Magnetic Systems for Regenerative Medicine

DOI: 10.1002/adfm.202211925 M. E. Gomes, R. M. A. Domingues 3B’s Research Group I3Bs Research Institute on Biomaterials Biodegradables and Biomimetics University of Minho Headquarters of the European Institute of Excellence on issue Engineering and Regenerative Medicine AvePark Parque de Ciência e Tecnologia ona Industrial da Gandra Barco, 4805-017 Guimarães, Portugal E-mail: megomes@i3bs.uminho.pt; rui.domingues@i3bs.uminho.pt M. E. Gomes, R. M. A. Domingues ICVS/3B’s PT Government Associate Laboratory Braga Guimarães, Portugal The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adfm.202211925. constructs, 3D in vitro tissue/organ models and biohybrid microrobots. Most human tissue have ordered cellular and extracellular matrix (ECM) patterns that are key for organ function. However, recreating tissue-specific anisotropic patterns and gradients in bioengineered tissues has been a major challenge. In article number 202202468, Laura De Laporte and co-workers use high aspect-ratio and magneto-responsive microgels that can be oriented within hydrogel matrices (Anisogel) by external magnetic fields to recapitulate the complex and anisotropic architecture of native ECM. In this study, the authors explore in detail how different local physical, biochemical, and mechanical properties of Anisogel affect oriented nerve cell growth. Jerome Crassous and co-workers (article number 202202430) further demonstrate how the angle of microgel alignment in Anisogel under static external magnetic field can be pre-programmed depending on the alignment of ellipsoidal maghemite nanoparticles, integrated as responsive fillers within the microgels. This approach allows to fabricate hydrogel-based constructs with both parallel and orthogonal microgel orientation, broadening the potential of bioengineering tools to recreate the architectural complexity of living tissues. The induction of specific cellular patterns can be promoted not only by controlling the biochemical and biophysical properties of the encapsulating material, but also by manipulating the organisation and bioassembly of cells itself. The contactless implementation of this concept can be achieved by the prior “magnetization” of cells for their subsequent manipulation with magnetic fields. Christina Janko and her team (article number 202203672) compare the cellular labelling efficiency of superparamagnetic iron oxide nanoparticles (SPIONs) with different coatings, and evaluate their respective magnetic control potential for induction of 2D patterns and 3D spheroid aggregates. Claire Wilhelm and colleagues (article number 202204850) applied a similar concept to produce magnetic muscle cells spheroids. These magnetic muscle microunits were then aligned by magnetic fields within collagen hydrogels, creating spheroid stings that fuse into 3D fiber-like muscle structures during in vitro culture time. A different approach was proposed by Orit Shefi and co-workers (article number 202204925) that used SPIONs labelled nerve cells to produce 3D cell clusters within collagen-based hydrogels controlled by the applied magnetic fields. These patterned hydrogel units can be assembled into multi-layered constructs, creating functional 3D microarchitectures of neural networks. While the fabrication of defined 3D cellular structures with magnetic manipulation often relies on their labelling with magnetic nanoparticles (MNPs), diamagnetic levitation, a method where cells are made susceptible to magnetic manipulation by contact with paramagnetic media (e.g. gadolinium based solutions), is an attractive alternative for cell manipulation in 3D space. In article 202204092, Gozde Durmus and co-workers demonstrate Over the last decade, magnetic-based systems have made remarkable breakthroughs in the field of tissue engineering and regenerative medicine. The ability for contactless manipulation of magnetic responsive biomaterials, or even living cells, has been leveraged to devise innovative concepts that are widening the available bioengineering design space that can be explored in this multidisciplinary field. From the fabrication of cellular constructs with bioinspired patterns and hierarchical structures up to the concepts of levitational bioassembly, magnetic systems are enabling to engineer 3D tissues that better recapitulate the complex biophysical and biological cues of their native counterparts. Moreover, the inherent magnetic responsiveness of this living systems is being explored as mechanical and electrical nanotransducers to further stimulate cell functions, not only in vitro but also in vivo. Remarkably, recent advances in the convergence of microfabrication technologies with magnetic materials is also opening prospects to further fabricate advanced living microrobots and microphysiological systems with new added functionalities. Due to their good track record of biological tolerance and biodegradability, iron oxide-based nanoparticles remain the first choice of (superpara)magnetic nanomaterials, but new variants and combinations of nanomaterial are being increasingly explored in this field. Altogether, magnetic systems are contributing in multiple ways to boost the regenerative potential of bioengineered constructs and may lead to the development of in vitro tissue/organ models with improved physiological relevance. In this Special Issue we invited world experts to report their latest findings and revise recent advances on the field of Magnetic Systems for Regenerative Medicine. This collection of 12 articles highlight how different magnetic systems are being explored for cell manipulation and tracking and directly interact with its specific receptors. Moreover, particular focus is dedicated to the convergence of magnetic systems with other interface technologies for the fabrication of living tissue engineered