Guixing Qiu

Skin tissue repair materials from bacterial cellulose by a multilayer fermentation method

Using an improved method, the multilayer fermentation method, bacterial cellulose (BC) was produced by Gluconacetobacter xylinus. The structure and morphology were analysed by an electronic microscope. The surface area and tensile strength were characterised. In vitro, the cytotoxicity of BC was determined by the proliferation, adhesion property, morphology, and viability of human adipose-derived stem cells (hASCs). Full-thickness skin wounds were made on the backs of 35 mice. The wounds were subsequently treated with two types of gauzes, two types of BC films, and three types of skin grafts using 5 mice per group, respectively. The improved method was reproducible and more efficient to control the thickness and homogeneity of BC. Low cytotoxicity of the BC film and good proliferation of hASCs on the BC film were observed. Histological examinations demonstrated significant fresh tissue regeneration and capillary formation in the wound area in the BC groups on day 7 compared with those in other groups. Pathological studies also showed a faster and better healing effect and less inflammatory response in the BC groups than those in other groups. These results indicate high clinical potential of the BC biosynthesized by our improved method.

Investigation on artificial blood vessels prepared from bacterial cellulose

BC (bacterial cellulose) exhibits quite distinctive properties than plant cellulose. The outstanding properties make BC a promising material for preparation of artificial blood vessel. By taking advantage of the high oxygen permeability of PDMS (polydimethylsiloxane) as a tubular template material, a series of BC tubes with a length of 100 mm, a thickness of 1mm and an outer diameter of 4 or 6mm were biosynthesized with the help of Gluconacetobacter xylinum. Through characterization by SEM (scanning electron microscope), tensile testing and thermal analysis, it is demonstrated that BC tubes are good enough for artificial blood vessel with elaborated nano-fiber architecture, qualified mechanical properties and high thermal stability. In addition, measurement of biocompatibility also shows that BC tubes are greatly adaptable to the in vivo environment. The results indicate that BC tubes have great potential for being utilized as tubular scaffold materials in the field of tissue engineering.

Osteogenic effect of controlled released rhBMP-2 in 3D printed porous hydroxyapatite scaffold

Recently, 3D printing as effective technology has been highlighted in the biomedical field. Previously, a porous hydroxyapatite (HA) scaffold with the biocompatibility and osteoconductivity has been developed by this method. However, its osteoinductivity is limited. The main purpose of this study was to improve it by the introduction of recombinant human bone morphogenetic protein-2 (rhBMP-2). This scaffold was developed by coating rhBMP-2-delivery microspheres with collagen. These synthesized scaffolds were characterized by Scanning Electron Microscopy (SEM), a delivery test in vitro, cell culture, and the experiments in vivo by a Micro-computed tomography (μCT) scan and histological evaluation of VanGieson staining. SEM results indicated the surface of scaffolds were more fit for the adhesion of hMSCs to coat collagen/rhBMP-2 microspheres. Biphasic release of rhBMP-2 could continue for more than 21 days, and keep its osteoinductivity to induce osteogenic differentiation of hMSCs in vitro. In addition, the experiments in vivo showed that the scaffold had a good bone regeneration capacity. These findings demonstrate that the HA/Collagen/Chitosan Microspheres system can simultaneously achieve localized long-term controlled release of rhBMP-2 and bone regeneration, which provides a promising route for improving the treatment of bone defects.

Epimedium Extract Promotes Peripheral Nerve Regeneration in Rats

Effects of Epimedium extract and its constituent icariin on peripheral nerve repair were investigated in a crush injury rat model. Animals were divided into four groups: sham, control, Epimedium extract, and icariin groups. At postoperative weeks 1, 2, 4, and 8, nerve regeneration and functional recovery were evaluated by sciatic functional index (SFI), nerve electrophysiology, nerve pinch test, and muscle wet weight. Results showed that at 2 and 4 weeks after surgery rats in the Epimedium group displayed a better recovery of nerve function than that in the icariin and control groups, with better recovery in the icariin group than in the control group. The nerve pinch test showed that nerve regeneration was greater in the Epimedium group and the icariin group as compared to the control group. In addition, the muscle wet weight in the Epimedium group was significantly improved when compared with the icariin group, and the improvement in the icariin group was better than that in the control group at 8 weeks after operation. Our findings suggest that Epimedium extract effectively promotes peripheral nerve regeneration and improves the function of damaged nerves.

