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. 

Dental implantation is a common clinical procedure used to replace missing teeth and maintain bone structure and facial aesthetics. However, it leads to unexpected side effects, including bone loss or peri-implantitis in 1 out of 10 cases due to failure of osseointegration, defined as improper integration of the implant into the mineralized bone. To enhance osseointegration, the present study aimed to form a layer of hydroxyapatite that could facilitate the integration of the implant (Titanium or Zirconia) with the alveolar bone that lead, while also having antimicrobial property to prevent local infection. Our previous study demonstrated that titanium-binding peptides (TiBPs) are able to bind specifically to the surface of Ti and that amelogenin-derived peptide (ADPs) can be used for direct remineralization on the bone surface. We also identified antimicrobial peptides (AMPs) that can inhibit common oral bacterial growth. These results imply that there is an opportunity to design two of heterofunctional peptides, both binding to Ti with one has the function of directing biomimetic remineralization process, while the other providing antimicrobial activity. The Ti-surface is modified by chimerizing the TiBPs and the ADPs, and TiBPs and AMPs, with short amino acid sequences. The overall process is separated into two main steps: 1. Designing and synthesizing the chimeric peptide; 2. Characterizing (a) binding, (b) mineralization and (c) antimicrobial efficacy of chimeric peptides on the implant surface. We predict that the chimeric peptides will have high binding affinity to the titanium surface while simultaneously enabling mineralization on the implant surface and inhibiting the growth of bacteria. The present aims to contribute to the foundation of finding a long-term novel dental implant treatment via the molecular biomimetic approach towards a clinical strategy to enhance the long-term durability of dental implants. The research is supported by Mary Gates Scholarship (YL), Spencer Funds from School of Dentistry, and CoMotion.