Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

As nano-scale biological vesicles, extracellular vesicles (EVs)/exosomes, in particular, exosomes derived from mesenchymal stem cells (MSC-exosomes), have been studied in the diagnosis, prevention, and treatment of many diseases. In addition, through the combination of nanotechnology and biotechnology, exosomes have emerged as innovative tools for the development of nanomedicine. This review focuses on a profound summarization of MSC-exosomes as a powerful tool in bionanomedicine. It systemically summarizes the role of MSC-exosomes as a nanocarrier, drug loading and tissue engineering, and their potential contribution in a series of diseases as well as the advantages of exosomes over stem cells and synthetic nanoparticles and potential disadvantages. The in-depth understanding of the functions and mechanisms of exosomes provides insights into the basic research and clinical transformation in the field of nanomedicine.

Three-dimensional (3D) bioprinting, known as a promising technology for bioartificial organ manufacturing, has provided unprecedented versatility to manipulate cells and other biomaterials with precise control their locations in space. Over the last decade, a number of 3D bioprinting technologies have been explored. Natural polymers have played a central role in supporting the cellular and biomolecular activities before, during and after the 3D bioprinting processes. These polymers have been widely used as effective cell-loading hydrogels for homogeneous/heterogeneous tissue/organ formation, hierarchical vascular/neural/lymphatic network construction, as well as multiple biological/biochemial/physiological/biomedical/pathological functionality realization. This review aims to cover recent progress in natural polymers for bioartificial organ 3D bioprinting. It is structured as introducing the important properties of 3D printable natural polymers, successful models of 3D tissue/organ construction and typical technologies for bioartificial organ 3D bioprinting.

Hard tissues and organs, including the bones, teeth and cartilage, are the most extensively exploited and rapidly developed areas in regenerative medicine field. One prominent character of hard tissues and organs is that their extracellular matrices mineralize to withstand weight and pressure. Over the last two decades, a wide variety of 3D printing technologies have been adapted to hard tissue and organ engineering. These 3D printing technologies have been defined as 3D bioprinting. Especially for hard organ regeneration, a series of new theories, strategies and protocols have been proposed. Some of the technologies have been applied in medical therapies with some successes. Each of the technologies has pros and cons in hard tissue and organ engineering. In this review, we summarize the advantages and disadvantages of the historical available innovative 3D bioprinting technologies for used as special tools for hard tissue and organ engineering.

Crosslinking is an effective way to improve the physiochemical and biochemical properties of hydrogels. In this study, we describe an interpenetrating polymer network (IPN) of alginate/gelatin hydrogels (i.e., A-G-IPN) in which cells can be encapsulated for in vitro three-dimensional (3D) cultures and organ bioprinting. A double crosslinking model, i.e., using Ca²⁺ to crosslink alginate molecules and transglutaminase (TG) to crosslink gelatin molecules, is exploited to improve the physiochemical, such as water holding capacity, hardness and structural integrity, and biochemical properties, such as cytocompatibility, of the alginate/gelatin hydrogels. For the sake of convenience, the individual ionic (i.e., only treatment with Ca²⁺) or enzymatic (i.e., only treatment with TG) crosslinked alginate/gelatin hydrogels are referred as alginate-semi-IPN (i.e., A-semi-IPN) or gelatin-semi-IPN (i.e., G-semi-IPN), respectively. Tunable physiochemical and biochemical properties of the hydrogels have been obtained by changing the crosslinking sequences and polymer concentrations. Cytocompatibilities of the obtained hydrogels are evaluated through in vitro 3D cell cultures and bioprinting. The double crosslinked A-G-IPN hydrogel is a promising candidate for a wide range of biomedical applications, including bioartificial organ manufacturing, high-throughput drug screening, and pathological mechanism analyses.

Peripheral nerve injury has a high incidence and often leads to severe losses of sensory and motor functions in the afflicted limb. Autologous nerve grafts are widely accepted as the gold standard for peripheral nerve repair, but the presence of inherent drawbacks dramatically reduces their usability. Numerous tissue engineering nerve grafts are developed as alternatives to autologous nerve grafts, and a variety of cells and neurotrophic factors are introduced into these grafts for improvement. However, they are still difficult to obtain satisfactory clinical results. Peripheral nerve regeneration following injury remains a significant challenge for researchers and clinicians. Exosomes are extracellular membranous nanovesicles that are secreted by most cells. As the key players of intercellular communication, exosomes play a fundamental role in the physiological and pathological processes of the nervous system. Accumulating evidence has suggested that exosomes can exert neurotherapeutic effects via mediating axonal regrowth, Schwann cell activation, vascular regeneration, and inflammatory regulation. Exosomes are emerging as a promising approach for treating peripheral nerve injury. Furthermore, they also provide possibilities for enhancing the repairing capacity of various nerve grafts. This review primarily highlights the regenerative effects of exosomes on peripheral nerve injury. The exosomes from distinct sources reported so far in the literature are summarized to understand their roles in the process of nerve repair. Moreover, the challenges that must be addressed in their clinical transformation are outlined as well. This review also provides further insight into the potential application of exosomes for peripheral nerve repair.