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1. Cell-Laden Composite Hydrogel Bioinks with Human Bone Allograft Particles to Enhance Stem Cell Osteogenesis

   https://doi.org/10.3390/polym14183788  

   Gharacheh, Hadis; Guvendiren, Murat (September 2022, Polymers)

   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. 

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2. Simple design for membrane-free microphysiological systems to model the blood-tissue barriers

   https://doi.org/10.1016/j.ooc.2023.100032  

   Young, By Ashlyn; Deal, Halston; Rusch, Gabrielle; Pozdin, Vladimir A.; Brown, Ashley C.; Daniele, Michael (December 2023, Organs-on-a-Chip)

   Microphysiological systems (MPS) incorporate physiologically relevant microanatomy, mechanics, and cells to mimic tissue function. Reproducible and standardized in vitro models of tissue barriers, such as the blood-tissue interface (BTI), are critical for next-generation MPS applications in research and industry. Many models of the BTI are limited by the need for semipermeable membranes, use of homogenous cell populations, or 2D culture. These factors limit the relevant endothelial-epithelial contact and 3D transport, which would best mimic the BTI. Current models are also difficult to assemble, requiring precise alignment and layering of components. The work reported herein details the engineering of a BTI-on-a-chip (BTI Chip) that addresses current disadvantages by demonstrating a single layer, membrane-free design. Laminar flow profiles, photocurable hydrogel scaffolds, and human cell lines were used to construct a BTI Chip that juxtaposes an endothelium in direct contact with a 3D engineered tissue. A biomaterial composite, gelatin methacryloyl and 8-arm polyethylene glycol thiol, was used for in situ fabrication of a tissue structure within a Y-shaped microfluidic device. To produce the BTI, a laminar flow profile was achieved by flowing a photocurable precursor solution alongside phosphate buffered saline. Immediately after stopping flow, the scaffold underwent polymerization through a rapid exposure to UV light (<300 mJ/cm2). After scaffold formation, blood vessel endothelial cells were introduced and allowed to adhere directly to the 3D tissue scaffold, without barriers or phase guides. Fabrication of the BTI Chip was demonstrated in both an epithelial tissue model and blood-brain barrier (BBB) model. In the epithelial model, scaffolds were seeded with human dermal fibroblasts. For the BBB models, scaffolds were seeded with the immortalized glial cell line, SVGP12. The BTI Chip microanatomy was analyzed post facto by immunohistochemistry, showing the uniform production of a patent endothelium juxtaposed with a 3D engineered tissue. Fluorescent tracer molecules were used to characterize the permeability of the BTI Chip. The BTI Chips were challenged with an efflux pump inhibitor, cyclosporine A, to assess physiological function and endothelial cell activation. Operation of physiologically relevant BTI Chips and a novel means for high-throughput MPS generation was demonstrated, enabling future development for drug candidate screening and fundamental biological investigations. 

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3. Gradient scaffolds for osteochondral tissue engineering and regeneration

   https://doi.org/10.1039/D0TB00688B  

   Zhang, Bin; Huang, Jie; Narayan, Roger J. (September 2020, Journal of Materials Chemistry B)

   null (Ed.)

   The tissue engineering approach for repairing osteochondral (OC) defects involves the fabrication of a biological tissue scaffold that mimics the physiological properties of natural OC tissue ( e.g. , the gradient transition between the cartilage surface and the subchondral bone). The OC tissue scaffolds described in many research studies exhibit a discrete gradient ( e.g. , a biphasic or tri/multiphasic structure) or a continuous gradient to mimic OC tissue attributes such as biochemical composition, structure, and mechanical properties. One advantage of a continuous gradient scaffold over biphasic or tri/multiphasic tissue scaffolds is that it more closely mimics natural OC tissue since there is no distinct interface between each layer. Although research studies to this point have yielded good results related to OC regeneration with tissue scaffolds, differences between engineered scaffolds and natural OC tissue remain; due to these differences, current clinical therapies to repair OC defects with engineered scaffolds have not been successful. This paper provides an overview of both discrete and continuous gradient OC tissue scaffolds in terms of cell type, scaffold material, microscale structure, mechanical properties, fabrication methods, and scaffold stimuli. Fabrication of gradient scaffolds with three-dimensional (3D) printing is given special emphasis due to its ability to accurately control scaffold pore geometry. Moreover, the application of computational modeling in OC tissue engineering is considered; for example, efforts to optimize the scaffold structure, mechanical properties, and physical stimuli generated within the scaffold–bioreactor system to predict tissue regeneration are considered. Finally, challenges associated with the repair of OC defects and recommendations for future directions in OC tissue regeneration are proposed. 

