Chitosan-Gelatin Hydrogel Crosslinked With Oxidized Sucrose for the Ocular Delivery of Timolol Maleate

Ocular hypertension due to increased intraocular pressure is a major risk factor for the development of glaucoma. Rapid clearance and low ocular bioavailability are drawbacks of conventional ocular treatments. This requires frequent and long-term application of antiglaucoma drugs which in turn cause local side effects and are a major cause of therapeutic failure due to loss of persistence in using glaucoma therapy. In this study, a semisynthetic, biocompatible, oxidized sucrose crosslinker was developed and used in the formulation of chitosan-gelatin hydrogel for the sustained release of timolol to control ocular hypertension. The swelling properties of the hydrogel showed a strong relationship with the oxidized sucrose concentration. Mucoadhesive properties of the hydrogel were studied and the in vitro release profiles demonstrated that crosslinking with oxidized sucrose reduced the release rate of the entrapped timolol. The results of both in vitro and in vivo studies supported that the formulated hydrogel maintained the release and in turn the efficacy of timolol for a longer period of time compared to the conventional eye drops. This is expected to reduce the frequency of drug application onto the eye surface and in turn enhances patients’ convenience. In conclusion, the developed formulation represents a promising platform for an effective and compliant treatment of ocular hypertension.     

海地瓜海参胶对胰岛素抵抗模型小鼠慢性炎症的改善作用

目的 研究海地瓜海参胶对胰岛素抵抗模型小鼠慢性炎症的改善作用。方法 建立高脂高果糖饮食诱导胰岛素抵抗小鼠模型。雄性C57BL/6J小鼠随机分为正常对照组、模型对照组、海地瓜海参胶低剂量组（100 mg · (kg ·bw· d)-1）、海地瓜海参胶高剂量组（200 mg · (kg ·bw· d)-1）。饲喂9周后,检测小鼠空腹血糖、胰岛素、促炎因子游离脂肪酸、肿瘤坏死因子-α、白介素6及抗炎因子脂联素、白介素10水平;qRT-PCR 检测小鼠肝脏炎症因子mRNA表达水平。结果 海地瓜海参胶显著降低胰岛素抵抗模型小鼠空腹血糖、空腹胰岛素水平;显著降低血清促炎因子含量,升高抗炎因子含量;显著下调肝脏肿瘤坏死因子-α、白介素6 mRNA表达,上调脂联素、白介素10 mRNA表达。结论 海地瓜海参胶可显著改善胰岛素抵抗小鼠的慢性炎症。     

大鼠胎脑神经细胞与胶原复合体移植对脑损伤的修复

目的:评价胶原蛋白(Collagen)的细胞相容性;研究胶原蛋白(C)与大鼠胎脑神经细胞(FBN)复合体(C-FBN)脑内移植对脑损伤的修复作用。方法:将大鼠FBN与胶原蛋白联合体外培养,进行光镜、扫描电镜观察。并将体外联合培养3～5d的C-FBN(移植前48h培养液中加入BrdU)移植到大脑皮质损伤模型的大鼠脑损伤部位,术后3,6,10,15及30d光镜、BrdU免疫细胞化学染色(ICC)、透射电镜观察脑组织对移植物的反应、移植细胞生长状态及载体在体内的降解情况等。结果:胶原蛋白对FBN生长无不良影响;脑组织对移植物无明显的免疫排斥反应;胶原蛋白与周围脑组织整合好,有血管长入移植物中;载体内有大量存活神经细胞,而且术后各时段都检出BrdU阳性细胞;移植区有突触形成;胶原蛋白海绵吸收、降解快,可诱导组织再生。结论:胶原具有良好的细胞相容性和组织相容性,是神经组织工程的一种较为理想的生物载体材料;生物材料与胎脑神经细胞联合培养移植是治疗脑损伤较有前途的新方法。     

耳内镜下贝复新明胶海绵修补外伤性鼓膜穿孔临床观察

目的探讨耳内镜下贝复新明胶海绵修补外伤性鼓膜穿孔的临床疗效。方法选取我科2008年1月至2012年12月接诊的132例外伤性鼓膜穿孔患者为研究对象,将其随机分为治疗组(76例)和对照组(56例)。治疗组行耳内镜下贝复新明胶海绵修补外伤性鼓膜穿孔,对照组予以传统干燥保守治疗,对两组患者的临床疗效进行分析和比较。结果在相同时间(4周,2个月,3个月),治疗组鼓膜穿孔愈合率均明显高于对照组,差异有统计学意义(P<0.01);4周内,治疗组的愈合时间明显快于对照组,差异有统计学意义(P<0.01)。结论贝复新明胶海绵修补外伤性鼓膜穿孔可提高鼓膜穿孔愈合率及加快鼓膜穿孔愈合速度,是一种操作简单、安全、有效的治疗方法。     

Fabrication of a Novel Protein Sponge with Dual-Scale Porosity and Mixed Wettability Using a Clean and Versatile Microwave-Based Process

An open-porous protein sponge with mixed wettability is presented made entirely from whey proteins and with promising applications in biomedicine, pharmaceutical, and food industry. The fabrication relies on an additive-free, clean and scalable process consisting of foaming followed by controlled microwave-convection drying. Volumetric heating throughout the matrix induced by microwaves causes fast expansion and elongation of the foam bubbles, retards crust formation and promotes early protein denaturation. These effects counteract collapse and shrinkage typically encountered in convection drying of foams. The interplay of high protein content, tailored gas incorporation and controlled drying result in a dried structure with dual-scale porosity composed of open macroscopic elongated foam bubbles and microscopic pores in the surrounding solid lamellae induced by water evaporation. Due to the insolubility and mixed wettability of the denatured protein network, polar and non-polar liquids are rapidly absorbed into the interconnected capillary system of the sponge without disintegrating. While non-watery liquids penetrate the pores by capillary suction, water diffuses also into the stiff protein matrix, inducing swelling and softening. Consequently, the water-filled soft sponge can be emptied by compression and re-absorbs any wetting liquid into the free capillary space.     

