelMA hydrogel scaffold, indicating its biocompatibility property. In vivo results demonstrated that ASCs + HPL-loaded GelMA scaffolds could delay wound contraction, markedly enhanced collagen deposition, and promoted the formation of new blood vessels, especially at the wound edge, compared to the untreated group. Therefore, this newly fish skin-based GelMA bio-ink developed in this study has the potential to be utilized for the printing of 3D GelMA skin substitutes.

Artificial skin involves multidisciplinary efforts, including materials science, biology, medicine, and tissue engineering. Recent studies have aimed at creating skins that are multifunctional, intelligent, and capable of regenerating tissue. In this work, we present a specialized 3D printing ink composed of polyurethane and bioactive glass (PU-BG) and prepare dual-function skin patch by microfluidic-regulated 3D bioprinting (MRBP) technique. The MRBP endows the skin patch with a highly controlled microstructure and superior strength. Besides, an asymmetric tri-layer is further constructed, which promotes cell attachment and growth through a dual transport mechanism based on hydrogen bonds and gradient structure from hydrophilic to superhydrophilic. More importantly, by combining the features of biomedical skin with electronic skin (e-skin), we achieved a biomedical and electronic dual-function skin patch. In vivo experiments have shown that this skin patch can enhance hemostasis, resist bacterial growth, stimulate the regeneration of blood vessels, and accelerate the healing process. Meanwhile, it also mimics the sensory functions of natural skin to realize signal detection, where the sensitivity reached up to 5.87 kPa−1, as well as cyclic stability (over 500 cycles), a wide detection range of 0–150 kPa, high pressure resolution of 0.1 % under the pressure of 100 kPa. This work offers a versatile and effective method for creating dual-function skin patches and provide new insights into wound healing and tissue repair, which have significant implications for clinical applications.

In recent years, 3D bioprinting technology has developed rapidly, becoming an essential tool in the fields of cancer research, tissue engineering, disease modeling and mechanistic studies. This paper reviewed the fundamental principles of bioprinting technology and its current applications in cancer research and tissue engineering. Bioprinting is an additive manufacturing technology that constructs complex three-dimensional tissue structures by digitally controlling the layer-by-layer deposition of biomaterials and living cells. The core steps of bioprinting include designing a 3D model, selecting appropriate bioprinting techniques and materials, printing layer by layer, followed by post-processing involving cell culture and functionalization. In cancer research, 3D bioprinting can create complex tumor models that simulate the tumor microenvironment, revealing new mechanisms of tumor initiation and progression. Traditional in vitro models, such as 2D cell cultures or animal models, often fail to accurately replicate the complexity of human tumors. However, 3D bioprinted tumor models, which mimic the dynamic interactions between tumor cells and their environment such as immune cells, stroma and blood vessels, offer a more biomimetic platform for studying tumor growth, invasion and metastasis. These models provide a research platform that closely mirrors actual tumor behavior. Additionally, Bioprinted models and scaffolds can be leveraged in personalized precision therapies by efficiently constructing patient-specific 3D models from their own cells. These models enable the prediction of patient’s sensitivity to drugs and radiotherapy. Additionally, localized scaffolds can be developed to meet individual patient needs, allowing for the formulation of appropriate drug types and dosages. Furthermore, 3D-printed scaffolds can support drug delivery by targeting specific areas, reducing drug-related side effects. They can also be used to facilitate local immunotherapy, cytokine therapy, cancer vaccines, and chimeric antigen receptor cell therapy, enhancing therapeutic outcomes. In tissue engineering, traditional tissue repair methods often struggle to address the complex requirements of constructing intricate tissue structures. 3D bioprinting offers a novel solution by enabling the creation of complex tissue architectures and promoting tissue regeneration. Basic tissues, such as bone, cartilage and skin, which have higher regenerative capacities, are gradually being incorporated into clinical practice. Significant progress has also been made in the repair and reconstruction of more complex organs like the liver and heart, though considerable challenges remain before these advancements can be fully translated into clinical applications. Finally, this paper discussed the current challenges and future directions of 3D bioprinting in these fields, aiming to provide reference for researchers.

