Periodontitis is a chronic inflammatory infection caused by the overgrowth of bacteria harbored in tooth-retained plaque. It is estimated to affect 50% of American adults over 30, with an increased incidence of up to 70% for those over 65. The disease is characterized by the destruction of the periodontal tissues, including the periodontal ligament (PDL), root cementum, and alveolar bone. As the PDL provides tooth anchorage by connecting the root cementum to the alveolar bone, damage to this tissue results in a loss of integration with the surrounding bone and cementum, eventually leading to complete tooth detachment. This is the primary reason for tooth extractions and/or loss. Current treatments for periodontitis fail to achieve consistent PDL regeneration and integration of soft and hard tissues, thus alternative approaches are needed to improve long term outcomes. This thesis focuses on the development of a biomimetic, fiber-based, polymer composite scaffold that will enable the regeneration and integration of the hard and soft tissues comprising the periodontium, while also controlling residual infection at the wound site. This work is guided by the hypothesis that a multi-phased scaffold optimized in structure and composition to promote tissue regeneration and integration, as well as control the presence of pathogenic organisms, will augment integrative periodontal healing.

The first aim of this thesis investigated scaffold design parameters for ligament regeneration, exploring polymer chemistry, fiber alignment, and antibiotic dose for the support of PDL cell growth and matrix biosynthesis. In addition, the efficacy of antibiotic-containing scaffolds in controlling the growth of periodontal pathogens was evaluated. With the overarching goal of supporting hard tissue integration, aim two optimized scaffold fiber diameter, mineral composition and dose, as well as method of mineral incorporation in order to promote PDL cell viability, growth, differentiation, and mineralized matrix deposition. In the third aim of this thesis a composite scaffold was fabricated, combining the optimized elements from the previous two aims into a multi-phased system that is mimetic of the native periodontal structure. The composite scaffold was then evaluated for tissue healing as well as for integrative potential with native tissue in a tooth-in-bone explant model. Collectively, the results of this thesis demonstrates that a scaffold with optimal structure and composition for PDL growth and integration supports enhanced periodontal healing as assessed through functional evaluation and tissue biosynthesis.

In summary, the studies in this thesis led to the development of a novel, anti-infective, multiphased scaffold which promotes integrative periodontal ligament healing. The broader implications of this work, which includes the elucidation of cell-biomaterial interactions and the implementation of complex scaffold design strategies, can be extended toward the integrative and functional repair of other composite tissue systems.