Search for: All records

Decellularized extracellular matrix (dECM)‐based hydrogels are widely applied to additive biomanufacturing strategies for relevant applications. The extracellular matrix components and growth factors of dECM play crucial roles in cell adhesion, growth, and differentiation. However, the generally poor mechanical properties and printability have remained as major limitations for dECM‐based materials. In this study, heart‐derived dECM (h‐dECM) and meniscus‐derived dECM (Ms‐dECM) bioinks in their pristine, unmodified state supplemented with the photoinitiator system of tris(2,2‐bipyridyl) dichlororuthenium(II) hexahydrate and sodium persulfate, demonstrate cytocompatibility with volumetric bioprinting processes. This recently developed bioprinting modality illuminates a dynamically evolving light pattern into a rotating volume of the bioink, and thus decouples the requirement of mechanical strengths of bioprinted hydrogel constructs with printability, allowing for the fabrication of sophisticated shapes and architectures with low‐concentration dECM materials that set within tens of seconds. As exemplary applications, cardiac tissues are volumetrically bioprinted using the cardiomyocyte‐laden h‐dECM bioink showing favorable cell proliferation, expansion, spreading, biomarker expressions, and synchronized contractions; whereas the volumetrically bioprinted Ms‐dECM meniscus structures embedded with human mesenchymal stem cells present appropriate chondrogenic differentiation outcomes. This study supplies expanded bioink libraries for volumetric bioprinting and broadens utilities of dECM toward tissue engineering and regenerative medicine.

 

Digital light processing bioprinting favors biofabrication of tissues with improved structural complexity. However, soft-tissue fabrication with this method remains a challenge to balance the physical performances of the bioinks for high-fidelity bioprinting and suitable microenvironments for the encapsulated cells to thrive. Here, we propose a molecular cleavage approach, where hyaluronic acid methacrylate (HAMA) is mixed with gelatin methacryloyl to achieve high-performance bioprinting, followed by selectively enzymatic digestion of HAMA, resulting in tissue-matching mechanical properties without losing the structural complexity and fidelity. Our method allows cellular morphological and functional improvements across multiple bioprinted tissue types featuring a wide range of mechanical stiffness, from the muscles to the brain, the softest organ of the human body. This platform endows us to biofabricate mechanically precisely tunable constructs to meet the biological function requirements of target tissues, potentially paving the way for broad applications in tissue and tissue model engineering.

 

Although various (bio)fabrication technologies have achieved revolutionary progress in the past decades, engineered constructs still fall short of expectations owing to their inability to attain precisely designable functions. Shrinkable and expandable (bio)materials feature unique characteristics leading to size‐/shape‐shifting and thus have exhibited a strong potential to equip current engineering technologies with promoted capacities toward applications in biomedicine. In this progress report, the advances of size‐/shape‐shifting (bio)materials enabled by various stimuli, are evaluated; furthermore, representative biomedical applications associated with size‐/shape‐shifting (bio)materials are also exemplified. Toward the future, the combination of size‐/shape‐shifting (bio)materials and 3D/4D fabrication technologies presents a wide range of possibilities for further development of intricate functional architectures.

 

Recapitulation of complex tissues signifies a remarkable challenge and, to date, only a few approaches have emerged that can efficiently reconstruct necessary gradients in 3D constructs. This is true even though mimicry of these gradients is of great importance to establish the functionality of engineered tissues and devices. Here, a composable‐gradient Digital Light Processing (DLP)‐based (bio)printing system is developed, utilizing the unprecedented integration of a microfluidic mixer for the generation of either continual or discrete gradients of desired (bio)inks in real time. Notably, the precisely controlled gradients are composable on‐the‐fly by facilely by adjusting the (bio)ink flow ratios. In addition, this setup is designed in such a way that (bio)ink waste is minimized when exchanging the gradient (bio)inks, further enhancing this time‐ and (bio)ink‐saving strategy. Various planar and 3D structures exhibiting continual gradients of materials, of cell densities, of growth factor concentrations, of hydrogel stiffness, and of porosities in horizontal and/or vertical direction, are exemplified. The composable fabrication of multifunctional gradients strongly supports the potential of the unique bioprinting system in numerous biomedical applications.

