Search

Carpal tunnel syndrome (CTS) is the most common peripheral entrapment neuropathy, and endoscopic carpal tunnel release (ECTR) is one of the minimally invasive procedures for the treatment of CTS. Based on the shortcomings of ECTR, we designed the "Modified Soft Tissue Release Kit" to assist the endoscopic operation. This study aimed to evaluate the effectiveness and safety of endoscopic treatment of CTS using this kit.This retrospective review included 57 patients (86 wrists) who underwent ECTR using the "Modified Soft Tissue Release Kit" at our department between January 2017 and August 2019. Three scale scores (i.e., Quick-Disabilities of the Arm, Shoulder, and Hand [QDASH]; Boston Carpal Tunnel Syndrome Questionnaire [BCTSQ]: symptom severity [BCTSQ-SS] and functional status [BCTSQ-FS]) were recorded to assess hand function and symptoms preoperatively, 1 month postoperatively, 3 months postoperatively, and at the last follow-up. We also asked patients to answer a satisfaction question during follow-up. Pre- and post-operation scores were compared using paired Wilcoxon signed-rank test. Spearman's rank-order correlation was used to evaluate the relationship between scale scores and patient satisfaction.A total of 55 patients (83 wrists) were followed up, with an average follow-up of 27.2 ± 9.3 months. The median preoperative QDASH score was 45.5; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 4.5, 0, and 0, respectively, with a significant decrease noted compared with the preoperative scores (P 0.001). The median preoperative BCTSQ-SS and BCTSQ-FS scores were 3.3 and 2.8, respectively; the scores at 1 month postoperatively, 3 months postoperatively, and the last follow-up were 1.2, 1.0, and 1.0, and 1.1, 1.0, and 1.0, respectively, all of which decreased significantly compared with the preoperative scores (P 0.001). The incidence of nerve injury was 0. The incidence of pillar pain was 0 at the last follow-up. One patient showed no improvement in hand symptoms and function postoperatively, and two patients showed long-term recurrence despite postoperative symptom remission. Approximately 94.5% (52/55) of the patients were satisfied or very satisfied with the outcome.ECTR with the "Modified Soft Tissue Release Kit" can significantly relieve symptoms and improve function in patients with CTS, with significant short- and mid-term efficacy and high safety. more...

Osteochondral lesion of the talus (OLT) is a common cause of ankle pain that often occurs in the talar dome and leads to talar cartilage and subchondral bone damage. Osteochondral autograft transplantation is a logical treatment option. It is known that if the cartilage does not heal properly after injury, it degenerates, and osteoarthritis worsens. A three dimensional (3D)-printed guide plate can be used to find the curved articular surface from the donor site which optimally fits the defect in the talus. Herein, we present the case of a 28-year-old man who had an open injury from the crash of a tricycle in the right ankle at the age of 5. Radiographs revealed a large defect in the medial talar dome that affected nearly half of the talar dome. We performed the debridement of the ankle lesion. An osteochondral autograft was harvested from the medial femoral condyle (MFC) with the help of a personalised 3D-printed guide plate. This 3D-printed guide plate simulated the contour of a specific area in the talar dome, which involved the site of the defect. The autograft was then transplanted into the talus defect. The efficacy of this technique was evaluated at 2, 4, and 7 months after surgery and proven to be reliable. more...

Bone defect is a serious orthopedic disease which has been studied for a long time. Alternative degradable biomaterials are required for bone repairing and regeneration to address the limitation of autogenous bone. β-tricalcium phosphate (β-TCP) is an alternative material with good cytocompatibility and has been used in bone defect treatment. However, whether β-TCP contributes to osteogenesis of bone marrow stem cells (BMSCs) through N6-methyladenosine (m6A) modification remains unknown. To address this issue, we verified the effects of β-TCP on osteogenesis of BMSCs. We also studied the expression of m6A-related enzymes in BMSCs after β-TCP treatment. Furthermore, the m6A level and stability of Runt-related transcription factor 2 (RUNX2) mRNA were investigated after β-TCP treatment. Finally, rat calvarial defect models were performed to detect expression level of osteogenic factors and m6A-related enzymes after the stimulation of three-dimension (3D)-printed β-TCP scaffolds. We found that β-TCP showed good biocompatibility and was osteoinductive. Meanwhile, methyltransferase-like 3 (METTL3) increased, causing the elevation of m6A level of RUNX2, results in stabler RUNX2 mRNA level. At last, based on the animal experiments, we demonstrated that the increase of RUNX2 and METTL3 levels was induced by β-TCP. These findings suggest that METTL3 increases the m6A level of RUNX2 mRNA after β-TCP induction, contributing to its stability, and the results in vivo also confirmed the osteogenic and bone-repair properties of β-TCP. more...

