Personalized and Tissue-Specific Melt Electrowritten Scaffolds for Coordinated Regeneration of Soft and Hard Periodontal Tissues

Periodontitis is a chronic inflammatory, bacteria-triggered disorder affecting nearly half of American adults. If left untreated, it leads to severe destruction of the periodontium, i.e., the alveolar bone, periodontal ligament (PDL), and cementum, ultimately leading to tooth loss. Current clinical therapeutic approaches include subgingival scaling, periodontal flap surgery, guided tissue regeneration (GTR), and guided bone regeneration (GBR).1 The formation of new bone, cementum, and periodontal ligament (PDL) is a possible objective of these modalities; however, outcomes are not always predictable, due to varying degrees of destruction and highly complex tissue architecture. This underscores the urgent need for superior strategies to amplify regenerative capacity, regardless of damage severity. Melt electrowriting (MEW) is a novel strategy that allows customization to the desired size, configuration, and architecture of a given scaffold. It allows for the production of consistent fiber morphology and diameter approaching submicron magnitudes, which, in turn, allows for the recapitulation of the tissue-specific cell microenvironment. Thus, a MEW-based approach to form fiber-guiding scaffold would offer a geometric organization for bone-PDL interface. In this dissertation work, we show the potential of highly ordered scaffolds engineered via melt electrowriting (MEW) in guiding soft (PDL) and hard (bone) periodontal tissue regeneration. Our in vitro findings show that the presence of the aligned fibers result in a robust expression of ligamentogenic markers, while the strands’ spacing of MEW constructs play a vital role in the upregulation of osteogenic markers. Moreover, in vitro findings strongly suggest that aligned and porous MEW constructs promote macrophage elongation and further polarization toward M2 macrophage, the prohealing phenotype. Meanwhile, the incorporation of osteoconductive fluorinated calcium phosphate coating, has been shown to positively impact mineralized tissue formation. The fiber morphology of F/CaP-coated scaffolds revealed a unique nanostructured surface depicted as irregular-shaped nanoparticles (~ 50-150 nm) and a homogenous rough layer covering each individual fiber. The presence of a nanostructured F/CaP coating led to a marked upregulation of osteogenic genes and attenuated bacterial growth. The reduced bacterial growth, even with a rougher F/CaP coated surface, suggests an antimicrobial action due to the coating’s composition. Collectively, to regenerate tissue-specific architecture and recapitulate the physiological function of native periodontal tissues, a scaffold with tailored properties and bioactive functional was developed. Altogether, our findings confirmed that the tissue-specific scaffolds with F/CaP-coated, bone compartment, and aligned PDL compartment are biocompatible and lead to periodontal tissue regeneration when implanted in a well-established rat mandibular periodontal fenestration defect modelPhDOral Health SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169852/1/daghrery_1.pd