Study of osteogenic differentiation of human adipose-derived stem cells (HASCs) on bacterial cellulose

Bacterial cellulose (BC) has been proposed as a biomaterial applied in biomedical scope due to its good biocompatibility. Recent reports showed that human adipose-derived stem cells (HASCs) have become a new choice to be used as seeding cells in tissue engineering. The objective of this study is to explore the potential of using BC and HASCs as scaffold and seeding cells in bone tissue engineering. The osteogenic differentiation was investigated by Von Kossa, Alizarin Red, ALP cellular staining and RT-PCR. The results showed that HASCs took a successful osteogenic differentiation on BC. Moreover, the in vivo animal test also provided the confirmation of the repair ability of BC on damaged bone. In conclusion, the author demonstrates the osteogenic differentiation of HASCs on BC and the feasibility of using BC and HASCs as scaffold and seeding cells in bone tissue engineering.

Corrective Surgery for Congenital Scoliosis Associated with Split Cord Malformation: It May Be Safe to Leave Diastematomyelia Untreated in Patients with Intact or Stable Neurological Status.

BACKGROUND The treatment of congenital scoliosis associated with split cord malformation (SCM) raises the issue of how to best manage such patients to avoid neurological deficit while achieving a satisfactory correction. METHODS This prospective clinical study was performed at our center from March 2000 through June 2013. We enrolled a total of 214 patients (61 male and 153 female) with congenital scoliosis associated with SCM who were undergoing spinal correction surgery. The mean age at surgery was 14.1 years. The inclusion criteria were congenital scoliosis with confirmed SCM; status as neurologically intact or stable over the preceding 2 years; and no neurological deterioration as evidenced on traction, side-bending, or fulcrum-bending radiographs. Patients with unstable neurological status or for whom vertebral column resection surgery was planned were excluded. All patients underwent scoliosis surgery without prophylactic detethering. RESULTS On the basis of the Pang classification, 73 patients were in the type-I SCM group, and 141 were in the type-II SCM group. The groups did not differ significantly with respect to preoperative characteristics, operative time, blood loss, or number of levels fused. The mean follow-up was 37 months (range, 24 to 108 months). The rate of scoliosis correction was lower in the type-I group than in the type-II group (p < 0.05). In the type-I group, the correction rate was 48.9% at 1 week postoperatively and 42.2% at the last follow-up. In the type-II group, the correction rate was 54.7% at 1 week postoperatively and 47.9% at the last follow-up. Eleven (5.1%) of the patients experienced transient neurological complications, with no significant difference between the groups (p = 0.415). No patient experienced permanent neurological deficit during surgery or follow-up. CONCLUSIONS Patients with congenital scoliosis associated with SCM, regardless of type, can safely and effectively undergo spinal deformity correction and achieve spinal balance without neurological intervention. For such patients with intact or stable neurological status, prophylactic detethering prior to scoliosis surgery may not be necessary. LEVEL OF EVIDENCE Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Surgical Treatments of Tumor-Induced Osteomalacia Lesions in Long Bones: Seventeen Cases with More Than One Year of Follow-up.

BACKGROUND Tumor-induced osteomalacia is a rare and fascinating paraneoplastic syndrome usually caused by a small, benign phosphaturic mesenchymal tumor. Most tumors are treated surgically, but we are unaware of any reports that compare the results of curettage and segmental resection for lesions in long bones. METHODS Seventeen patients (ten male and seven female) with tumor-induced osteomalacia lesions in long bones, who underwent surgical treatment from December 2004 to August 2013 in our hospital, were included in this retrospective study. The mean follow-up (and standard deviation) was 35 ± 27 months (range, twelve to 116 months). The characteristics of the tumor and the effects of different surgical treatments (curettage compared with segmental resection) were evaluated. RESULTS All patients showed typical clinical characteristics of tumor-induced osteomalacia, including elevated serum fibroblast growth factor-23 (FGF-23); 82% of tumors were in the epiphysis, and 82% grew eccentrically. The mean maximum diameter of the tumors was 2.4 ± 2.0 cm. The complete resection rates were similar for curettage (67%) and segmental resection (80%). However, the recurrence rate after curettage (50%) was higher than that after segmental resection (0%). The complete resection rate for secondary segmental resection (75%) was not different from that for primary segmental resection (83%). All of our cases of tumor-induced osteomalacia were caused by phosphaturic mesenchymal tumors. After successful removal of tumors, serum FGF-23 returned to normal within twenty-four hours and serum phosphorus levels returned to normal at a mean of 6.5 ± 3.5 days. CONCLUSIONS Most lesions in long bones are located in the epiphysis, so curettage is first suggested to maintain joint function. If curettage is incomplete or there is a recurrence, secondary segmental resection should be considered curative. Changes of serum FGF-23 and phosphorus levels before and after the operation may be of prognostic help.