BackgroundAs current stem cell tissue engineering always requires in vitro cell culture, it is subject to restrictions such as extra time cost, ethical problems, and contamination. A novel device named the bone mesenchymal stem cells screen-enrich-combine circulating system(SECCS) was designed to rapidly enrich stem cells and combine with β-tricalcium phosphate to immediately produce bioactive stem cells/β-tricalcium phosphate composites during surgery and implant them into the intervertebral space for intervertebral fusion. Methods37 patients who underwent transforaminal lumbar interbody fusion surgery were included in this study and randomly divided into two groups. One group underwent decompressed laminal bone graft for intervertebral fusion, and the other was given SECCS-prepared β-tricalcium phosphate particles. Cells adhered to β-tricalcium phosphate were eluted for stem cell identification, including scanning electron microscope observation, ALP staining, flow cytometry analysis, and induction for three-line differentiation. Bone marrow was collected before and after enrichment for efficient enrichment analysis. The fusion rate, decrease in intervertebral height, and functional improvement, including Japanese Orthopaedic Association and Oswestry Disability Index scores, were compared between the two groups preoperatively and at 3, 6 and 12 months postoperatively.ResultsThe cells eluted from the β-tricalcium phosphate after screen-enrich-combine circulating system possessed characteristics of stem cell, including fiber-like morphology, positivity for CD44, CD73, CD90, and CD105, negativity for CD34, CD11b, CD19, CD45, and HLA-DR, and could been induced towards osteogenic, adipogenic, and chondrogenic differentiation. The screen-enrich-combine circulating system selectively enriched approximately 84.1% stem cells from the bone marrow in 6 minutes and could be simultaneously implanted into the intervertebral space during operation. Higher early fusion rate, similar intervertebral height decreases, and functional improvement tendencies were observed when stem cells/β-tricalcium phosphate particles were used as fusion scaffolds.ConclusionsThe screen-enrich-combine circulating system could quickly enrich stem cells from bone marrow, and the β-tricalcium phosphate particles prepared by the system showed higher early osteogenic efficiency than autologous laminal bone when used in intervertebral fusion, which provided a new bone scaffold substitute to autologous bone. Trial registration:ChiCTR,ChiCTR-INR-17010805,Registered 6 March, 2017, http://www.chictr.org.cn/showproj.aspx?proj=18386 more...

Tendinopathy is a common disease influencing life quality and tendon function of patients, especially in the elderly and athletes. Inflammation is an important pathologic process of tendinopathy. Hypoxia inducible factor-1 alpha (HIF-1α) participates actively in inflammatory process. However, little is known about the role of HIF-1α in tendinopathy. To address this issue, we verified the expression level of HIF-1α in tendinopathy in vivo and in vitro. Furthermore, the severity of tendinopathy in vivo and in vitro was assessed after HIF-1α inhibition. At the same time, inflammatory signaling cascades were evaluated. The expression level of HIF-1α increased in tendinopathy in vivo and in vitro. The migration and proliferation of tendon cells (TDCs) were reduced after HIF-1α inhibition. In the meantime, HIF-1α inhibition alleviated the severity of tendinopathy and promoted tendon repairing. We also found that HIF-1α inhibition reduced the phosphorylation levels of p65 in NF-κB signaling pathway and the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and Jun N-terminal kinase (JNK) in MAPK signaling pathway. These findings suggest that HIF-1α increases in tendinopathy in vivo and vitro, and HIF-1α inhibition can suppress the severity of tendinopathy by blocking NF-κB and MAPK signaling pathways. more...

