A Magnetically Actuated Microscaffold Containing Mesenchymal Stem Cells for Articular Cartilage Repair

Abstract

This study proposes a magnetically actuated microscaffold with the capability of targeted mesenchymal stem cell (MSC) delivery for articular cartilage regeneration. The microscaffold, as a 3D porous microbead, is divided into body and surface portions according to its materials and fabrication methods. The microscaffold body, which consists of poly(lactic-co-glycolic acid) (PLGA), is formed through water-in-oil-in-water emulsion templating, and its surface is coated with amine functionalized magnetic nanoparticles (MNPs) via amino bond formation. The porous PLGA structure of the microscaffold can assist in cell adhesion and migration, and the MNPs on the microscaffold can make it possible to steer using an electromagnetic actuation system that provides external magnetic fields for the 3D locomotion of the microscaffold. As a fundamental test of the magnetic response of the microscaffold, it is characterized in terms of the magnetization curve, velocity, and 3D locomotion of a single microscaffold. In addition, its function with a cargo of MSCs for cartilage regeneration is demonstrated from the proliferation, viability, and chondrogenic differentiation of D1 mouse MSCs that are cultured on the microscaffold. For the feasibility tests for cartilage repair, 2D/3D targeting of multiple microscaffolds with the MSCs is performed to demonstrate targeted stem cell delivery using the microscaffolds and their swarm motion.

3D‐Printed Microrobotic Transporters with Recapitulated Stem Cell Niche for Programmable and Active Cell Delivery

“…Recently, magnetic gradient‐based pulling of magnetic nickel coated microstructures has been demonstrated for stem cell delivery. [10c,12] However, magnetic gradient‐based pulling of magnetic micromaterials pertains significant challenges for medical applications. First, it creates a jerky pulling motion, which makes the stability of the robot motion control difficult, and the robot positioning precision low.…”

“…To impart magnetization to the MCTs, a nanocomposite of SPIONs was prepared with TMPETA. We avoided metal coatings, such as cobalt and nickel, for their strong acute toxicity . However, the colloidal stability of the nanoparticles inside the polymer solutions is the limiting factor to make it compatible with two‐photon polymerization.…”

Mobile Microrobots for Active Therapeutic Delivery

“…In another study, Go et al. reported spherical scaffolds made from porous PLGA microbeads for targeted articular cartilage regeneration . Mesenchymal stromal cells were transported in vitro along the preprogrammed trajectory using electromagnetic actuation.…”

Wearable Fixation Device for a Magnetically Controllable Therapeutic Agent Carrier: Application to Cartilage Repair

“…Although the proposed method can be applied to an MCTAC containing agents such as stem cells [25], doxorubicin [26], macrophages [27], ferumoxytol [28], and a multifunctional nanorobot [1], this study uses stem cells as a therapeutic agent for cartilage repair in order to validate the proposed method. Here, the required magnetic field intensity is assumed to be a minimum of 40 mT, based on previous studies on magnetically actuated micro-scaffolding containing MSCs and a magnetoresponsive stem cell spheroid [12,13]. As this particular application of the proposed method is aimed at stem cell therapy through the repair of surrounding cartilage, the assumption of the desired magnetic field intensity is reasonable.…”

“…Once the cartilage is damaged, it is not easily self-repaired as the chondrocytes do not contain blood vessels [7]. Therefore, in the case of heavily damaged cartilage, therapeutics employing collagen or stem cells are used for artificial cartilage or cartilage regeneration, respectively [8][9][10][11][12][13][14][15]. In particular, research on cartilage regeneration using stem cell-based therapeutic agents has attracted significant attention.…”