Bioinspired scaffolds based on aligned polyurethane nanofibers mimic tendon and ligament fascicles.

Topographical factors of scaffolds play an important role in regulating cell functions. Although the effects of alignment topography and three-dimensional (3D) configuration of nanofibers as well as surface stiffness on cell behavior have been investigated, there are relatively few reports that attempt to understand the relationship between synergistic effects of these parameters and cell responses. Herein, the influence of biophysical and biomechanical cues of electrospun polyurethane (PU) scaffolds on mesenchymal stem cells (MSCs) activities was evaluated. To this aim, multiscale bundles were developed by rolling up the aligned electrospun mats mimicking the fascicles of tendons/ligaments and other similar tissues. Compared to mats, the 3D bundles not only maintained the desirable topographical features (i.e., fiber diameter, fiber orientation, and pore size), but also boosted tensile strength (∼40 MPa), tensile strain (∼260%), and surface stiffness (∼1.75 MPa). Alignment topography of nanofibers noticeably dictated cell elongation and a uniaxial orientation, resulting in tenogenic commitment of MSCs. MSCs seeded on the bundles expressed higher levels of tenogenic markers compared to mats. Moreover, the biomimetic bundle scaffolds improved synthesis of extracellular matrix components compared to mats. These results suggest that biophysical and biomechanical cues modulate cell-scaffold interactions, providing new insights into hierarchical scaffold design for further studies.

Biophysical cues to improve the immunomodulatory capacity of mesenchymal stem cells: The progress and mechanisms.

Mesenchymal stem cells (MSCs) can maintain immune homeostasis and many preclinical trials with MSCs have been carried out around the world. In vitro culture of MSCs has been found to result in the decline of immunomodulatory capacity, migration and proliferation. To address these problems, simulating the extracellular environment for preconditioning of MSCs is a promising and inexpensive method. Biophysical cues in the external environment that MSCs are exposed to have been shown to affect MSC migration, residency, differentiation, secretion, etc. We review the main ways in which MSCs exert their immunomodulatory ability, and summarize recent advances in mechanical preconditioning of MSCs to enhance immunomodulatory capacity and related mechanical signal sensing and transduction mechanisms.

Materials and extracellular matrix rigidity highlighted in tissue damages and diseases: Implication for biomaterials design and therapeutic targets.

Rigidity (or stiffness) of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors, such as contractility, motility, and spreading, and the resultant pathophysiological phenomena. Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events, including migration, lineage specification, and mechanical memory. Moreover, the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control, tissue repair, and disease progression. Thus, here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors, with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems, further discussion of the events and considerations in tissue-mimicking 3D conditions, and then examination of the in vivo findings that concern material/matrix rigidity. The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.

Combinatorial biophysical cue sensor array for controlling neural stem cell fate.

Biophysical cues, such as electrical stimulus, mechanical feature, and surface topography, enable the control of neural stem cell (NSC) differentiation and neurite outgrowth. However, the effect of these biophysical cues on NSC behavior has not been fully elucidated. In the present study, we developed an innovative combinatorial biophysical cue sensor array combining a surface modified nanopillar array with conductive hydrogel micropatterns. The micro/nanopattern comprised silicon oxide-coated polyurethane nanopillar arrays on a flexible film and conductive hydrogel micropatterns including polyethylene glycol (PEG) hydrogel, silver nanowires (AgNW), and reduced graphene oxide (rGO). A computational fluid dynamic (CFD) model was used to optimize the design parameters of the nanopillar arrays. In the study, we successfully demonstrated that SiO2-coated nanopillar array enhanced the differentiation of NSCs and efficiently regulated neuronal behavior, such as neurite outgrowths, by conductive hydrogel micropatterns combined with electrical stimuli. Therefore, our innovative combinatorial biophysical cue sensor array to control NSC behavior via electrical stimuli can be potentially useful to study neurodegenerative and neurological disorder therapy applications.