Interleukin-12 (IL-12) and IL-23 are thought to have central roles in inflammation and are critical to pathologies associated with inflammation-induced bone disorders. The deletion of IL-12p40 (a common subunit of IL-12 and IL-23) can improve bone regeneration. However, the relative roles of IL-12 and IL-23 in bone disorders are largely unknown. Methods: Ectopic bone formation and skull defect models were established to evaluate the relative roles of IL-12 and IL-23 in inflammatory bone disorders. Differences in bone mass among WT, IL-12p35-/-, and IL-12p40-/- mice (young and elderly) were detected by micro-CT. Osteogenic and osteoclastic activities were explored using ELISA, qRT-PCR, and histological analysis. Moreover, the mechanisms by which IL-12 and IL-23 regulated the differentiation of BMMSCs and RAW264.7 cells were explored using Alizarin Red and tartrate-resistant acid phosphatase staining in vitro. Apilimod was used to inhibit IL-12 and IL-23 production in vivo. Results: Mice deficient in IL-12p40 promoted bone formation and protected against aging-related bone loss. By contrast, bone loss was aggravated in IL-12-/- mice, suggesting that IL-23 may play a dominant role in inflammation-related bone disorders. Mechanistically, IL-12 and IL-23 coupled osteogenesis and osteoclastic activities to regulate bone homeostasis and repair. IL-23 deficiency increased bone formation and inhibited bone resorption. Finally, apilimod treatment significantly improved bone regeneration and calvarial defect repair. Conclusion: These data collectively uncover a previously unrecognized role of IL-23 in skeletal tissue engineering. Thus, IL-23 can act as a biomarker to predict diseases and treatment efficacy, and apilimod can be used as an effective therapeutic drug to combat inflammatory bone disorders. more...

Background With the development of medical technology, credible options for defect reconstructions after the resection of benign bone tumors of the lower extremities have become a high priority. As the current reconstructive methods commonly used in clinical practice have some flaws, new methods of reconstruction need to be explored. We aimed to prepare a new kind of bioactive scaffold for the repair of bone defects through a stem cell rapid screening–enrichment–composite technology system developed by our team. Furthermore, we aimed to investigate the curative effects of these bioactive scaffolds. Methods Firstly, cell count, trypan blue exclusion rate, and ALP staining were used to evaluate changes in enrichment efficiency, cell activity, and osteogenic ability before and after enrichment. Then, the scaffolds were placed under the skin of nude mice to verify their osteogenic effects in vivo. Finally, the scaffolds were used for the reconstruction of bone defects after operations for benign bone tumors in a patient’s lower limb. The healing status of the defect site at 1 and 3 months was assessed by X-ray, and the Musculoskeletal Tumor Society (MSTS) score was applied to reflect the recovery of patient limb function. Results The system effectively enriched stem cells without affecting the activity and osteogenic abilities of the bone marrow mesenchymal stem cells (BMSCs). Meanwhile, the bioactive scaffolds obtained better osteogenic effects. In patients, the active scaffolds showed better bone integration and healing status, and the patients also obtained higher MSTS scores at 1 and 3 months after surgery. Conclusion As a new technique, the rapid screening–enrichment–composite technology of stem cells demonstrates a better therapeutic effect in the reconstruction of bone defects after surgery for benign bone tumors of the lower extremities, which will further improve patient prognosis. more...

Background: Repairing complex anatomical load-bearing bone defects is difficult because it requires restoration of load-bearing function, reconstruction of anatomical shape and repair by regenerated bone. We previously developed a Screen–Enrich–Combine(-biomaterials) Circulating System (SECCS) for rapid intraoperative enrichment of autologous bone marrow mesenchymal stem cells (MSCs) to enhance the osteogenic ability of porous bone substitutes. In this study, we prepared a 3D-printed Ti6A14V macroporous frame matching the defect shape to provide early load-bearing support and evaluated the efficacy of filling the frame with SECCS-processed MSCs/beta tricalcium phosphate (β-TCP) for long-term bone growth. Method: Mechanical testing of the cylindrical Ti6Al4V frame identified optimal 3D printing parameters. The lateral part of a goat distal femur was used as the defect model, and a matching electron beam melting technology-prepared (EBM) Ti6Al4V frame was fitted. Three frames filled with nothing, pure porous β-TCP or SECCS-processed MSCs/β-TCP were fixed onto the defect site. Repair efficacy was evaluated by X-ray radiography, computed tomography, histology and histomorphology. Results: In the basic regular hexagon printing unit, the combined side width (w) and inscribed circle diameter (d) determines the printing frame’s mechanical strength. The compressive load was significantly higher for w = 1.9 mm, d = 4.4 mm than for w = 1.7 mm, d = 4.0 mm or w = 2.0 mm, d = 5.0 mm (P < 0.05). The EBM-prepared Ti6Al4V defect-matched frame was well maintained 9 months after implantation. The MSCs successfully adhered to the wall of the porous β-TCP in the SECCS-processed group and had spread fully in the test samples. Each goat in the MSCs/β-TCP–filling group had approximately 31,321.7 ± 22,554.7 MSCs and a larger area of new bone growth inside the frame than the areas in the control and blank groups.Conclusion: Filling the 3D-printed Ti6Al4V large-aperture frame with osteogenic materials achieved biological reconstruction over a larger area of regenerated bone for repair of complex anatomical weight-bearing bone defects under the condition of early frame-supported load bearing. MSCs/β-TCP prepared by SECCS can be used as a filling material for this type of bone defect to obtain more efficacious bone repair. more...

