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1. 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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2. Spatial organization of biochemical cues in 3D-printed scaffolds to guide osteochondral tissue engineering

   https://doi.org/10.1039/D1BM00859E  

   Camacho, Paula; Behre, Anne; Fainor, Matthew; Seims, Kelly B.; Chow, Lesley W. (October 2021, Biomaterials Science)

   Functional repair of osteochondral (OC) tissue remains challenging because the transition from bone to cartilage presents gradients in biochemical and physical properties necessary for joint function. Osteochondral regeneration requires strategies that restore the spatial composition and organization found in the native tissue. Several biomaterial approaches have been developed to guide chondrogenic and osteogenic differentiation of human mesenchymal stem cells (hMSCs). These strategies can be combined with 3D printing, which has emerged as a useful tool to produce tunable, continuous scaffolds functionalized with bioactive cues. However, functionalization often includes one or more post-fabrication processing steps, which can lead to unwanted side effects and often produce biomaterials with homogeneously distributed chemistries. To address these challenges, surface functionalization can be achieved in a single step by solvent-cast 3D printing peptide-functionalized polymers. Peptide-poly(caprolactone) (PCL) conjugates were synthesized bearing hyaluronic acid (HA)-binding (HAbind–PCL) or mineralizing (E3–PCL) peptides, which have been shown to promote hMSC chondrogenesis or osteogenesis, respectively. This 3D printing strategy enables unprecedented control of surface peptide presentation and spatial organization within a continuous construct. Scaffolds presenting both cartilage-promoting and bone-promoting peptides had a synergistic effect that enhanced hMSC chondrogenic and osteogenic differentiation in the absence of differentiation factors compared to scaffolds without peptides or only one peptide. Furthermore, multi-peptide organization significantly influenced hMSC response. Scaffolds presenting HAbind and E3 peptides in discrete opposing zones promoted hMSC osteogenic behavior. In contrast, presenting both peptides homogeneously throughout the scaffolds drove hMSC differentiation towards a mixed population of articular and hypertrophic chondrocytes. These significant results indicated that hMSC behavior was driven by dual-peptide presentation and organization. The downstream potential of this platform is the ability to fabricate biomaterials with spatially controlled biochemical cues to guide functional tissue regeneration without the need for differentiation factors. 

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3. On the Impacts of Flow on the Migration and Growth of Cancer Cells

   https://doi.org/10.1115/dmd2022-1050  

   Akerkouch, Lahcen; Le, Trung; Jasuja, Haneesh; Katti, Kalpana; Katti, Dinesh (April 2022, Proceedings of the 2022 Design of Medical Devices Conference)

   Our study aims to identify the role of fluid flow in the growth of human bone cancer cells during metastasis. In our experiments, the cancer cells are seeded on the surface of cylindrical scaffolds in a bioreactor. The flow is laminar flow, which mimics the physiological conditions of the human body. A full-scale 3D high-resolution computational mesh of scaffold was created based on the physical scaffold's Micro-CT scans using open-source imaging software Slicer3D and Meshmixer. To investigate the influences of the flow on the seeded cells, we performed Computational Fluid Dynamics (CFD) simulations with the immersed boundary method (Gilmanov, Le, Sotiropoulos, JCP 300, 1, 2015). The computational domain was generated using the commercial software Gridgen. Our results show that the fluid flow velocity is highly dependent on the shape and pore sizes. In addition, the magnitude of the velocity on the surface where the cells are seeded is in between [0-0.05] μm/sallowing the cells to grow without being detached from the surface of the scaffold. Our future work will focus on (i) investigating the role of the shear stress on the distribution and orientation of the cancer cells. (ii) Simulating multiple scaffolds within the bioreactor to further quantify the impact of the gap on the flow velocity and shear. 

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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. Fabricating spatially functionalized 3D-printed scaffolds for osteochondral tissue engineering

   Camacho, P; Fainor, M; Seims, KB; Tolbert, JW; Chow, LW. (January 2021, Journal of biological methods)

   null (Ed.)

   Three-dimensional (3D) printing of biodegradable polymers has rapidly become a popular approach to create scaffolds for tissue engineering. This technique enables fabrication of complex architectures and layer-by-layer spatial control of multiple components with high resolution. The resulting scaffolds can also present distinct chemical groups or bioactive cues on the surface to guide cell behavior. However, surface functionalization often includes one or more post-fabrication processing steps, which typically produce biomaterials with homogeneously distributed chemistries that fail to mimic the biochemical organization found in native tissues. As an alternative, our laboratory developed a novel method that combines solvent-cast 3D printing with peptide-polymer conjugates to spatially present multiple biochemical cues in a single scaffold without requiring post-fabrication modification. Here, we describe a detailed, stepwise protocol to fabricate peptide-functionalized scaffolds and characterize their physical architecture and biochemical spatial organization. We used these 3D-printed scaffolds to direct human mesenchymal stem cell differentiation and osteochondral tissue formation by controlling the spatial presentation of cartilage-promoting and bone-promoting peptides. This protocol also describes how to seed scaffolds and evaluate matrix deposition driven by peptide organization. 

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