3D reconstructed image of the magnetically responsive scaffold. The polymeric matrix is represented in blue and iron oxide magnetic nanoparticles are observed in white. Upon remote activation of the TGF-ß/Smad2/3 signaling pathway in magnetic constructs, the transcription of tendon specific markers is induced (green). Adapted from [Matos et al., Acta Biomaterialia 113 (2020) 488-500].
3D reconstructed image of the magnetically responsive scaffold. The polymeric matrix is represented in blue and iron oxide magnetic nanoparticles are observed in white. Upon remote activation of the TGF-ß/Smad2/3 signaling pathway in magnetic constructs, the transcription of tendon specific markers is induced (green). Adapted from [Matos et al., Acta Biomaterialia 113 (2020) 488-500].

Biomimetic polymer scaffolds embedded with magnetic nanoparticles could trigger human stem cells to differentiate, stimulating the regeneration of damaged tendons, according to researchers. The team from 3B’s Research Group at the University of Minho in Portugal, together with Alicia El Haj at Birmingham University, designed a polymer scaffold made of a mixture of starch and poly-e-caprolactone impregnated with functionalized magnetic nanoparticles that can trigger biological responses in human stem cells [Matos et al., Acta Biomaterialia 113 (2020) 488-500, https://doi.org/10.1016/j.actbio.2020.07.009].

“Tendon injuries remain a major challenge for treatment with current approaches based on surgical repair unable to restore the original properties of a functional tendon,” explain Manuela E. Gomes, who led the research, and Ana I. Gonçalves.

Tendons are the connective tissue between muscles and bone, vital to the body’s movement, but are susceptible to injury and damage. Rather than regenerate after damage, tendons undergo a repair process that leads to the formation of scar tissue, with which pain and the risk of re-injury are associated. Apart from anti-inflammatory drugs, physiotherapy or surgery, tissue engineering offers the best – and only – hope of encouraging the regeneration of tendons to avoid these problems. Tissue engineering strategies for the regeneration of tendon require scaffolds that recreate the native tendon environment, encouraging the differentiation of cells and supporting the regrowth of cells into active tissue.

“Using magnetic nanoparticles (MNPs) and magnetic stimulation, one can remotely deliver mechanical forces directly to cells, activating membrane receptors and ultimately inducing mechanotransduction effects,” say Gomes and Gonçalves.

Using 3D printing technology, the researchers fabricated the magnetically responsive scaffold from a biodegradable polymer blend. Stem cells were then tagged with functionalized magnetic nanoparticles to target specific cell receptors and activate a signaling pathway associated with tendon formation, differentiation, and homeostasis. An external magnetic field applied to the polymer matrix induces a physical response in the embedded magnetic nanoparticles that produces local deformation of the material, which translate into cues to stem cells.

“An exciting feature of our approach is the ability to activate cells remotely, potentially from outside the patient’s body using biomagnetic approaches,” point outs El Haj. “We can control stem cell behavior and remotely promote differentiation into tendon precursors.”

The scaffold not only offers physical support to regrowing tendon cells but also provides highly tuned mechano-magnetic triggers to which cells respond. The researchers believe their findings represent the first step towards the mechanical stimulation of the regeneration of functional tendon tissue.

“This is an exciting advance which opens many possibilities for new ways to help people with tendon injury repair,” say the researchers. “Using biomagnetic approaches enables one to stimulate growth, potentially remotely, after surgical transplantation.”