Tailoring of the titanium surface by preparing cardiovascular endothelial extracellular matrix layer on the hyaluronic acid micro-pattern for improving biocompatibility.

It has been proved that high molecular weight hyaluronic acid (HMW-HA, 1×10(6) Da) micro-strips on titanium (Ti) surface can elongate the human vascular endothelial cell (EC) morphology, subsequently enhance endothelial extracellular matrix (ECM) deposition in our previous work. The HMW-HA micro-strips were anticipated to possess good hemocompatibility and EC compatibility simultaneously. However, the single HMW-HA micro-strips on Ti substrate showed bad hemocompatibility. To solve this problem, a method combining HA micro-pattern and EC decellularization was developed, and the endothelial extracellular matrix layer on the HA micro-pattern (ECM/HAP) showed excellent hemocompatibility and endothelial progenitor cells (EPCs) compatibility (cell number: 14.3±0.5×10(5) cells/cm2>2.2±0.7×10(5) cells/cm2 on ECM/TiOH, 7.5±1.3×10(5) cells/cm2 on TiOH, 3.4±0.9×10(5) cells/cm2 on TiOH/HAP and 3.6±1.2×10(5) cells/cm2 on Ti). We also found that the ECM/HAP coating could significantly inhibit the excessive proliferation of smooth muscle cells (SMCs) (cck-8 absorption: 0.25±0.06<1.18±0.09 A.U. on ECM/TiOH, 0.87±0.15 A.U. on TiOH and 1.55±0.11 A.U. on Ti) and the attachment of macrophages (cell number: 1.3±0.1×10(3)<9.2±1.5×10(3) cells/cm2 on ECM/TiOH, 8.8±0.3×10(3) cells/cm2 on TiOH, 7.3±0.7×10(3) cells/cm2 on TiOH/HAP and 9.6±0.9×10(3) cells/cm2 on Ti in 12 h). These data suggest that the multifunctional ECM/HAP coating can be used to build the bionic human endothelial ECM on the biomaterials surface, which might provide a potential and effective method for surface modification of cardiovascular devices.