Abstract Food nutrition and safety are the cornerstones of food industry, and appropriate research models are crucial. Unlike traditional animal models, the novel organoid model with unique humanization and genome stability has attracted great attentions in food research. However, there lacks systematic review on the application of organoids in food research. This review compared the organoid model with traditional animal and two‐dimensional cell models, followed by a systemic evaluation of the organoid model in food nutrition and safety regarding foodborne pathogenic bacteria, functional food factors, toxicology, flavor perception, and so on. Furthermore, emerging micromachining technologies such as microfluidic technology and three‐dimensional (3D) bioprinting were analyzed to improve the microenvironment and maturity of organoids. Although organoids overcome some shortcomings associated with traditional models, there are still some challenges to simulate the in vivo microenvironment fully. The development direction of organoids is integrating advanced technologies such as microfluidic technology, novel biomaterial scaffold, and 3D bioprinting with multi‐organ coculture technology and multi‐scale real‐time monitoring systems. The innovative development of organoid technology is expected to provide a theoretical basis for developing future foods represented by cell‐cultured meat and synthetic biological foods and for the research of food nutrition and safety.

Cartilage tissue, characterized by its limited regenerative capacity, presents significant challenges in clinical therapy. Recent advancements in cartilage regeneration have focused on integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to overcome existing limitations. Stem cells, particularly Mesenchymal Stem Cells (MSCs) and induced pluripotent stem cells (iPSCs), hold promise for cartilage repair due to their ability to differentiate into chondrocytes, the key cells responsible for cartilage formation. Tissue engineering approaches, including 3D models, organ-on-a-chip systems, and organoids, offer innovative methods to mimic natural tissue microenvironments and evaluate potential treatments. MSC-based techniques, such as cell sheet tissue engineering, address challenges associated with traditional therapies, including cell availability and culture difficulties. Furthermore, advancements in 3D bioprinting enable the fabrication of complex tissue structures, while organ-on-a-chip systems provide microfluidic platforms for disease modeling and physiological mimicry. Organoids serve as simplified models of organs, capturing some complexity and enabling the monitoring of pathophysiological aspects of cartilage diseases. This comprehensive review underscores the transformative potential of integrating stem cell therapies, tissue engineering strategies, and advanced modeling techniques to improve cartilage regeneration and pave the way for more effective clinical treatments.

Injectable hydrogels are increasingly explored for the delivery of cells to tissue. These materials exhibit both liquid-like properties, protecting cells from mechanical stress during injection, and solid-like properties, providing a stable 3D engraftment niche. Many strategies for modulating injectable hydrogels tune liquid- and solid-like material properties simultaneously, such that formulation changes designed to improve injectability can reduce stability at the delivery site. The ability to independently tune liquid- and solid-like properties would greatly facilitate formulation development. Here, such a strategy is presented in which cells are ensconced in the pores between microscopic granular hyaluronic acid (HA) hydrogels (microgels), where elasticity is tuned with static covalent intra-microgel crosslinks and flowability with mechanosensitive adamantane-cyclodextrin (AC) inter-microgel crosslinks. Using the same AC-free microgels as a 3D printing support bath, the location of each cell is preserved as it exits the needle, allowing identification of the mechanism driving mechanical trauma-induced cell death. The microgel AC concentration is varied to find the threshold from microgel yielding- to AC interaction-dominated injectability, and this threshold is exploited to fabricate a microgel with better injection-protecting performance. This delivery strategy, and the balance between intra- and inter-microgel properties it reveals, may facilitate the development of new cell injection formulations.

Digital light processing (DLP)-based bioprinting technology holds immense promise for the advancement of hydrogel constructs in biomedical applications. However, creating high-performance hydrogel constructs with this method is still a challenge, as it requires balancing the physicochemical properties of the matrix while also retaining the cellular activity of the encapsulated cells. Herein, we propose a facile and practical strategy for the 3D bioprinting of high-performance hydrogel constructs through the in-situ birth of stem cell spheroids. The strategy is achieved by loading the cell/dextran microdroplets within gelatin methacryloyl (GelMA) emulsion, where dextran functions as a decoy to capture and aggregate the cells for bioprinting while GelMA enables the mechanical support without losing the structural complexity and fidelity. Post-bioprinting, the leaching of dextran results in a smooth curved surface that promotes in-situ birth of spheroids within hydrogel constructs. This process significant enhances differentiation potential of encapsulated stem cells. As a proof-of-concept, we encapsulate dental pulp stem cells (DPSCs) within hydrogel constructs, showcasing their regenerative capabilities in dentin and neovascular-like structures in vivo. The strategy in our study enables high-performance hydrogel tissue construct fabrication with DLP-based bioprinting, which is anticipated to pave a promising way for diverse biomedical applications.

