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Spinal cord injury (SCI) is a common traumatic disease of the nervous system. The pathophysiological process of SCI includes primary injury and secondary injuries. An excessive inflammatory response leads to secondary tissue damage, which in turn exacerbates cellular and organ dysfunction. Due to the irreversibility of primary injury, current research on SCI mainly focuses on secondary injury, and the inflammatory response is considered the primary target. Thus, modulating the inflammatory response has been suggested as a new strategy for the treatment of SCI. In this study, microglial cell lines, primary microglia, and a rat SCI model were used, and we found that WKYMVm/FPR2 plays an anti-inflammatory role and reduces tissue damage after SCI by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways. FPR2 was activated by WKYMVm, suppressing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by inhibiting M1 microglial polarization. Moreover, FPR2 activation by WKYMVm could reduce structural disorders and neuronal loss in SCI rats. Overall, this study illustrated that the activation of FPR2 by WKYMVm repressed M1 microglial polarization by suppressing the ERK1/2 and NF-κB signaling pathways to alleviate tissue damage and locomotor decline after SCI. These findings provide further insight into SCI and help identify novel treatment strategies.

Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

Animal models play an important role in preclinical studies, especially in tissue engineering scaffolds for cartilage repair, which require large animal models to verify the safety and effectiveness for clinical use. The small ruminant models are most widely used in this field than other large animals because they are cost-effective, easy to raise, not to mention the fact that the aforementioned animal presents similar anatomical features to that of humans. This review discusses the experimental study of tissue engineering scaffolds for knee articular cartilage regeneration in small ruminant models. Firstly, the selection of these scaffold materials and the preparation process in vitro that have been already used in vivo are briefly reviewed. Moreover, the major factors influencing the rational design and the implementation as well as advantages and limitations of small ruminants are also demonstrated. As regards methodology, this paper applies principles and methods followed by most researchers in the process of experimental design and operation of this kind. By summarizing and comparing different therapeutic concepts, this paper offers suggestions aiming to increase the effectiveness of preclinical research using small ruminant models and improve the process of developing corresponding therapies.

Hyaline articular cartilage lacks blood vessels, lymphatics, and nerves and is characterised by limited self-repair ability following injury. Traditional techniques of articular cartilage repair and regeneration all have certain limitations. The development of tissue engineering technology has brought hope to the regeneration of articular cartilage. The strategies of tissue-engineered articular cartilage can be divided into three types: “cell-scaffold construct,” cell-free, and scaffold-free. In “cell-scaffold construct” strategies, seed cells can be autologous chondrocytes or stem. Among them, some commercial products with autologous chondrocytes as seed cells, such as BioSeed®-C and CaReS®, have been put on the market and some products are undergoing clinical trials, such as NOVOCART® 3D. The stem cells are mainly pluripotent stem cells and mesenchymal stem cells from different sources. Cell-free strategies that indirectly utilize the repair and regeneration potential of stem cells have also been used in clinical settings, such as TruFit and MaioRegen. Finally, the scaffold-free strategy is also a new development direction, and the short-term repair results of related products, such as NOVOCART® 3D, are encouraging. In this paper, the commonly used techniques of articular cartilage regeneration in surgery are reviewed. By studying different strategies and different seed cells, the clinical application status of tissue-engineered articular cartilage is described in detail.

Seed cells of articular cartilage tissue engineering face many obstacles in their application because of the dedifferentiation of chondrocytes or unstable chondrogenic differentiation status of pluripotent stem cells. To overcome mentioned dilemmas, a simulation of the articular cartilage microenvironment was constructed by primary articular cartilage cells (pACs) and acellular cartilage extracellular matrix- (ACECM-) oriented scaffold cocultured with human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJMSCs) in vitro. The coculture groups showed more affluent cartilage special matrix ingredients including collagen II and aggrecan based on the results of histological staining and western blotting and cut down as many pACs as possible. The RT-PCR and cell viability experiments also demonstrated that hWJMSCs were successfully induced to differentiate into chondrocytes when cultured in the simulated cartilage microenvironment, as confirmed by the significant upregulation of collagen II and aggrecan, while the cell proliferation activity of pACs was significantly improved by cell-cell interactions. Therefore, compared with monoculture and chondrogenic induction of inducers, coculture providing a simulated native articular microenvironment was a potential and temperate way to regulate the biological behaviors of pACs and hWJMSCs to regenerate the hyaline articular cartilage.

