In recent years, owing to the ongoing advancements in polymer materials, hydrogels have found increasing applications in the biomedical domain, notably in the realm of stimuli-responsive "smart" hydrogels. Nonetheless, conventional single-network stimuli-responsive "smart" hydrogels frequently exhibit deficiencies, including low mechanical strength, limited biocompatibility, and extended response times. In response, researchers have addressed these challenges by introducing a second network to create stimuli-responsive "smart" Interpenetrating Polymer Network (IPN) hydrogels. The mechanical strength of the material can be significantly improved due to the topological entanglement and physical interactions within the interpenetrating structure. Simultaneously, combining different network structures enhances the biocompatibility and stimulus responsiveness of the gel, endowing it with unique properties such as cell adhesion, conductivity, hemostasis/antioxidation, and color-changing capabilities. This article primarily aims to elucidate the stimulus-inducing factors in stimuli-responsive "smart" IPN hydrogels, the impact of the gels on cell behaviors and their biomedical application range. Additionally, we also offer an in-depth exposition of their categorization, mechanisms, performance characteristics, and related aspects. This review furnishes a comprehensive assessment and outlook for the advancement of stimuli-responsive "smart" IPN hydrogels within the biomedical arena. We believe that, as the biomedical field increasingly demands novel materials featuring improved mechanical properties, robust biocompatibility, and heightened stimulus responsiveness, stimuli-responsive "smart" IPN hydrogels will hold substantial promise for wide-ranging applications in this domain.

Platelet‐rich plasma (PRP), due to its promising therapeutic properties, has been used in regenerative medicine for more than 30 years and numerous encouraging outcomes have been obtained. Currently, by benefiting from new insights into PRP mechanisms and the excellent performance of extracellular vesicles (EVs) in the field of tissue repair and regeneration, studies have found that a large number of EVs released from activated platelets also participate in the regulation of tissue repair. A growing number of preclinical studies are exploring the functions of PRP‐derived EVs (PRP‐EVs), especially in tissue regeneration. Here, we summarize the latest progress in PRP‐EVs as a superior alternative cell‐free therapeutic strategy in regenerative medicine, clarify their underlying molecular mechanisms, and discuss the advantages and limitations of the upcoming clinical applications. This review highlights the potential of PRP‐EVs to replace the application of PRP or even become a superior alternative in regenerative medicine.

Spinal cord injury (SCI) can lead to permanent and severe functional impairment below the lesion level and is still one of the most challenging clinical problems. The treatment of SCI has progressed with the development of tissue engineering techniques. Insulin-like growth factor 1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are growth factors closely related to nerve regeneration. In this study, IGF-1 and BDNF were successfully immobilized on biodegradable graphene oxide (GO)-incorporated PLGA (PLGA/GO) electrospun nanofibres. The effect of PLGA/GO nanofibres with immobilized IGF-1 and BDNF on neurogenesis was investigated in vitro and in vivo utilizing MTT assays, immunofluorescence, motor function detection and histology observations. We demonstrated that PLGA/GO nanofibres loaded with IGF-1 and BDNF not only protected NSCs from oxidative stress induced by H₂O₂ but also enhanced NSC proliferation and neuronal differentiation in vitro. The in vivo study of an SCI animal model demonstrated that local delivery of IGF-1 and BDNF immobilized to PLGA/GO nanofibres significantly improved functional locomotor recovery, reduced cavity formation and increased the number of neurons at the injury site. Our study indicated that PLGA/GO is an effective carrier for IGF-1 and BDNF delivery and that immobilization of IGF-1 and BDNF onto PLGA/GO nanofibres has a great potential as a nerve implant for spinal cord injury applications.

Many human tissues exhibit a highly oriented architecture that confers them with distinct mechanical properties, enabling adaptation to diverse and challenging environments. Hydrogels, with their water-rich "soft and wet" structure, have emerged as promising biomimetic materials in tissue engineering for repairing and replacing damaged tissues and organs. Highly oriented hydrogels can especially emulate the structural orientation found in human tissue, exhibiting unique physiological functions and properties absent in traditional homogeneous isotropic hydrogels. The design and preparation of highly oriented hydrogels involve strategies like including hydrogels with highly oriented nanofillers, polymer-chain networks, void channels, and microfabricated structures. Understanding the specific mechanism of action of how these highly oriented hydrogels affect cell behavior and their biological applications for repairing highly oriented tissues such as the cornea, skin, skeletal muscle, tendon, ligament, cartilage, bone, blood vessels, heart, etc., requires further exploration and generalization. Therefore, this review aims to fill that gap by focusing on the design strategy of highly oriented hydrogels and their application in the field of tissue engineering. Furthermore, we provide a detailed discussion on the application of highly oriented hydrogels in various tissues and organs and the mechanisms through which highly oriented structures influence cell behavior.

Spinal cord injury (SCI) compromises the blood-spinal cord barrier (BSCB) and induces neuroinflammation, potentially exacerbating neuronal damage. This underscores the importance of maintaining BSCB integrity and mitigating neuroinflammation in SCI treatment. Our study explores an innovative approach to treating SCI by utilizing platelet-rich plasma-derived exosomes (PRP-Exos) to stabilize BSCB function and alleviate neuroinflammation. We successfully isolated exosomes from platelet-rich plasma and conducted both in vivo and in vitro experiments to assess the therapeutic effects of PRP-Exos and explore their potential mechanisms in stabilizing the BSCB, reducing neuroinflammation, and promoting neural functional recovery.In vitro results demonstrate that PRP-Exos significantly reduce the permeability of bEnd.3 cells under hypoxic-hypoglycemic conditions, thereby restoring the integrity of tight junctions. Additionally, our study elucidates the critical role of the NF-κB signaling pathway in the amelioration of neuroinflammation by PRP-Exos. In the SCI model, local injection of hydrogel-encapsulated PRP-Exos reduced Evans blue dye leakage, enhanced the expression of tight junction proteins, alleviated the inflammatory environment in the damaged area, and improved neural functional recovery. In conclusion, PRP-Exos presents a promising and effective treatment option for SCI.

Spinal cord injury (SCI) is considered to be one of the most challenging central nervous system injuries. The poor regeneration of nerve cells and the formation of scar tissue after injury make it difficult to recover the function of the nervous system. With the development of tissue engineering, three-dimensional (3D) bioprinting has attracted extensive attention because it can accurately print complex structures. At the same time, the technology of blending and printing cells and related cytokines has gradually been matured. Using this technology, complex biological scaffolds with accurate cell localization can be manufactured. Therefore, this technology has a certain potential in the repair of the nervous system, especially the spinal cord. So far, this review focuses on the progress of tissue engineering of the spinal cord, landmark 3D bioprinting methods, and landmark 3D bioprinting applications of the spinal cord in recent years.