Electrodeposited Janus collagen membrane with tunable barrier protection, controlled degradation, and synergistic immunomodulation for bone regeneration in complex defects.

Bone regeneration in complex pathological environments (e.g., infection or diabetes) is particularly challenging. Traditional collagen barrier membranes often degrade quickly and lack multifunctional bioactivity, limiting their effectiveness under such conditions. Here, we describe a collagen-based Janus membrane for advanced guided bone regeneration in these challenging settings. The membrane features an asymmetric bilayer architecture: the soft-tissue side comprises a dense barrier layer formed by electrodeposition, whereas the bone-defect side consists of a porous repair layer. The repair layer incorporates copper-doped hydroxyapatite particles and PLGA microspheres loaded with the natural polyphenol proanthocyanidin, endowing the membrane with potent antibacterial, antioxidant, and osteoconductive properties. Copper ions released from the mineral phase stimulate angiogenic signaling and promote neovascularization, while proanthocyanidin stabilizes the collagen matrix and mitigates inflammation. Meanwhile, the electrodeposited barrier layer confers enhanced mechanical strength and structural integrity, effectively preventing soft-tissue infiltration and bacterial invasion. Moreover, the membrane modulates macrophage glucose metabolism and mitophagy, thereby reducing reactive oxygen species and promoting macrophage polarization toward the anti-inflammatory M2 phenotype, creating an osteoimmune environment conducive to new bone formation. In rat models of infected calvarial and diabetic periodontal defects, the membrane preserves its barrier protection and microenvironmental modulation capacity under pathological stress, leading to enhanced tissue regeneration. This collagen-based Janus membrane thus represents a promising strategy for guided bone regeneration in complex clinical scenarios such as infection or metabolic disorders.