美开发出新型水凝胶 可修复膝盖软骨

2013-01-16 14:07 · lobu

美国科学家开发出一种新型水凝胶生物材料,在软骨修复手术中将其注入骨骼小洞,能帮助刺激病人骨髓产生干细胞,长出新的软骨。在临床试验中,新生软骨覆盖率达到86%,术后疼痛也大大减轻。

美国约翰·霍普金斯大学医学院报告称,他们开发出一种新型水凝胶生物材料,在软骨修复手术中将其注入骨骼小洞,能帮助刺激病人骨髓产生干细胞,长出新的软骨。在临床试验中,新生软骨覆盖率达到86%,术后疼痛也大大减轻。相关论文发表在1月9日出版的《科学·转化医学》上。

人体关节骨的两端都有一层很薄的软骨,就像覆盖在骨头上的薄膜,外伤、磨损、疾病或基因缺陷都可能伤害软骨,软骨一旦受损是不会自行生长的。微骨折术也叫关节镜软骨手术,是在缺少软骨覆盖的骨头上钻几个小洞,刺激骨髓细胞产生干细胞生成软骨。但手术未必都能成功,可能无法刺激新的软骨生长,或者新长出的软骨不如原来的坚硬。

Jennifer Elisseeff实验室成员(图片来自Elisseeff实验室网站)

理论上,干细胞需要附着在一种营养支架上才能更好生长。约翰·霍普金斯大学医学院转化组织工程中心(TTEC)主任Jennifer Elisseeff说,“水凝胶”支架在愈合过程中能为细胞提供“营养”,促进健康组织生长,加速伤口愈合。她们在实验室里和山羊身上进行了多年实验,以寻找最理想的植入材料,最终选定了一种水凝胶生物材料和一种黏合剂,黏合剂用来使水凝胶牢牢地黏在骨骼上。

研究小组随后对15位病人进行了首次临床试验,通过微骨折术在受伤软骨附近的骨骼上打出一些微小的洞,将水凝胶和黏合剂注入其中。为了对照实验,她们对另外3位病人仅实施了微骨折术。6个月后,植入物并未产生大的问题。核磁共振显示,植入凝胶的病人长出了新软骨,对膝盖骨骼的平均覆盖率达到86%,未植入凝胶的病人平均覆盖率为64%,而且在术后的6个月中,植入凝胶的病人膝盖疼痛也大幅度减轻。

“初步研究显示,植入的生物材料在患者体内和在实验室里一样表现良好,所以我们希望该方法能成为护理与促进愈合的一种常规措施。”Elisseeff说,这一成果还属于概念论证性实验,要证明水凝胶的安全有效性和临床价值,还需要更多时间和更大规模的实验。目前他们已经招募到更多病人参与进一步实验。

Elisseeff还说,研究小组正在开发下一代移植材料,水凝胶和黏合剂就是其中之一,二者将被整合为一种材料。此外,她们还在研究关节润滑和减少发炎的技术。

Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite

Blanka Sharma, Sara Fermanian, Matthew Gibson, Shimon Unterman, Daniel A. Herzka, Brett Cascio, Jeannine Coburn, Alexander Y. Hui, Norman Marcus, Garry E. Gold and Jennifer H. Elisseeff

Surgical options for cartilage resurfacing may be significantly improved by advances and application of biomaterials that direct tissue repair. A poly(ethylene glycol) diacrylate (PEGDA) hydrogel was designed to support cartilage matrix production, with easy surgical application. A model in vitro system demonstrated deposition of cartilage-specific extracellular matrix in the hydrogel biomaterial and stimulation of adjacent cartilage tissue development by mesenchymal stem cells. For translation to the joint environment, a chondroitin sulfate adhesive was applied to covalently bond and adhere the hydrogel to cartilage and bone tissue in articular defects. After preclinical testing in a caprine model, a pilot clinical study was initiated where the biomaterials system was combined with standard microfracture surgery in 15 patients with focal cartilage defects on the medial femoral condyle. Control patients were treated with microfracture alone. Magnetic resonance imaging showed that treated patients achieved significantly higher levels of tissue fill compared to controls. Magnetic resonance spin-spin relaxation times (T2) showed decreasing water content and increased tissue organization over time. Treated patients had less pain compared with controls, whereas knee function [International Knee Documentation Committee (IKDC)] scores increased to similar levels between the groups over the 6 months evaluated. No major adverse events were observed over the study period. With further clinical testing, this practical biomaterials strategy has the potential to improve the treatment of articular cartilage defects.

文献链接:Human Cartilage Repair with a Photoreactive Adhesive-Hydrogel Composite