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Abstract 3D bioprinting has enabled the fabrication of tissue‐mimetic constructs with freeform designs that include living cells. In the development of new bioprinting techniques, the controlled use of diffusion has become an emerging strategy to tailor the properties and geometry of printed constructs. Specifically, the diffusion of molecules with specialized functions, including crosslinkers, catalysts, growth factors, or viscosity‐modulating agents, across the interface of printed constructs will directly affect material properties such as microstructure, stiffness, and biochemistry, all of which can impact cell phenotype. For example, diffusion‐induced gelation is employed to generate constructs with multiple materials, dynamic mechanical properties, and perfusable geometries. In general, these diffusion‐based bioprinting strategies can be categorized into those based on inward diffusion (i.e., into the printed ink from the surrounding air, solution, or support bath), outward diffusion (i.e., from the printed ink into the surroundings), or diffusion within the printed construct (i.e., from one zone to another). This review provides an overview of recent advances in diffusion‐based bioprinting strategies, discusses emerging methods to characterize and predict diffusion in bioprinting, and highlights promising next steps in applying diffusion‐based strategies to overcome current limitations in biofabrication.
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Integrating Engineered Living Materials with 3D Bioprinting
Abstract Engineered living materials (ELMs) are an emerging class of biohybrid materials with genetically programmable functionalities. Integrating ELMs with 3D bioprinting synergizes their biological programmability with the geometry‐driven functionality of 3D‐printed constructs, transforming these materials into practical products and engineering solutions. This integration also introduces a new paradigm in additive manufacturing that harnesses the “livingness” of encapsulated microorganisms as an active element in the fabrication process to create adaptive and evolving 3D constructs. This Perspective presents recent advances in 3D bioprinting and discusses current developments at the intersection of 3D bioprinting and ELMs. It highlights opportunities at the interface of these two emerging fields, including understanding the interactions between living and nonliving components of ELMs for bioink design, incorporating synthetic biology into bioprinting workflows, utilizing microbial growth as a postprinting fabrication process, and integrating shape‐morphing materials to enable the 4D printing of ELMs.
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- PAR ID:
- 10598059
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Functional Materials
- ISSN:
- 1616-301X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Bioprinting is an additive manufacturing technique that combines living cells, biomaterials, and biological molecules to develop biologically functional constructs. Three-dimensional (3D) bioprinting is commonly used as anin vitromodeling system and is a more accurate representation ofin vivoconditions in comparison to two-dimensional cell culture. Although 3D bioprinting has been utilized in various tissue engineering and clinical applications, it only takes into consideration the initial state of the printed scaffold or object. Four-dimensional (4D) bioprinting has emerged in recent years to incorporate the additional dimension of time within the printed 3D scaffolds. During the 4D bioprinting process, an external stimulus is exposed to the printed construct, which ultimately changes its shape or functionality. By studying how the structures and the embedded cells respond to various stimuli, researchers can gain a deeper understanding of the functionality of native tissues. This review paper will focus on the biomaterial breakthroughs in the newly advancing field of 4D bioprinting and their applications in tissue engineering and regeneration. In addition, the use of smart biomaterials and 4D printing mechanisms for tissue engineering applications is discussed to demonstrate potential insights for novel 4D bioprinting applications. To address the current challenges with this technology, we will conclude with future perspectives involving the incorporation of biological scaffolds and self-assembling nanomaterials in bioprinted tissue constructs.more » « less
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Engineered living materials (ELMs) are an emerging class of biohybrid materials that have shown great promise with advanced capabilities unachievable by conventional materials. However, application of ELMs outside of the laboratory has been limited due to the need for periodic media replenishment or complete media immersion. We herein demonstrated the integration of capillary microfluidics for the autonomous and pump-free hydration of ELM hydrogels. We optimized 3D printing parameters, including exposure time and build plate lift and retract distances, to obtain microchannel dimensions capable of spontaneous capillary flow using a low-cost liquid crystal display stereolithographic apparatus (LCD-SLA) 3D printer and two hydrogel resins that are suitable for ELMs. Microchannel dimensions were accurate with ≤ 10% deviation between designed and measured widths and precise with coefficients of variation (CVs) <5% for microchannels ≥ 206.4 µm. We demonstrated proof-of-concept spontaneous capillary flow in 3D printed microfluidic devices using dye-incorporated lysogeny broth (LB). Snapshots of the devices captured up to 24 hours showed the diffusion of dye-incorporated LB throughout the bulk material. Through this proof-of-concept study, we have showcased the feasibility of integrating capillary microfluidics with ELMs for the autonomous and pump-free flow of fluids towards self-sustaining and long-term hydration.more » « less
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null (Ed.)The encapsulation of cells within gel-phase materials to form bioinks offers distinct advantages for next-generation 3D bioprinting. 3D bioprinting has emerged as a promising tool for patterning cells, but the technology remains limited in its ability to produce biofunctional, tissue-like constructs due to a dearth of materials suitable for bioinks. While early demonstrations commonly used viscous polymers optimized for printability, these materials often lacked cell compatibility and biological functionality. In response, advanced materials that exist in the gel phase during the entire printing process are being developed, since hydrogels are uniquely positioned to both protect cells during extrusion and provide biological signals to embedded cells as the construct matures during culture. Here, an overview of the design considerations for gel-phase materials as bioinks is presented, with a focus on their mechanical, biochemical, and dynamic gel properties. Current challenges and opportunities that arise due to the fact that bioprinted constructs are active, living hydrogels composed of both acellular and cellular components are also evaluated. Engineering hydrogels with consideration of cells as an intrinsic component of the printed bioink will enable control over the evolution of the living construct after printing to achieve greater biofunctionality.more » « less
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Abstract Three-dimensional (3D) bioprinting is a promising technique for spatially patterning cells and materials into constructs that mimic native tissues and organs. However, a trade-off exists between printability and biological function, where weak materials are typically more suited for 3D cell culture but exhibit poor shape fidelity when printed in air. Recently, a new class of assistive materials has emerged to overcome this limitation and enable fabrication of more complex, biologically relevant geometries, even when using soft materials as bioinks. These materials include support baths, which bioinks are printed into, and sacrificial inks, which are printed themselves and then later removed. Support baths are commonly yield-stress materials that provide physical confinement during the printing process to improve resolution and shape fidelity. Sacrificial inks have primarily been used to create void spaces and pattern perfusable networks, but they can also be combined directly with the bioink to change its mechanical properties for improved printability or increased porosity. Here, we outline the advantages of using such assistive materials in 3D bioprinting, define their material property requirements, and offer case study examples of how these materials are used in practice. Finally, we discuss the remaining challenges and future opportunities in the development of assistive materials that will propel the bioprinting field forward toward creating full-scale, biomimetic tissues and organs.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1002/adfm.202500934
