Synthetic morphogen fields for directed dental pulp stem cell differentiation

Statement of Purpose: Tooth decay and gum disease are amongst the most prevalent human disease. Despite being completely preventable by good oral hygiene and proper diet, a lack of access to affordable dental care due to a broad range of factors, such as education and socioeconomic status, have added to the global burden of dental diseases (1). A great number of patients present to dental offices with significant tooth decay necessitating either direct or indirect placement of a pulp capping (protective) agents such as Calcium hydroxide, Mineral Trioxide Aggregate (MTA) and Biodentine among others (2). These agents have shown variable clinical efficacy based on their ability to modulate inflammatory responses and stimulate dentin repair (3). The induced mineralized reparative tissue has a lamellar morphology and its composition has been shown to resemble an intermediate bone-like tissue and is termed Osteodentin. We have previously demonstrated the use of modular scaffolds with controlled release of agonist-antagonists are capable of promoting mesenchymal stem cell differentiation to dentin (4). In contrast to normal tubular dentin, osteodentin lacks neuroproprioception and increased risk of loss of tooth vitality. The stem cell niche enables asymmetrical divisions for stem cell maintenance and propagation where a central role for extracellular matrix (ECM) has been well described (5). Biomaterial techniques that generate nanotopological features simulating natural ECM have been noted to promote specific morphogen pathways that can evoke directed biological responses (6). Such elegant strategies have inspired several studies using electrospun 3D matrices for neuronal (axonal extension) regeneration (7). Electrospinning involves generation of polymer fibers can generate nanoscale (~10nm) fibers that mimic natural ECM topology. We recently noted the ability of specific topological features of electrospun scaffolds were able to promote mineralized dentin differentiation (8). To better understand and optimize the dentin regenerative process, this study examined the combination of specific topological and biological cues for dentin regeneration.