In vivo Scaffold Delivery Of Antisense For Treatment Of Irreversible Pulpitis

Objectives: Inflammation is a complex response which requires intimate cellular communication and coordination. To facilitate this, gap junctions and hemichannels are essential portals for information exchange. However, pathologic expression of these conduits result in an excessive inflammatory response that causes increased host collateral destruction. Short- to mid- term failure of partial pulpotomy allude to poorly controlled inflammation of the remaining dental pulp.
The objective of this study is to investigate if the downregulation of Connexin-43 (Cx43), a building block of gap junctions and hemichannels, via antisense therapeutics would result in better wound healing following partial pulpotomy in a rodent irreversible pulpitis model.
Methods: Irreversible pulpitis was created in maxillary molars of 8-10 week old male Sprague-Dawley rats by mechanical exposure for 2 days. Partial pulpotomy was then performed and the pulpal wound was treated with Cx43 antisense delivered using either pluronic F-127 gel, polycaprolactone or collagen sponge. Cavities were then sealed with a calcium silicate cement (Biodentine®). Tissues were harvested at days 1 and 5 for evaluation of Cx43 downregulation as well as neutrophilic ingress via immunofluorescence. Histological characteristics of inflammation were also scored. One-way ANOVA was performed to evaluate treatment effects in various groups.
Results: Antisense therapeutics were successfully employed as an adjuvant during partial pulpotomy for the treatment of irreversible pulpitis. Pluronic-delivered antisense had the most favourable histologic outcome at day 1, which was matched PCL- and collagen-delivered antisense groups at day 5.
Conclusions: Various delivery agents differ in the rate of Cx43 downregulation, and is affected by (i) mechanism of antisense release (ii) biocompatibility and (iii) physical properties of the agents. Selection of an ideal delivery agent will require a balanced consideration of all factors to improve resolution of inflammation and wound healing following partial pulpotomy.