Nanofibrous Spongy Microspheres Enhance Odontogenic Differentiation of Human Dental Pulp Stem Cells

Abstract

While dental caries afflicts nearly 100% adults and 60–70% children, dentin regeneration is challenging due to its complicated anatomical structure and the shortage of odontoblasts. In this study, a novel injectable cell carrier, nanofibrous spongy microspheres (NF-SMS), was developed for dentin regeneration. Biodegradable and biocompatible poly(L-lactic acid)-block-poly(L-lysine) copolymers were synthesized and fabricated into NF-SMS using self-assembly and thermally-induced phase separation techniques. We hypothesized that NF-SMS with interconnected pores throughout the nanofibrous microspheres could enhance the proliferation and odontogenic differentiation of human dental pulp stem cells (hDPSCs), compared to nanofibrous microspheres (NF-MS) without pore structure and conventional solid microspheres (S-MS) with neither nanofibers nor pore structure. During the first 9 d in culture, hDPSCs proliferated significantly faster on NF-SMS than on NF-MS and S-MS (p < 0.05). Following in vitro odontogenic induction, all the examined odontogenic markers including ALP content, OCN, BSP, COL1, DSPP gene expression levels, calcium content and DSPP protein content were found significantly higher in the NF-SMS group than in the NF-MS and S-MS control groups. Furthermore, 6 wk after subcutaneous injection of hDPSCs and microspheres into nude mice, histological analysis showed that NF-SMS supported superior dentin-like tissue formation compared to NF-MS and S-MS. Taken together, the results supported our hypothesis and suggest that the novel NF-SMS have great potential as an injectable cell carrier for dentin regeneration.

Injectable nanofibrous spongy microspheres for NR4A1 plasmid DNA transfection to reverse fibrotic degeneration and support disc regeneration

“…The sustained local delivery of pDNA from nanocarriers can overcome shortcomings associated with systemic drug delivery, including rapid clearance and side effects in unintended tissues [63]. The nano-scale and micro-scale structures of NF-SMS may advantageously support tissue regeneration [64-66]. On the nanometer scale, a nanofibrous architecture mimicking the structure of extracellular matrix (ECM) can promote tissue regeneration [56, 67].…”

Encapsulation of grape seed extract in polylactide microcapsules for sustained bioactivity and time-dependent release in dental material applications

“…For example, self-healing resin composites were demonstrated using core-shell microcapsules that release a healing agent in response to mechanical damage [16-18]. Microcapsules have also been used for the time-release (also known as sustained release) of useful agents for antimicrobial activities [19,20], remineralization [21-23], and regeneration [24-27]. Time-release is generally achieved via the degradation of the encapsulating wall material, diffusion through the shell wall, or a combination of these two mechanisms [28].…”

Advanced Scaffolds for Dental Pulp and Periodontal Regeneration

“…The NF-SMS microspheres supported DPSC proliferation and demonstrated DSPP expression in vitro . 75,76 Interestingly, DPSCs in NF-SMS microspheres, when exposed to hypoxic conditions, demonstrated increased VEGF expression. Following 4-weeks’ implantation in an in situ pulp regeneration model, the cells in the hypoxia-primed group demonstrated columnar odontoblastic cell arrangement at the dentin–pulp interface, similar to that of native teeth.…”

“…3A–B) to deliver DPSCs into the pulpal space. 75,76 The authors reported on the synthesis of a novel, star-shaped block copolymer, poly(L-lactic acid)-block-poly-(L-lysine), capable of self-assembling into nanofibrous microspheres (NF-SMS). The NF-SMS microspheres supported DPSC proliferation and demonstrated DSPP expression in vitro .…”