Sharpey's fibers and PDL regeneration

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

Periodontitis is one of the most prevalent diseases. In the United States, 42% of adults are affected by periodontitis, with 7.8% having severe cases. Destructive periodontitis is characterized by irreversible loss of periodontal tissues, including periodontal ligament (PDL) and alveolar bone. While many efforts have been made to develop tissue engineering-based approaches to reconstructing the structures and functions of the lost/damaged periodontal tissues, none of those approaches can achieve predictable and long-term functional periodontal tissue regeneration. One of the major obstacles is the difficulty in regenerating well-organized Sharpey’s fibers that are the terminal ends of PDL principal fibers and are embedded in alveolar bone and cementum. Without these highly oriented Sharpey’s fibers, there would be no functional connection between PDL and alveolar bone/cementum; and the integrity of the periodontal tissues would be impaired, leading to tooth loss. To date, there is no effective bioengineering approach to regenerating PDL Sharpey’s fibers. The overall objective of this proposal is to develop a bio-inspired scaffold (periopatch) for Sharpey’s fiber and periodontal tissue regeneration. The hypothesis is that integration of crucial biophysical and biochemical cues into a bio-inspired matrix will provide a suitable microenvironment to guide periodontal ligament stem cells (PDLSCs) migration, growth, and form well-aligned PDL principal and Sharpey’s fibers. In the preliminary study, tubular architecture of the matrix and tenascin-c (a PDL glycoprotein) were identified as the pivotal biophysical and biochemical factors, respectively, to regulate PDLSC migration and form PDL principal fibers. A unique pyrophosphate/alkaline phosphatase (PPi/ALPase) system in the tubular matrix were further developed to precisely control mineral deposition at the PDL/bone interface to guide Sharpey’s fiber formation. In addition, a bioengineering technology was developed to integrate these crucial elements into a bio-inspired triphasic scaffold for functional Sharpey’s fibers and periodontal tissue regeneration. Based on these exciting preliminary data, three aims are proposed in this proposal. Aim 1 will focus on developing and optimizing a bio-inspired tubular matrix to guide PDL principal fiber formation. Aim 2 is to rebuild the microenvironment for Sharpey’s fiber formation. Aim 3 will focus on regenerating Sharpey’s fibers and periodontal tissues using a periodontal fenestration defect model. Successful completion of this project will address one of the major challenges in periodontal regeneration, making a significant step toward regenerative periodontal therapy in clinic settings.