Exosomes, nanoscale extracellular vesicles functioning as cell-to-cell communicators, are an emerging promising therapeutic in the field of bone tissue engineering. Here, we report the construction and evaluation of a novel cell-free tissue-engineered bone that successfully accelerated the restoration of critical-sized mouse calvarial defects through combining exosomes derived from human adipose-derived stem cells (hASCs) with poly(lactic-co-glycolic acid) (PLGA) scaffolds. The exosomes were immobilized on the polydopamine-coating PLGA (PLGA/pDA) scaffolds under mild chemical conditions. Specifically, we investigated the effects of hASC-derived exosomes on the osteogenic, proliferation, and migration capabilities of human bone marrow-derived mesenchymal stem cells in vitro and optimized their osteoinductive effects through osteogenic induction. Furthermore, an in vitro assay showed exosomes could release from PLGA/pDA scaffold slowly and consistently and in vivo results showed this cell-free system enhanced bone regeneration significantly, at least partially through its osteoinductive effects and capacities of promoting mesenchymal stem cells migration and homing in the newly formed bone tissue. Therefore, overall results demonstrated that our novel cell-free system comprised of hASC-derived exosomes and PLGA/pDA scaffold provides a new therapeutic paradigm for bone tissue engineering and showed promising potential in repairing bone defects.

Among various classes of biomaterials, the majority of non-centrosymmetric crystalline materials exhibit piezoelectric properties, i.e., the accumulation of charge in response to applied mechanical stress or deformation. Due to the growing interest in nanomaterials, piezoelectric nano-biomaterials have been widely investigated, leading to remarkable advancements throughout the last two decades. Piezoelectric properties, high surface energy, targeting properties, and intricate cell-material interactions render piezoelectric nanomaterials highly attractive for application in therapeutics as well as regenerative medicine. Herein, the major focus is to highlight the wide range of applications of piezoelectric nano-biomaterials in drug delivery, theranostics, and tissue regeneration. After a brief introduction to piezoelectricity, an overview is provided on the major classes of piezoelectric biomaterials as well as a description of the origin of biopiezoelectricity in different tissues and macromolecules. Subsequently, relevant properties and postfabrication strategies of nanostructured piezoelectric biomaterials are discussed aiming to maximize piezoresponse. Finally, recent studies on nano-piezoceramics and piezopolymers are presented, with specific focus on barium titanate, zinc oxide, and polyvinylidene fluoride.

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