Wenwen Yu

Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone) nerve conduit with tailored degradation rate

BackgroundTo cope with the limitations faced by autograft acquisitions particularly for multiple nerve injuries, artificial nerve conduit has been introduced by researchers as a substitute for autologous nerve graft for the easy specification and availability for mass production. In order to best mimic the structures and components of autologous nerve, great efforts have been made to improve the designation of nerve conduits either from materials or fabrication techniques. Electrospinning is an easy and versatile technique that has recently been used to fabricate fibrous tissue-engineered scaffolds which have great similarity to the extracellular matrix on fiber structure.ResultsIn this study we fabricated a collagen/poly(ε-caprolactone) (collagen/PCL) fibrous scaffold by electrospinning and explored its application as nerve guide substrate or conduit in vitro and in vivo. Material characterizations showed this electrospun composite material which was made of submicron fibers possessed good hydrophilicity and flexibility. In vitro study indicated electrospun collagen/PCL fibrous meshes promoted Schwann cell adhesion, elongation and proliferation. In vivo test showed electrospun collagen/PCL porous nerve conduits successfully supported nerve regeneration through an 8 mm sciatic nerve gap in adult rats, achieving similar electrophysiological and muscle reinnervation results as autografts. Although regenerated nerve fibers were still in a pre-mature stage 4 months postoperatively, the implanted collagen/PCL nerve conduits facilitated more axons regenerating through the conduit lumen and gradually degraded which well matched the nerve regeneration rate.ConclusionsAll the results demonstrated this collagen/PCL nerve conduit with tailored degradation rate fabricated by electrospinning could be an efficient alternative to autograft for peripheral nerve regeneration research. Due to its advantage of high surface area for cell attachment, it is believed that this electrospun nerve conduit could find more application in cell therapy for nerve regeneration in future, to further improve functional regeneration outcome especially for longer nerve defect restoration.

In vitro behavior of MC3T3‐E1 preosteoblast with different annealing temperature titania nanotubes

OBJECTIVE Titanium oxide nanotube layers by anodization have excellent potential for dental implants because of good bone cell promotion. It is necessary to evaluate osteoblast behavior on different annealing temperature titania nanotubes for actual implant designs. MATERIALS AND METHODS  Scanning Electron Microscopy, X-Ray polycrystalline Diffractometer (XRD), X-ray photoelectron Spectroscope, and Atomic Force Microscopy (AFM) were used to characterize the different annealing temperature titania nanotubes. Confocal laser scanning microscopy, MTT, and Alizarin Red-S staining were used to evaluate the MC3T3-E1 preosteoblast behavior on different annealing temperature nanotubes. RESULTS  The tubular morphology was constant when annealed at 450°C and 550°C, but collapsed when annealed at 650°C. XRD exhibited the crystal form of nanotubes after formation (amorphous), after annealing at 450°C (anatase), and after annealing at 550°C (anatase/rutile). Annealing led to the complete loss of fluorine on nanotubes at 550°C. Average surface roughness of different annealing temperature nanotubes showed no difference by AFM analysis. The proliferation and mineralization of preostoblasts cultured on anatase or anatase/rutile nanotube layers were shown to be significantly higher than smooth, amorphous nanotube layers. CONCLUSION  Annealing can change the crystal form and composition of nanotubes. The nanotubes after annealing can promote osteoblast proliferation and mineralization in vitro.

A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral nerve regeneration

For artificial nerve conduits, great improvements have been achieved in mimicking the structures and components of autologous nerves. However, there are still some problems in conduit construction, especially in terms of mechanical properties, biomimetic surface tomography, electrical conductivity and sustained release of neurotrophic factors or cells. In this study, we designed and fabricated a novel electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on the basis of a collagen/poly(ε-caprolactone) (collagen/PCL) fibrous scaffold. Our aim was to provide further knowledge about the mechanical effects and efficacy of MWNTs on nerve conduits as well as the biocompatibility and toxicology of MWNTs when applied in vivo.The results showed that as one component, carboxyl MWNTs could greatly alter the composite scaffolds hydrophilicity, mechanical properties and degradability. The electrospun fibers enhanced by MWNTs could support Schwann cell adhesion and elongation as a substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced collagen/PCL conduit could effectively promote nerve regeneration of sciatic nerve defect in rats and prevent muscle atrophy without invoking body rejection or serious chronic inflammation. All of these results showed that this MWNT-enhanced scaffold possesses good biocompatibility and MWNTs might be excellent candidates as engineered nanocarriers for further neurotrophic factor delivery research.

Effects of TiO2 nanotube layers on RAW 264.7 macrophage behaviour and bone morphogenetic protein-2 expression.

To investigate behaviour and osteogenic cytokine expression of RAW264.7 macrophages grown on TiO2 nanotube layers.

Maintenance of phenotype and function of cryopreserved bone-derived cells.