Regenerative potential of basic fibroblast growth factor contained in biodegradable gelatin hydrogel microspheres applied following vocal fold injury: Early effect on tissue repair in a rabbit model

IntroductionPostoperative dysphonia is mostly caused by vocal fold scarring, and careful management of vocal fold surgery has been reported to reduce the risk of scar formation. However, depending on the vocal fold injury, treatment of postoperative dysphonia can be challenging.ObjectiveThe goal of the current study was to develop a novel prophylactic regenerative approach for the treatment of injured vocal folds after surgery, using biodegradable gelatin hydrogel microspheres as a drug delivery system for basic fibroblast growth factor.MethodsVideoendoscopic laryngeal surgery was performed to create vocal fold injury in 14 rabbits. Immediately following this procedure, biodegradable gelatin hydrogel microspheres with basic fibroblast growth factor were injected in the vocal fold. Two weeks after injection, larynges were excised for evaluation of vocal fold histology and mucosal movement.ResultsThe presence of poor vibratory function was confirmed in the injured vocal folds. Histology and digital image analysis demonstrated that the injured vocal folds injected with gelatin hydrogel microspheres with basic fibroblast growth factor showed less scar formation, compared to the injured vocal folds injected with gelatin hydrogel microspheres only, or those without any injection.ConclusionA prophylactic injection of basic fibroblast growth factor -containing biodegradable gelatin hydrogel microspheres demonstrates a regenerative potential for injured vocal folds in a rabbit model.     

Effects of 3-dimensional Bioprinting Alginate/Gelatin Hydrogel Scaffold Extract on Proliferation and Differentiation of Human Dental Pulp Stem Cells

IntroductionAlginate/gelatin hydrogel (Alg-Gel) scaffold has been applied in tissue engineering, but the research on its application in dental tissues regeneration is still lacking. We investigated the effect of this scaffold on human dental pulp stem cells (hDPSCs).MethodshDPSCs were cultured in both Alg-Gel and 3D-printed Alg-Gel scaffolds. Cell growth and adhesion were compared using fluorescein isothiocyanate–phalloidin staining and scanning electron microscopic micrographs. Changes in the proliferation in hDPSCs cultured in the complete culture medium containing aqueous extracts of the Alg-Gel or 3D-printed Alg-Gel scaffolds were examined using Cell Counting Kit-8 assay and flow cytometry analysis. Cells were cultured in the mineralization medium containing aqueous extracts of the Alg-Gel or 3D-printed Alg-Gel scaffolds for 7 or 14 days, and the differentiation of cells was shown by alizarin red S staining and alkaline phosphatase staining. The messenger RNA and protein expression of mineralization-related genes were detected with real-time polymerase chain reaction and Western blotting. Elemental analysis was used to test the material extract composition.ResultsMore cells were grown and adhered to the 3D-printed Alg-Gel scaffolds than the Alg-Gel scaffolds. The aqueous extracts of 3D-printed scaffolds can promote cell proliferation, and compared with Alg-Gel scaffolds, the extracts of 3D-printed scaffolds were more effective. Compared with the negative control group, 3D-printed Alg-Gel scaffold and Alg-Gel scaffold aqueous extracts promoted osteogenic/odontoblastic differentiation of hDPSCs with the enhanced formation of bone-like nodules and the alkaline phosphatase staining. The expression of mineralization-related genes was also up-regulated. 3D-printed scaffold aqueous extract contained more calcium and phosphorus ions than the Alg-Gel scaffold.ConclusionsThese findings suggest that compared with the Alg-Gel scaffold, 3D-printed Alg-Gel is more suitable for the growth of hDPSCs, and the scaffold extracts can better promote cell proliferation and differentiation.     

介入栓塞治疗30例巨块型肝癌破裂出血的回顾性分析

目的：观察巨块型肝癌破裂出血患者行血管介入栓塞和栓塞加化疗药物灌注治疗的疗效。方法：选取2006年12月-2014年2月在我院住院的30例巨块型肝癌破裂出血行急诊介入栓塞的患者,按栓塞方法不同分为单纯明胶海绵栓塞组（简称单纯组）15例,栓塞时加化疗药物灌注组（简称联合组）15例。观察两组患者术后不良反应及并发症。结果：两组患者均1次栓塞止血成功,住院期间无复发破裂出血;两组患者术后恶心、呕吐、腹痛、食欲不振等症状发生率比较,差异有统计学意义（P〈0.05）;联合组患者术后ALT、GGT、TBil等检测结果均高于单纯组,差异有统计学意义（P〈0.05）;联合组有1例死亡。结论：巨块型肝癌破裂出血急诊介入栓塞治疗时宜选择单纯用明胶海绵栓塞,其安全有效,不良反应少。