The epithelium is one of the important tissues in the body as it plays a crucial barrier role serving as a gateway into and out of the body. Most organs in the body contain an epithelial tissue component, where the tightly connected, organ-specific epithelial cells organize into cysts, invaginations, or tubules, thereby performing distinct to endocrine or exocrine secretory functions. Despite the significance of epithelium, engineering functional epithelium in vitro has remained a challenge due to it is special architecture, heterotypic composition of epithelial tissues, and most importantly, difficulty in attaining the apico-basal and planar polarity of epithelial cells. Bioprinting has brought a paradigm shift in fabricating such apico-basal polarized tissues. In this review, we provide an overview of epithelial tissues and provide insights on recapitulating their cellular arrangement and polarization to achieve epithelial function. We describe the different bioprinting techniques that have been successful in engineering polarized epithelium, which can serve as in vitro models for understanding homeostasis and studying diseased conditions. We also discuss the different attempts that have been investigated to study these 3D bioprinted engineered epithelium for preclinical use. Finally, we highlight the challenges and the opportunities that need to be addressed for translation of 3D bioprinted epithelial tissues towards paving way for personalized healthcare in the future.

The healing of large skin defects remains a significant challenge in clinical settings. The lack of epidermal sources, such as autologous skin grafting, limits full-thickness skin defect repair and leads to excessive scar formation. Skin organoids have the potential to generate a complete skin layer, supporting in-situ skin regeneration in the defect area. In this study, skin organoid spheres, created with human keratinocytes, fibroblasts, and endothelial cells, showed a specific structure with a stromal core surrounded by surface keratinocytes. We selected an appropriate bioink and innovatively combined an extrusion-based bioprinting technique with dual-photo source cross-linking technology to ensure the overall mechanical properties of the 3D bioprinted skin organoid. Moreover, the 3D bioprinted skin organoid was customized to match the size and shape of the wound site, facilitating convenient implantation. When applied to full-thickness skin defects in immunodeficient mice, the 3D bioprinted human-derived skin organoid significantly accelerated wound healing through in-situ regeneration, epithelialization, vascularization, and inhibition of excessive inflammation. The combination of skin organoid and 3D bioprinting technology can overcome the limitations of current skin substitutes, offering a novel treatment strategy to address large-area skin defects.

Wound healing, an intricate biological process, comprises orderly phases of simple biological processed including hemostasis, inflammation, angiogenesis, cell proliferation, and ECM remodeling. The regulation of the shift in these phases can be influenced by systemic or environmental conditions. Any untimely transitions between these phases can lead to chronic wounds and scarring, imposing a significant socio-economic burden on patients. Current treatment modalities are largely supportive in nature and primarily involve the prevention of infection and controlling inflammation. This often results in delayed healing and wound complications. Recent strides in regenerative medicine and tissue engineering offer innovative and patient-specific solutions. Mesenchymal stem cells (MSCs) and their secretome have gained specific prominence in this regard. Additionally, technologies like tissue nano-transfection enable in situ gene editing, a need-specific approach without the requirement of complex laboratory procedures. Innovating approaches like 3D bioprinting and ECM bioscaffolds also hold the potential to address wounds at the molecular and cellular levels. These regenerative approaches target common healing obstacles, such as hyper-inflammation thereby promoting self-recovery through crucial signaling pathway stimulation. The rationale of this review is to examine the benefits and limitations of both current and emerging technologies in wound care and to offer insights into potential advancements in the field. The shift towards such patient-centric therapies reflects a paradigmatic change in wound care strategies. Promising Modes of Treating Skin Wounds [ABSTRACT FROM AUTHOR]

