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在牛软骨打孔模型中,使用三维聚乙二醇酸(PGA)植入物进行体外软骨再生。

In Vitro Cartilage Regeneration with a Three-Dimensional Polyglycolic Acid (PGA) Implant in a Bovine Cartilage Punch Model.

机构信息

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.

出版信息

Int J Mol Sci. 2021 Oct 29;22(21):11769. doi: 10.3390/ijms222111769.

Abstract

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".

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f46/8583898/1898a29378e7/ijms-22-11769-g001.jpg

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