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Optimizing 3D cell culture environments via tuning of the GelMA properties via molecular weight and degree of functionalization modulation and targeting the mechanical profile of soft tissues. A) storage moduli at the 7 min mark (G′) B) Compressive mechanical properties and C) the stress relaxation % after 2 min for the different GelMA formulations at 5% w/v concentration (n = 4). D) Recapitulating an optimal environment for the iβ‐cell line leveraging 90p60 GelMA mechanical properties. i) Effect of molecular weight of GelMA bioresins (90p60 and 160p60) at 5% w/v concentration (1%w/v LAP, dissolved in PBS 1X) on ii) ability to proliferate and form islet‐like clusters iβ‐cell line and iii) metabolic activity (n = 4). Scale bars: 500 µm E) i) Effect of selected salient macromolecules from the pancreatic ECM on ii) metabolic activity, iii) overall, and iv) fold‐increment normalized luciferase secretion of iβ‐cell line volumetric printed in GelMA 90p60 (n = 4). Scale bar: 300 µm.
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Volumetric Bioprinting (VBP), enables to rapidly build complex, cell‐laden hydrogel constructs for tissue engineering and regenerative medicine. Light‐based tomographic manufacturing enables spatial‐selective polymerization of a bioresin, resulting in higher throughput and resolution than what is achieved using traditional techniques. However, meth...
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Bioprinting of microtissues has become a standard technique in medical and biotechnological research, offering a more accurate replication of the in vivo setting than conventional 2D cell culture. However, widespread adoption is limited by the absence of a universally accepted printing benchmark—common in standard fused deposition modeling (FDM) pr...
Citations
... GelMA is now a popular semi-synthetic hydrogel, finding many applications in 3D cell culture and bioprinting. 22,23 It consists of the natural polymer gelatin, derived from collagen, and modified with methacryloyl functional groups (MA). 21 Photo-crosslinking is used to form a covalently bound network of MA groups, which results in a GelMA hydrogel. ...
Xenogeneic tumour origin and batch-to-batch variability of Engelbreth-Holm-Swarm sarcoma tumour cell-derived hydrogels (Matrigel, Cultrex) limit the biomedical application of organoids in tissue engineering. The gelatin-methacryloyl (GelMA) hydrogels represent a defined, tunable, and GMP-friendly alternative, but they are rarely studied as alternative to Matrigel. Here, we studied effects of mechanical properties of GelMA and addition of laminin-111 on encapsulation and growth of small intestinal organoids. GelMA-embedded organoids displayed polarity reversion, resulting in apical-out and apical-basal phenotypes, independent from the matrix stiffness. Addition of laminin-111 softened hydrogels and also resulted in a partial restoration of the basal-out phenotype. Interestingly, despite the incomplete polarity restoration, GelMA-organoids still showed minor growth. GelMA stiffness and concentration influenced the transition from 3D to 2D organoid cultures. Collectively, our study confirms that tuning of GelMA mechanical properties alone cannot recapitulate the basal membrane matrix. However, controlled polarity reversion offers a tool for engineering organoids and enabling apical membrane access.
... [13] This approach optimizes the printed structure and enhances various mechanical and biological properties By integrating diverse biomaterials, multimaterial bioprinting also improves the complexity and functionality of the constructs, creating more accurate biological models and engineered tissues. [14] Moreover, traditional single-material bioprinting fails to meet the dynamic demands of complex tissue structures due to its limited material choices and lack of spatiotemporal control. This shortfall is addressed by multidimensional bioprinting, which introduces a higher level of versatility and adaptability. ...
3D bioprinting has been advanced from creating simple, static structures with single materials to sophisticated multimaterial and multidimensional designs. This evolution has improved printing precision, the range of application and dynamic functionality. Multimaterial and multidimensional bioprinting represent significant advancements in regenerative medicine. By integrating a range of materials and employing diverse printing techniques, these approaches address the limitations of single‐material and fixed‐dimension methods, thereby overcoming the constraints of traditional, uniform complexity. Multimaterial bioprinting fabricates additive manufacturing structures simultaneously with materials vary in composition and mechanical strength, which increases the complexity in biomedical applications. Meanwhile, multidimensional bioprinting involves incorporating additional dimensions (such as time or space) into printing process, which allows for dynamic configuration transformations and functional responses. Here, the basic concepts and components are summarized of multimaterial and multidimensional bioprinting, the medical adaptation is discussed and the advantages, challenges as well as future perspectives of current approaches are analyzed. Moreover, this review provides perspective on multimaterial and multidimensional bioprinting, and highlights new opportunities in regenerative medicine tissue engineering, particularly in bone tissue engineering bioprinting.
