3种可注射性支架体内构建组织工程软骨的比较研究

目的比较以纤维蛋白封闭剂(FS)、P luron ic-F 127(PF)、透明质酸(HA)3种可注射性支架体内构建组织工程软骨的效果。方法常规分离、消化、体外单层培养新生兔软骨细胞,分别将软骨细胞与3种支架材料混合接种于裸鼠皮下,并于第10周取材通过大体观察,湿重测定,GAG含量测定和组织化学检查来判断体内形成软骨的能力。结果三组均可形成软骨样组织块,其中FS组体积最大,质地较硬,表面光滑,软骨细胞位于成熟的陷窝中,阿尔新兰及Ⅱ型胶原免疫组化染色强阳性;PF组体积中等,质地柔韧,陷窝清楚,可以检测到阳性的阿尔新兰及Ⅱ型胶原表达。HA组只形成很小的组织块,硬度较差,含有的细胞数和分泌的基质最少,三组的GAG含量分别为(8.8±0.4)m g/g,(6.8±0.3)m g/g,(4.2±0.3)m g/g,各组间差异具有显著性(P<0.05,n=3)。结论3种可注射性支架中,FS成软骨作用最强,PF较好、HA组最差,FS和PF可以用于组织工程软骨的构建。     

Injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels for drug release

A series of injectable in situ cross-linking hyaluronic acid/carboxymethyl cellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability. The gelling time of HA/CMC hydrogels ranged from 1.4 to 7.0 min, and the values of the storage modulus, complex shear modulus, dynamic viscosity, and yield stress of HA3/CMC3 hydrogel were about 5869 Pa, 5870 Pa, 587 Pa·s, and 1969 Pa, respectively. The degradation percentage of HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels were about 60, 49, and 41% after incubating 42 days, and the in vitro cumulative release percentage of BSA from HA1/CMC1, HA2/CMC2, and HA3/CMC3 drug-loaded hydrogels were about 99, 91, and 82% after 30 days. The series of injectable in situ cross-linking HA/CMC hydrogels exhibited good comprehensive performance, signifying that these hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering.     

Self-curing acrylic formulations with applications in intervertebral disk restoration: drug release and biological behaviour

New injectable acrylic formulations have been prepared to be applied in restoration processes for intervertebral disks (IVDs). The solid phase of the formulations is composed of poly(methyl methacrylate) (PMMA), incorporating in some cases chondroitin sulphate (CS) as a regenerative bioactive molecule, whereas the liquid phase is constituted by an amphiphilic macromonomer (MT), 2-hydroxyethyl methacrylate (HEMA) and, in some formulations, acrylic acid (AA). The curing parameters and the mechanical properties of the IVD formulations make them excellent candidates for intervertebral application. In vitro and in vivo evaluation of the prepared IVD formulations is described in terms of CS release, surface analysis after immersion in SBF solutions, and biocompatibility studies based on MTT assay and Alamar blue test, as well as in vivo implantation in female Wistar rats, by injection of the IVD formulations followed by histological evaluations to assess tissue response.     

Injectable liquid alkali alloy based-tumor thermal ablation therapy

The alkali metal was recently found to be a very useful agent for inducing minimally invasive tumor hyperthermia therapy. However, the solid-like metal makes it somewhat inconvenient to perform the surgery. Here, to overcome this drawback, the NaK alloy in liquid state at room temperature was proposed as a highly efficient thermal ablative agent for tumor treatment. For illustration purposes, the functionalized liquid NaK alloy at a mass ratio 1:1 was obtained and an amount of 0.35ml was injected into in vitro pork. The sizes of the damage region and temperature response were measured. It was found that significant temperature increase by a magnitude of > 80°C can easily be obtained. This produced a large coagulation and necrotic area within selected areas for in vitro tests and the necrotic region volume is three times that of the NaK injection quantity. Furthermore, for the in vivo experiment, breast EMT6 tumor in mouse was subjected to treatment by NaK alloy. Tumor was harvested after the experiment to assess its viability. Histological section showed complete necrosis at the target site. These conceptual results demonstrate that using injectable liquid alkali alloy to ablate tumor is rather promising. This study also raised interesting issues waiting for clarification in future technical and animal studies aiming to assess efficacy, side effects and safety of the new therapy.     

Effect of pretreatment counseling on discontinuation rates in Chinese women given depo-medroxyprogesterone acetate for contraception

The study examined the effect of pretreatment counseling upon discontinuation of 150 mg depo-medroxyprogesterone acetate (Depo-Provera^® (DMPA)), given for contraception. A total of 421 chinese women participated, 204 receiving detailed structured pretreatment and ongoing counseling on the hormonal effects and probable side effects of DMPA and 217 receiving only routine counseling. The primary study endpoint was termination rate; secondary endpoints were frequency of medical events and reasons for termination.

Study termination rates were significantly lower in the intensive structured counseling group than in the routine counseling group. At one year, the total cumulative termination rates were 11% (23/204) and 42% (92/217), respectively (p < 0.0001). The most common reasons for terminating DMPA were menstrual changes. No pregnancy, serious or unexpected medical events were reported, nor were statistically or clinically significant changes in vital signs observed. We conclude that pretreatment counseling on expected side effects increases the acceptability of DMPA.     

Severe hypersensitivity reaction to injectable Gallium 67 in a worker exposed to silica

Gallium 67 scintigraphy is employed in the evaluation of workers with possible pneumoconiosis. To our knowledge, however, a severe hypersensitivity reaction following the intravenous injection of Gallium 67 has not been described. We report the ease of a worker chronically exposed to silica who developed an allergic cutaneous and severe articular reaction following the injection of Gallium 67 while being investigated for possible silicosis. Hilar adenopathy was noted on the chest roentgenogram and, retrospectively, circulating immune complexes were found in the patient's serum. The presence of a positive prick skin test to benzyl alcohol suggests that this preservative caused the hypersensitivity reaction.     

Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of cyclofem® in Chinese women

To provide pharmacokinetic data for safety evaluation on prolonged treatment with Cyclofem®, which contains 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate in 0.5 mL microcrystalline aqueous suspension, the pharmacokinetic profiles of MPA after single and multiple administration of this monthly injectable contraceptive were investigated in Chinese women. Nine healthy fertile women received Cyclofem based on a once-a-month regimen for up to 1 year. Blood samples were collected immediately prior to drug administration and on days 1, 3, 5, 7, 14, 21, and 28 after injection. After the 1st, 6th, and 12th injection, the maximum serum concentrations (C_max) of MPA were observed on days 3.4 ± 0.9, 4.3 ± 2.2, and 3.7 ± 2.6, respectively. C_max of serum MPA during the 1st, 6th, and 12th treatment cycles were 3.75 ± 1.27, 5.54 ± 1.79, and 5.55 ± 1.80 nmol/L, whereas the areas under the curve (AUC_{0–28 days}) were 55.84 ± 28.15, 95.45 ± 26.56, and 98.81 ± 21.84 nmol/L·day, respectively. There was significant interindividual variation in the pharmacokinetics of MPA after intramuscular injection of Cyclofem. No significant change was demonstrated in mean residence time (MRT) of MPA after single and multiple injection. There was a tendency of increase in C_max and AUC_{0–28 days} of MPA during the first 6 months of treatment, whereas no further enhancement was found between the 6th and 12th injection (p > 0.05). Peak levels of estradiol (E₂) observed in Cyclofem users were within the normal range of the preovulatory phase. Results of this long-term study suggest that no drug accumulation occurred after repeated administration of Cyclofem in the Chinese women.