Tissue regeneration by stem cells is driven by the paracrine activity of shedding vesicles and exosomes, which deliver specific cargoes to the recipient cells. Proteins, RNA, cytokines and subsequent gene expression, orchestrate the regeneration process by improving the microenvironment to promote cell survival, controlling inflammation, repairing injury and enhancing the healing process. The action of microRNA is widely accepted as an essential driver of the regenerative process through its impact on multiple downstream biological pathways, and its ability to regulate the host immune response. Here, we present an overview of the recent potential uses of exosomes for regenerative medicine and tissue engineering. We also highlight the differences in composition between shedding vesicles and exosomes that depend on the various types of stem cells from which they are derived. The conditions that affect the production of exosomes in different cell types are deliberated. This review also presents the current status of candidate exosomal microRNAs for potential therapeutic use in regenerative medicine, and in applications involving widely studied organs and tissues such as heart, lung, cartilage and bone.

Novel disc-like microparticles, herein termed as “topodiscs”, with grooved surface nanotopography effectively enhanced cell culture and allowed for a bottom-up engineering of 3D mineralized microtissues.

Cell encapsulation systems must ensure the diffusion of molecules to avoid the formation of necrotic cores. The architectural design of hydrogels, the gold standard tissue engineering strategy, is thus limited to a microsize range. To overcome such limitation, liquefied microcapsules encapsulating cells and microparticles are proposed. Microcapsules with controlled average diameters of 608.5±122.3 μm are produced at high rates by electrohydrodynamic atomization, and RGD domains are introduced in the multilayered membrane. While cells and microparticles interact towards the production of confined microaggregates, on the outside cell-mediated macroaggregates are formed due to the aggregation of microcapsules. The concept of simultaneous aggregation is herein termed as 3D+3D bottom-up tissue engineering. Microcapsules are cultured alone (microcapsule1) or on top of 2D cell beds composed of HUVECs alone (microcapsule2) or co-cultured with fibroblasts (microcapsule3). Microcapsules are able to support cell encapsulation shown by LiveDead, MTS and dsDNA assays. Only microcapsule 3 are able to form macroaggregates, as shown by F-actin immunofluorescence. The bioactive 3D system also presented alkaline phosphatase activity, thus allowing osteogenic differentiation. Upon implantation using the chick chorioallontoic membrane (CAM) model, microcapsules recruit a similar number of vessels with alike geometric parameters in comparison with CAMs supplemented with bFGF.

From an “over‐engineering” era in which biomaterials played a central role, now it is observed to the emergence of “developmental” tissue engineering (TE) strategies which rely on an integrative cell‐material perspective that paves the way for cell self‐organization. The current challenge is to engineer the microenvironment without hampering the spontaneous collective arrangement ability of cells, while simultaneously providing biochemical, geometrical, and biophysical cues that positively influence tissue healing. These efforts have resulted in the development of low‐material based TE strategies focused on minimizing the amount of biomaterial provided to the living key players of the regenerative process. Through a “minimalist‐engineering” approach, the main idea is to fine‐tune the spatial balance occupied by the inanimate region of the regenerative niche toward maximum actuation of the key living components during the healing process.