The integration of three-dimensional (3D) bioprinted scaffold’s structure and function for critical-size bone defect repair is of immense significance. Inspired by the basic component of innate cortical bone tissue—osteons, many studies focus on biomimetic strategy. However, the complexity of hierarchical microchannels in the osteon, the requirement of mechanical strength of bone, and the biological function of angiogenesis and osteogenesis remain challenges in the fabrication of osteon-mimetic scaffolds. Therefore, we successfully built mimetic scaffolds with vertically central medullary canals, peripheral Haversian canals, and transverse Volkmann canals structures simultaneously by 3D bioprinting technology using polycaprolactone and bioink loading with bone marrow mesenchymal stem cells and bone morphogenetic protein-4. Subsequently, endothelial progenitor cells were seeded into the canals to enhance angiogenesis. The porosity and compressive properties of bioprinted scaffolds could be well controlled by altering the structure and canal numbers of the scaffolds. The osteon-mimetic scaffolds showed satisfactory biocompatibility and promotion of angiogenesis and osteogenesis in vitro and prompted the new blood vessels and new bone formation in vivo. In summary, this study proposes a biomimetic strategy for fabricating structured and functionalized 3D bioprinted scaffolds for vascularized bone tissue regeneration. more...

Fracture nonunion, a serious bone fracture complication, remains a challenge in clinical practice. Although the molecular pathogenesis of nonunion remains unclear, a better understanding may provide better approaches for its prevention, diagnosis and treatment at the molecular level. This review tries to summarise the progress made in studies of the pathogenesis of fracture nonunion. We discuss the evidence supporting the concept that the development of nonunion is related to genetic factors. The importance of several cytokines that regulate fracture healing in the pathogenesis of nonunion, such as tumour necrosis factor-α, interleukin-6, bone morphogenetic proteins, insulin-like growth factors, matrix metalloproteinases and vascular endothelial growth factor, has been proven in vitro, in animals and in humans. Nitric oxide and the Wnt signalling pathway also play important roles in the development of nonunion. We present potential strategies for the prevention, diagnosis and treatment of nonunion, and the interaction between genetic alteration and abnormal cytokine expression warrants further investigation. The translational potential of this article: A better understanding of nonunion molecular pathogenesis may provide better approaches for its prevention, diagnosis and treatment in clinical practice. Keywords: Cytokine, Gene, Molecular pathogenesis, Nonunion more...

Bone defects are a common challenge in clinic, usually warranting bone grafts. However, current strategies to obtain effective graft materials have many drawbacks. Mesenchymal stem cell (MSC)-based therapy is a promising alternative. We designed an innovative appliance named the stem cell screen–enrich–combine(-biomaterials) circulating system (SECCS). In this study, 42 patients who required bone graft underwent SECCS-based treatment. Their bone marrow samples and beta-tricalcium phosphate (β-TCP) granules were processed in the SECCS for 10–15 minutes, to produce MSC/β-TCP composites. These composites were grafted back into bone defect sites. The results showed 85.53% ± 7.95% autologous MSCs were successfully screened, enriched, and seeded on the β-TCP scaffolds synchronously. The cell viability remained unchanged after SECCS processing. Clinically, all patients obtained satisfactory bone healing. Thus, without in vitro culture, the SECCS can produce bioactive MSC/β-TCP composites for bone regeneration during surgery. The SECCS represents a convenient, rapid, low-cost, and safe method for bone regeneration. more...

