Spatiotemporally Controlling the Release of Biological Effectors Enhances Their Effects on Cell Migration and Neurite Outgrowth

Abstract

It is a major challenge to coordinate topographic cues from scaffolds with the on‐demand, sustained release of biological effectors to maximize their performance in tissue regeneration. Here, a system involving masked, photo‐triggered release of biological effectors from a temperature‐sensitive scaffold for augmented cell migration and neurite outgrowth is reported. The scaffold contains microparticles of a phase‐change material (PCM) sandwiched between two layers of electrospun fibers. The biological effectors are co‐loaded with a photothermal dye in the PCM microparticles. Under irradiation with a near‐infrared laser, the PCM will be melted to swiftly release the biological effectors. By imposing a photomask between the scaffold and the laser, only those microparticles in the irradiated region are melted, enabling a spatial control over the release. By adjusting the photomask, different regions of the scaffold can be sequentially irradiated at designated times, realizing on‐demand and sustained release of the biological effectors with spatiotemporal controls. In one demonstration, this method is used to accelerate the directional migration of NIH‐3T3 fibroblasts along the uniaxial or radial direction of fiber alignment by controlling the release of epidermal growth factor. In another demonstration, the release of nerve growth factor is managed to significantly promote neurite outgrowth from PC12 cells.

Neural tissue engineering: From bioactive scaffolds and in situ monitoring to regeneration

“…In one study, microparticles made of phase‐change materials were encapsulated with NGF and indocyanine green and then integrated between two layers of electrospun fibers with the top layer made of uniaxially aligned fibers. [ 42 ] Upon a near‐infrared laser irradiation, the phase‐change particles underwent solid‐liquid transition, allowing the triggered release of the encapsulated NGF, promoting the neurites extension. When a size‐tunable photomask was further introduced between the laser and the scaffold, a spatiotemporally controlled release of NGF was achieved (Figure 3E).…”

Electrospun nanofibers for manipulating soft tissue regeneration

“…For example, NIH-3T3 fibroblasts were cultured on normal tissue culture plates and uniaxially aligned PCL nanofibers, respectively. 39 After 9 days, the cells were stained to observe cell migration. As shown in Fig.…”

“…18 Combined with a photomask, the spatiotemporally controlled release of NGF could further enhance neurite extension. 39…”

Integrating Inflammation-Responsive Prodrug with Electrospun Nanofibers for Anti-Inflammation Application

“…The viability of the cells proliferated on the electrospun nanofiber scaffolds loaded with PIDCM 35 and PIDCM 14 were evaluated using MC3T3-E1 osteoblasts and L929 fibroblasts by using CCK-8 assay, respectively. Briefly, the electrospun nanofiber scaffolds were cut into 13 mm diameter sheets with a 13 mm diameter cutter, sterilized by an Ultraviolet lamp, then fixed in a 24-well plate, and 4.0 × 10 3 cells were plated onto the surfaces of samples carefully, followed by moving to an incubator at 37 • C. The number of cells that proliferated on the scaffolds at a determined time interval (day 1, 3, 5, and 7) was quantified using the CCK-8 assay referring to previous reports [39,52]. As for the electrospun nanofiber scaffolds loaded with PIDCM 35 , the samples co-cultured with cells were firstly washed with PBS three times, followed by fixing cell morphology via 3% glutaraldehyde.…”