Progress and perspective of TBX6 gene in congenital vertebral malformations.

Congenital vertebral malformation is a series of significant health problems affecting a large number of populations. It may present as an isolated condition or as a part of an underlying syndromes occurring with other malformations and/or clinical features. Disruption of the genesis of paraxial mesoderm, somites or axial bones can result in spinal deformity. In the course of somitogenesis, the segmentation clock and the wavefront are the leading factors during the entire process in which TBX6 gene plays an important role. TBX6 is a member of the T-box gene family, and its important pathogenicity in spinal deformity has been confirmed. Several TBX6 gene variants and novel pathogenic mechanisms have been recently revealed, and will likely have significant impact in understanding the genetic basis for CVM. In this review, we describe the role which TBX6 plays during human spine development including its interaction with other key elements during the process of somitogenesis. We then systematically review the association between TBX6 gene variants and CVM associated phenotypes, highlighting an important and emerging role for TBX6 and human malformations.

Identification of candidate diagnostic biomarkers for adolescent idiopathic scoliosis using UPLC/QTOF-MS analysis: a first report of lipid metabolism profiles.

Adolescent idiopathic scoliosis (AIS) is a complex spine deformity, affecting approximately 1–3% adolescents. Earlier diagnosis could increase the likelihood of successful conservative treatment and hence reduce the need for surgical intervention. We conducted a serum metabonomic study to explore the potential biomarkers of AIS for early diagnosis. Serum metabolic profiles were firstly explored between 30 AIS patients and 31 healthy controls by ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Then, the candidate metabolites were validated in an independent cohort including 31 AIS patients and 44 controls. The results showed that metabolic profiles of AIS patients generally deviated from healthy controls in both the discovery set and replication set. Seven differential metabolites were identified as candidate diagnostic biomarkers, including PC(20:4), 2-hexenoylcarnitine, beta-D-glucopyranuronicacid, DG(38:9), MG(20:3), LysoPC(18:2) and LysoPC(16:0). These candidate metabolites indicated disrupted lipid metabolism in AIS, including glycerophospholipid, glycerolipid and fatty acid metabolism. Elevated expressions of adipose triglyceride lipase and hormone sensitive lipase in adipose tissue further corroborated our findings of increased lipid metabolism in AIS. Our findings suggest that differential metabolites discovered in AIS could be used as potential diagnostic biomarkers and that lipid metabolism plays a role in the pathogenesis of AIS.

VEGF-loaded biomimetic scaffolds: a promising approach to improve angiogenesis and osteogenesis in an ischemic environment

The treatment of bone defects in an ischemic environment is a huge challenge. Improving angiogenesis, which is regulated by angiogenic growth factors such as vascular endothelial growth factor (VEGF), may have the potential to enhance bone regeneration. This study was conducted to investigate whether VEGF-loaded biomimetic scaffolds could improve angiogenesis and osteogenesis in an ischemic limb. The biomimetic hydroxyapatite–collagen scaffold (HC scaffold) was fabricated by adopting the freeze-drying approach. In the HC-VEGF group, VEGF was incorporated into HC scaffolds. The cytocompatibility of the HC scaffold was evaluated by CCK-8 testing. The release profile of VEGF from the HC-VEGF scaffold was detected by using VEGF ELISA kits. The femoral artery of Sprague-Dawley rats was resected to induce an ischemic environment. HC scaffolds with or without VEGF were implanted into intramuscular pockets in the ischemic limb. Eight weeks after implantation, samples were retrieved for histological and immunohistochemical analysis. The HC scaffolds showed good cytocompatibility according to the results of a CCK-8 test. In vitro, an initial burst release (∼80%) of VEGF was detected during the first 3 days. Angiogenesis and osteogenesis were significantly enhanced in the HC-VEGF group, compared to the control group of HC scaffolds without VEGF. This study provided a very promising approach to enhance angiogenesis and osteogenesis in an ischemic environment by incorporating VEGF into biomimetic bone scaffolds.