RESUMO
OBJECTIVE: This systematic review evaluates the purpose, materials, physio-mechanical, and biological effects of bilayer scaffolds/membranes used for bone tissue engineering applications. METHODS: A comprehensive electronic search of English-language literature from 2012 to October 2022 was conducted in PubMed, Scopus, ScienceDirect, and Google Scholar online databases according to the PRISMA 2020 guidelines. The quality of animal studies was evaluated through the SYRCLE's risk of bias tool. RESULTS: A total of 77 studies were sought for retrieval, and 39 studies met the inclusion criteria. According to the synthesis results, most bilayers had a dense barrier layer that prevented connective tissue penetration and a loose osteogenic layer that supported cell migration and osteogenesis. PLGA, PCL, and chitosan were the most common polymers in the barrier layers, while the most utilized polymers in osteogenic layers were PLGA and gelatin. Electrospinning and solvent casting were the most common fabrication methods to design the bilayer structures. Many studies reported higher biological results for bilayers compared to their single layers. Also, fabricated bilayers' in vitro osteogenesis and in vivo new bone formation were significantly superior or at least comparable to the frequently used commercial membranes. CONCLUSION: 1) Bilayers with two distinct layers and different materials, porosities, mechanical properties, and biological behavior can significantly improve heterogeneous bone regeneration; 2) the addition of ceramics and/or drugs to the osteogenic layer enhances the osteogenic properties of the bilayers; 3) fabrication method and pore size of the layers play an important role in determining the mechanical and biological behavior of them.
