Proteoglycan Bioactivation of Barrier Membranes in GTR Improve Healing

In periodontal regeneration, barrier membranes are an important adjunct to procedures aimed at restoring the form and function of the mouth. However, an unnecessarily high failure rate exists in GTR procedures due to failure of the flaps to heal with primary closure over the membranes and regenerative site, typically leading to exposure of the regenerative site to the oral environment. Heparan sulfate proteoglycans, such as perlecan, have been shown to play many roles in biological processes, including cell attachment, growth factor delivery, and cell proliferation. Objective: In a wound closure model, our object was to measure the effects of GTR membranes that had been bioactivated to induce heparan sulfate proteoglycans. Methods: The first domain (D1) of the proteoglycan perlecan was cloned behind the CMV5 promoter in a replication-defective adenoviral vector. Bioactivation of BioMend GTR membranes by wetting with adenovirus in buffered saline was confirmed in vitro with assessment of rD1 and heparan sulfate expression. In anesthetized rats, incisions were made on the maxillary ridge, approximately 5mm long. Full-thickness flaps were elevated and a single, 4mm diameter membrane was inserted under the flaps. The ends of the incision were closed leaving a 2.7±0.1mm2 area of the membrane center directly exposed to the oral environment post-surgery. The exposed membrane area was measured by calibrated image analysis of photographs made during the healing period. Results: GTR membranes bioactivated to induce heparan sulfate proteoglycan resulted in less exposure of membranes after two days healing than control membranes (paired t-test, mean difference 1.65 mm2±0.8, p=0.076, n=4). Conclusion: Bioactivation of surgical membranes in GTR to induce heparan sulfate proteoglycans could promote wound closure and GTR success rates in cases where primary closure was not achieved. Funded by NIH grant 1 R43 DE017254-01A1.