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Abstract Biological processes are inherently dynamic, necessitating biomaterial platforms capable of spatiotemporal control over cellular organization and matrix stiffness for accurate study of tissue development, wound healing, and disease. However, most in vitro platforms remain static. In this study, a dynamic biomaterial platform comprising a stiffening hydrogel is introduced and achieved through a stepwise approach of addition followed by light‐mediated crosslinking, integrated with an elastomeric substrate featuring strain‐responsive lamellar surface patterns. Employing this platform, the response of human induced pluripotent stem cell‐derived cardiomyocytes (hIPSC‐CMs) is investigated to dynamic stiffening from healthy to fibrotic tissue stiffness. The results demonstrate that culturing hIPSC‐CMs on physiologically relevant healthy stiffness significantly enhances their function, as evidenced by increased sarcomere fraction, wider sarcomere width, significantly higher connexin‐43 content, and elevated cell beating frequency compared to cells cultured on fibrotic matrix. Conversely, dynamic matrix stiffening negatively impacts hIPSC‐CM function, with earlier stiffening events exerting a more pronounced hindering effect. These findings provide valuable insights into material‐based approaches for addressing existing challenges in hIPSC‐CM maturation and have broader implications across various tissue models, including muscle, tendon, nerve, and cornea, where both cellular alignment and matrix stiffening play pivotal roles in tissue development and regeneration. 

Abstract Embedded bioprinting is an emerging technology for precise deposition of cell-laden or cell-only bioinks to construct tissue like structures. Bioink is extruded or transferred into a yield stress hydrogel or a microgel support bath allowing print needle motion during printing and providing temporal support for the printed construct. Although this technology has enabled creation of complex tissue structures, it remains a challenge to develop a support bath with user-defined extracellular mimetic cues and their spatial and temporal control. This is crucial to mimic the dynamic nature of the native tissue to better regenerate tissues and organs. To address this, we present a bioprinting approach involving printing of a photocurable viscous support layer and bioprinting of a cell-only or cell-laden bioink within this viscous layer followed by brief exposure to light to partially crosslink the support layer. This approach does not require shear thinning behavior and is suitable for a wide range of photocurable hydrogels to be used as a support. It enables multi-material printing to spatially control support hydrogel heterogeneity including temporal delivery of bioactive cues (e.g. growth factors), and precise patterning of dense multi-cellular structures within these hydrogel supports. Here, dense stem cell aggregates are printed within methacrylated hyaluronic acid-based hydrogels with patterned heterogeneity to spatially modulate human mesenchymal stem cell osteogenesis. This study has significant impactions on creating tissue interfaces (e.g. osteochondral tissue) in which spatial control of extracellular matrix properties for patterned stem cell differentiation is crucial. 

Abstract Polymeric systems displaying spontaneous formation of surface wrinkling patterns are useful for a wide range of applications, such as diffraction gratings, flexible electronics, smart adhesives, optical devices, and cell culture platforms. Conventional fabrication techniques for wrinkling patterns involves multitude of processing steps and impose significant limitations on fabrication of hierarchical patterns, creating wrinkles on 3D and nonplanar structures, the scalability of the manufacturing process, and the integration of wrinkle fabrication process into a continuous manufacturing process. In this work, 4D printing of surface morphing hydrogels enabling direct fabrication of wrinkling patterns on curved and/or 3D structures with user‐defined and spatially controlled pattern geometry and size is reported. The key to successful printing is to tailor the photopolymerization time and partial crosslinking time of the hydrogel inks. The interplay between crosslinker concentration and postprinting crosslinking time allow for the control over wrinkling morphology and the characteristic size of the patterns. The pattern alignment is controlled by the print strut size—the size of the solid material extruded from the print nozzle in the form of a line. To demonstrate the utility of the approach, tunable optical devices, a solvent/humidity sensor for microchips, and cell culture platforms to control stem cell shape are fabricated. 

Abstract Extrusion‐based 3D printing of polymeric biomaterials has emerged as a promising approach for the fabrication of complex tissue engineering constructs. However, the large pore and feature size lead to low cell seeding efficiency and limited control of spatial distribution of cells within the scaffolds. We developed hybrid scaffolds that are composed of 3D‐printed layers and airbrushed fibrous membranes. Airbrushing time was adjusted to fabricate low (L), medium (M), and high (H) density membranes to effectively control stem cell infiltration. When two distinct populations of stem cells were seeded from top or bottom of the scaffolds, scaffolds composed ofLLLmembranes showed gradual mixing of the cells with depth, whereasLHLmembranes led to two distinct regions of cells separated by theHmembrane. Our results demonstrate that fibrous membranes incorporated within 3D‐printed layers enable user‐defined and spatially controlled cell compositions within hybrid scaffolds. 

Solution and melt 3D printing techniques were compared for fabricating PCL/HA scaffolds. Solution printing resulted in porous, rougher scaffolds, while melt printing produced stiffer scaffolds with enhanced bone formation. 

There is a growing demand for bone graft substitutes that mimic the extracellular matrix properties of the native bone tissue to enhance stem cell osteogenesis. Composite hydrogels containing human bone allograft particles are particularly interesting due to inherent bioactivity of the allograft tissue. Here, we report a novel photocurable composite hydrogel bioink for bone tissue engineering. Our composite bioink is formulated by incorporating human allograft bone particles in a methacrylated alginate formulation to enhance adult human mesenchymal stem cell (hMSC) osteogenesis. Detailed rheology and printability studies confirm suitability of our composite bioinks for extrusion-based 3D bioprinting technology. In vitro studies reveal high cell viability (~90%) for hMSCs up to 28 days of culture within 3D bioprinted composite scaffolds. When cultured within bioprinted composite scaffolds, hMSCs show significantly enhanced osteogenic differentiation as compared to neat scaffolds based on alkaline phosphatase activity, calcium deposition, and osteocalcin expression.