Preparation of Icariin and Deferoxamine Functionalized Poly(l-lactide)/chitosan Micro/Nanofibrous Membranes with Synergistic Enhanced Osteogenesis and Angiogenesis.

Osteogenesis is tightly complemented with angiogenesis during the bone regeneration process. In this study, to synergistically enhance the osteogenesis and angiogenesis of poly(l-lactide) (PLLA), PLLA/chitosan (PLLA/CS) composite fibrous membrane was prepared first by combining electrospinning and thermally induced phase separation technologies. Then, with the aid of polydopamine (PDA) coating, two types of bioactive molecules of icariin (ICA) and deferoxamine (DFO) were chosen to singly or simultaneously surface modify the as-prepared PLLA/CS-PDA membrane, thereby fabricating PLLA/CS-PDA/ICA, PLLA/CS-PDA/DFO, and PLLA/CS-PDA/ICA/DFO membranes. The morphology and properties of the pristine and modified PLLA fibrous membranes were studied, which revealed that the modified PLLA membrane's own hierarchical fibrous structure improved hydrophilicity and had better tensile properties by introducing PDA and ICA or DFO. On account of the synergetic contributions of ICA and DFO as well as the hierarchical fibrous structure, the PLLA/CS-PDA/ICA/DFO membrane exhibited superior cytocompatibility and osteogenic activity of MC3T3-E1 cells compared to other membranes, which was confirmed by the enhanced cell adhesion, proliferation, osteogenic differentiation, and mineralization. Besides, compared with those without or single immobilization of ICA or DFO, the PLLA/CS-PDA/ICA/DFO membrane with ICA and DFO together could significantly promote the growth and expression of angiogenic-related factors of HUVECs. Particularly, ICA not only exhibits favorable osteogenic activity but also shows superior angiogenic activity even compared to DFO. On the contrary, DFO possesses well-known angiogenic activity but manifests a better osteogenic activity compared with ICA. Overall, our study demonstrated that the PLLA/CS-PDA/ICA/DFO membrane exerts synergistic effects on osteogenesis and angiogenesis, thereby holding great potentials as a substitute for bone repair.