Abstract
Cells exhibit distinct 3D morphologies in vivo, and recapitulation of physiological cell morphologies in vitro is pivotal not only to elucidate many fundamental biological questions, but also to develop new approaches for tissue regeneration and drug screening. However, conventional cell culture methods in either a 2D petri dish or a 3D scaffold often lead to the loss of the physiological morphologies for many cells, such as bone cells (osteocytes) and dentinal cells (odontoblasts). Herein, a unique approach in developing a 3D extracellular matrix (ECM)-like micropatterned synthetic matrix as a physiologically relevant 3D platform is reported to recapitulate the morphologies of osteocytes and odontoblasts in vitro. The bio-inspired micropatterned matrix precisely mimics the hierarchic 3D nanofibrous tubular/canaliculi architecture as well as the compositions of the ECM of mineralized tissues, and is capable of controlling one single cell in a microisland of the matrix. Using this bio-inspired 3D platform, individual bone and dental stem cells are successfully manipulated to recapitulate the physiological morphologies of osteocytes and odontoblasts in vitro, respectively. This work provides an excellent platform for an in-depth understanding of cell-matrix interactions in 3D environments, paving the way for designing next-generation biomaterials for tissue regeneration.