As the cornerstone of tissue engineering and regeneration medicine research, developing a cost‐effective and bionic extracellular matrix (ECM) that can precisely modulate cellular behavior and form functional tissue remains challenging. An artificial ECM combining polysaccharides and fibrillar proteins to mimic the structure and composition of natural ECM provides a promising solution for cardiac tissue regeneration. In this study, we developed a bionic hydrogel scaffold by combining a quaternized β‐chitin derivative (QC) and fibrin‐matrigel (FM) in different ratios to mimic a natural ECM. We evaluated the stiffness of those composite hydrogels with different mixing ratios and their effects on the growth of human umbilical vein endothelial cells (HUVECs). The optimal hydrogels, QCFM1 hydrogels were further applied to load HUVECs into nude mice for in vivo angiogenesis. Besides, we encapsulated human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) into QCFM hydrogels and employed 3D bioprinting to achieve batch fabrication of human‐engineered heart tissue (hEHT). Finally, the myocardial structure and electrophysiological function of hEHT were evaluated by immunofluorescence and optical mapping. Designed artificial ECM has a tunable modulus (220–1380 Pa), which determines the different cellular behavior of HUVECs when encapsulated in these. QCFM1 composite hydrogels with optimal stiffness (800 Pa) and porous architecture were finally identified, which could adapt for in vitro cell spreading and in vivo angiogenesis of HUVECs. Moreover, QCFM1 hydrogels were applied in 3D bioprinting successfully to achieve batch fabrication of both ring‐shaped and patch‐shaped hEHT. These QCFM1 hydrogels‐based hEHTs possess organized sarcomeres and advanced function characteristics comparable to reported hEHTs. The chitin‐derived hydrogels are first used for cardiac tissue engineering and achieve the batch fabrication of functionalized artificial myocardium. Specifically, these novel QCFM1 hydrogels provided a reliable and economical choice serving as ideal ECM for application in tissue engineering and regeneration medicine. [ABSTRACT FROM AUTHOR]

Recent advancements in 3D-bioprinting technology have sparked a growing interest in its application for brain repair, encompassing tissue regeneration, drug delivery, and disease modeling. This literature review examines studies conducted over the past five years to assess the current state of research in this field. Common bioprinting methods and key parameters influencing their selection are explored, alongside an analysis of the diverse types of bioink utilized and their associated parameters. The extrusion-based 3D-bioprinting method emerged as the most widely studied and popular topic, followed by inkjet-based and laser-based bioprinting and stereolithography. Regarding bioinks, fibrin-based and collagen-based bioinks are predominantly utilized. Furthermore, this review elucidates how 3D bioprinting holds promise for neural tissue repair, regeneration, and drug screening, detailing the steps involved and various approaches employed. Neurovascular 3D printing and bioscaffold 3D printing stand out as the top two preferred methods for brain repair. The recent studies’ shortcomings and potential solutions to address them are also examined and discussed. Overall, by synthesizing recent findings, this review provides valuable insights into the potential of 3D bioprinting for advancing brain repairment strategies.

The technology of 3D bioprinting has sparked interest in improving tendon repair and regeneration, promoting quality of life. To perform this procedure, surgical intervention is often necessary to restore functional capacity. In this way, 3D bioprinting offers a scaffold design, producing tendons with precise microarchitectures, promoting the growth of new tissues. Furthermore, it may incorporate bioactive compounds that can further stimulate repair. This review elucidates how 3D bioprinting holds promise for tendon repair and regeneration, detailing the steps involved and the various approaches employed. They demonstrate future challenges and perspectives and provide valuable information on the concept, bioprinting design, and 3D bioprinting techniques for the repair of tendon injuries.

Gelatin methacryloyl (GelMA) hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties, which has been widely used in a variety of tissue engineering and tissue regeneration. However, pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment, which is difficult to meet the needs of bone repair. Moreover, GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments. This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration. The synthesis process of GelMA hydrogel was described in details, and various functional methods to meet the requirements of bone regeneration, including mechanical strength, porosity, vascularization, osteogenic differentiation, and immunoregulation for patient specific repair, etc. In addition, the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation, as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases (such as inflammation, infection, tumor) are also briefly reviewed. Finally, we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.

