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We present an in-plane beam converter scheme that can focus a large Gaussian slab mode into a tightly focused spot approximately hundreds of micrometers away from the chip facet. Our approach involves designing the modal expander that converts a photonic waveguide mode to a large Gaussian slab mode and engineering the two-dimensional (2D) gradient-index subwavelength grating arrays that modify modal wavefront to be focused as the beam propagates. The device is designed on a monolithic silicon nitride scheme, which is transparent at the visible wavelength regime and readily available for the complementary metal-oxide-semiconductor process. Our device can be utilized in various chip-scale photonic applications, especially involving biochemical species and target samples ranging from one to tens of micrometer scales. 

Abstract Microgels have recently received widespread attention for their applications in a wide array of domains such as tissue engineering, regenerative medicine, and cell and tissue transplantation because of their properties like injectability, modularity, porosity, and the ability to be customized in terms of size, form, and mechanical properties. However, it is still challenging to mass (high-throughput) produce microgels with diverse sizes and tunable properties. Herein, we utilized an air-assisted co-axial device (ACAD) for continuous production of microgels in a high-throughput manner. To test its robustness, microgels of multiple hydrogels and their combination, including alginate (Alg), gelatin methacrylate (GelMA) and Alg–GelMA, were formed at a maximum production rate of ∼65 000 microgels s⁻¹while retaining circularity and a size range of 50–500µm based on varying air pressure levels. The ACAD platform allowed single and multiple cell encapsulation with 74 ± 6% efficiency. These microgels illustrated appealing rheological properties such as yield stress, viscosity, and shear modulus for bioprinting applications. Specifically, Alg microgels have the potential to be used as a sacrificial support bath while GelMA microgels have potential for direct extrusion both on their own or when loaded in a bulk GelMA hydrogel. Generated microgels showed high cell viability (>90%) and proliferation of MDA-MB-231 and human dermal fibroblasts over seven days in both encapsulation and scaffolding applications, particularly for GelMA microgels. The developed strategy provides a facile and rapid approach without any complex or expensive consumables and accessories for scalable high-throughput microgel production for cell therapy, tissue regeneration and 3D bioprinting applications. 

Abstract The engineering of osteochondral interfaces remains a challenge. MicroRNAs (miRs) have emerged as significant tools to regulate the differentiation and proliferation of osteogenic and chondrogenic formation in the human musculoskeletal system. Here, we describe a novel approach to osteochondral reconstruction based on the three-dimensional (3D) bioprinting of miR-transfected adipose-derived stem cell (ADSC) spheroids to produce a heterotypic interface that addresses the intrinsic limitations of the traditional approach to inducing zonal differentiation via the use of diffusible cytokines. We evaluated the delivery of miR-148b for osteogenic differentiation and the codelivery of miR-140 and miR-21 for the chondrogenic differentiation of ADSC spheroids. Our results demonstrated that miR-transfected ADSC spheroids exhibited upregulated expression of osteogenic and chondrogenic differentiation related gene and protein markers, and enhanced mineralization and cell proliferation compared to spheroids differentiated using a commercially-available differentiation medium. Upon confirmation of the osteogenic and chondrogenic potential of miR-transfected ADSC spheroids, using aspiration-assisted bioprinting, these spheroids were 3D bioprinted into a dual-layer heterotypic osteochondral interface with a stratified arrangement of distinct osteogenic and chondrogenic zones. The proposed approach holds great promise for the biofabrication of stratified tissues, not only for the osteochondral interfaces presented in this work, but also for other composite tissues and tissue interfaces, such as, but not limited to, the bone-tendon-muscle interface and craniofacial tissues. 

Abstract Aspiration-assisted freeform bioprinting (AAfB) has emerged as a promising technique for precise placement of tissue spheroids in three-dimensional (3D) space enabling tissue fabrication. To achieve success in embedded bioprinting using AAfB, an ideal support bath should possess shear-thinning behavior and yield-stress to facilitate tight fusion and assembly of bioprinted spheroids forming tissues. Several studies have demonstrated support baths for embedded bioprinting in the past few years, yet a majority of these materials poses challenges due to their low biocompatibility, opaqueness, complex and prolonged preparation procedures, and limited spheroid fusion efficacy. In this study, to circumvent the aforementioned limitations, we present the feasibility of AAfB of human mesenchymal stem cell (hMSC) spheroids in alginate microgels as a support bath. Alginate microgels were first prepared with different particle sizes modulated by blending time and concentration, followed by determination of the optimal bioprinting conditions by the assessment of rheological properties, bioprintability, and spheroid fusion efficiency. The bioprinted and consequently self-assembled tissue structures made of hMSC spheroids were osteogenically induced for bone tissue formation. Alongside, we investigated the effects of peripheral blood monocyte-derived osteoclast incorporation into the hMSC spheroids in heterotypic bone tissue formation. We demonstrated that alginate microgels enabled unprecedented positional accuracy (∼5%), transparency for visualization, and improved fusion efficiency (∼97%) of bioprinted hMSC spheroids for bone fabrication. This study demonstrates the potential of using alginate microgels as a support bath for many different applications including but not limited to freeform bioprinting of spheroids, cell-laden hydrogels, and fugitive inks to form viable tissue constructs.