It is evident that remote field systems have the potential to greatly advance in vitro tissue engineering.
However, the convergence of magnetic, optical, and acoustic technologies with in vitro tissue engineering is a relatively new development and, as a result, many studies exist only in the academic sphere and are far from disrupting the clinical status quo.
The authors propose three key challenges that must be addressed in order to realize the benefit of remote fields in translational tissue engineering (see Outstanding Questions).
First, it is imperative that ‘proof-of-concept’ studies using arbitrary feature dimensions and model cell types are replaced with methods that enable the engineering of mature, multicellular tissues with native structural dimensions. For instance, while ultrasound standing waves have been used to create multilayer sheets of endothelial cells in collagen hydrogels, the next step for this technology is the creation of functional networks of blood vessels, replete with support cells (e.g., smooth muscle cells), formed not in a bare hydrogel but in a real tissue structure (e.g., muscle, bone, liver).
The second challenge is to use materials and protocols that support remote manipulation without affecting other aspects of the engineered tissue. This statement is made in light of the fact that many remote field technologies necessitate the use materials with defined properties: certain levels of optical transparency, viscosity, magnetic susceptibility, photoresponsivity, or acoustic attenuation.
As a result, many strategies rely on either: (i) a customized material, designed and synthesized with the appropriate set of characteristics; or (ii) the selection of an existing material system that has compatible properties within an operational parameter space. While a carefully designed or selected material can evidently be used to enable remote organization of structural features, this benefit must not be at the expense of the biological, physical, and mechanical properties required to support cell survival, differentiation, and extracellular matrix production.
Ideally, a tissue engineering protocol that is recognized as the academic or clinical gold standard would be used with remote field application as the sole change to the established procedure.
The final challenge is to improve the accessibility of remote field instrumentation. Apparatus is often assembled in house, however, the need for users to assemble and operate their own devices restricts usage to a small number of groups with specialist expertise. This situation could be alleviated by more active dissemination of academic knowledge through protocols and methods papers, or by making devices available through user collaboration or product commercialization.
Alternatively, many remote field technologies use high-end equipment that is already commercially available, such as multiphoton lithography, optical tweezers or focused ultrasound systems. These systems, which can require considerable expense and expertise to operate and maintain, tend to be sold as multifunctional apparatus rather than tailored to particular end-user applications. Therefore, a major challenge can be tuning and integrating commercial apparatus to meet biological requirements (cytocompatibility, sterility, etc.).
Overall, the creation of more integrated, accessible technologies would enable research groups around the world to embrace remote fields as a mainstream tool for complex tissue engineering.