Polydopamine-assisted one-step modification of nanofiber surfaces with adenosine to tune the osteogenic differentiation of mesenchymal stem cells and the maturation of osteoclasts

Adenosine and its receptors have emerged as alternative targets to control cellular functions for bone healing. However, the soluble delivery of adenosine has shown limited therapeutic outcomes due to its fast degradation in vivo. Given that, we designed a stable coating of adenosine on biomaterial surface through polydopamine chemistry to control osteogenesis and osteoclastogenesis via A2bR signaling. Firstly, we prepared electrospun poly (ι-lactic acid) (PLLA) nanofiber sheets, which were modified through a one-step adenosine polydopamine coating process. The SEM revealed the deposition of a number of particles on the adenosine polydopamine-coated PLLA (AP-PL) sheets compared to the polydopamine-only group. Moreover, X-ray photoelectron spectroscopy analysis confirmed the increase in nitrogen signals due to adenosine. Further, the adenosine loading efficiency and retention were significantly enhanced in AP-PL. Then, human adipose-derived stem cells (hADSCs) cultured on AP-PL showed a significant increase in the expression of A2bR (1.30 ± 0.19 fold). This in turn significantly elevated the expression levels of Runx2 (16.94 ± 1.68 and 51.69 ± 0.07 fold), OPN (1.63 ± 0.16 and 30.56 ± 0.25 fold), OCN (1.16 ± 0.13 and 5.23 ± 0.16 fold), and OSX (10.01 ± 0.81 and 62.48 ± 0.25 fold) in growth media upon days 14 and 21, respectively. Similarly, the mineral deposition was also enhanced in AP-PL compared to that of the polydopamine group, while the blocking of A2bR significantly downregulated the osteogenesis. Finally, AP-PL showed significant inhibition of the osteoclast differentiation of RAW 264.7 cells. However, the osteoclast differentiation was significantly stimulated after the A2bR receptor was blocked. Taken together, we propose that the polydopamine-assisted one-step coating of adenosine could be utilized as an alternative method for the surface modification of biomaterials to control osteogenic differentiation of stem cells and bone healing.