Remote Cell Activation for Bone Regeneration - a Pre Clinical Animal Study

Markides, H.; Telling, N.D.; Henstock, J.R.; El Haj, A.J.

Abstract

We aim to develop a cell-based injectable solution for treatment of non-union bone fractures. Our approach is based on the use of functionalised magnetic particles (MNPs) targeted to the TREK-1 mecho-sensative receptor on the mesenchymal stem cell (MSCs) membrane. Attached MNPs respond to the application of an oscillating external magnetic field resulting in remote receptor activation and enhanced osteogenic differentiation. In this way, we can remotely deliver functional mechanical stimuli to therapeutic cell populations in vivo following injection either systemically or to the repair site. This concept has been validated through a series of in vitro, ex vivo and small animal studies and is currently being tested in a pre-clinical sheep model for bone repair.

A key element in the remote activation of MNP tagged cells is the application of an oscilating magnetic field applied externally. Here, we describe the design of a magnetic array used to stimulate cell populations in vivo in a large animal model. The minimum magnetic field strength required to activate cells was identified as 0.16 KG by using a HEK-293 reporter cell line with field strengths ranging from 0 KG-3.5 KG. This was validated in vitro with ovine MSCs where enhanced osteogenesis was demonstrated in stimulated groups. Magnet shape, orientation and grade was simulated in 2D using FEMM software to identify optimal magnet arrangement and 6 prototypes fabricated for thorough 3D analysis. An ex vivo sheep model was established to compare the tissue penetration depth of the 6 prototype and the final design incorporated into a sheep harness.

• Journal Article Type: Conference Paper
• Online Publication Date: Aug 28, 2015
• Publication Date: Aug 28, 2015
• Deposit Date: Jun 12, 2023
• Journal: Tissue Engineering Part A
• Print ISSN: 1937-3341
• Publisher: Mary Ann Liebert
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Pages: S7-S8