Experimental Rheumatology Unit, Orthopedic Professorship, Jena University Hospital, Waldkliniken Eisenberg GmbH, 07607 Eisenberg, Germany.
Department of Orthopedics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China.
Int J Mol Sci. 2021 Oct 29;22(21):11769. doi: 10.3390/ijms222111769.
Resorbable polyglycolic acid (PGA) chondrocyte grafts are clinically established for human articular cartilage defects. Long-term implant performance was addressed in a standardized in vitro model. PGA implants (+/- bovine chondrocytes) were placed inside cartilage rings punched out of bovine femoral trochleas (outer Ø 6 mm; inner defect Ø 2 mm) and cultured for 84 days (12 weeks). Cartilage/PGA hybrids were subsequently analyzed by histology (hematoxylin/eosin; safranin O), immunohistochemistry (aggrecan, collagens 1 and 2), protein assays, quantitative real-time polymerase chain reactions, and implant push-out force measurements. Cartilage/PGA hybrids remained vital with intact matrix until 12 weeks, limited loss of proteoglycans from "host" cartilage or cartilage-PGA interface, and progressively diminishing release of proteoglycans into the supernatant. By contrast, the collagen 2 content in cartilage and cartilage-PGA interface remained approximately constant during culture (with only little collagen 1). Both implants (+/- cells) displayed implant colonization and progressively increased aggrecan and collagen 2 mRNA, but significantly decreased push-out forces over time. Cell-loaded PGA showed significantly accelerated cell colonization and significantly extended deposition of aggrecan. Augmented chondrogenic differentiation in PGA and cartilage/PGA-interface for up to 84 days suggests initial cartilage regeneration. Due to the PGA resorbability, however, the model exhibits limitations in assessing the "lateral implant bonding".
可吸收聚乙二醇酸（PGA）软骨细胞移植物已在临床上用于治疗人类关节软骨缺损。本研究采用标准化的体外模型来评估其长期植入性能。PGA 植入物（含/不含牛软骨细胞）被放置在从牛股骨滑车中切出的软骨环（外直径 6 毫米；内缺损直径 2 毫米）内，并培养 84 天（12 周）。随后通过组织学（苏木精/伊红；番红 O）、免疫组织化学（聚集蛋白聚糖、胶原 1 和 2）、蛋白测定、实时定量聚合酶链反应和植入物推出力测量对软骨/PGA 杂交体进行分析。直到 12 周，软骨/PGA 杂交体仍保持活力，基质完整，“宿主”软骨或软骨-PGA 界面处的蛋白聚糖仅有限丢失，并且蛋白聚糖逐渐释放到上清液中。相比之下，在培养过程中，软骨和软骨-PGA 界面中的胶原 2 含量保持相对恒定（仅含有少量胶原 1）。两种植入物（含/不含细胞）均显示出植入物的定植，并逐渐增加聚集蛋白聚糖和胶原 2 的 mRNA，但随着时间的推移，推出力显著降低。负载细胞的 PGA 显示出明显加速的细胞定植和明显延长的聚集蛋白聚糖沉积。PGA 和软骨/PGA 界面中高达 84 天的增强的软骨生成分化表明初始软骨再生。然而，由于 PGA 的可吸收性，该模型在评估“横向植入物结合”方面存在局限性。
