Loss of periodontal ligament tissue (PDL) and attachment is a serious complication of periodontal diseases - the most prevalent dental health problems. PDL-degeneration leads to alveolar bone degeneration, infection, gingivitis, and eventual tooth loss. There is currently no product that can cure PDL-degeneration as regeneration requires the combinatorial process of regenerating cementum, signaling the existing relevant cells to proliferate and form PDL, and its integration into a functional system. Current restorative treatments utilize cell-based tissue regeneration, synthetic scaffolds, tissue grafts with limited, temporary success. A market product, e.g., claims to restore periodontium using harvested fetal swine periodontal tissue with highly variable clinical outcomes. Although these traditional procedures are well-established and show some success, their efficacy is limited due to the lack of structural and functional integration of a deposited layer with the underlying tooth, specifically integration into the remineralized cementomimetic layer. GEMSEC labs have developed a proprietary technology dubbed “peptide-guided remineralization” which facilitates new mineral formation using protein-derived peptides and have successfully restored dental hard tissues via several case studies including enamel, cementum, dentin under in-vitro and in-vivo conditions. Translating this technology into a daily-use product, we propose a PDL-regenerating chimeric construct which includes a biomineralizing peptide, ADP5, derived from the key enamel protein, amelogenin, with cell signaling moieties. Herein, we aim to use established bioinformatics, machine-learning tools, and high-throughput experimentation to identify peptides from proteins involved in PDL development cell-signaling towards controlled biomineralization, bioadhesion, and cell-signaling functionalities necessary for PDL regeneration. Addressing current treatment protocol limitations, the interdisciplinary approaches developed in this project are designed for the regeneration and formation of fully functional PDL.