BMSC-derived exosomes promote tendon-bone healing after anterior cruciate ligament reconstruction by regulating M1/M2 macrophage polarization in rats. Stem cell research & therapy BACKGROUND:Recent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism. METHODS:Highly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro. The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis. RESULTS:Bioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased. CONCLUSIONS:BMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR. 10.1186/s13287-022-02975-0

Current State of Platelet-Rich Plasma and Cell-Based Therapies for the Treatment of Osteoarthritis and Tendon and Ligament Injuries. The Journal of bone and joint surgery. American volume ➤:Orthobiologics encompass numerous substances that are naturally found in the human body including platelet-rich plasma (PRP), isolated growth factors, and cell therapy approaches to theoretically optimize and improve the healing of cartilage, fractures, and injured muscles, tendons, and ligaments. ➤:PRP is an autologous derivative of whole blood generated by centrifugation and is perhaps the most widely used orthobiologic treatment modality. Despite a vast amount of literature on its use in osteoarthritis as well as in tendon and ligament pathology, clinical efficacy results remain mixed, partly as a result of insufficient reporting of experimental details or exact compositions of PRP formulations used. ➤:Mesenchymal stromal cells (MSCs) can be isolated from a variety of tissues, with the most common being bone marrow aspirate concentrate. Similar to PRP, clinical results in orthopaedics with MSCs have been highly variable, with the quality and concentration of MSCs being highly contingent on the site of procurement and the techniques of harvesting and preparation. ➤:Advances in novel orthobiologics, therapeutic targets, and customized orthobiologic therapy will undoubtedly continue to burgeon, with some early promising results from studies targeting fibrosis and senescence. 10.2106/JBJS.21.01112

Effect of Autologous Platelet-Rich Plasma and Gelatin Sponge for Tendon-to-Bone Healing After Rabbit Anterior Cruciate Ligament Reconstruction. Zhang Mingyu,Zhen Jiang,Zhang Xian,Yang Zhen,Zhang Liang,Hao Dinjun,Ren Bo Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association PURPOSE:To investigate platelet-rich plasma (PRP) combined with gelatin sponge (GS) to improve tendon-bone interface healing and structure formation. METHODS:Characterization of the GS scaffold was performed with a scanning electron microscope, and the release curve after loading with PRP was evaluated. A real-time reverse transcription quantitative polymerase chain reaction assay was performed to test the levels of tendon-to-bone healing-related gene expression. Finally, 18 New Zealand white rabbits were randomly divided into 3 groups and underwent semitendinosus autograft anterior cruciate ligament reconstruction: autograft group without PRP, PRP group, and PRP-GS group. All rabbits were killed 8 weeks after the operation. Magnetic resonance imaging scans, biomechanical testing, and histologic evaluation were performed. RESULTS:An enzyme-linked immunosorbent assay and cell counting kit-8 assay showed that the GS could control the release of PRP and prolong its bioactivity time, as well as promote bone marrow mesenchymal stem cell proliferation. In the PRP-GS group, the levels of related genes were upregulated compared with the PRP group (P < .05). Lower signal in the magnetic resonance images indicated fibrocartilage formation in the 2 groups with PRP. In addition, histologic staining showed that the tendon-bone connection had a greater fibrocartilaginous transition region in the PRP-GS group, and the histologic scores were higher (vs the PRP group, P = .039). The maximum failure load and stiffness were higher in the PRP-GS group than in the other 2 groups. CONCLUSIONS:GS loading with PRP could prolong the bioactivity time of PRP and promote bone marrow mesenchymal stem cell proliferation and osteogenic gene expression in vitro. It also promoted the early healing process at the tendon-bone junction in a rabbit anterior cruciate ligament reconstruction model. CLINICAL RELEVANCE:GS is a natural material and offers satisfactory biocompatibility. Using GS as a scaffold to control the release of bioactive factors in bone tunnels may be useful, but additional studies in human subjects will be necessary to evaluate its clinical prospects. 10.1016/j.arthro.2018.11.014