The Phase-Transited Lysozyme Coating Modified Small Intestinal Submucosa Membrane Loaded with Calcium and Zinc Ions for Enhanced Bone Regeneration

Bone defects caused by severe trauma, tumors, infections and diseases remain a global challenge due to limited natural regeneration capacity of bone tissue in large-scale or complex injuries. Guided bone regeneration (GBR) has emerged as a pivotal technique in addressing these issues, relying on barrier membranes to facilitate osteoprogenitor cell infiltration. Current clinical GBR membranes function solely as physical barriers, lacking antibacterial and osteoinductive properties, which underscores the need for advanced alternatives. This study focuses on resorbable GBR membranes made from small intestinal submucosa (SIS), known for biocompatibility and tissue regeneration but hindered by low mechanical strength and rapid degradation. In addition, SIS lacks both antibacterial properties and strong osteogenic capabilities. Enhancements involve crosslinking treatment and dual incorporation of calcium (Ca²⁺) and zinc (Zn²⁺), which address the physical property shortcomings and synergistically boost osteoinductivity by activating osteogenic signaling pathways. Additionally, phase-transited lysozyme (PTL) nanofilm technique enables efficient ion loading and controlled release, while offering antibacterial properties. In this study, a multifunctional SIS membrane is constructed by PTL-ions layers, providing a potential solution to the challenge of clinical bone defects.