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1. Bone Adaptation-Driven Design of Periodic Scaffolds

   https://doi.org/10.1115/1.4050928  

   Cohen, David O.; Aboutaleb, Sohaila M.; Johnson, Amy Wagoner; Norato, Julian A. (December 2021, Journal of Mechanical Design)

   null (Ed.)

   Abstract This work introduces a computational method for designing bone scaffolds for maximum bone growth. A mechanobiological model of bone adaptation is used to compute the bone growth, taking into account the shape of the defect, the applied loading, and the existing density distribution of the bone in which the scaffold has been implanted. Numerical homogenization and a geometry projection technique are used to efficiently obtain surrogates of the effective elastic and diffusive properties of the scaffold as a function of the scaffold design and the bone density. These property surrogates are in turn used to perform bone adaptation simulations of the scaffold–bone system for a sampling of scaffold designs. Surrogates of the bone growth in the scaffold at the end of the simulated time and of the strain energy of the scaffold at implantation time are subsequently constructed from these simulations. Using these surrogates, we optimize the design of a scaffold implanted in a rabbit femur to maximize volume bone growth into the scaffold while ensuring a minimum stiffness at implantation. The results of the optimization demonstrate the effectiveness of the proposed method by showing that maximizing bone growth with a constraint on structural compliance renders scaffold designs with better bone growth than what would be obtained by only minimizing compliance. 

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2. Parametric design and characterization of novel TPMS porous scaffolds for bone tissue engineering

   https://doi.org/10.1016/j.mfglet.2025.06.106  

   Smith, Haley; Hanlon, Hannah; Salary, Roozbeh “Ross” (August 2025, Manufacturing Letters)

   Mears, Laine (Ed.)

   Bone scaffolds are essential in regenerative medicine treatments for bone defects, fractures, and disease. Despite the popularity in bone scaffold research, many challenges still remain including mechanical strength. This study focuses on compression analysis of 10 novel bone scaffold designs with each design created using Rhino 7 with the Grasshopper extension. This coding software took existing scaffold design equations and converted them into 3D models utilizing code based on previous studies. The equations were created by combining and manipulating popular equations used for bone scaffold fabrication. The scaffold models were 3D printed using SimuBone, a PLA biomaterial known for its bone-like properties and printability. The results concluded that Design 6 had the highest compression modulus and mass/density, while Design 9 had a moderate compression modulus and mass/density. Design 8 had the lowest compression modulus and Design 2 had the lowest mass/density. Additionally, Design 6 exhibits the highest stiffness but increased weight, and Design 8 performs the worst in these categories. Therefore, Design 2 was the most optimal for balancing stiffness, mass, and density. The evolution of failure between all 10 designs was also analyzed. This concluded that Design 9 and Design 6 had the highest strength with minimal collapse. Design 8 had the lowest strength with little to no collapse, while Design 2 had medium compression strength with significant collapse. Although Design 2 was found to have significant collapse, it is still considered the most optimal scaffold within this study due to having the best overall mass/density ratio and stiffness modulus with a moderate compression strength. 

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3. Evaluation of bone formation on orthopedic implant surfaces using an ex-vivo bone bioreactor system

   https://doi.org/10.1038/s41598-021-02070-z  

   Dua, Rupak; Jones, Hugh; Noble, Philip C. (December 2021, Scientific Reports)

   Abstract Recent advances in materials and manufacturing processes have allowed the fabrication of intricate implant surfaces to facilitate bony attachment. However, refinement and evaluation of these new design strategies are hindered by the cost and complications of animal studies, particularly during early iterations in the development process. To address this problem, we have previously constructed and validated an ex-vivo bone bioreactor culture system that can maintain the viability of bone samples for an extended period ex-vivo. In this study, we investigated the mineralization of a titanium wire mesh scaffold under both static and dynamic culturing using our ex vivo bioreactor system. Thirty-six cancellous bone cores were harvested from bovine metatarsals at the time of slaughter and divided into five groups under the following conditions: Group 1) Isolated bone cores placed in static culture, Group 2) Unloaded bone cores placed in static culture in contact with a fiber-mesh metallic scaffold, Group 3) Bone cores placed in contact with a fiber-mesh metallic scaffold under the constant pressure of 150 kPa, Group 4) Bone core placed in contact with a fiber-mesh metallic scaffold and exposed to cyclic loading with continuous perfusion flow of media within the ex-vivo culture system and Group 5) Bone core evaluated on Day 0 to serve as a positive control for comparison with all other groups at weeks 4 and 7. Bone samples within Groups 1–4 were incubated for 4 and 7 weeks and then evaluated using histological examination (H&E) and the Live-Dead assay (Life Technologies). Matrix deposits on the metallic scaffolds were examined with scanning electron microscopy (SEM), while the chemical composition of the matrix was measured using energy-dispersive x-ray spectroscopy (EDX). We found that the viability of bone cores was maintained after seven weeks of loading in our ex vivo system. In addition, SEM images revealed crystallite-like structures on the dynamically loaded metal coupons (Group 4), corresponding to the initial stages of mineralization. EDX results further confirmed the presence of carbon at the interface and calcium phosphates in the matrix. We conclude that a bone bioreactor can be used as an alternate tool for in-vivo bone ingrowth studies of new implant surfaces or coatings. 