... Such a system, when effectively combined with wavelengthspecific photocrosslinking or photodegradation chemistries, can allow in situ photo-bioprinting or photodegradation of multimaterial constructs. [51,52] As a conceptual demonstration of synergistic multi-wavelength projection, we activated each laser wavelength in pulses synchronized with the image sequence displayed on the DMD (illustrated in Figure 8A). For instance, the images for the FaSt-Light and ETH logo were divided into three separate images and synchronized with laser activation at 405, 450, or 520 nm, respectively, to create multicolor image projections ( Figure 8B). ...
Light‐based biofabrication techniques have revolutionized the field of tissue engineering and regenerative medicine. Specifically, the projection of structured light, where the spatial distribution of light is controlled at both macro and microscale, has enabled precise fabrication of complex three dimensional structures with high resolution and speed. However, despite tremendous progress, biofabrication processes are mostly limited to benchtop devices which limit the flexibility in terms of where the fabrication can occur. Here, a Fiber‐assisted Structured Light (FaSt‐Light) projection apparatus for rapid in situ crosslinking of photoresins is demonstrated. This approach uses image‐guide fiber bundles which can project bespoke images at multiple wavelengths, enabling flexibility and spatial control of different photoinitiation systems and crosslinking chemistries and also the location of fabrication. Coupling of different sizes of fibers and different lenses attached to the fibers to project small (several mm) or large (several cm) images for material crosslinking is demonstrated. FaSt‐Light allows control over the cross‐section of the crosslinked resins and enables the introduction of microfilaments which can further guide cellular infiltration, differentiation, and anisotropic matrix production. The proposed approach can lead to a new range of in situ biofabrication techniques which improve the translational potential of photofabricated tissues and grafts.
... While volumetric AM achieves remarkable printing speeds by curing entire volumes in a single step, [73][74][75] integrating multi-material capability typically requires additional extrusion systems, which may introduce design complexity. [76][77][78] In contrast, the DF-μCLIP approach is specifically designed for high-resolution, real-time material switching, enabling finely tuned multi-material gradients with minimal overhead. At the same time, the introduction of intermixed interfaces enhances mechanical properties and potentially transfer properties. ...
Functionally gradient materials emulate nature's ability to seamlessly blend properties through variations in material composition, unlocking advanced engineering applications such as biomedical devices and high‐performance composites. Additive manufacturing, particularly stereolithography, enables sophisticated 3D geometries with diverse materials. However, current stereolithography‐based multi‐material 3D printing is constrained by time‐intensive material switching and compromised interfacial properties. To overcome these challenges, we present dynamic fluid‐assisted micro continuous liquid interface production (DF‐µCLIP), a high‐speed multi‐material 3D printing platform that integrates varying compositions in a fully continuous fashion. By utilizing the polymerization‐free “dead zone”, vliquid resins are seamlessly replenished within a resin bath equipped with dynamic fluidic channels and a synchronized material supply system. DF‐µCLIP achieves ultra‐fast printing speeds of 90 mm/hour with 7.4 µ m pixel‐1 resolution while enabling on‐the‐fly material transitions. This strategy enhances mechanical strength at multi‐material interface through entangled polymer networks and promotes seamless material transitions between distinct materials ilike fragile hydrogels and rigid polymers, addressing interfacial failure caused by mismatch of swelling behavior. Additionally, dynamic material replenishment with real‐time composition control enables continuous gradient printing instead of the conventional step‐wise controlled gradient. Demonstrations include polymers with gradient color transitions and gradient carbon nanotube (CNT) composites with seamlessly varying conductivity.