AC-100, a Novel Biological Agent for Dentin and Bone Regeneration

AC-100 (Dentonin®), a 23-amino acid fragment of matrix extracellular phosphoglycoprotein (MEPE), contains motifs regulating important cellular activities in the bone and dentin microenvironment. Objectives: To evaluate the safety and efficacy of AC-100, a novel agent for dentin and bone regeneration in oral applications. Methods: Class V preparations were made in the maxillary teeth in Beagle dogs and treated with AC-100, placebo or positive control (Dycal). In the same study, mandibular premolars were extracted and sockets filled with collagen sponges containing AC-100 or placebo. Animals were sacrificed at 3 and 28 days post surgery. Teeth and extraction sockets were analyzed histologically. Results: Dentin regeneration: At 3 days post surgery application of AC-100 completely abolished pulp inflammation and decreased the number of apoptotic cells seen in the placebo group. At 28 days post surgery AC-100 induced new dentin growth comparable to and better than Dycal in a dose and application method dependent manner. Oral bone regeneration: At 3 days post surgery AC-100 treatment groups showed denser fibroblastic infiltrate and increased deposition of new collagenous matrix. At 28 days, AC-100 induced highly significant and dose-dependent improvement in the quality of newly formed bone (p<0.005). AC-100 treated sockets contained mainly lamellar bone with mature osteonic structures versus predominantly woven bone in the control group. There was no significant difference between groups with respect to amount of newly-formed bone due to the young age of the animals. Conclusion: AC-100 is a novel and well tolerated biological agent that can promote dentin and bone formation in oral applications. Importantly, AC-100 achieves its activity in a tissue protective manner, stimulating the existing pulp cells to produce dentin with reduced inflammatory and apoptotic responses. Furthermore, the ability of AC-100 to expedite the formation of high quality mature bone may enable the faster placement and loading of implants.