Natural biomaterials, such as collagen, gelatin, and chitosan, are considered as promising candidates for use in tissue regeneration treatment, given their similarity to natural tissues regarding components and structure. Nevertheless, only receiving a crosslinking process can these biomaterials exhibit sufficient strength to bear high tensile loads for use in skeletal system regeneration. Recently, genipin, a natural chemical compound extracted from gardenia fruits, has shown great potential as a reliable crosslinking reagent, which can reconcile the crosslinking effect and biosafety profile simultaneously. In this review, we briefly summarize the genipin extraction process, biosafety, and crosslinking mechanism. Subsequently, the applications of genipin regarding aiding skeletal system regeneration are discussed in detail, including the advances and technological strategies for reconstructing cartilage, bone, intervertebral disc, tendon, and skeletal muscle tissues. Finally, based on the specific pharmacological functions of genipin, its potential applications, such as its use in bioprinting and serving as an antioxidant and anti-tumor agent, and the challenges of genipin in the clinical applications in skeletal system regeneration are also presented.

The ongoing biomedical nanotechnology has intrigued increasingly intense interests in cerium oxide nanoparticles, ceria nanoparticles or nano-ceria (CeO₂-NPs). Their remarkable vacancy-oxygen defect (VO) facilitates the redox process and catalytic activity. The verification has illustrated that CeO₂-NPs, a nanozyme based on inorganic nanoparticles, can achieve the anti-inflammatory effect, cancer resistance, and angiogenesis. Also, they can well complement other materials in tissue engineering (TE). Pertinent to the properties of CeO₂-NPs and the pragmatic biosynthesis methods, this review will emphasize the recent application of CeO₂-NPs to orthopedic biomedicine, in particular, the bone tissue engineering (BTE). The presentation, assessment, and outlook of the orthopedic potential and shortcomings of CeO₂-NPs in this review expect to provide reference values for the future research and development of therapeutic agents based on CeO₂-NPs.

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.

One of the goals of bone tissue engineering is to mimic native ECM in architecture and function, creating scaffolds with excellent biocompatibility, osteoinductive ability and mechanical properties. The aim of this study was to fabricate nanofibrous matrices by electrospinning a blend of poly (L-lactic-co-glycolic acid) (PLGA), hydroxyapatite (HA), and grapheme oxide (GO) as a favourable platform for bone tissue engineering. The morphology, biocompatibility, mechanical properties, and biological activity of all nanofibrous matrices were compared. The data indicate that the hydrophilicity and protein adsorption rate of the fabricated matrices were significantly increased by blending with a small amount of HA and GO. Furthermore, GO significantly boosted the tensile strength of the nanofibrous matrices, and the PLGA/GO/HA nanofibrous matrices can serve as mechanically stable scaffolds for cell growth. For further test in vitro, MC3T3-E1 cells were cultured on the PLGA/HA/GO nanofbrous matrices to observe various cellular activities and cell mineralization. The results indicated that the PLGA/GO/HA nanofibrous matrices significantly enhanced adhesion, and proliferation in MCET3-E1 cells and functionally promoted alkaline phosphatase (ALP) activity, the osteogenesis-related gene expression and mineral deposition. Therefore, the PLGA/HA/GO composite nanofibres are excellent and versatile scaffolds for applications in bone tissue regeneration.

Traffic accidents, falls, and many other events may cause traumatic spinal cord injuries (SCIs), resulting in nerve cells and extracellular matrix loss in the spinal cord, along with blood loss, inflammation, oxidative stress (OS), and others. The continuous development of neural tissue engineering has attracted increasing attention on the application of fibrin hydrogels in repairing SCIs. Except for excellent biocompatibility, flexibility, and plasticity, fibrin, a component of extracellular matrix (ECM), can be equipped with cells, ECM protein, and various growth factors to promote damage repair. This review will focus on the advantages and disadvantages of fibrin hydrogels from different sources, as well as the various modifications for internal topographical guidance during the polymerization. From the perspective of further improvement of cell function before and after the delivery of stem cell, cytokine, and drug, this review will also evaluate the application of fibrin hydrogels as a carrier to the therapy of nerve repair and regeneration, to mirror the recent development tendency and challenge.

Spinal cord injury (SCI) treatment represents a major challenge in clinical practice. In recent years, the rapid development of neural tissue engineering technology has provided a new therapeutic approach for spinal cord injury repair. Implanting functionalized electroconductive hydrogels (ECH) in the injury area has been shown to promote axonal regeneration and facilitate the generation of neuronal circuits by reshaping the microenvironment of SCI. ECH not only facilitate intercellular electrical signaling but, when combined with electrical stimulation, enable the transmission of electrical signals to electroactive tissue and activate bioelectric signaling pathways, thereby promoting neural tissue repair. Therefore, the implantation of ECH into damaged tissues can effectively restore physiological functions related to electrical conduction. This article focuses on the dynamic pathophysiological changes in the SCI microenvironment and discusses the mechanisms of electrical stimulation/signal in the process of SCI repair. By examining electrical activity during nerve repair, we provide insights into the mechanisms behind electrical stimulation and signaling during SCI repair. We classify conductive biomaterials, and offer an overview of the current applications and research progress of conductive hydrogels in spinal cord repair and regeneration, aiming to provide a reference for future explorations and developments in spinal cord regeneration strategies.