Bone non-union after fracture, considered a therapeutic challenge for orthopedics, always needs a reversion surgery, including autograft transplantation (AGT). However, adverse events related to autograft harvest cannot be ignored. Our group designed a novel system called the bone marrow stem cell Screen-Enrich-Combine Circulating System (SECCS) by seeding mesenchymal stem cells (MSCs) into β-tricalcium phosphate (β-TCP) during surgery to thereafter rapidly process bioactive bone implantation. In this retrospective case-control study, 30 non-union patients who accepted SECCS therapy and 20 non-union patients who accepted AGT were enrolled. By SECCS therapy, the MSC-enriched β-TCP particles were implanted into the non-union gap. During the enrichment procedure, a significant proportion of MSCs were screened and enriched from bone marrow into porous β-TCP particles, and the cells possessed the capacity for three-line differentiation and were CD90+/CD105+/CD34-/CD45-. Approximately 82.0±10.7% of MSCs were enriched from 60 mL bone marrow without damaging cell viability, and approximately 11,444.0±6,018 MSCs were transplanted per patient. No implant-related infections occurred in any case. After 9 months of follow-up, 27 patients (90%) in the SECCS group acquired clinical union, compared with 18 patients (90%) in the AGT group (clinical union time, P = 0.064), and postoperative radiographic union score at 9 months post-operation was similar between the two groups. In conclusion, the SECCS could concentrate a large proportion of MSCs from bone marrow to acquire enough effective cells for therapy without in vitro cell culture. Bone substitutes processed by SECCS demonstrated encouraging promotion of bone regeneration and showed a satisfactory clinical curative effect for diaphyseal bone non-union, which was non-inferior to AGT.
Chemoresistance is the main obstacle in osteosarcoma (OS) treatment; however, the underlying mechanism remains unclear. In this study, it is discovered that DDRGK domain‐containing protein 1 (DDRGK1) plays a fundamental role in chemoresistance induced in OS. Bioinformatic and tissue analyses indicate that higher expression of DDRGK1 correlates with advanced tumor stage and poor clinical prognosis of OS. Quantitative proteomic analyses suggest that DDRGK1 plays a critical role in mitochondrial oxidative phosphorylation. DDRGK1 knockout trigger the accumulation of reactive oxygen species (ROS) and attenuate the stability of nuclear factor erythroid‐2‐related factor 2 (NRF2), a major antioxidant response element. Furthermore, DDRGK1 inhibits ubiquitin‐proteasome‐mediated degradation of NRF2 via competitive binding to the Kelch‐like ECH‐associated protein 1 (KEAP1) protein, which recruits NRF2 to CULLIN(CUL3). DDRGK1 knockout attenuates NRF2 stability, contributing to ROS accumulation, which promotes apoptosis and enhanced chemosensitivity to doxorubicin (DOX) and etoposide in cancer cells. Indeed, DDRGK1 knockout significantly enhances osteosarcoma chemosensitivity to DOX in vivo. The combination of DDRGK1 knockdown and DOX treatment provides a promising new avenue for the effective treatment of OS.
Purpose. We utilized a novel approach of combined photochemical tissue bonding (PTB) and human amniotic membrane (HAM) to improve hand tendon repair and also evaluated its efficacy. Methods. Subei chickens underwent surgical transection of the flexor digitorum profundus tendons and repair by (1) SR (standard Kessler suture; n = 24; 6-0 prolene) and (2) HAM/PTB (n = 24), where a section of HAM was stained with 0.1% Rose Bengal, wrapped around the ruptured tendon and bonded with 532 nm light (0.5 W/cm 2 , 200 J/cm 2). Total active motion, gross appearance, extent of adhesion formation, biochemical properties, and inflammatory cells of the repaired tendon were evaluated on days 3, 7, 14, and 28 postoperatively. Results. PTB strongly bonded HAM with flexor digitorum profundus tendon surface. No significant difference was observed between the tensile properties of either group on all postoperative time points. The joint activities and the adhesion formation levels were significantly better in the HAM/PTB group compared with those in the SR group on day 14. Histological examination revealed drastically reduced number of inflammatory cells in the HAM/PTB group than in the SR group on days 7 and 14 after surgery. Conclusions. These findings revealed that PTB sealing of HAM around the tendon repair site provided considerable benefits for hand tendon repair by eliminating technical difficulties and obvious contraindications. Thus, this novel procedure has considerable benefits in repairing hand tendon damage.
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