3D-Printed Demineralized Bone Matrix-Based Conductive Scaffolds Combined with Electrical Stimulation for Bone Tissue Engineering Applications.

ABSTRACT

Bone is remodeled through a dynamic process facilitated by biophysical cues that support cellular signaling. In healthy bone, signaling pathways are regulated by cells and the extracellular matrix and transmitted via electrical synapses. To this end, combining electrical stimulation (ES) with conductive scaffolding is a promising approach for repairing damaged bone tissue. Therefore, "smart" biomaterials that can provide multifunctionality and facilitate the transfer of electrical cues directly to cells have become increasingly more studied in bone tissue engineering. Herein, 3D-printed electrically conductive composite scaffolds consisting of demineralized bone matrix (DBM) and polycaprolactone (PCL), in combination with ES, for bone regeneration were evaluated for the first time. The conductive composite scaffolds were fabricated and characterized by evaluating mechanical, surface, and electrical properties. The DBM/PCL composites exhibited a higher compressive modulus (107.2 MPa) than that of pristine PCL (62.02 MPa), as well as improved surface properties (i.e., roughness). Scaffold electrical properties were also tuned, with sheet resistance values as low as 4.77 × 105 Ω/sq for our experimental coating of the highest dilution (i.e., 20%). Furthermore, the biocompatibility and osteogenic potential of the conductive composite scaffolds were tested using human mesenchymal stromal cells (hMSCs) both with and without exogenous ES (100 mV/mm for 5 min/day four times/week). In conjunction with ES, the osteogenic differentiation of hMSCs grown on conductive DBM/PCL composite scaffolds was significantly enhanced when compared to those cultured on PCL-only and nonconductive DBM/PCL control scaffolds, as determined through xylenol orange mineral staining and osteogenic protein analysis. Overall, these promising results suggest the potential of this approach for the development of biomimetic hybrid scaffolds for bone tissue engineering applications.