Meng Tian

Delivery of demineralized bone matrix powder using a thermogelling chitosan carrier

Demineralized bone matrix (DBM) powder is widely used for bone regeneration due to its osteoinductivity and osteoconductivity. However, difficulties with handling, its tendency to migrate from graft sites, and lack of stability after surgery can sometimes limit the clinical utility of this material. In this work, the possibility of using a thermogelling chitosan carrier to deliver DBM powder was assessed. The DBM-thermogelling putty improved handling and formed a gel-like composite in situ at body temperature within a clinically relevant time period. The properties of the formed composite, including morphology, porosity, mechanical properties, equilibrium swelling as well as degradability, are significantly influenced by the ratio of DBM to thermogelling chitosan. The in vitro study showed that the alkaline phosphatase activity of C2C12 cells encapsulated in the composite was steadily increased with culture time. The in vivo study showed that increased DBM content in the DBM-thermogelling chitosan induced ectopic bone formation in a nude rat model. The diffusion of growth factor from the DBM-thermogelling chitosan as well as the host-implant interactions are discussed.

Preparation and characterization of galactosylated alginate-chitosan oligomer microcapsule for hepatocytes microencapsulation.

Galactosylated alginate (GA)-chitosan oligomer microcapsule was prepared to provide a sufficient mechanical stability, a selective permeability and an appropriate three-dimensional (3D) microenvironment for hepatocytes microencapsulation. The microcapsule has a unique asymmetric membrane structure, with a dense layer located in the inner surface and gradually decreasing toward the outside surface. The stable microcapsule was obtained when GA lower than 50%, while the permeability was increased with increasing of GA. A balance between mechanical stability and permeability was achieved through modulating membrane porosity and thickness. The optimal microcapsule displays a selective permeability allowing efficient transport of human serum albumin while effectively blocking immunoglobulin G. Hepatocytes exhibited high and long term viability (>92%), proliferability, multicellular spheroid morphology, and enhancement of liver-specific functions in the microcapsule wherein galactose moieties present chemical cues to support cell-matrix interactions while the 3D structure of the microcapsule behaves physical cues to facilitate cell-cell interactions.

Molecular weight dependence of structure and properties of chitosan oligomers

In this work, chitosan oligomers (COS) with molecular weights decreasing continuously and covering the region of insoluble–soluble transition and with low polydispersity were prepared, and then the molecular weight (MW) dependence on the structure and properties were studied. FTIR, 1H and 13C NMR analyses showed that the prepared COS maintained the chemical structure of the initial chitosan and some signal shifts were observed resulting from the increase of the degree of acetylation. In contrast, it was found that the crystalline structure, thermal stability, and water solubility were significantly influenced by the MW, that is, with the decrease of the MW, the crystalline structure transformed from “L-2” to “tendon” and then to “annealed” polymorph, in which the MW corresponding to the conversion from “tendon” to “annealed” polymorph was 4.67 kDa. The thermal stability decreased with the reduction of the MW, while for the similar MW, the stability increased with the increase of the crystallinity. For water solubility, the MW ranging from 3.82 to 4.67 × 103 kDa corresponded to the insoluble–soluble transition. A mechanism of water solubility dependence on MW was proposed.

Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening

To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening.

Perioperative Antihypertensive Treatment in Patients With Spontaneous Intracerebral Hemorrhage

Background— Studies on antihypertensive treatment for surgical patients with spontaneous intracerebral hemorrhage are insufficient. This pilot study was conducted to investigate the safety of the perioperative intensive blood pressure lowering in surgical patients with spontaneous intracerebral hemorrhage. Methods— This study was a prospective, parallel, randomized, assessor-blinded trial. Patients allocated to the intensive group received perioperative intensive antihypertensive treatment aiming to achieve a target systolic blood pressure between 120 and 140 mm Hg, whereas the patients in the conservative group received conservative treatment aiming to achieve a target systolic blood pressure between 140 and 180 mm Hg for 7 days. The primary outcome was the rate of rehemorrhage at 7 days after surgery. Results— Rehemorrhage was noted in 11 patients (11%) in the intensive group and 14 (14%) in the conservative group (P=0.689). There was no significant difference in mortality at 7 days (4.0% versus 10.0%; P=0.164), 30 days (10.4% versus 17.2%; P=0.247), and 90 days (13.5% versus 18.2%; P=0.490) between the 2 groups. Conclusions— Perioperative intensive blood pressure lowering was not associated with a reduced incidence of rehemorrhage, death, or other serious adverse events. Clinical Trial Registration— URL: http://www.chictr.org.cn/. Unique identifier: ChiCTR-TRC-13004304.

Synthesis and evaluation of oxidation-responsive alginate-deferoxamine conjugates with increased stability and low toxicity

Deferoxamine is commonly used for iron-overload related diseases, its drawbacks such as instability and toxicity, however, significantly limited its utility in clinic. To address these issues, oxidation-responsive alginate-deferoxamine (Alg-DFO) conjugates were synthesized and their structure was characterized. The metabolism studies shown the conjugation of alginate significantly increased the stability of the DFO, with half-life more than 10 times longer than that of the free DFO. Moreover, the conjugates could not only quickly respond to oxidative stimuli and degradation, suggesting their potential to be cleared from the body by responding to iron-overload associated oxidative environment to avoid its accumulation and safety concern, but also protect iron binding capacity of the attached DFO from oxidation. The degradation mechanism for oxidative-response was proposed. In addition, the conjugates shown lower cytotoxicity compared to the free DFO. Taken together, the Alg-DFO conjugates synthesized in this work has promise for treating iron-overload related conditions.

