Dissecting the Interplay Mechanism among Process Parameters toward the Biofabrication of High-Quality Shapes in Embedded Bioprinting.

Embedded bioprinting overcomes the barriers associated with the conventional extrusion-based bioprinting process as it enables the direct deposition of bioinks in 3D inside a support bath by providing in situ self-support for deposited bioinks during bioprinting to prevent their collapse and deformation. Embedded bioprinting improves the shape quality of bioprinted constructs made up of soft materials and low-viscosity bioinks, leading to a promising strategy for better anatomical mimicry of tissues or organs. Herein, the interplay mechanism among the printing process parameters toward improved shape quality is critically reviewed. The impact of material properties of the support bath and bioink, printing conditions, cross-linking mechanisms, and post-printing treatment methods, on the printing fidelity, stability, and resolution of the structures is meticulously dissected and thoroughly discussed. Further, the potential scope and applications of this technology in the fields of bioprinting and regenerative medicine are presented. Finally, outstanding challenges and opportunities of embedded bioprinting as well as its promise for fabricating functional solid organs in the future are discussed.

Biofabrication of Composite Tendon Constructs with the Fibrous Arrangement, High Cell Density, and Enhanced Cell Alignment.

Current tissue-engineered tendons are mostly limited to the replication of fibrous organizations of native tendons, which lack the biomimicry of a densely packed cell arrangement. In this study, composite tendon constructs (CTCs) with fibrous arrangement, high cell density, and enhanced cell alignment were developed by integrating the electrohydrodynamic jet 3D printing (e-jetting) technique and the fabrication of tissue strands (TSs). A tubular polycaprolactone (PCL) scaffold was created using e-jetting, followed by coating a thin layer of alginate. Human mesenchymal stem cells were then microinjected into the PCL scaffolds, aggregated into TSs, and formed CTCs with a core-shell structure. Owing to the presence of TSs, CTCs demonstrated the anatomically relevant cell density and morphology, and cells migrated from the TSs onto e-jetted scaffolds. Also, the mechanical strength of CTCs approached that of native tendons due to the existence of e-jetted scaffolds (Young's modulus: ∼21 MPa, ultimate strength: ∼5 MPa). During the entire culture period, CTCs maintained high survival rates and good structural integrity without the observation of necrotic cores and disintegration of two portions. In addition, CTCs that were cultured with uniaxial cyclic stretching revealed not only the increased expression of tendon-related proteins but also the enhanced cellular orientation. The promising results demonstrated the potential of this novel biofabrication strategy for building tissue-engineered tendon constructs with the proper biological, mechanical, and histological relevance..

Organ bioprinting: progress, challenges and outlook.

Bioprinting, as a groundbreaking technology, enables the fabrication of biomimetic tissues and organs with highly complex structures, multiple cell types, mechanical heterogeneity, and diverse functional gradients. With the growing demand for organ transplantation and the limited number of organ donors, bioprinting holds great promise for addressing the organ shortage by manufacturing completely functional organs. While the bioprinting of complete organs remains a distant goal, there has been considerable progress in the development of bioprinted transplantable tissues and organs for regenerative medicine. This review article recapitulates the current achievements of organ 3D bioprinting, primarily encompassing five important organs in the human body (i.e., the heart, kidneys, liver, pancreas, and lungs). Challenges from cellular techniques, biomanufacturing technologies, and organ maturation techniques are also deliberated for the broad application of organ bioprinting. In addition, the integration of bioprinting with other cutting-edge technologies including machine learning, organoids, and microfluidics is envisioned, which strives to offer the reader the prospect of bioprinting in constructing functional organs.

Development of digital light processing-based multi-material bioprinting for fabrication of heterogeneous tissue constructs.

Human tissues and organs have heterogeneous structures with multiple property gradients, which are difficult to restore by single-material bioprinting technology. The advances in multi-material bioprinting technologies have shown great promise in replicating tissue-engineered constructs with one or more functional gradients. In this study, a multi-material 3D printing system based on digital light processing (DLP) was developed, which could efficiently complete multi-material bioprinting tasks. An appropriate concentration of an ultraviolet absorber was selected to improve the printability of channels, and meanwhile, curing parameters were optimized to improve the printing accuracy. The regulation of the mechanical properties of 3D printed constructs was also explored, which offered guidance on the printing of constructs with mechanical anisotropy. In addition, a cell-laden tracheal construct was bioprinted with a biomimetic heterogeneous structure and mechanical gradient, which could support superior cell viability during a 7-day culture. This study showed that the DLP-based process has the capability of building constructs with complex structures and multiple materials, exhibiting the potential to be used in the biofabrication of heterogeneous and functionally-graded tissues and organs for regenerative medicine.