Varisized 3D-Printed Lunate for Kienböck's Disease in Different Stages: Preliminary Results.

OBJECTIVE: To evaluate the feasibility of arthroplasty with varisized three-dimensional(3D) printing lunate prosthesis for the treatment of advanced Kienböck's disease (KD). METHODS: From 2016 November to 2018 September, a retrospective study was performed for the patients of KD in our hospital. Five patients (two males, three females) were included in this study. The mean age of the patients at the time of surgery was 51.6 years (range, 37-64 years). Varisized prosthesis identical to the live model in a ratio of 1:0.85, 1:1, and 1:1.1 were fabricated by 3D printing. All patients (one in Lichtman IIIA stage, two in Lichtman IIIB stage, one in Lichtman IIIC stage, and one in Lichtman IV stage) were treated with lunate excision and 3D printing prosthetic arthroplasty. Visual analog scale score (VAS), the active movement of wrist (extension, flexion) and strength were assessed preoperatively and postoperatively. The Mayo Modified Wrist Score (MMWS), Disabilities of the Arm, Shoulder and Hand (DASH) Score, and patient's satisfaction were evaluated during the follow-up. RESULTS: Prosthesis identical to the live model in a ratio of 1:0.85 or 1:1 were chosen for arthroplasty. The mean operation time (range, 45 to 56 min) was 51.8 ± 4.44 min. Follow-up time ranged from 11 months to 33 months with the mean value of 19.4 months. The mean extension range of the wrist significantly increased from preoperative 44° ± 9.6° to postoperative 60° ± 3.5° (P < 0.05). The mean flexion range of the wrist significantly increased from preoperative 40° ± 10.6° to postoperative 51° ± 6.5° (P < 0.05). The active movement of wrist and strength were improved significantly in all patients. VAS was significantly reduced from 7.3 preoperatively to 0.2 at the follow-up visit (P < 0.05). The mean DASH score was 10 (range, 7.2-14.2), and the mean MMWS was 79 (range, 70-90). There were no incision infection. All patients were satisfied with the treatment. CONCLUSIONS: For patients suffering advanced Kienböck's disease, lunate excision followed by 3D printing prosthetic arthroplasty can reconstruct the anatomical structure of the carpal tunnel, alleviate pain, and improve wrist movement.

Molecular pathogenesis of fracture nonunion.

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.

Autologous Stem Cell Transplantation Promotes Mechanical Stretch Induced Skin Regeneration: A Randomized Phase I/II Clinical Trial.

BACKGROUND: Mechanical stretch, in term of skin expansion, can induce effective but limited in vivo skin regeneration for complex skin defect reconstruction. We propose a strategy to obtain regenerated skin by combining autologous stem cell transplantation with mechanical stretch. METHODS: This randomized, blinded placebo-controlled trial enrolled 38 adult patients undergoing skin expansion presenting with signs of exhausted regenerative capacity. Patients randomly received autologous bone marrow mononuclear cell (MNC) or placebo injections intradermally. Follow-up examinations were at 4, 8weeks and 2years. The primary endpoint was the volume achieved in relation to the designed size of the expander (expansion index, EI). Secondary endpoints were surface area, thickness and texture of expanded skin. This trial is registered with ClinicalTrial.gov, NCT01209611. FINDINGS: The MNC group had a significantly higher EI at 4weeks (mean difference 0.59 [95% CI, 0.03-1.16]; p=0.039) and 8weeks (1.05 [95% CI, 0.45-1.66]; p=0.001) versus controls. At 8weeks, the MNC group had significantly thicker skin (epidermis: p<0.001, dermis: p<0.001) and higher subjective scores for skin quality/texture (24.8 [95% CI, 17.6-32.1]; p<0.001). The MNC group had more skin surface area (70.34cm2 [95% CI, 39.75-100.92]; p<0.001). Patients in the MNC group gained up to the quadrupled surface area of expanded skin compared to pre-expansion at the end of expansion. No severe adverse events occurred. INTERPRETATION: Intradermal transplantation of autologous stem cells represents a safe and effective strategy to promote in vivo mechanical stretch induced skin regeneration, which can provide complex skin defect reconstruction with plentiful of tissue.

Increased number of mesenchymal stem cell-like cells in peripheral blood of patients with bone sarcomas.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: Flow cytometric analysis demonstrated an >9-fold increase in the number of cells with MSC-like phenotypes (CD34(-), CD45(-), CD105(+)) in patients with bone sarcomas compared with control subjects (p<0.05). 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 (p<0.05), 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. CONCLUSIONS: 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.

[Clinical study of lumbar fusion by hybrid construct of stem cells technique and biodegradable material].

OBJECTIVE: To explorer the effectiveness of enriched bone marrow stem cells technique for lumbar fusion. METHODS: With the randomization and control principles, 2 graft materials [Enrichment bone marrow mesenchymal stem cells hybridized with beta-tri calcium phosphate (composite graft group), autologous iliac crest bone graft (autograft group)] were compared in posterior lumbar fusion procedures. 56 patients with degenerative disc disease, lumbar instability or spinal stenosis, were included. The volume of cells suspension in pre- and post-enrichment and the number of nucleated cells (NCs) were identified. The number of osteoprogenitor cells was estimated by counting the colony-forming units which express alkaline phosphatase (CFUs/ALP+). Then the efficiency of the enrichment was evaluated. Clinical follow-up with roentgenogram and Oswestry scale scores was performed for outcome evaluation. RESULTS: (249 +/- 31) ml bone marrow per patient from bilateral iliac crests was aspirated peri-operatively. About (43 +/- 11) ml enriched bone marrow was collected. The number of NCs was concentrated from (15.9 +/- 3.3) x 10(6)/ml to (44.1 +/- 10.8) x 10(6)/ml, CFUs/ALP+ was significantly increased from (118 +/- 86)/ml to(486 +/- 305)/ml. The follow-up was about (26.3 +/- 7.5) months. There was no significant differences in age, gender, disease and fusion segments between the two groups. The fusion rate was 93.3% and 96.2% for composite graft group and autograft group, respectively (chi2 = 0.2146, P = 0.6432). There was no difference in operation time between the two group (t = 0.5243, P = 0.6022), but blood loss in composite graft group was more than that in autograft group (t = 6.4664, P < 0.01). Cell salvage for auto-transfusion could transfuse back half of the blood loss during operation. No hematoma or chronic soreness in the bone marrow donor sites of composite graft group occurred, but a little exudation or moderate swelling in the wound happened in 4 cases which disappeared under medical treatment. Meanwhile, 15.4% patients had hematoma in the iliac bone donor site and 26.9% patients had chronic soreness, but no case had wound problem in autograft group. As for Oswestry scale scores, there was no significant difference between the two groups. CONCLUSIONS: The enrichment technique of autologous bone marrow stem cells can greatly increase the concentration of MSCs. It is a rapid and safe method used peri-operatively. The composite material of enriched MSCs and porous beta-TCP is a good bone substitute in posterior spinal fusion.