Multilayered nanocomposite membrane orchestrating targeted dual release strategies for enhanced guided bone regeneration

Abstract

Presently, guided bone regeneration (GBR) stands as a preeminent strategy for rectifying periodontal and maxillofacial bone imperfections. Nonetheless, the current GBR membranes encounter limitations in terms of antibacterial efficacy and osteogenic potential, impeding their overall effectiveness. To address this, our study endeavors to engineer an innovative GBR membrane with dual attributes of osteoinductiveness and antibacterial activity. This novel asymmetric nanocomposite integrates an intricate structure comprising a compact chitosan hydrogel layer embedded with tetracycline (TCH) and a porous polycaprolactone fibrous layer incorporating chitosan nanoparticles loaded with icariin (IcA@CNps). In the initial phase, IcA@CNps, exhibiting a balanced CNps to IcA ratio of 1:2, an average dimension of 80.94 ± 33.78 nm, and a zeta potential of −19.3 mV, were synthesized and affixed onto nanofibers. This integration facilitated the controlled release of icariin over a span of 22 days. Subsequently, the asymmetric nanocomposite GBR membrane (referred to as GBR+) was meticulously crafted. This involved the application of a TCH hydrogel laden with a drug concentration of 120 µg/ml onto the IcA@CNps-coated nanofibrous layer through an intermediary hydrogel stratum. Impressive results were witnessed during in vitro trials against Staphylococcus aureus, showcasing the remarkable antibacterial prowess of the GBR+ membrane. Notably, human alveolar bone marrow stem cells (aBMSCs) cultivated on the GBR+ membrane exhibited favorable cell adhesion and proliferation rates, devoid of any cytotoxic manifestations. Gene expression analyses further unveiled elevated expressions of SPP1, BMP2, and RUNX2 in the proximity of the fabricated membrane, indicating the promotion of bone formation pathways. Consequently, this asymmetric GBR membrane presents a promising therapeutic avenue for bolstering bone regeneration, underscored by its dual action of fostering bone growth while concurrently displaying antibacterial attributes.