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Cold physical plasma (CPP), a partially ionized gas that simultaneously generates reactive oxygen and nitrogen species, is suggested to provide advantages in regenerative medicine. Intraoperative CPP therapy targeting pathologies related to diminished bone quality could be promising in orthopedic surgery. Assessment of a clinically approved plasma jet regarding cellular effects on primary bone marrow mesenchymal stromal cells (hBM-MSCs) from relevant arthroplasty patient cohorts is needed to establish CPP-based therapeutic approaches for bone regeneration. Thus, the aim of this study was to derive biocompatible doses of CPP and subsequent evaluation of human primary hBM-MSCs’ osteogenic and immunomodulatory potential. Metabolic activity and cell proliferation were affected in a treatment-time-dependent manner. Morphometric high content imaging analyses revealed a decline in mitochondria and nuclei content and increased cytoskeletal compactness following CPP exposure. Employing a nontoxic exposure regime, investigation on osteogenic differentiation did not enhance osteogenic capacity of hBM-MSCs. Multiplex analysis of major hBM-MSC cytokines, chemokines and growth factors revealed an anti-inflammatory, promatrix-assembling and osteoclast-regulating secretion profile following CPP treatment and osteogenic stimulus. This study can be noted as the first in vitro study addressing the influence of CPP on hBM-MSCs from individual donors of an arthroplasty clientele.
Background: The use of cold atmospheric plasma (CAP) in oncology has been intensively investigated over the past 15 years as it inhibits the growth of many tumor cells. It is known that reactive oxidative species (ROS) produced in CAP are responsible for this effect. However, to translate the use of CAP into medical practice, it is essential to know how CAP treatment affects non-malignant cells. Thus, the current in vitro study deals with the effect of CAP on human bone cancer cells and human osteoblasts. Here, identical CAP treatment regimens were applied to the malignant and non-malignant bone cells and their impact was compared. Methods: Two different human bone cancer cell types, U2-OS (osteosarcoma) and A673 (Ewing’s sarcoma), and non-malignant primary osteoblasts (HOB) were used. The CAP treatment was performed with the clinically approved kINPen MED. After CAP treatment, growth kinetics and a viability assay were performed. For detecting apoptosis, a caspase-3/7 assay and a TUNEL assay were used. Accumulated ROS was measured in cell culture medium and intracellular. To investigate the influence of CAP on cell motility, a scratch assay was carried out. Results: The CAP treatment showed strong inhibition of cell growth and viability in bone cancer cells. Apoptotic processes were enhanced in the malignant cells. Osteoblasts showed a higher potential for ROS resistance in comparison to malignant cells. There was no difference in cell motility between benign and malignant cells following CAP treatment. Conclusions: Osteoblasts show better tolerance to CAP treatment, indicated by less affected viability compared to CAP-treated bone cancer cells. This points toward the selective effect of CAP on sarcoma cells and represents a further step toward the clinical application of CAP.
Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary.
We aimed to determine the accuracy and reliability of measures characterizing anterior, lateral, and posterior acetabular coverage on intraoperative fluoroscopic images compared to postoperative radiographs when performing periacetabular osteotomies (PAOs). A study involving 100 PAOs was initiated applying a standardized intraoperative imaging protocol. Coverage was determined by the lateral center edge angle (LCEA), the Tönnis angle (TA), and the anterior and posterior wall index (AWI, PWI). An intraclass correlation coefficient (ICC) model was used to assess interrater (ICC (3,2)) and intrarater (ICC (2,1)) reliability. The ICC (2,2) between analyses obtained from intraoperative fluoroscopy and postoperative radiographs and the corresponding 95% confidence interval (CI) were determined and complemented by Bland–Altman analysis, the mean difference, and 95% limits of agreement (LOA). The ICCs were 0.849 for the LCEA (95% CI 0.783–0.896), 0.897 for the TA (95% CI 0.851–0.930), 0.864 for the AWI (95% CI 0.804–0.907), and 0.804 for the PWI (0.722–0.864). The assessed interrater reliability was excellent except for the AWI, which was graded good (ICC = 0.857, 95% CI 0.794–0.902). Interrater agreement was generally good and fair for the AWI (ICC = 0.715, 95% CI 0.603–0.780). For each postoperative radiograph, interrater reliability was good with ICCs ranging from 0.813 (TA) to 0.881 (PWI). Intrarater reliability was good for all measurements and excellent for the preoperative TA (ICC = 0.993, 95% CI 0.984–0.997) and PWI (ICC = 0.954, 95% CI 0.919–0.97). In summary, we confirm the validity and reliability of intraoperative fluoroscopy as an alternative imaging modality to radiography to evaluate acetabular fragment orientation during PAO. We affirm the LCEA and TA as precise measures for lateral head coverage, and show the suitability of the AWI and PWI to steadily assess acetabular version.
