Human adipose–derived mesenchymal stem cell–based medical microrobot system for knee cartilage regeneration in vivo

Abstract

Targeted cell delivery by a magnetically actuated microrobot with a porous structure is a promising technique to enhance the low targeting efficiency of mesenchymal stem cell (MSC) in tissue regeneration. However, the relevant research performed to date is only in its proof-of-concept stage. To use the microrobot in a clinical stage, biocompatibility and biodegradation materials should be considered in the microrobot, and its efficacy needs to be verified using an in vivo model. In this study, we propose a human adipose–derived MSC–based medical microrobot system for knee cartilage regeneration and present an in vivo trial to verify the efficacy of the microrobot using the cartilage defect model. The microrobot system consists of a microrobot body capable of supporting MSCs, an electromagnetic actuation system for three-dimensional targeting of the microrobot, and a magnet for fixation of the microrobot to the damaged cartilage. Each component was designed and fabricated considering the accessibility of the patient and medical staff, as well as clinical safety. The efficacy of the microrobot system was then assessed in the cartilage defect model of rabbit knee with the aim to obtain clinical trial approval.

Medical Micro/Nanorobots in Precision Medicine

“…Once in there, a permanent magnet was used to hold in place the cell loaded microrobots facilitating the adhesion and proliferation of the stem cells in the target location. [231] Microrobots have also been used to transport individual cells without functioning as a scaffold, but rather by using chemical interactions or physical stimulation. Different types of blood cells have been coupled with motile robots to take advantage of their biological function.…”

Micro/Nanorobot: A Promising Targeted Drug Delivery System

“…However, in such a transport process, cell viability may be affected by fluid shear force and magnetic field. Cells loaded micro/nanorobot was also applied in knee cartilage regeneration in vivo [88]. The human adipose-derived MSCs (hADMSCs)-located microrobot could move to the lesion of rabbit knee cartilage under the guidance of magnetic field.…”

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

“…The required magnitude of the magnetic field is determined by considering the size of the MCTAC and the region of interest (ROI). 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].…”

“…Therefore, to achieve external wireless active actuation, an electromagnetic system was incorporated into the MCTAC based on previous microrobot motion control technology [2,23,24]. As a promising result of the combination of the EMA and the MCTAC, Go et al were able to develop a biodegradable scaffold with a porous structure carrying MSCs [25]. Similarly, Yoo et al demonstrated a magnetoresponsive stem cell spheroid-based cartilage recovery platform that enabled precise targeting using magnetic control and low-frequency electromagnetic fields [13].…”

“…Furthermore, Go et al demonstrated the possibility of using a single magnet to fix the targeted micro-scaffolds. However, this is a passive system that can only generate a pulling force, and the direction of the magnetic field and strength of the fixation device cannot be determined considering subject-specific conditions [25].…”