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4. High-Fidelity Simulation of Flows in Bone-Like Environment to Investigate the Growth of Cancer Cells

   https://doi.org/10.1115/DMD2021-1081  

   Akerkouch, Lahcen; Le, Trung; Jasuja, Haneesh; Katti, Kalpana; Katti, Dinesh (April 2021, 2021 Design of Medical Devices Conference)

   Abstract Metastatic cancer in bones is incurable, which causes significant mobility and mortality to the patients. In this work, we investigate the role of interstitial fluid flow on cancer cells' growth within the interconnected pores of human bone. In-vitro experiments were carried out in a bio-reactor which includes bone-like scaffold specimens. A pump is used to maintain a laminar flow condition inside the bioreactor to resemble fluid flow in bones. The scaffold specimens are harvested after 23 days in the bioreactor. The scaffold specimen is scanned with Micro-CT under the resolution of 70 micrometers. We created a full-scale 3D computational model of the scaffold based on the micro-CT data using the open-source software Seg3D and Meshmixer. Based on the geometrical models, we generated the computational grids using the commercial software Gridgen. We performed Computational Fluid Dynamics (CFD) simulations with the immersed boundary method (Gilmanov, Le, Sotiropoulos, JCP 300, 1, 2015) to investigate the flow patterns inside the pores of the scaffolds. The results reveal a non-uniform flow distribution in the vicinity of the scaffold. The flow velocity and the shear stress distributions inside the scaffold are shown to be convoluted and very sensitive to the pore sizes. Our future work will further quantify these distributions and correlate them to cancer cells' growth observed in the experiments. 

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5. A hierarchically porous and SLIT3-releasing scaffold for bone tissue engineering applications

   https://doi.org/10.1007/s10853-024-10379-z  

   Al-Goraee, Ashraf; Al-Shami, Abdulrahman; Alshami, Ali S; Dhasarathy, Archana; Ismail, Nadhem; Guidinger, Jadyn; Tayyebi, Arash; Talukder, Musabbir Jahan (January 2025, Journal of Materials Science)

   Abstract One of the most fundamental characteristics of a biomaterial tailored for bone repair and regeneration is its ability to promote bone regeneration and healing of large defects. This work reports producing a functionalized and hieratically porous bone scaffold that significantly supports cell adhesion and proliferation by providing bone mimicry structure and controlled release of protein. The Slit Guidance Ligand 3 (SLIT3) protein was previously tested to promote bone formation and control the resorption process in natural bone healing. In this study, our goal was to design a nanocomposite bone scaffold to be functionalized with SLIT3 protein and then evaluate the uptake and release profile from surface into culture media to support bone marrow-derived mesenchymal stem cells (MSC) 3D culture. Indirect 3D printing of a polylactic-co-glycolic acid (PLGA), hydroxyapatite nanoparticles, and polydopamine coated (PLGA-HANPs-PDA) was utilized to obtain a hierarchically porous and SLIT3 protein-releasing scaffold. The produced scaffold was evaluated and optimized using chemical, architectural, mechanical, and biological characterization techniques. Optimal physicochemical properties resulted in a unique microstructure with an average pore size of 178.06 ± 45 µm, 63% porosity, and stable and homogenous chemical composition. Mechanical testing demonstrated a compression strength up to 1.5 MPa at 75% strain, with a compression modulus of 0.58 ± 0.05 MPa. Preliminary biological experiments showed that the scaffold exhibited gradual SLIT3 protein release, biodegradability, and reliable biocompatibility for MSC cell culture. Finally, we showed for first time the bioactivity of SLIT3 protein within PLGA-HANPs-PDA scaffold to promote attachment and growth of mesenchymal stem cell (MSCs) seeded in bone mimicry scaffold matrix. The collected findings will serve as a bedrock for thorough and targeted in vitro studies to evaluate anticipated osteogenesis the MSCs. 

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