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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. Biodegradable zinc oxide composite scaffolds promote osteochondral differentiation of mesenchymal stem cells

   https://doi.org/10.1002/bit.27173  

   Khader, Ateka; Arinzeh, Treena_Livingston (October 2019, Biotechnology and Bioengineering)

   Abstract Osteoarthritis (OA) involves the degeneration of articular cartilage and subchondral bone. The capacity of articular cartilage to repair and regenerate is limited. A biodegradable, fibrous scaffold containing zinc oxide (ZnO) was fabricated and evaluated for osteochondral tissue engineering applications. ZnO has shown promise for a variety of biomedical applications but has had limited use in tissue engineering. Composite scaffolds consisted of ZnO nanoparticles embedded in slow degrading, polycaprolactone to allow for dissolution of zinc ions over time. Zinc has well‐known insulin‐mimetic properties and can be beneficial for cartilage and bone regeneration. Fibrous ZnO composite scaffolds, having varying concentrations of 1–10 wt.% ZnO, were fabricated using the electrospinning technique and evaluated for human mesenchymal stem cell (MSC) differentiation along chondrocyte and osteoblast lineages. Slow release of the zinc was observed for all ZnO composite scaffolds. MSC chondrogenic differentiation was promoted on low percentage ZnO composite scaffolds as indicated by the highest collagen type II production and expression of cartilage‐specific genes, while osteogenic differentiation was promoted on high percentage ZnO composite scaffolds as indicated by the highest alkaline phosphatase activity, collagen production, and expression of bone‐specific genes. This study demonstrates the feasibility of ZnO‐containing composites as a potential scaffold for osteochondral tissue engineering. 

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3. 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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4. Industrial‐scale fabrication of an osteogenic and antibacterial PLA/silver‐loaded calcium phosphate composite with significantly reduced cytotoxicity

   https://doi.org/10.1002/jbm.b.34185  

   Cai, Shaobo; Pourdeyhimi, Behnam; Loboa, Elizabeth G. (September 2018, Journal of Biomedical Materials Research Part B: Applied Biomaterials)

   Abstract In this study, we report an industrial‐scale fabrication method of a multifunctional polymer composite as a scaffold material for bone tissue engineering. This study successfully demonstrated the potential of applying industrial polymer processing technologies to produce specially functionalized tissue engineering scaffolds. With the inclusion of a newly synthesized multifunctional additive, silver‐doped‐calcium phosphate (silver‐CaP), the composite material exhibited excellent osteogenic inducibility of human adipose‐derived stem cells (hASC) and satisfactory antibacterial efficacy againstEscherichia coliandStaphylococcus aureus. Also, relative to previously reported methods of direct loading silver particles into polymeric materials, our composite exhibited significantly reduced silver associated cytotoxicity. The enhanced biocompatibility could be a significant advantage for materials to be used for regenerative medicine applications where clinical safety is a major consideration. The impact of different silver loading methodologies on hASC’ osteogenic differentiation was also studied. Overall, the results of this study indicate a promising alternative approach to produce multifunctional scaffolds at industrial‐scale with higher throughput, lower cost, and enhanced reproducibility. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 900–910, 2019. 

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5. 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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