Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
3Bs Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Guimarães, Portugal.
J Biomed Mater Res A. 2018 Jul;106(7):1987-1996. doi: 10.1002/jbm.a.36406. Epub 2018 Apr 10.
Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non-treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non-treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno-free biomaterial to be used with chondrogenic cells for a cost-effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987-1996, 2018.
甲基丙烯酰化凝胶多糖(GGMA)制剂被提议作为第二代水凝胶,用于将软骨形成细胞递送到局灶性软骨病变部位,从而允许细胞立即原位保留和 3D 填充病变体积,这种方法被认为与关节镜程序兼容。使用软骨细胞和脂肪间充质基质/干细胞(ASCs)在体外进行制剂优化。使用诱导的软骨病变兔模型进行了概念验证的体内研究。通过宏观、组织学和免疫组织化学分析,将结果与微骨折或未治疗的对照组进行比较。三个分级评分用于在 8 周后评估组织修复情况。通过 ASC+GGMA 制剂,在体外实现了强烈的 II 型胶原和低 I 型胶原基因和蛋白表达,与健康软骨组织的发展一致。在体内,与未治疗组相比,该制剂促进了明显更优的新生软骨形成。还进一步实现了软骨高度的维持和与原生组织的整合。所提出的 GGMA 水凝胶的物理化学性质在体外和体内均表现出非常理想的特性和生物学性能,将其定位为一种有吸引力的无动物源性生物材料,可与软骨细胞一起用于治疗局灶性软骨病变,具有成本效益。© 2018 威利父子公司