Biofabrication最新文献

Colorectal cancer is a prominent global malignancy that highlights the pressing need for reliable preclinical models to expedite therapeutic efficacy and drug discovery. Traditional models, such as cell lines and patient-derived xenografts, are constrained by their inability to fully replicate tumor heterogeneity and support scalable drug screening. While patient-derived organoids more accurately preserve tumor pathophysiology, their clinical translation is impeded by technical challenges related to standardization, reproducibility, and high-throughput compatibility. In this study, we developed a microfluidic-engineered platform that employed a laminin-enhanced decellularized small intestinal submucosa extracellular matrix (dSISML) to produce uniform organoid-laden microspheres (MP). This biohybrid system eliminated the need for tumor-derived matrices (e.g. Matrigel) and provided a physiologically relevant microenvironment. When integrated with microfluidics, the platform facilitated rapid and scalable production of size-tunable MP, thereby effectively addressing critical bottlenecks in organoid handling and drug testing workflows. Our study demonstrated that dSISML could sustain organoid growth and drug responsiveness comparable to Matrigel, while offering improved operational simplicity and reduced batch variability. Moreover, dSISML enabled simpler and controllable high-throughput microsphere preparation. This advanced methodology not only delivers precision equivalent to conventional cell culture techniques but also empowers large-scale pharmacological evaluation through its automated media processing system. By integrating biomimetic design with scalable fabrication, this strategy advances personalized oncology through robustin vitromodels for high-throughput therapeutic screening and mechanistic studies.

Blindness caused by corneal stroma disease affects millions worldwide, the regeneration of corneal stroma has always been a challenge due to its sophisticated curvature structure and keratocyte-fibroblast transformation. In this study, we developed and optimized a series of gelatin methacrylate/collagen-based bioinks to fabricate convex corneal implants via 3D printing techniques. A novel method was proposed to enhance collagen solubility in neutral solutions by combining 2,3-epoxypropyltrimethylammonium chloride with high-molecular-weight type I collagen, with simulations suggesting that the mechanism primarily involved electrostatic interactions. To evaluate whether keratocytes respond to a convex microenvironment and to verify the effectiveness of the proposed printing strategy for corneal stromal regeneration, particularly in mitigating corneal fibrosis, we fabricated topological structures of both flat and convex corneas. These structures were systematically analyzed for their influence on keratocyte-to-fibroblast transformation and keratocyte phenotype maintenance. Morphological observations, along with gene and protein expression analyses, demonstrated that the convex architecture provided an optimal microenvironment for preserving the keratocyte phenotype. Moreover,in vivotransplantation revealed the convex cornea effectively suppressed corneal fibrosis compared to the flat cornea. These findings suggest that convex cornea holds promise as a potential translational approach for treating corneal stroma regeneration.

The minimally invasive and painless microneedle (MN) technology has become a promising platform for drug delivery and disease diagnosis. In this review, we first introduce the classification of MNs according to their sources and then summarize the preparation methods of MNs, including the stretching method, droplet-born air blowing, micromolding method, and 3D printing method. Subsequently, we also introduce how to prepare different types of MNs, such as solid, coated, hollow, dissolving, and frozen MNs, through material structure design. More importantly, the development of MNs in drug delivery, biosensing, wearable devices, cancer therapy and tissue regeneration in recent years has been reviewed. Finally, several significant challenges for further exploration in the field of MNs as well as perspectives and outlooks on future MN research, are also discussed in this review.

Melt electrowriting (MEW) is capable of generating highly defined microarchitectures suitable for tissue engineering applications. The main biodegradable polymer typically utilized for MEW processing, poly(ϵ-caprolactone), is prone to creep under dynamic loads and plasticization due to water absorption, making its use problematic for situations demanding dynamic loading in aqueous media. Photocrosslinking during processing can eliminate these problems while also allowing for manipulation of mechanical properties. However, photocrosslinking strategies utilized to date have either limited processing time or require prolonged UV irradiation. Herein we demonstrate the potential of a cyclic trimethylene carbonate monomer bearing a pendant coumarin moiety (MUM) for creating MEW processable copolymers that are thermally stable and photocrosslinkable. The MUM was copolymerized with caprolactone to form copolymers that were MEW processed into both linear and crimped fiber structures followed by long-wave UV photocrosslinking yielding high modulus scaffolds with very low sol content. The photocrosslinked scaffolds were also cytocompatible. The ability to copolymerize MUM with other cyclic lactone monomers allows for the generation of a variety of MEW processable polymers with tunable properties. Collectively, the findings demonstrate the potential of MUM containing copolymers for MEW generation of scaffolds for a range of tissue engineering applications.

The treatment of infected bone defects remains a challenge due to the complex biological processes involved, including antibacterial, anti-inflammatory, angiogenesis and bone regeneration. Polyetherimide (PEI) has promising applications in orthopaedics, but its biological inertness limits its clinical efficacy. In this study, a smart near-infrared (NIR) light and magnetic field responsive 3D printed scaffold was developed by combining PEI and Fe₃O₄nanoparticles. Gelatin methacrylate hydrogel containing aloe-emodin (AE), a natural antimicrobial and antioxidant compound, was subsequently injected into the 3D printed scaffold to create the P-Fe₃O₄@GM-AE composite scaffold. This composite scaffold exhibited several key functionalities: Firstly, it effectively eliminated methicillin-resistantStaphylococcus aureuswhen exposed to NIR light, achieving anin vivoantimicrobial rate of 99.97 ± 0.1%. Secondly, it effectively removed reactive oxygen species and prevented the pro-inflammatory M1 polarization of macrophages in the infected bone defect microenvironment, creating favorable conditions for bone reconstruction. Moreover, during the reconstruction stage, the magnetic composite scaffold, when combined with a static magnetic field, promoted osteogenesis-angiogenesis coupling, thereby accelerating bone repair. Thus, this study provides new insights and methods for the sequential treatment of infected bone defects.

