Fabrication of Scaffolds with a Hexagonal Array of Interconnected Pores (SHAIPs) as a Cell Delivery Platform for Tendon-to-Bone Repair

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Lee, Fred Seol
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Wallace H. Coulter Department of Biomedical Engineering
The joint Georgia Tech and Emory department was established in 1997
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Monolayer inverse opal scaffolds, conventionally known as scaffolds with a hexagonal array of interconnected pores (SHAIPs), possess a well-defined pore structure and high pore interconnectivity. These SHAIPs, however, have shown limited implementation in tissue engineering applications due to their complex fabrication process and poor scalability. This research explored a modified SHAIP fabrication procedure based on traditional inverse opal scaffold techniques that offered greater scalability and solely depended on readily available laboratory equipment. Furthermore, the use of SHAIPs had been proposed as a cell delivery platform for hedgehog agonist (HhAg)-stimulated stem cells to improve tendon-to-bone healing outcomes in rotator cuff repair. Rat bone marrow-derived stem cells (rBMSCs) were seeded in polycaprolactone (PCL) SHAIPs and then primed with HhAg for cell-seeded scaffold characterization to confirm viability as a cell delivery platform in tendon-to-bone regeneration. The study was split into three main sections: monodisperse microsphere preparation, SHAIP fabrication, and cell-seeded scaffold characterization. Uniform gelatin microspheres were obtained by optimizing the experimental parameters of a microfluidic emulsion procedure, which provided a reliable source of templating beads for SHAIP fabrication. This modified SHAIP fabrication procedure enabled the simultaneous production of multiple gelatin templates, addressing the bottleneck of the original process. Although the heating duration required for sufficient thermal annealing increased, large batches of these templates could be produced in a single trial, enhancing overall process throughput and scalability. No apparent signs of cytotoxicity were observed when assessed via live/dead staining. Moreover, HhAg-stimulated rBMSCs showed upregulated Gli1 expression relative to in vitro controls, comparable to previous studies on HhAg-stimulated mesenchymal stem cells (MSCs) that demonstrated improved enthesis healing. Ultimately, the histological analysis of the in vivo rat model illustrated the successful delivery of primed rBMSCs to the repair site, validating the feasibility of SHAIPs as a cell delivery platform.
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2025-05-05
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