Biomaterials have been widely used as bone grafts for bone tissue repair. The application of biomaterials needs to consider various aspects of material properties such as biocompatibility, mechanical strength and plasticity. It is also necessary for bone repair to consider the degradability of materials. Previous studies have shown that biomaterials can be degraded by physical, chemical and biological ways. Cell-mediated degradation is an important part of the biodegradation process of , mainly carried out by the biological behavior of macrophages and osteoclasts and reactive oxygen species, enzymes and acidic metabolites secreted by them. Illustration of cell-mediated degradation of biological materials helps us understand the biological behavior of cells better, to accurately design and manufacture more effective bone repair materials, which is conducive to initial stability during material implantation, in line with the consistence of material degradation and new bone formation, promoting bone regeneration and bone repair.生物材料作为移植物已广泛应用于骨组织修复，在应用生物材料时需要考虑材料各个方面的性能，如生物兼容性、力学强度、可塑性等。材料的可降解性也是骨修复材料不得不考虑的方面。既往研究表明，生物材料可以通过物理、化学和生物三种方式进行降解。在材料的生物降解过程中，经细胞途径降解是其中重要的一环。这种降解途径主要是通过巨噬细胞、破骨细胞的生物学行为及其所分泌的生物活性氧、酶、酸性代谢物等作用机制进行。认识细胞作用对生物材料的降解有助于更好地理解细胞的生物学行为，精准设计、制造更合理的骨修复材料，既利于材料植入时的初始稳定，也可以符合材料降解与新骨形成的匹配，促进骨再生和骨修复。. more...

Aim: To evaluate the clinical efficacy of mesenchymal stem cell/β-tricalcium phosphate composites (MSC/β-TCP) prepared with a screen-enrich-combine circulating system (SECCS) in patients with depressed tibial plateau fractures. Materials & methods: Bone defects in depressed tibial plateaus were filled with MSC/β-TCP (n = 16) or with β-TCP only (n = 23). Enrichment efficiency and effect of enrichment on cell viability were evaluated. Clinical results were assessed by imaging examination and Lysholm score. Results: SECCS effectively integrated MSCs with β-TCP. At 18 months postimplantation, new bone ratio was significantly higher in patients treated with MSC/β-TCP than in those treated with β-TCP only (p = 0.000). Patients with MSC/β-TCP implants had better functional recovery (p = 0.028). Conclusion: MSC/β-TCP prepared by SECCS were effective in the treatment of bone defects in patients with depressed tibial plateau fractures, promoted bone regeneration and improved joint function recovery. more...

Transforming growth factor-β1 (TGF-β1) is a key factor in bone reconstruction. However, its pathophysiological role in non-union and bone repair remains unclear. Here we demonstrated that TGF-β1 was highly expressed in both C57BL/6 mice where new bone formation was impaired after autologous bone marrow mesenchymal stem cell (BMMSC) implantation in non-union patients. High doses of TGF-β1 inhibited BMMSC osteogenesis and attenuated bone regeneration in vivo. Furthermore, different TGF-β1 levels exhibited opposite effects on osteogenic differentiation and bone healing. Mechanistically, low TGF-β1 doses activated smad3, promoted their binding to bone morphogenetic protein 2 (Bmp2) promoter, and upregulated Bmp2 expression in BMMSCs. By contrast, Bmp2 transcription was inhibited by changing smad3 binding sites on its promoter at high TGF-β1 levels. In addition, high TGF-β1 doses increased tomoregulin-1 (Tmeff1) levels, resulting in the repression of Bmp2 and bone formation in mice. Treatment with the TGF-β1 inhibitor SB431542 significantly rescued BMMSC osteogenesis and accelerated bone regeneration. Our study suggests that high-dose TGF-β1 dampens BMMSC-mediated bone regeneration by activating canonical TGF-β/smad3 signaling and inhibiting Bmp2 via direct and indirect mechanisms. These data collectively show a previously unrecognized mechanism of TGF-β1 in bone repair, and TGF-β1 is an effective therapeutic target for treating bone regeneration disability. © 2019 American Society for Bone and Mineral Research. more...

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. more...

