Bioregulator Peptides.
Forty years of evidence.
Bioregulator peptides are short-chain amino acid sequences — two to seven amino acids — that occur naturally in the human body and decline with age. Vladimir Khavinson's institute has produced over 800 peer-reviewed publications on these compounds since the 1970s. Three have published evidence of direct activity in human gingival and periodontal tissue specifically.
The Tissue Repair Signal
A naturally occurring tripeptide found in human plasma and saliva. Levels decline from ~200 ng/mL at age 20 to ~80 ng/mL by age 60 — a greater than 60% reduction that tracks directly with reduced healing capacity. Published gene array analysis demonstrates GHK up- or down-regulates more than 4,000 human genes simultaneously — collagen synthesis, ECM remodeling, angiogenesis, antimicrobial defense, and anti-inflammatory signaling. In a comparative human trial with biopsy confirmation, GHK produced collagen increases in 70% of subjects vs. 50% for Vitamin C and 40% for retinoic acid.
Pickart & Margolina, Int J Mol Sci 2018 · Abdulghani et al., 1998 · Pickart, saliva research
Read the Research Brief →The Stem Cell Activator
The dual-terminus modified analog of AEDG (Epitalon) — N-terminal acetylation and C-terminal amidation provide proteolytic stability in oral mucosal environments. Published studies using human gingival mesenchymal stem cells (hGMSCs) showed AEDG reduced replicative senescence markers p16 by 1.92-fold and p21 by 2.44-fold (p<0.01) — directly restoring proliferative capacity required for gingival tissue self-renewal. In human periodontal ligament stem cells (hPDLSCs), AEDG restored proliferative capacity past replicative passage limits.
Khavinson et al., Molecules 2020 (hGMSC, p<0.01) · Sinjari et al., Stem Cell Rev. Reps. 2020 (hPDLSC)
Read the Research Brief →The Immune Regulator
The dual-terminus modified analog of KE (Vilon), a thymic dipeptide. Periodontal disease and peri-implantitis are immune dysregulation diseases — a dysregulated host inflammatory response drives progressive tissue destruction independent of continued bacterial load. Ac-KE-NH₂ directly modulates NFκB — the master transcription factor driving IL-1β, TNF-α, and RANKL production. RANKL drives osteoclast activation and alveolar bone resorption. In a 6-year prospective human study of 266 subjects, the KE-class peptide produced a 4.1-fold reduction in mortality with normalization of immune and metabolic indices.
Khavinson & Morozov, Neuroendocrinol Lett 2003 · Khavinson et al., Front Genet 2019
Read the Research Brief →Why Oral Mucosal Delivery Works
Buccal Mucosal Absorption
The oral mucosa is a highly vascularized absorptive surface with direct access to the sublingual venous plexus. Short-chain peptides of 2–7 amino acids are absorbed transmucosally at clinically relevant concentrations during a 60–90 second hold. Chitosan in the OptiOral Rinse and OptiOral Care Rinse formulations transiently opens tight junctions for paracellular transport into the subepithelial tissue where gingival fibroblasts and stem cells reside.
Full Brief →Dual-Terminus Modification
Native peptide sequences are rapidly cleaved by salivary aminopeptidases and carboxypeptidases. The Ac-X-NH₂ analogs — Ac-AEDG-NH₂ and Ac-KE-NH₂ — bear N-terminal acetylation and C-terminal amidation. These modifications block the proteolytic attack points at both termini, extending active compound half-life in the oral environment from minutes to hours. This is the key innovation enabling therapeutic tissue exposure from a non-injectable oral format.
Full Brief →