Tackling Microbial Contamination in Polydioxanone-Based Membranes for Regenerative Therapy: Bioengineering an Antibiotic-Loaded Platform

Barrier membranes are essential components of tissue regenerative therapies, acting as physical barriers to protect the healing site. Although collagen-based membranes are widely used, they degrade enzymatically, often triggering inflammation and cytotoxicity arising from residual cross-linking agents. Synthetic polymer-based membranes, such as polydioxanone (PDO), present customizable properties, predictable degradation rates, and induce bone formation more effectively. However, both materials are at risk of exposure to the microbial contamination. To address this, antibiotics have been loaded onto membranes as drug-delivery systems, a strategy that has not yet been explored for PDO membranes. In this study, the oral polymicrobial contamination of PDO-based membranes was evaluated and compared with collagen membranes and aimed to develop an amoxicillin-loaded PDO (AMX-PDO) membrane. For this purpose, PDO membranes with different pore sizes (0.25, 0.50, and 1.00 mm) and two commercially available collagen membranes were evaluated, using in vitro and in situ models, in terms of polymicrobial accumulation. Next, AMX-PDO membranes were developed by glow discharge plasma using Ar and O<sub>2</sub> gases and an amoxicillin compound. The findings revealed similar microbial levels for both PDO and collagen-based membranes, but PDO membranes modulated microbial composition with reduced (∼3-5 fold-decrease) levels of specific oral pathogens. The AMX-PDO membrane maintained similar physical and chemical properties to those of untreated membranes, but it significantly reduced polymicrobial accumulation and prevented microbial cells from passing through them. Thus, they acted as more than passive physical barriers only, but rather as biologically active barriers. Therefore, amoxicillin loading on PDO barrier membranes by means of plasma technology seems to be a promising strategy to prevent local infection during regenerative therapy.