Background Efficacious bone substitute is essential for the treatment of a critical size bone defect. Currently, the bone substitutes commonly used in clinical practice lack osteogenic capacity and the therapeutic efficacy is not ideal. Herein, a novel stem cell screen-enrich-combine(−biomaterials) circulating system (SECCS) was introduced to provide the substitutes with osteogenic ability. The stem cell screening, enrichment, and recombination with substitutes could be integrated during the surgical operation. Using SECCS, the bioactive mesenchymal stem cells (MSCs) and porous β-tricalcium phosphate (β-TCP) composites (MSCs/β-TCP) were rapidly prepared for critical size bone defect repair and validated in goat models of critical size tibia defects. Methods Twelve goats with right hind limb tibia defects of 30 mm were randomly divided into two groups: six (the experimental group) were treated with MSCs/β-TCP prepared by SECCS and the other six goats (the control group) were treated with pure porous β-TCP. The repair effect was assessed by x-ray, computed tomography (CT), micro-CT, histology and histomorphology 6 months after the operation. In addition, the enrichment efficacy of MSCs and the characteristics of the MSCs/β-TCP prepared by SECCS were evaluated. Results The SECCS could compound about 81.3 ± 3.0% of the MSCs in bone marrow to the porous β-TCP without affecting the cell viability. The average number of MSCs for retransplantation was 27,655.0 ± 5011.6 for each goat from the experimental group. In vitro, satisfactory biocompatibility of the MSCs/β-TCP was performed, with the MSCs spreading adequately, proliferating actively, and retaining the osteogenic potential. In vivo, the defect repair by MSCs/β-TCP with good medullary cavity recanalization and cortical remodeling was significantly superior to that of pure porous β-TCP. Conclusions The MSCs/β-TCP prepared through SECCS demonstrated significant therapeutic efficacy in goat models of critical size bone defect. This provides a novel therapeutic strategy for critical size bone defects caused by severe injury, infection, and bone tumor resection with a high profile of safety, effectiveness, simplicity, and ease. more...

To prospectively evaluate the functional and radiological outcomes of Isobar semi-rigid dynamic posterior stabilization adjacent to single-level fusion up to and including 24 months postoperatively.A prospective follow-up for 24 months of 36 patients who underwent posterior Isobar dynamic stabilization due to single-level degenerative lumbar discopathy and instability (DLDI) with mild adjacent level degeneration, with collection of functional [visual analog scale (VAS) and Oswestry Disability Index (ODI)] and radiological data (resting, functional X-rays and MRI).Functional outcomes at 24 months showed significant improvement in mean VAS score by 38.9 points (P 0.01) and ODI by 22.4 points (P 0.01). Compared with data preoperatively, disc height at the index and adjacent levels and intervertebral angle (IVA) at the index level showed a slight decreasing trend at each follow-up (P 0.05), while IVA at the adjacent level showed a slight increasing trend (P 0.05). Range of motion averaged 2.84° at the index level and remained unchanged at the adjacent level (P 0.05). The mean Pfirrmann score changed from 2.86 preoperatively to 2.92 at 24 months postoperatively at the index level (P 0.05), and from 1.92 preoperatively to 1.96 at 24 months postoperatively at the adjacent level (P 0.05). No reoperation, loosening of screws or infection was recorded.Patients with single-level DLDI and mild adjacent level degeneration treated with Isobar stabilization show a clinical improvement after 2 years. However, disc degeneration at the index and adjacent levels seems to continue despite using semi-rigid dynamic stabilization. more...

Summary Translational medicine has been well accepted as a concept and trend in medical sciences. China is a late starter in the development of translational medicine, yet the Chinese medical community has already demonstrated its determination towards the realisation of this concept. There are many questions that need to be answered prior to when translational medicine can proceed from being a concept to reality. This paper highlights the essential requirements for developing “patients and clinic oriented” translational medicine and shares “an enriched stem cells technique” as an example of orthopaedic translation. Enormous collaborative and multidisciplinary work is required prior to when the results of scientific research can be translated into effective clinical practice. more...

