Abstract
Recently, significant research efforts have been devoted toward the development of magnetically controllable drug delivery systems, however, drug fixation after targeting remains a challenge hindering long-term therapeutic efficacy. To overcome this issue, we present a wearable therapeutic fixation device for fixing magnetically controllable therapeutic agent carriers (MCTACs) at defect sites and its application to cartilage repair using stem cell therapeutics. The developed device comprises an array of permanent magnets based on the Halbach array principle and a wearable band capable of wrapping the target body. The design of the permanent magnet array, in terms of the number of magnets and array configuration, was determined through univariate search optimization and 3D simulation. The device was fabricated for a given rat model and yielded a strong magnetic flux density (exceeding 40 mT) in the region of interest that was capable of fixing the MCTAC at the desired defect site. Through in-vitro and in-vivo experiments, we successfully demonstrated that MCTACs, both a stem cell spheroid and a micro-scaffold for cartilage repair, could be immobilized at defect sites. This research is expected to advance precise drug delivery technology based on MCTACs, enabling subject-specific routine life therapeutics. Further studies involving the proposed wearable fixation device will be conducted considering prognostics under actual clinical settings.
Highlights
Magnetically controllable therapeutic agent carriers (MCTACs) have emerged as a suitable candidate facilitating the development of precisely targeted drug delivery systems
Cartilage model, in created werewere loaded intointo the the defect lesion onon thethe cartilage phantom model, in which whichthe thedefect defectwas was created by were loadedainto defect lesion of on4the phantom model, in which the defect created by drilling holethe with a diameter mmcartilage and depth of 2 mm, whereas the spheroid hadwas a diameter drilling a hole with a diameter of mm and depth of mm, whereas the spheroid had a diameter of by a diameter of 4phantom mm and was depthfilled of 2 mm, the spheroid hadthe a diameter ofdrilling
The proposed methodology was applied to design and fabricate stem cell-based therapeutic agent carriers containing magnetic nanoparticles (MNPs) for cartilage regeneration
Summary
Magnetically controllable therapeutic agent carriers (MCTACs) have emerged as a suitable candidate facilitating the development of precisely targeted drug delivery systems. Owing to the advantages of minimally invasive surgery and accompanied by a strong targeting ability and reduced side effects, MCTACs have been highlighted for their precise therapeutic delivery, in terms of cell-based therapeutics and triggered drug releases [5]. Most of the previous research pertaining to MCTACs has focused on the targeting mechanism and its clinical efficacy. The fixation of MCTACs at targeted lesions after precise delivery has not been addressed far. Considering the cell proliferation period, a fixation mechanism suitable for routine life after the procedure at the clinical site is essential to ensure effective therapeutics.
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