The meniscus plays a vital role in protecting the articular cartilage of the knee joint. The inner two-thirds of the meniscus are avascular, and injuries to this region often fail to heal without intervention. The use of tissue engineering and regenerative medicine techniques may offer novel and effective approaches to repairing meniscal injuries. Meniscal tissue engineering and regenerative medicine typically use one of two techniques, cell-based or cell-free. While numerous cell-based strategies have been applied to repair and regenerate meniscal defects, these techniques possess certain limitations including cellular contamination and an increased risk of disease transmission. Cell-free strategies attempt to repair and regenerate the injured tissues by recruiting endogenous stem/progenitor cells. Cell-free strategies avoid several of the disadvantages of cell-based techniques and, therefore, may have a wider clinical application. This review first compares cell-based to cell-free techniques. Next, it summarizes potential sources for endogenous stem/progenitor cells. Finally, it discusses important recruitment factors for meniscal repair and regeneration. In conclusion, cell-free techniques, which focus on the recruitment of endogenous stem and progenitor cells, are growing in efficacy and may play a critical role in the future of meniscal repair and regeneration.

The histological features of cartilage call attention to the fact that cartilage has a little capacity to repair itself owing to the lack of a blood supply, nerves, or lymphangion. Stem cells have emerged as a promising option in the field of cartilage tissue engineering and regenerative medicine and could lead to cartilage repair. Much research has examined cartilage regeneration utilizing stem cells. However, both the potential and the limitations of this procedure remain controversial. This review presents a summary of emerging trends with regard to using stem cells in cartilage tissue engineering and regenerative medicine. In particular, it focuses on the characterization of cartilage stem cells, the chondrogenic differentiation of stem cells, and the various strategies and approaches involving stem cells that have been used in cartilage repair and clinical studies. Based on the research into chondrocyte and stem cell technologies, this review discusses the damage and repair of cartilage and the clinical application of stem cells, with a view to increasing our systematic understanding of the application of stem cells in cartilage regeneration; additionally, several advanced strategies for cartilage repair are discussed.

Meniscus injuries remain a significant challenge due to the poor healing potential of the inner avascular zone. Following a series of studies and clinical trials, tissue engineering is considered a promising prospect for meniscus repair and regeneration. As one of the key factors in tissue engineering, cells are believed to be highly beneficial in generating bionic meniscus structures to replace injured ones in patients. Therefore, cell-based strategies for meniscus tissue engineering play a fundamental role in meniscal regeneration. According to current studies, the main cell-based strategies for meniscus tissue engineering are single cell type strategies; cell coculture strategies also were applied to meniscus tissue engineering. Likewise, on the one side, the zonal recapitulation strategies based on mimicking meniscal differing cells and internal architectures have received wide attentions. On the other side, cell self-assembling strategies without any scaffolds may be a better way to build a bionic meniscus. In this review, we primarily discuss cell seeds for meniscus tissue engineering and their application strategies. We also discuss recent advances and achievements in meniscus repair experiments that further improve our understanding of meniscus tissue engineering.

The meniscus plays a crucial role in maintaining knee joint homoeostasis. Meniscal lesions are relatively common in the knee joint and are typically categorized into various types. However, it is difficult for inner avascular meniscal lesions to self-heal. Untreated meniscal lesions lead to meniscal extrusions in the long-term and gradually trigger the development of knee osteoarthritis (OA). The relationship between meniscal lesions and knee OA is complex. Partial meniscectomy, which is the primary method to treat a meniscal injury, only relieves short-term pain; however, it does not prevent the development of knee OA. Similarly, other current therapeutic strategies have intrinsic limitations in clinical practice. Tissue engineering technology will probably address this challenge by reconstructing a meniscus possessing an integrated configuration with competent biomechanical capacity. This review describes normal structure and biomechanical characteristics of the meniscus, discusses the relationship between meniscal lesions and knee OA, and summarizes the classifications and corresponding treatment strategies for meniscal lesions to understand meniscal regeneration from physiological and pathological perspectives. Last, we present current advances in meniscal scaffolds and provide a number of prospects that will potentially benefit the development of meniscal regeneration methods.

Cartilage extracellular matrix (ECM) is composed primarily of the network type II collagen (COLII) and an interlocking mesh of fibrous proteins and proteoglycans (PGs), hyaluronic acid (HA), and chondroitin sulfate (CS). Articular cartilage ECM plays a crucial role in regulating chondrocyte metabolism and functions, such as organized cytoskeleton through integrimmediated signaling via cell-matrix interaction. Cell signaling through integrins regulates several chondrocyte functions, including differentiation, metabolism, matrix remodeling, responses to mechanical stimulation, and cell survival. The major signaling pathways that regulate chondrogenesis have been identified as wnt signal, nitric oxide (NO) signal, protein kinase C (PKC), and retinoic acid (RA) signal. Integrins are a large family of molecules that are central regulators in multicellular biology. They orchestrate cell-cell and cell-matrix adhesive interactions from embryonic development to mature tissue function. In this review, we emphasize the signaling molecule effect and the biomechanics effect of cartilage ECM on chondrogenesis. [ABSTRACT FROM AUTHOR]