Background: Administering intraoperative analgesia in patients undergoing periacetabular osteotomy (PAO) is challenging due to both the relevant surgical approach and osteotomies, which are associated with pain. The aim of this study was to assess the effect of the transversus abdominis plane block (TAPb) on intraoperative opioid consumption and circulation parameters in PAO patients. Patients and Methods: We conducted a two-group randomized-controlled trial involving 42 consecutive patients undergoing PAO for symptomatic developmental dysplasia of the hip (DDH) in our department. Patients assigned to the study group received an ultrasound-guided TAPb with 0.75% ropivacaine before the beginning of the surgery and after general anesthesia induction. Patients assigned to the control group did not receive a TAPb. General anesthesia was conducted according to a defined study protocol. The primary endpoint of the study was the intraoperative opioid consumption, measured in morphine equivalent dose (MED). Secondary endpoints were the assessment of intraoperative heart rate, mean arterial pressure (MAP), need for hypotension treatment, and length of hospital stay (LOHS). A total of 41 patients (n = 21 TAPb group, n = 20 control group) completed the study; of these, 33 were women (88.5%) and 8 were men (19.5%). The mean age at the time of surgery was 28 years (18–43, SD ± 7.4). All operations were performed by a single high-volume surgeon and all TAPb procedures were performed by a single experienced senior anesthesiologist. Results: We observed a significantly lower intraoperative opioid consumption in the TAPb group compared to the control group (930 vs. 1186 MED per kg bodyweight; p = 0.016). No significant differences were observed in the secondary outcome parameters. We observed no perioperative complications. Conclusion: Ultrasound-guided TAPb significantly reduces intraoperative opioid consumption in patients undergoing PAO.
Although Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC20 and IC50 were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine.
Recently, there was a debate about whether borderline dysplastic hips should be treated surgically with hip arthroscopy or periacetabular osteotomy (PAO). Current studies recommend a classification into stable and unstable hips. Therefore, radiological scores have been described in recent years. Likewise, a new clinical stability test with the Prone Apprehension Relocation Test (PART) has been described. However, there has been no correlation between the modern radiological scores and the PART. We prospectively studied a consecutive group of patients who presented to our clinic. The PART and radiological scores were assessed in these patients. We divided the patients into a PART-positive and a PART-negative group and analyzed the associated clinical and radiological findings. Out of 126 patients (126 hips) included, 36 hips (29%) were evaluated as PART positive. There were significantly more females in the PART positive group (P = 0.005). Comparing the PART groups, significant differences (P < 0.0001) were found for the lateral center edge angle (LCEA), Femoro-Epiphyseal Acetabular Roof (FEAR) index, Gothic arch angle (GAA), anterior wall index (AWI), the occurrence of the upsloping lateral sourcil (ULS) and signs of acetabular retroversion. The correlation analysis showed an association between LCEA, FEAR index, GAA, AWI, ULS and the PART. A chi-square automatic interaction detection algorithm revealed that the strongest predictor of positive PART was the GAA. In conclusion, a high correlation between the PART and known radiological instability parameters was found. Consequently, a combination of clinical instability testing and radiological instability parameters should be applied to detect unstable hips.