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4. Design and additive manufacturing of porous titanium scaffolds for optimum cell viability in bone tissue engineering

   https://doi.org/10.1177/0954405420937565  

   Li, Bingbing; Hesar, Bani Davod; Zhao, Yiwen; Ding, Li (July 2020, Proceedings of the Institution of Mechanical Engineers, Part B: Journal of Engineering Manufacture)

   Pore size, external shape, and internal complexity of additively manufactured porous titanium scaffolds are three primary determinants of cell viability and structural strength of scaffolds in bone tissue engineering. To obtain an optimal design with the combination of all three determinants, four scaffolds each with a unique topology (external geometry and internal structure) were designed and varied the pore sizes of each scaffold 3 times. For each topology, scaffolds with pore sizes of 300, 400, and 500 µm were designed. All designed scaffolds were additively manufactured in material Ti6Al4V by the direct metal laser melting machine. Compression test was conducted on the scaffolds to assure meeting minimum compressive strength of human bone. The effects of pore size and topology on the cell viability of the scaffolds were analyzed. The 12 scaffolds were ultrasonically cleaned and seeded with NIH3T3 cells. Each scaffold was seeded with 1 million cells. After 32 days of culturing, the cells were fixed for their three-dimensional architecture preservation and to obtain scanning electron microscope images. 

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5. Design and fabrication of biodegradable bone tissue scaffolds based on the nuclear pasta theory

   https://doi.org/10.1016/j.mfglet.2025.06.045  

   Al-Qawasmi, Hamzeh; Salary, Roozbeh “Ross” (August 2025, Manufacturing Letters)

   Mears, Laine (Ed.)

   Globally, around 2.2 million bone graft procedures are performed annually, with costs reaching approximately $664 million as of 2021. The number of surgeries to repair bone defects is projected to increase by about 13 % each year. However, traditional bone grafts often carry risks such as donor site morbidity and limited availability, driving the need for innovative solutions. This study explores the fabrication of biodegradable bone tissue scaffolds inspired by the nuclear pasta theory using extrusion-based Fused Deposition Modeling (FDM). The nuclear pasta theory, which describes complex geometrical formations within neutron stars, serves as a novel source of inspiration for designing scaffolds with enhanced mechanical properties and optimized porosity. Two bio-based, biodegradable polymers, Luminy LX175 and ecoPLAS, were used to fabricate scaffolds via an in-house filament extrusion process utilizing the Filabot EX6 system. The extrusion parameters were optimized to achieve a consistent filament diameter of 1.75 mm suitable for 3D printing on a Creality K1C printer. Seven scaffold designs were developed, including five based on Triply Periodic Minimal Surfaces (TPMS) and two inspired by nuclear pasta configurations, namely “lasagna” and a hybrid “lasagna-spaghetti” structure. The scaffolds were evaluated for their mechanical properties using uniaxial compression testing. Results showed that TPMS-inspired designs generally achieved a favorable balance between porosity and mechanical strength, while the nuclear pasta-inspired designs exhibited unique anisotropic and isotropic compression characteristics. The study concluded that nuclear pasta-inspired scaffold architectures exhibit unique mechanical properties and porosity characteristics, emphasizing their potential for future optimization in bone tissue engineering applications. Additionally, these structures can be further reinforced through material modifications or hybrid scaffold designs to enhance their load-bearing capabilities. This work demonstrates the potential of using bio-inspired designs in conjunction with sustainable, biodegradable materials for bone tissue engineering. Future research will focus on optimizing co-extrusion techniques and exploring composite materials to further enhance scaffold properties for clinical applications. 

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