In its highly developed form, the evolving three-dimensional (3D) bioprinting technology aims to create 3D structures with living cells to mimic real tissue and organ functions. It would offer significant benefits across research, personalized medicine, and multiple other applications when adequately developed for human medicine. Presently, more technological activities are witnessed in North America, followed by Europe, Asia Pacific countries, Israel among the Middle East countries, and some South American countries. Around 75 commercial companies are active in 3D bioprinting, with only about a dozen making significant commercial progress. This number is expected to rise phenomenally as breakthroughs in manufacturing and the safe use of 3D bioprinted tissues and organs emerge. Legal frameworks for 3D bioprinting will likely be established, incorporating additions to existing drug laws once countries like the United States of America authorize using 3D bioprinted products in personalized medicine. The demand for 3D bioprinting products is rising based on expectations of future benefits. Therefore, intense research and development activities are ongoing, resulting in demands for the supply of research materials. The legal framework still needs to be put in place for the commercial use of 3D bioprinted tissues and organs in personalized medicine; therefore, laws are to be created for their safe use. This review provides a flavor of the evolution of 3D bioprinting startup companies globally using these technologies.

Abstract The aim of this study was to develop a three-dimensional (3D) cell model in order to evaluate the effectiveness of a traditional Chinese medicine decoction in the treatment of arthritis. Chondrocytes (ATDC5) and osteoblasts (MC3T3-E1) were 3D printed separately using methacryloyl gelatin (GelMA) hydrogel bioinks to mimic the natural 3D cell environment. Both cell types showed good biocompatibility in GelMA. Lipopolysaccharide (LPS) was added to the cell models to create inflammation models, which resulted in increased expression of inflammatory factors IL-1β, TNF-α, iNOS, and IL-6, and decreased expression of cell functional genes such as Collagen II (COLII), transcription factor SOX-9 (Sox9), Aggrecan, alkaline phosphatase (ALP), RUNX family transcription factor 2 (Runx2), Collagen I (COLI), Osteopontin (OPN), and bone morphogenetic protein-2 (BMP-2). The created inflammation model was then used to evaluate the effectiveness of Dangguiniantongtang (DGNT) decoctions. The results showed that DGNT reduced the expression of inflammatory factors and increased the expression of functional genes in the cell model. In summary, this study established a 3D cell model to assess the effectiveness of traditional Chinese medicine (TCM) decoctions, characterized the gene expression profile of the inflammatory state model, and provided a practical reference for future research on TCM efficacy evaluation for arthritis treatment.

In situ monitoring of bone regeneration enables timely diagnosis and intervention by acquiring vital biological parameters. However, an existing gap exists in the availability of effective methodologies for continuous and dynamic monitoring of the bone tissue regeneration process, encompassing the concurrent visualization of bone formation and implant degradation. Here, we present an integrated scaffold designed to facilitate real-time monitoring of both bone formation and implant degradation during the repair of bone defects. Laponite (Lap), CyP-loaded mesoporous silica (CyP@MSNs) and ultrasmall superparamagnetic iron oxide nanoparticles (USPIO@SiO2) were incorporated into a bioink containing bone marrow mesenchymal stem cells (BMSCs) to fabricate functional scaffolds denoted as C@M/GLU using 3D bioprinting technology. In both in vivo and in vitro experiments, the composite scaffold has demonstrated a significant enhancement of bone regeneration through the controlled release of silicon (Si) and magnesium (Mg) ions. Employing near-infrared fluorescence (NIR-FL) imaging, the composite scaffold facilitates the monitoring of alkaline phosphate (ALP) expression, providing an accurate reflection of the scaffold's initial osteogenic activity. Meanwhile, the degradation of scaffolds was monitored by tracking the changes in the magnetic resonance (MR) signals at various time points. These findings indicate that the designed scaffold holds potential as an in situ bone implant for combined visualization of osteogenesis and implant degradation throughout the bone repair process.

Highlights This review provides a comprehensive summary associated with recent progress in the preparation and application of microgels. The characteristics and applications of microgels and microgel-based scaffolds for cell culture and delivery are elaborated with an emphasis on the advantages of these carriers in cell therapy. This review expounds on the ongoing and foreseeable applications and current limitations of microgels and their aggregate in the field of biomedical engineering. Through stimulating innovative ideas, the present review paves new avenues for expanding the application of microgels in cell delivery techniques.