Bone defects are common in elderly patients suffering from osteoporosis. Current methods of bone defect treatment for osteoporosis are not always satisfactory. In this study, we demonstrated that bone marrow mesenchymal stem cells (MSCs) harvested from goats with long-term estrogen deficiencies exhibited a lower proliferation rate and decreased osteogenic capacity, which are critical obstacles for bone defect repair in the elderly. However, by combining autologous enriched bone marrow mesenchymal stem cells with porous β-TCP, we successfully repaired critical-sized bone defects in the medial femoral condyle of the osteoporotic goats. Both micro-CT images and histomorphometry analysis illustrated improved bone formation following the enriched MSC therapy. Thus, we proposed autologous enriched bone marrow mesenchymal stem cells as a quick, safe therapeutic strategy to treat osteoporotic bone defects. more...

Rationale Necrotizing fasciitis (NF) is defined as a rare, rapidly progressive, and highly lethal skin infection characterized by necrosis of the fascia and subcutaneous tissue. Patient concerns The present study aims to discuss the case of a 35-year-old man who developed NF following a routine sterile right distal radius bone plate removal surgery. Diagnoses The patient was suspected of NF based on his clinical manifestations, laboratory tests, and imaging results. The diagnosis of NF was confirmed by histological examinations. Interventions Serial prompt and extensive debridement was performed during the rapid and aggressive extension of the skin infection, together with antibiotics and supportive treatments. Outcomes The condition of the patient finally improved on the sixth day of disease progression. Skin grafting of his right forearm wound was performed successfully 2 months after the admission. Lessons NF can occur during the perioperative period for routine clean radius plate removal operation in patients with no risk factor for NF. The objective is to remind the physicians to stay aware of this disease, especially its early clinical signs and symptoms. Urgent subsequent treatment, including surgical debridement, antibiotic therapy, and supporting management, is the key to ensure the survival and better prognosis of patients. more...

The number of peripheral blood mesenchymal stem cells (PBMSCs) may increase under pathological conditions. We sought to compare the number of MSC-like cells in the peripheral blood of patients with bone sarcomas with healthy controls and to analyze related cytokines in the peripheral blood plasma.Peripheral blood mononuclear cells (PBMNs) of patients with bone sarcomas and control subjects were isolated for culture and analyzed by flow cytometry for MSC phenotype. Cytokines in the plasma obtained after cell separation were analyzed using enzyme-linked immunosorbent assay (ELISA). Annexin-V and beta-galactosidase staining were used to investigate whether the cells died from apoptosis or senescence.Flow cytometric analysis demonstrated an9-fold increase in the number of cells with MSC-like phenotypes (CD34(-), CD45(-), CD105(+)) in patients with bone sarcomas compared with control subjects (p0.05). ELISA results showed that concentrations of hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) in patients with bone sarcomas were statistically higher than those in the control subjects (p0.05), whereas there was no significant difference in plasma concentrations of leptin and stromal cell-derived factor 1 between the two groups. A significant, positive correlation between the percentages of PBMSC-like cells and concentrations of HGF in all samples (R=0.618; p=0.011). Annexin-V staining of MSC-like cells was positive, whereas beta-galactosidase staining was negative.Peripheral blood of patients with bone sarcomas has more cells with MSC phenotypes than blood of healthy persons. The increased number is accompanied by increased HGF and VEGF in the plasma. more...

Cytotherapy for bone regeneration has not been widely used clinically. A new method based on enriched bone-marrow-derived mesenchymal stem cells (MSCs) combined with porous beta-tricalcium phosphate (beta-TCP) was used for posterior spinal fusion in 41 patients. The aim of the present study was to assess the clinical feasibility of peri-operative bone marrow stem cell enrichment and their combination with tricalcium phosphate. About 252 ml marrow per patient was harvested from bilateral iliac crest, the enriched MSCs were produced by a cell processor peri-operatively, then combined with porous beta-TCP granules by a negative pressure and a short-time incubation in the meantime of conventional operation, which were finally implanted back into the patient. About 45 ml enriched MSC suspension was collected, and 78+/-16% of MSCs were recovered. By enrichment technique, the number of colony-forming units which expressed alkaline phosphatase (CFUs-ALP+, to estimate the prevalence of MSCs) was increased 4.3 times; the increasing folds of bone marrow nucleated cells (NCs) and MSCs had a positive correlation. The natural log (ln) of MSC number declined with age, and also, the MSC number of younger subjects (or =40 years) was more than that of older ones (40 years), but none for NCs. The number of NCs and MSCs was not different significantly between men and women. However, the patients with thoracolumbar fracture (TLF) had significantly more MSCs than those with degenerative disc disease (DDD), but not for NCs. On the other hand, enriched MSCs could adhere to the wall of porous beta-TCP within 2h combination, and proliferate well during culture in vitro. After 34.5 months, 95.1% cases had good spinal fusion results. None of the samples before grafting was positive in bacterial culture. Only four patients had a little exudation or moderate swelling in their wounds, and recovered with conservative treatment. more...