 

A new approach is described for fabricating 3D poly(ε‐caprolactone) (PCL)/gelatin (1:1) nanofiber aerogels with patterned macrochannels and anisotropic microchannels by freeze‐casting with 3D‐printed sacrificial templates. Single layer or multiple layers of macrochannels are formed through an inverse replica of 3D‐printed templates. Aligned microchannels formed by partially anisotropic freezing act as interconnected pores between templated macrochannels. The resulting macro‐/microchannels within nanofiber aerogels significantly increase preosteoblast infiltration in vitro. The conjugation of vascular endothelial growth factor (VEGF)‐mimicking QK peptide to PCL/gelatin/gelatin methacryloyl (1:0.5:0.5) nanofiber aerogels with patterned macrochannels promotes the formation of a microvascular network of seeded human microvascular endothelial cells. Moreover, nanofiber aerogels with patterned macrochannels and anisotropic microchannels show significantly enhanced cellular infiltration rates and host tissue integration compared to aerogels without macrochannels following subcutaneous implantation in rats. Taken together, this novel class of nanofiber aerogels holds great potential in biomedical applications including tissue repair and regeneration, wound healing, and 3D tissue/disease modeling.

 

With the rapid development and popularization of additive manufacturing, different technologies, including, but not limited to, extrusion-, droplet-, and vat-photopolymerization-based fabrication techniques, have emerged that have allowed tremendous progress in three-dimensional (3D) printing in the past decades. Bioprinting, typically using living cells and/or biomaterials conformed by different printing modalities, has produced functional tissues. As a subclass of vat-photopolymerization bioprinting, digital light processing (DLP) uses digitally controlled photomasks to selectively solidify liquid photocurable bioinks to construct complex physical objects in a layer-by-layer manner. DLP bioprinting presents unique advantages, including short printing times, relatively low manufacturing costs, and decently high resolutions, allowing users to achieve significant progress in the bioprinting of tissue-like complex structures. Nevertheless, the need to accommodate different materials while bioprinting and improve the printing performance has driven the rapid progress in DLP bioprinters, which requires multiple pieces of knowledge ranging from optics, electronics, software, and materials beyond the biological aspects. This raises the need for a comprehensive review to recapitulate the most important considerations in the design and assembly of DLP bioprinters. This review begins with analyzing unique considerations and specific examples in the hardware, including the resin vat, optical system, and electronics. In the software, the workflow is analyzed, including the parameters to be considered for the control of the bioprinter and the voxelizing/slicing algorithm. In addition, we briefly discuss the material requirements for DLP bioprinting. Then, we provide a section with best practices and maintenance of a do-it-yourself DLP bioprinter. Finally, we highlight the future outlooks of the DLP technology and their critical role in directing the future of bioprinting. The state-of-the-art progress in DLP bioprinter in this review will provide a set of knowledge for innovative DLP bioprinter designs. 

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. 

Cardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy‐induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with preexisting cardiac dysfunctions may lead to different incident levels of CIC. Here, a model is presented for investigating CIC where not only induced pluripotent stem cell (iPSC)‐derived cardiac tissues are interacted with BC tissues on a dual‐organ platform, but electrochemical immuno‐aptasensors can also monitor cell‐secreted multiple biomarkers. Fibrotic stages of iPSC‐derived cardiac tissues are promoted with a supplement of transforming growth factor‐β 1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno‐aptasensors well‐matches the outcomes from conventional enzyme‐linked immunosorbent assay, demonstrating the accuracy of the authors’ sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle‐based DOX‐delivery system. The proposed platform would potentially help allow early detection and prediction of CIC in individual patients in the future.