Biomimetic Mineralization and Enzymatic Tailoring of Bacterial Cellulose Towards Degradable, Mechanically Adaptive Substitutes with Enhanced Bioactivity and Cerebrospinal Fluid Barrier Properties.

Abstract

Artificially degradable dura mater substitutes are critical for protecting brain tissue and cerebrospinal fluid (CSF), yet current materials struggle with biomechanical mismatches, uncontrolled degradation, permeability, and limited bioactivity. To address this, we engineered an absorbable bacterial cellulose (BC)-based composite dural substitute via microbial synergism, combining strontium-doped hydroxyapatite (Sr-HAp) biomimetic mineralization with cellulase enzymatic functionalization. A sustainable alternating assembly technique yielded gradient mineralization, constructing a multilayered micro-nano architecture within the BC matrix. With ceramic content tuned from 52.7% to 82.7%, the BC-SrHAp membrane exhibited remarkable mechanical enhancement, 578%-1172% higher compressive strength and 9.4%-58.4% greater tensile strength than pure BC. The rationally designed 3D nano-network architecture reinforces BC fibers while retarding degradation kinetics, enabling controlled release of Sr² ⁺/Ca² ⁺ ions. The sustained ion elution boosted fibroblast activity (enhanced by 8.0%-10.1%), migration (enhanced by 18.2%-22.7%), and osteoblast proliferation (enhanced by 3.2%-16.8%). Moreover, the dense mineralized mesh reduced CSF leakage by 12.8%, surpassing clinical sealing thresholds. Crucially, cellulase enabled degradation-regeneration coupling, ensuring material resorption aligned with tissue repair kinetics. Comprehensive evaluation confirms the BC-SrHAp6-Cel3 composite membrane's potential as an artificial dural material, effectively balancing structural support, controlled degradation, biological activity, and cerebrospinal fluid shielding properties. Its balanced performance underscores high translational potential for complex dural reconstructions.