Directing Osteogenesis of Stem Cells with Drug‐Laden, Polymer‐Microsphere‐Based Micropatterns Generated by Teflon Microfluidic Chips

Abstract

Human bone tissue is built in a hierarchical way by assembling various cells of specific functions; the behaviors of these cells in vivo are sophisticatedly regulated. However, the cells in an injured bone caused by tumor or other bone‐related diseases cannot properly perform self‐regulation behaviors, such as specialized differentiation. To address this challenge, a simple one‐step strategy for patterning drug‐laden poly(lactic‐co‐glycolic acid) (PLGA) microspheres into grooves by Teflon chips is developed to direct cellular alignment and osteogenic commitment of adipose‐derived stem cells (ADSCs) for bone regeneration. A hydrophilic model protein and a hydrophobic model drug are encapsulated into microsphere‐based grooved micropatterns to investigate the release of the molecules from the PLGA matrix. Both types of molecules show a sustained release with a small initial burst during the first couple of days. Osteogenic differentiated factors are also encapsulated in the micropatterns and the effect of these factors on inducing the osteogenic differentiation of ADSCs is studied. The ADSCs on the drug‐laden micropatterns show stronger osteogenic commitment in culture than those on flat PLGA film or on drug‐free grooved micropatterns cultured under the same conditions. The results demonstrate that a combination of chemical and topographical cues is more effective to direct the osteogenic commitment of stem cells than either is alone. The microsphere‐based groove micropatterns show potential for stem cell research and bone regenerative therapies.

Patterned substrates fabricated by a controlled freezing approach and biocompatibility evaluation by stem cells

“…Various scaffolds or substrates have been used to orientate the growth of stem cells [4][5][6][7][8][9][44][45][46]. With the newly prepared surface patterned substrates by the controlled freezing approach, this study with the mMSCs demonstrates the biocompatibility and the potential to direct cell growth.…”

“…One concern is whether all the silica colloids were excluded from the freezing front, i.e., located in the ridge but not on the slide surface between the ridges. This is important when such aligned surface patterns are used to direct cell growth where the surface properties of the ridge and the substrate play important roles [7][8][9]. Because the silica colloids are very small and the glass slide is mainly made of silica as well, it is not trivial to distinguish the silica colloids from the glass substrate.…”

“…A number of methods for directing cell alignment using patterned substrates have been described; for instance, a mould patterning method with solvent casting to form CeO 2 nanoparticle lines within a PLGA film could induce the CeO 2 -dependent alignment of cardiac stem cells and MSCs [8]. Drug-laden PLGA microspheres patterned into grooves by Teflon chips could direct cellular alignment and osteogenic commitment of adipose-derived stem cells for bone regeneration [9].…”

Generation of microgrooved silica nanotube membranes with sustained drug delivery and cell contact guidance ability by using a Teflon microfluidic chip

“…A Teflon microfluidic chip was fabricated by the method described in our previous study [20]. A polydimethylsiloxane (PDMS) master was fabricated by curing the PDMS prepolymer onto the photoresist patterns produced with standard photolithography and tightly sealed to a glass slide.…”

Laser-based three-dimensional multiscale micropatterning of biocompatible hydrogels for customized tissue engineering scaffolds

“…Examples illustrating the materials, results, and the performance of the machined geometries in vitro and in vivo are presented to demonstrate the versatility of the approach. T he ability to controllably shape biomaterials on the microscale in two, and especially three, dimensions is important given the utility of these structures in guiding cellular growth, differentiation, gene expression, and regeneration (1)(2)(3)(4). The use of soft, biocompatible materials, however, poses challenges in fabrication due to their mechanical characteristics.…”