Osteoarthritis (OA), known as one of the most common types of aseptic inflammation of the musculoskeletal system, is characterized by chronic pain and whole-joint lesions. With cellular and molecular changes including senescence, inflammatory alterations, and subsequent cartilage defects, OA eventually leads to a series of adverse outcomes such as pain and disability. CRISPR-Cas-related technology has been proposed and explored as a gene therapy, offering potential gene-editing tools that are in the spotlight. Considering the genetic and multigene regulatory mechanisms of OA, we systematically review current studies on CRISPR-Cas technology for improving OA in terms of senescence, inflammation, and cartilage damage and summarize various strategies for delivering CRISPR products, hoping to provide a new perspective for the treatment of OA by taking advantage of CRISPR technology.

Osteoarthritis refers to a degenerative disease with joint pain as the main symptom, and it is caused by various factors, including fibrosis, chapping, ulcers, and loss of articular cartilage. Traditional treatments can only delay the progression of osteoarthritis, and patients may need joint replacement eventually. As a class of organic compound molecules weighing less than 1000 daltons, small molecule inhibitors can target proteins as the main components of most drugs clinically. Small molecule inhibitors for osteoarthritis are under constant research. In this regard, by reviewing relevant manuscripts, small molecule inhibitors targeting MMPs, ADAMTS, IL-1, TNF, WNT, NF-κB, and other proteins were reviewed. We summarized these small molecule inhibitors with different targets and discussed disease-modifying osteoarthritis drugs based on them. These small molecule inhibitors have good inhibitory effects on osteoarthritis, and this review will provide a reference for the treatment of osteoarthritis.

Background: All-inside anterior cruciate ligament reconstruction (ACLR) is a novel technique that has gained attention due to its minimally invasive and graft-saving properties. However, studies comparing MRI-based graft maturity between all-inside and standard ACLR are lacking. Purpose: This study focused on the functional, knee laxity, and MRI-based graft maturity characteristics of all-inside and standard single-bundle ACLR. Study Design: Randomized controlled trial (RCT). Methods: Fifty-four patients were randomly assigned to an all-inside reconstruction group (n = 27) or standard reconstruction group (n = 27). Using the same rehabilitation strategy. The Tegner, International Knee Documentation Committee, and Lysholm scores were recorded at postoperative months 3, 6, and 12 to assess functional recovery. MRI was conducted to measure the signal/noise quotient (SNQ) of the intra-articular graft to assess the maturity. A higher SNQ indicates lower graft maturity. Knee laxity was assessed using GNRB arthrometer at the postoperative month 12. Results: The graft SNQ of the all-inside group was significantly higher than that of the standard group at postoperative month 6 (p < 0.05). There was no statistical difference in graft SNQ between the two groups at postoperative months 3 and 12 (p > 0.05). Both groups exhibited the highest SNQ in the middle region of the graft, followed by the proximal region, and the distal region. Functional scores improved significantly for both groups and had no statistical difference (p > 0.05). The knee laxity was higher in the all-inside group (p < 0.05) at postoperative month 12. There was no correlation between the functional scores and graft maturity in both groups (p > 0.05). Conclusions: All-inside and standard single-bundle ACLR show good functional outcomes; however, knee laxity was relatively higher in the all-inside ACLR group than in the standard ACLR group. Moreover, both techniques exhibited poor maturity in the middle graft region and the best in the distal region. Graft maturity with all-inside ACLR is inferior to that with standard ACLR in the early postoperative stages. There is no correlation between knee function and graft maturity. Trial registration: Clinical trial registration numbers: ChiCTR1800018543. Date of registration: 09/23/2018.

Purpose: This study aims to explore the emerging trends, dynamic development, and research hotspots of clustered regularly interspaced short palindromic repeats (CRISPR) technology associated with extracellular vesicles during the past 7 years and demonstrate them by visualization. Methods: A total of 219 records related to CRISPR technology associated with extracellular vesicles from 2015 to 2022 in the Web of Science Core Collection (WoSCC) database were collected. R language, VOSviewer, CiteSpace, and GraphpadPrism software packages were used to analyze the history of this research, the general characteristics of the literature, and keywords. Finally, the hotspots and latest trends in CRISPR technology associated with extracellular vesicles are predicted. Results: A total of 219 articles were collected for this study. The production of publications about CRISPR technology associated with extracellular vesicles has increased annually. Researchers from China, the USA, and Germany made the most important contributions to this trend, while RLUK Research Libraries UK offers the largest amount of literature in this field. Shenzhen University, Nanjing Medicine University, and Peking University exhibited the closest cooperation. Additionally, active topics burst during different periods, as identified according to 317 keywords belonging to 39 disciplines. Keywords were clustered into seven research subareas, namely exosome, nanovesicles, DNA, gene editing, gene therapy, cancer therapy, and endometrial stromal cells. The alluvial map of keywords reveals that the most enduring concepts are gene therapy, nanovesicles, etc., while the emerging keywords are genome, protein delivery, plasma, etc. Conclusions: We reviewed 219 previous publications and conducted the first bibliometric study of CRISPR technology related to extracellular vesicles from 2015 to 2022. This comprehensive summary constructed a knowledge map and demonstrates the trends in this area. The current trends and potential hotpots for this topic are also identified, which will be a great help for researchers in the future.

Clinical intervention for osteoarthritis (OA) has long been hampered by complex intra-articular physiological barriers, including rapid synovial clearance, the dense penetration resistance of the cartilage extracellular matrix (ECM), and a progressively deteriorating pro-inflammatory microenvironment. Conventional single-scale delivery systems frequently struggle to balance sustained retention with deep tissue penetration. Recently, micro-nano composite structures—engineered through the sophisticated integration of microscale matrices and nanoscale functional units—have catalyzed a paradigm shift from passive “space-filling” to active “fate modulation.” This review systematically delineates the recent advancements in micro-nano platforms for OA therapy. We first evaluate how advanced fabrication strategies, such as microfluidics, 3D bioprinting, and hierarchical emulsification, govern the spatiotemporal arrangement of these structures. Subsequently, we explore the mechanisms by which these trans-scale systems achieve prolonged joint residence, deep ECM infiltration, and precise immunomodulation of macrophages and stem cells. Furthermore, the roles of micro-nano architectures in recapitulating the biomimetic properties (topological, mechanical, and biochemical) of native cartilage and stimulating endogenous repair are highlighted. Finally, we provide a critical appraisal of the challenges hindering clinical translation, including scalability, biosafety margins, and the future of intelligent closed-loop designs. The development of micro-nano composite systems not only offers high-efficiency “cell-free therapy” for OA but also establishes a novel scientific paradigm for precision regenerative medicine in degenerative diseases.