Although Sox9 is essential for chondrogenic differentiation and matrix production, its application in cartilage tissue engineering has been rarely reported. In this study, the chondrogenic effect of Sox9 on bone marrow mesenchymal stem cells (BMSCs) in vitro and its application in articular cartilage repair in vivo were evaluated. Rabbit BMSCs were transduced with adenoviral vector containing Sox9. Toluidine blue, safranin O staining and real-time PCR were performed to check chondrogenic differentiation. The results showed that Sox9 could induce chondrogenesis of BMSCs both in monolayer and on PGA scaffold effectively. The rabbit model with full-thickness cartilage defects was established and then repaired by PGA scaffold and rabbit BMSCs with or without Sox9 transduction. HE, safranin O staining and immunohistochemistry were used to assess the repair of defects by the complex. Better repair, including more newly-formed cartilage tissue and hyaline cartilage-specific extracellular matrix and greater expression of several chondrogenesis marker genes were observed in PGA scaffold and BMSCs with Sox9 transduction, compared to that without transduction. Our findings defined the important role of Sox9 in the repair of cartilage defects in vivo and provided evidence that Sox9 had the potential and advantage in the application of tissue engineering. more...

The CaO-ZrO2-SiO2 (CZS) coating was prepared by plasma-spraying chemically synthesized CZS powder onto a Ti-6Al-4V substrate. This CZS coating has been demonstrated to have good bioactivity, high bonding strength with the substrate and a low degradation rate. However, the effect of CZS coating on the osseointegration of bone-implant is still unknown. In this study, human bone marrow-derived stromal cells (hBMSCs) were cultured on CZS coating in vitro, and cell behavior was investigated, with the classical hydroxyapatite (HA) coating as a control. Scanning electron microscopy (SEM) and immunofluorescence studies showed that the hBMSCs on the CZS coating spread well with organized cytoskeleton structure at 24 h following cell seeding. The MTT assay and the Alamar Blue assay indicated that CZS coating promoted the attachment and proliferation of hBMSCs. The results of alkaline phosphatase (ALP) activity test and the expression of osteogenic marker genes, such as ALP, collagen I (COLI), osteopontin (OPN), and osteocalcin (OCN), demonstrated that the osteoblastic differentiation of hBMSCs was enhanced more by CZS coating than by HA coating. These results suggest that CZS coating possess excellent biological properties and may have potential in biomedical applications. more...

Expansion of human mesenchymal stem cells (hMSCs) in medium supplemented with fetal bovine serum (FBS) has a potential risk of transmitting viral and prion diseases and causing immunological rejection. The aim of our present study was to find a substitute for the traditional FBS in culture of hMSCs to facilitate the clinical application of hMSCs. We used autologous plasma derived from bone marrow (APM) as a substitute for FBS and found that, when cultured with APM, the cell surface markers and the proportion of hMSCs in the G(0)/G(1) phase and the S+G(2)/M phase resembled those cultured with FBS. However, there were fewer early apoptotic cells in APM-supplemented medium than in FBS (p0.01). APM resulted in much greater thymidine incorporation than FBS (p0.001). There were significantly more alkaline phosphatase (ALP)-positive fibroblast colony-forming units (CFU-Fs) covering larger areas in APM than in FBS (p0.01). Also, APM induced greater ALP activity, more mineralized nodules, and greater expression of osteogenic genes than did FBS. In addition, when cultured in adipogenic medium, there were fewer oil-red O-positive cells and lower expression of adipogenic gene with APM than with FBS. In conclusion, expansion of hMSCs in APM-supplemented medium instead of traditional FBS is more advantageous. It could promote cell proliferation, enhance osteogenic differentiation, and suppress adipogenic differentiation of hMSCs and is therefore a safer and more effective substitute for FBS in clinical cytotherapy processes. more...