In recent decades, our understanding of biomaterials has shifted from seeing them simply as physical supports for cells or drug delivery platforms to recognizing their active and dynamic role in tissue repair, guided by their physicochemical, mechanical, and biological properties. Biologically derived materials such as the decellularized extracellular matrix (dECM) offer the advantage of replicating the biomolecular cellular environment and have been proposed for tissue regeneration. However, their use as scaffolds is hindered by poor mechanical properties and limited tunability of physical features. Herein, we fabricated a bioinspired hybrid hydrogel by integrating a chemically cross-linked microporous polysaccharide scaffold with native ECM directly secreted by cells. First, the scaffold synthesis and culture conditions were optimized to enhance ECM deposition by fibroblasts. To obtain an acellular scaffold, decellularization using supercritical CO₂was performed and compared to a conventional method, demonstrating its superiority in ensuring efficient decellularization while preserving an enriched ECM lining the surface of the pores and preventing scaffold damage. The biohybrid hydrogel was characterized by a very low amount of DNA (<5 ng DNA mg^-1) and a network of highly interconnected pores covered by an abundant ECM including collagen I, collagen IV, fibronectin, elastin and laminin. This work presents a new versatile strategy that can be adapted to various tissues to engineer biomimetic microstructured materials overcoming the limitations associated with polymer-based and dECM-based strategies when used independently.

Osteochondral tissue is a functional complex with crosstalk shown to occur between cartilage and subchondral bone, playing a pivotal role in joint function and mobility. Osteochondral tissue repair has long been an enormous challenge in regenerative medicine and tissue engineering. With the development of biofabrication and biomaterials innovations, organoid technology, which can mimic the biological architecture and characteristics of organs through the construction of 3D tissue structuresin vitro, provides novel insight into osteochondral (OC) tissue regeneration. This review explores the significance of OC organoid biofabrication and the related biological structures and functions of the joint OC unit. Furthermore, we summarize novel biofabrication technologies used for OC organoids, such as 3D printing and microfluidics, and propose construction strategies for OC organoids. Finally, the application directions and challenges of OC organoids are outlined, emphasizing their potential for OC disease treatment.

Reconstructive surgery seeks to restore the aesthetic appearance and functional integrity of damaged organs and tissues. However, traditional approaches are fundamentally constrained by donor tissue scarcity and associated morbidity, highlighting the urgent need for engineered tissue substitutes. Organ building block (OBB)-based bioprinting has emerged as a promising strategy, utilizing microtissues with defined microarchitectural features as modular building units for three-dimensional bioprinting. This bottom-up approach facilitates the fabrication of personalized grafts that closely mimic the structural and functional characteristics of native tissues. In this review, we comprehensively summarize the current advances in OBB-based bioprinting technologies and their applications in reconstructive surgery, with a particular emphasis on cartilage, bone, vessels, muscle, and skin tissue reconstruction. We discuss the translational potential of this strategy, highlight key technical challenges, and propose future directions to facilitate clinical adoption. With ongoing innovation, OBB-based bioprinting holds the potential to revolutionize reconstructive surgery by enabling the production of functional, patient-specific tissue substitutes.

The 3D hydrogel-based tumor model demonstrates significant potential in replicating the physiological characteristics ofin vivotumor environments for mechanistic studies and drug testing. However, the challenge persists in accurately mimicking a vascularized microtumor with a compartmentalized structure in a controlled, heterogeneous, and high-throughput manner. This study introduces a vascularized 3D tumor model that incorporates an endothelial cell (EC) barrier, created by encapsulating glioma cells and human umbilical vein endothelial cells (HUVECs) within the core (6% gelatin) and shell (10% GelMa) of core-shell microbeads, respectively. Upon culture, the tumor cells develop spheroids within the liquid core, while the HUVECs in the shell migrate and adhere to the GelMa surface, ultimately forming an EC barrier. This 3D microengineered tumor model exhibits angiogenesis in solid tumor spheroids, effectively mirroring thein vivostructure and providing relevant biochemical and biophysical properties. Notably, in comparison to 2D cell cultures, the vascularized tumor model shows significantly higher half-maximal inhibitory concentrations for the anticancer drug doxorubicin. Collectively, these findings highlight the considerable potential of engineered 3D tumor models in drug testing.

Currently, type 1 diabetes (T1D) can be treated through implantation of allogenic islets, which replenish the beta cell population, however this method requires an extensive post-implantation immunosuppressant regimen. Personalized cellular therapy can address this through implantation of an autologous cell population, induced pluripotent stem cells (iPSCs). Cellular therapy, however, requires an encapsulation device for implantation, and so to achieve this uniformly with cells in a clinical setting, bioprinting is a useful option. Bioprinting is dependent on having a bioink that is printable, retains structural fidelity after printing, and is supportive of cell type and function. While bioprinting of pancreatic islets has been demonstrated previously, success in maintaining islet function post-printing has been varied. The objective of this study is to investigate the feasibility of printing functional islets by determining the appropriate combination of bioink, printing parameters, and cell configuration. Here, we detail the successful bioprinting of both primary human islets and iPSC-derived islets embedded in an alginate/methylcellulose bioink, with functionality sustained within the construct for both cell lineages. Sc-RNAseq analysis also revealed that printing did not adversely affect the genetic expression and metabolic functionality of the iPSC-derived islets. Importantly, the iPSC-derived islets displayed comparable functionality to the primary islets, indicating the potential to act as a cell source alternative for T1D implantation.