Multi-level design of a chitosan-based membrane: from sisal fiber reinforcement to surface micropatterning and hybrid hap for enhanced bone regeneration

Overcoming the performance trade-offs among mechanical strength, bioactivity, and processability remains a pivotal challenge for Guided Bone Regeneration (GBR) membranes. Herein, we present a multi-level design strategy that systematically integrates material engineering across molecular, microstructural, and macroscopic scales to address this challenge. Specifically, at the macroscopic level, a sisal fiber-reinforced chitosan base layer provides robust structural support, achieving exceptional mechanical strength (39.48 MPa). At the molecular level, a hybrid hydroxyapatite co-functionalized with carboxymethyl cellulose, zoledronic acid, and phytic acid confers enhanced osteogenic activity and antioxidant capacity (87–95% DPPH scavenging). At the microstructural level, sophisticated surface micropatterning is constructed via a scalable process combining dynamic crosslinking and temperature-modulated phase separation, which actively guide cell behavior. This integrated design synergistically enhances osteogenic differentiation and mineralization, as evidenced by in vitro studies demonstrating the cooperative effects of its unique topology and sustained bioactive signals from the hybrid HAp. In a rat calvarial defect model, the membrane achieved exceptional bone regeneration (97.17 ± 1.7% BV/TV) at 8 weeks, markedly outperforming the control (64.04 ± 3.55%). This work presents a versatile platform highlighting the pivotal role of engineered carbohydrate polymers (chitosan and CMC) and plant-derived fibers in advanced bone biomaterials, offering a new design paradigm.