Surface modification to enhance cell migration on biomaterials and its combination with 3D structural design of occluders to improve interventional treatment of heart diseases

The dominant source of thromboembolism in heart comes from the left atrial appendage (LAA). An occluder can close LAA and significantly reduce the risk of strokes, particularly for those patients with atrial fibrillation. However, it is technically challenging to fabricate an LAA occluder that is appropriate for percutaneous implantation and can be rapidly endothelialized to accomplish complete closure and avoid severe complication. Hypothesizing that a fast migration rate of endothelial cells on the implant surface would lead to rapid endothelialization, we fabricated an LAA occlusion device for interventional treatment with a well-designed 3D architecture and a nanoscale 2D coating. Through screening of biomaterials surfaces with cellular studies in vitro including cell observations, qPCR, RNA sequencing, and implantation studies in vivo, we revealed that a titanium-nitrogen nanocoating on a NiTi alloy promoted high migration rate of endothelial cells on the surface. The effectiveness of this first nanocoating LAA occluder was validated in animal experiments and a patient case, both of which exhibited successful implantation, fast sealing and long-term safety of the device. The mechanistic insights gained in this study will be useful for the design of medical devices with appropriate surface modification, not necessarily for improved cell adhesion but sometimes for enhanced cell migration.