Precision-engineered niche for directed differentiation of MSCs to lineage-restricted mineralized tissues

Abstract

The major difference between tissue healing and regeneration is the extent of instructional cues available to precisely direct the biological response. A classic example is reparative or osteodentin that is seen in response to physicochemical injury to the pulp-dentin complex. Dentin regeneration can direct the differentiation of dental stem cells using concerted actions of both soluble (biomolecules, agonists, and antagonists) and insoluble (matrix topology) cues. The major purpose of this study was to examine the synergistic combination of two discrete biomaterial approaches by utilizing nanofiber scaffolds in discrete configurations (aligned or random) with incorporated polymeric microspheres capable of controlled release of growth factors. Further, to ensure appropriate disinfection for clinical use, Radio-Frequency Glow Discharge (RFGD) treatments were utilized, followed by seeding with a mesenchymal stem cell (MSC) line. SEM analysis revealed electrospinning generated controlled architectural features that significantly improved MSC adhesion and proliferation on the aligned nanofiber scaffolds compared to randomly oriented scaffolds. These responses were further enhanced by RFGD pre-treatments. These enhanced cell adhesion and proliferative responses could be attributed to matrix-induced Wnt signaling that was abrogated by pre-treatments with anti-Wnt3a neutralizing antibodies. Next, we incorporated controlled-release microspheres within these electrospun scaffolds with either TGF-β1 or BMP4. We observed that these scaffolds could selectively induce dentinogenic or osteogenic markers (DSPP, Runx2, and BSP) and mineralization. This work demonstrates the utility of a novel, modular combinatorial scaffold system capable of lineage-restricted differentiation into bone or dentin. Future validation of this scaffold system in vivo as a pulp capping agent represents an innovative dentin regenerative approach capable of preserving tooth pulp vitality.

Amyloid-mediated remineralization for tooth hypoplasia of cleidocranial dysplasia

“…Dental pulp stem cells can differentiate into odontoblast-like cells, forming secondary or reparative dentin. (Chen et al, 2021;Rahman et al, 2022). Exploring the function of the pulp-dentin complex facilitates comprehensive identification of the underlying mechanism of dental abnormalities in CCD.…”

Tideglusib-incorporated nanofibrous scaffolds potently induce odontogenic differentiation

“…Non parametric tests was used for the analysis between the groups and independent groups comparison Mann Whitney U test was used. 21 The representative results are presented as the Mean ± Standard deviation (SD) where p value equal or <0.05 was considered statistically significant.…”

“…These molecules can be incorporated into nanofibrous scaffolds for sustained and controlled drug delivery. 21 Therefore, we investigated the release of TG from the nanofibers and demonstrated a constant release from the nanofibers up to 7 days. The relative release profile of TG from PCLF-TG100 nanofibers showed that during 1 h, 1.69% w/v of incorporated TG was released (Table 2).…”

“…This study extends our prior work on directed differentiation of stem cells for dentin regeneration by generating precise nanoarchitecture fields with polymeric scaffolds. [20][21][22] In this work, we examine the role of TG incorporated in polycaporolactone (PCL) nanofibrous scaffold generated by electrospinning. Following careful mechanical and biochemical characterization of these scaffold systems, we assessed odontogenic differentiation of mesenchymal stem cells (MSCs) or odontoblast cells.…”

Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via photobiomodulation therapy: How to kill two birds with one stone

“… 48 Therefore, innovative approaches through therapeutic delivery vehicles and nanostructures were designed to preserve miRNAs and offer gene expression modulatory therapies for various biomedical applications. 48 – 50 Rahman et al 51 suggest that the application of biomaterial nanopatterning and controlled-release morphogens could enhance MSC differentiation towards an osteogenic bias. Hence, ‘training’ MSCs towards a specific functional identity, improving their intramural achievements or strengthening the MSC transplantation protocols have become imperative.…”