Novel alendronate and NHS-ester functionalized poly(2-oxazoline)s bone adhesive barrier membranes for guided bone regeneration: Prototype selection and experimental model comparison

In guided tissue regeneration procedures in dentistry and maxillofacial surgery, barrier membranes are generally fixated to prevent membrane dislodgement. However, fixation materials are mostly non-degradable and need to be removed after tissue healing. Novel barrier membranes with bone-adhesive polymer coatings were developed to overcome these disadvantages. Main objective was to assess whether membranes coated with poly(2-oxazoline) polymers modified with mineral-adhesive alendronate groups (POx-Ale and POx-OH-Ale) and/or amine-reactive N-hydroxysuccinimide groups (POx-OH-NHS) exhibit increased fixation to bone compared to uncoated membranes. Secondly, we aimed to validate initial membrane performance in a newly developed ex vivo model to reduce the use of animal experiments in future. Prototype membranes were evaluated on extraoral bone defects in in vivo and ex vivo experiments. Adhesion and cohesion of membranes were scored five minutes after application on a four-point (0–3) Likert scale. POx-OH-NHS-coated membranes showed highest bone-adhesion in both the ex vivo and in vivo pig model, median scores (IQR): 3 (2.75–3.0) and 2 (2.0–3.0), respectively. Additional functionalization of membranes with alendronate-functionalized POx polymers (POx-Ale and POx-OH-Ale) did not further enhance adhesion, whereas membranes coated with these polymers without NHS modifications showed no adhesion to in vivo bone (median 0 (0.0–1.0), both membranes). Although small differences in activating clotting time and temperature, both models were physiologically similar. This study showed a good initial performance of POx-OH-NHS-coated barrier membranes regarding bone adhesion and adhesion characteristics. The ex vivo model corresponded well to the in vivo model, which emphasizes the feasibility of using ex vivo models to test barrier membrane performance in maxillofacial surgery.