Recent advancements in organoid technology have heralded a transformative era in biomedical research, characterized by the emergence of gut organoids that replicate the structural and functional complexity of the human intestines. These stem cell-derived structures provide a dynamic platform for investigating intestinal physiology, disease pathogenesis, and therapeutic interventions. This model outperforms traditional two-dimensional cell cultures in replicating cell interactions and tissue dynamics. Gut organoids represent a significant leap towards personalized medicine. They provide a predictive model for human drug responses, thereby minimizing reliance on animal models and paving the path for more ethical and relevant research approaches. However, the transition from basic organoid models to more sophisticated, biomimetic systems that encapsulate the gut's multifaceted environment--including its interactions with microbial communities, immune cells, and neural networks--presents significant scientific challenges. This review concentrates on recent technological strides in overcoming these barriers, emphasizing innovative engineering approaches for integrating diverse cell types to replicate the gut's immune and neural components. It also explores the application of advanced fabrication techniques, such as 3D bioprinting and microfluidics, to construct organoids that more accurately replicate human tissue architecture. They provide insights into the intricate workings of the human gut, fostering the development of targeted, effective treatments. These advancements hold promise in revolutionizing disease modeling and drug discovery. Future research directions aim at refining these models further, making them more accessible and scalable for wider applications in scientific inquiry and clinical practice, thus heralding a new era of personalized and predictive medicine. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) bioprinting has made it possible to fabricate structures with intricate morphologies and architectures, which is considered difficult to do when using other conventional techniques like electrospinning. Although the 3D printing of thermoplastics has seen a huge boom in the past few years, it has been challenging to translate this technology to cell-based printing. A major limitation in bioprinting is the lack of inks that allow for the printing of 3D structures that meet the biological requirements of a specific organ or tissue. A bioink is a viscous polymer solution that cells are incorporated into before printing. Therefore, a bioink must have specific characteristics to ensure both good printability and biocompatibility. Despite the progress that has been made in bioprinting, achieving a balance between these two properties has been difficult. In this work, we developed a multimodal bioink that serves as both a cell carrier and a free radical scavenger for treating peripheral nerve injury. This bioink comprises poly-(vinyl alcohol) (PVA) and cerium oxide nanoparticles (also called nanoceria (NC)) and was developed with a dual crosslinking method that utilizes citric acid and sodium hydroxide. By employing this dual crosslinking method, good printability of the bioink and shape fidelity of the bioprinted structure were achieved. Additionally, a cell viability study demonstrated that the cells remained compatible and viable even after they underwent the printing process. The combination of this PVA/NC bioink and the dual crosslinking method proved to be effective in enhancing printability and cell biocompatibility for extrusion-based bioprinting applications. [ABSTRACT FROM AUTHOR]

Three dimensional (3D) bioprinting using photocrosslinkable hydrogels has gained considerable attention due to its versatility in various applications, including tissue engineering and drug delivery. Egg White (EW) is an organic biomaterial with excellent potential in tissue engineering. It provides abundant proteins, along with biocompatibility, bioactivity, adjustable mechanical properties, and intrinsic antiviral and antibacterial features. Here, a photocrosslinkable hydrogel derived from EW is developed through methacryloyl modification, resulting in Egg White methacryloyl (EWMA). Upon exposure to UV light, synthesized EWMA becomes crosslinked, creating hydrogels with remarkable bioactivity. These hydrogels offer adjustable mechanical and physical properties compatible with most current bioprinters. The EWMA hydrogels closely resemble the native extracellular matrix (ECM) due to cell‐binding and matrix metalloproteinase‐responsive motifs inherent in EW. In addition, EWMA promotes cell growth and proliferation in 3D cultures. It facilitates endothelialization when investigated with human umbilical vein endothelial cells (HUVECs), making it an attractive replacement for engineering hemocompatible vascular grafts and biomedical implants. In summary, the EWMA matrix enables the biofabrication of various living constructs. This breakthrough enhances the development of physiologically relevant 3D in vitro models and opens many opportunities in regenerative medicine. [ABSTRACT FROM AUTHOR]