The emerging fields of tissue engineering and regenerative medicine require large numbers of cells for therapy. Although the properties of cells obtained from a variety of fresh tissues have been delineated, the knowledge regarding cryopreserved grafts-derived cells remains elusive. Previous studies have shown that living cells could be isolated from cryopreserved bone grafts. However, whether cryopreserved bone-derived cells can be applied in regenerative medicine is largely unknown. The present study was to evaluate the potential application of cryopreserved grafts-derived cells for tissue regeneration. We showed that cells derived from cryopreserved bone grafts could maintain good proliferation activity and osteogenic phenotype. The biological phenotype of these cells could be well preserved. The transplantation of cryopreserved bone-derived cells on scaffold could promote new bone formation in nude mice and enhance the osteointegration for dental implants in canine, which confirmed their osteogenic capacity, and showed that cells derived from cryopreserved bone were comparable to that of fresh bone in terms of the ability to promote osteogenesis in vivo. This work demonstrates that cryopreserved bone grafts may represent a novel, accessible source of cells for tissue regeneration therapy, and the results of our study may also stimulate the development of other cryopreservation techniques in basic and clinical studies.

Autocrine epiregulin activates EGFR pathway for lung metastasis via EMT in salivary adenoid cystic carcinoma

Salivary adenoid cystic carcinoma (SACC) is characterized by invasive local growth and a high incidence of lung metastasis. Patients with lung metastasis have a poor prognosis. Treatment of metastatic SACC has been unsuccessful, largely due to a lack of specific targets for the metastatic cells. In this study, we showed that epidermal growth factor receptors (EGFR) were constitutively activated in metastatic lung subtypes of SACC cells, and that this activation was induced by autocrine expression of epiregulin (EREG), a ligand of EGFR. Autocrine EREG expression was increased in metastatic SACC-LM cells compared to that in non-metastatic parental SACC cells. Importantly, EREG-neutralizing antibody, but not normal IgG, blocked the autocrine EREG-induced EGFR phosphorylation and the migration of SACC cells, suggesting that EREG-induced EGFR activation is essential for induction of cell migration and invasion by SACC cells. Moreover, EREG-activated EGFR stabilized Snail and Slug, which promoted EMT and metastatic features in SACC cells. Of note, targeting EGFR with inhibitors significantly suppressed both the motility of SACC cells in vitro and lung metastasis in vivo. Finally, elevated EREG expression showed a strong correlation with poor prognosis in head and neck cancer. Thus, targeting the EREG-EGFR-Snail/Slug axis represents a novel strategy for the treatment of metastatic SACC even no genetic EGFR mutation.

Combined Counterclockwise Maxillomandibular Advancement and Uvulopalatopharyngoplasty Surgeries for Severe Obstructive Sleep Apnea

Abstract As the most effective surgical technique maxillomandibular advancement (MMA) has been used to treat severe obstructive sleep apnea (OSA) in adults, particularly for those who are intolerant of continuous positive airway pressure. Yet for large-scale advancement, it is faced with esthetic problems with marked skeletal protrusion especially for people with convex facial profile. In this study, the authors performed counterclockwise MMA combined with quantified uvulopalatopharyngoplasty (UPPP) surgeries on Chinese adult patients with severe OSA, in order to initially explore the efficacy of these procedures on Chinese populations and provide evidence for esthetic advantages. As the primary procedure counterclockwise MMA was applied on 10 patients, achieving a forward distance of the mandible and the maxilla for 10.6 and 6.7 mm, respectively, and the occlusion plane rotated counterclockwise of 6.2°. After a follow-up of beyond 12 months, polysomnography results showed the apnea-hypopnea index (AHI) significantly decreased from 64.3 to 11.0 per hour, achieving surgical success of 90%. Upper airway measurements demonstrated that the retropalatal and retrolingual spaces got enlarged greatly, resulting in significant AHI reduction and oxygen saturation elevation. More importantly, cephalometric analysis revealed that SNA and SNB were enlarged but in well control without visual abnormalities. Follow-up results showed large-scale advancement of the maxilla and mandible were stable in treating severe OSA. Quantified UPPP surgeries guaranteed no functional insufficiency in pronouncing and swallowing and played auxiliary role in enlarging the upper airway. Thus, procedures of counterclockwise MMA combined with quantified UPPP surgeries might find more application especially in patients with severe OSA with convex facial profile in future.

Study on the Short-Time Remolding of Upper Airway After Uvulopalatopharyngoplasty

Objective: To verify the short-time remolding of upper airway in patients diagnosed with obstructive sleep disordered breathing after Uvulopalatopharyngoplasty (UPPP). Methods: Twenty-one male adult patients aged 27 to 52 years followed up ranged from preoperation to 6 months after the operation. Lateral cephalometric radiographs (conventional and when pronouncing “i”) were obtained 2 weeks preoperatively, 3 days postoperatively, and 1, 2, 3, 6 months after the surgery. The anterolateral diameters of different levels of upper airway and parameters of hyoid position of the patients were then measured. SAS 8.02 was used to analyze the differences by time. Results: The study illustrated that the UPPP major affected the velopharyngeal and glossopharyngeal areas: parameters wane (P <0.05). On the other hand, UPPP leaded to the decline and retreat of hyoid. Most of the parameters remained metabolic. The nasopharynx kept statical (P >0.05) while the velopharyngeal parameters were increasing (P <0.05). The glossopharyngeal parameters increased in the first month after UPPP (P <0.05), while hypopharyngeal parameters underwent decline since 2 months after UPPP (P <0.05). The hyoid obtained decline and retreat (P <0.05) overall, while it endured a short-time climb in the first month after UPPP (P <0.05). Conclusion: Short-time upper airway remolding after UPPP existed.