"Despite the high incidence of tendon injuries globally, an optimal treatment strategy has yet to be defined1. A key challenge for tendon repair is the alignment of the repaired matrix into orientations which provide maximal mechanical strength2, 3. Using oriented implants for tissue growth combined with either exogenous or endogenous stem cells may provide a solution. Previous research has shown how oriented fiber-like structures within 3D scaffolds can provide a framework for organized extracellular matrix deposition4. In this paper, we present our data on the remote magnetic alignment of collagen hydrogels which facilitates long-term collagen orientation. Magnetic nanoparticles (MNPs) at varying concentrations and size can be contained within collagen hydrogels. In the presence of an external magnetic field, gelation is initiated by incubation at 37oC for 30-minutes. Our data shows how, in response to the magnetic field lines, MNPs align and form string-like structures orientating 90o from the applied magnetic field from our device. This can be visualized through light and fluorescence microscopy and persists 21-days post application of magnetic field. Confocal microscopy demonstrates anisotropic macroscale structure of MNP-laden collagen gels subjected to a magnetic field, compared to gels without MNP dosing. Matrix fibrillation was compared between non- and biofunctionalized MNP hydrogels, and different gels dosed with varying MNP concentrations. Human adipose stem cells (hASCs) seeded within the magnetically-aligned gels were seen to align in parallel to MNP and collagen orientation 7-days post application of magnetic field. hASCs seeded in isotropic gels were randomly organized. To summarize, we have developed a convenient, non-invasive protocol to control collagen I hydrogel architecture. Through the presence or absence of MNP dosing and a magnetic field, collagen can be remotely aligned or randomly organized, respectively, in situ. This can be considered as an innovative approach particularly useful in tissue engineering or organ-on-a-chip applications for remotely controlling collagen matrix organization. In this way cellular constructs analogous to healthy and diseased tendon can be engineered ex vivo for regenerative therapies.
- 1. Nichols, A. E. C. et al., Transl. Res. 209, 156–168 (2019). 2. Screen, H. R. C. J. Mech. Behav. Biomed. Mater. 1, 51–58 (2008). 3. Sahni, V. et al., Curr. Stem Cell Res. Ther. 10, 31–36 (2014). 4. Lim, W. L. et al., Tissue Eng. Regen. Med. 16, 549–571 (2019).