Long-term and oxidative-responsive alginate–deferoxamine conjugates with a low toxicity for iron overload

To address the drawbacks of deferoxamine, a clinical drug widely used for iron-overload-related conditions, oxidation-responsive alginate–deferoxamine (Alg–DFO) conjugates were prepared and their structure characterized by size-exclusion chromatography, FTIR, and 1H NMR. The prepared conjugates exhibited long-term stability, with a half-life 9.8–17.8 times longer than that of the free DFO, depending on the molecular weight of the conjugated alginate. On the other hand, the conjugates could quickly respond to oxidative stimuli and be degraded, which suggests they hold the potential to be cleared from the body in an iron-overload-related oxidative environment to avoid their accumulation and to address safety concerns. The degradation mechanism for the oxidative response is proposed. At the same time, it is interesting to find that the conjugates are capable of protecting the iron-binding capacity of the attached DFO from the oxidation environment, which probably is a result of the antioxidant activities of the conjugated alginate. In addition, the conjugates show a lower cytotoxicity in comparison with the free DFO. Overall, it is anticipated that the Alg–DFO conjugates prepared in this work will have the potential to be used for treating iron-overload-related disease.

Surgery for Patients With Spontaneous Deep Supratentorial Intracerebral Hemorrhage: A Retrospective Case-Control Study Using Propensity Score Matching

AbstractSpontaneous intracerebral hemorrhage (sICH) is one of the most dangerous cerebrovascular diseases, especially when in deep brain. The treatment of spontaneous deep supratentorial intracerebral hemorrhage is still controversial. We conducted a retrospective case-control study using propensity score matching to compare the efficacy of surgery and conservative treatment for patients with deep surpatentorial hemorrhage.We observed the outcomes of consecutive patients with spontaneous deep supratentorial hemorrhage retrospectively from December 2008 to July 2013. Clinical outcomes of surgery and conservative treatments were compared in patients with deep sICH using propensity score matching method. The primary outcome was neurological function status at 6 months post ictus. The second outcomes included mortality at 30 days and 6 months, and the incidence of complications. Subgroup analyses of 6-month outcome were conducted.Sixty-three (22.66%) of the 278 patients who received surgery had a favorable neurological function status at 6 months, whereas in the conservative group, 66 of 278 (23.74%) had the same result (P = 0.763). The 30-day mortality in the surgical group was 19.06%, whereas 30.58% in the conservative group (P = 0.002). There was significant difference in the mortality at 6 months after ictus as well (23.38% vs 36.33%, P = 0.001). The subgroup analyses showed significantly better outcomes for the surgical group when hematoma was >40 mL (13.33% vs 0%, P = 0.005) or complicated with intraventricular hemorrhage (16.67% vs 7.27%, P = 0.034). For complications, the risk of pulmonary infection, gastrointestinal hemorrhage, urinary infection, pulmonary embolus, and need for tracheostomy/long term ventilation in the surgical group was higher than the conservative group (31.29% vs 15.47%, P < 0.001; 6.83% vs 3.96%, P = 0.133; 2.88% vs 1.80%, P = 0.400; 1.80% vs 1.08%, P = 0.476; 32.73% vs 23.38%, P = 0.014).Surgery could reduce the short-term mortality as well as long-term mortality in patients with spontaneous deep supratentorial hemorrhage. Moreover, surgery might improve the functional outcome in patients with large hematoma or with IVH compared with conservative treatment. Surgery might be a beneficial choice for part of the patients with spontaneous deep supratentorial hemorrhage, but further detailed research is still needed.

Rat Brainstem Hemorrhage Model: Key Points to Success in Modeling

BACKGROUND A successful animal brainstem hemorrhage model can be used to study pathophysiology and molecular mechanisms of neurologic deterioration or recovery and therapeutic interventions after the brainstem hemorrhage. Herein, we provide a reproducible and reliable model for rat brainstem hemorrhage and summarize our key points to success in modeling. METHODS Twenty-four adult male Sprague-Dawley rats were divided into 3 groups and were injected with 30, 40, and 60 μL autologous blood into the right pontine basal tegmentum after being sedated. The initial model was evaluated with neurobehavior testing, autopsy, and histopathology. The modeling conditions were modified in Group IV rats, and 20 more rats were used to check the reproducibility and reliability of the modified model. Finally, magnetic resonance imaging (MRI) was used to confirm the brainstem hemorrhage. RESULTS Only 6 rats had significant pontine hemorrhage in initial 3 groups on autopsy. Whereas after the modification, all Group IV rats had serious pontine hemorrhage, and modified conditions model had a 90% success rate. MRI confirmed a stable hematoma in the right basal tegmental pons with oval shape 24 hours after of blood injection. Histopathologically, there was significant perihematomal swelling, migration of inflammatory cells and structural changes in neuronal shape and contents. CONCLUSIONS An ideal and repeatable rat brainstem hemorrhage model by injecting autologous blood stereotactically was created, and it mimics the natural onset of brainstem hemorrhage. This brainstem hemorrhage model shows promise that providing a better way for neurology researchers to investigate pathophysiologic procedure of brainstem intracranial hemorrhage and further explore the treatment.