In situ crosslinking elastin-like polypeptide gels for application to articular cartilage repair in a goat osteochondral defect model
In situ crosslinking elastin-like polypeptide gels for application to articular cartilage repair in a goat osteochondral defect model
复制标题
DOI：
10.1089/ten.tea.2007.0245
复制
发表时间：
2008-07-01
影响因子：
4.1
通讯作者：
Setton, Lori A.
中科院分区：
文献类型：
--
作者：
Nettles, Dana L.;Kitaoka, Kenichi;Setton, Lori A.
本研究的目的是评估一种可注射、可原位交联的弹性蛋白样多肽 (ELP) 凝胶，用于修复山羊膝盖严重缺损的软骨基质。七只动物中每只的一个圆柱形骨软骨缺损均填充有 ELP 水溶液和生物相容性化学交联剂，而对侧缺损保持未填充并用作内部对照。在 3 (n=3) 或 6 (n=4) 个月时牺牲关节进行 MRI、组织学和生物材料性能特征的总体评估，包括整合、细胞浸润、周围基质质量和缺陷中的新基质。 3 个月时，与未填充的缺损相比，ELP 填充的缺损在组织学和总体分级方面的整合得分显着更高。 ELP 不会阻碍细胞浸润，但似乎已部分降解。 6 个月时，未填充缺损中的新基质超过了 ELP 填充缺损中的新基质，并且在不良变化的 MRI 证据以及通过总体和组织学分级的整合和含有蛋白聚糖的基质方面得分明显更高。 ELP-交联剂溶液易于输送并形成稳定、整合良好的凝胶，支持细胞浸润和基质合成；然而，快速降解表明应优化 ELP 配方修改，以获得软骨修复应用中的长期益处。
The objective of this study was to evaluate an injectable, in situ crosslinkable elastin-like polypeptide (ELP) gel for application to cartilage matrix repair in critically sized defects in goat knees. One cylindrical, osteochondral defect in each of seven animals was filled with an aqueous solution of ELP and a biocompatible, chemical crosslinker, while the contralateral defect remained unfilled and served as an internal control. Joints were sacrificed at 3 (n=3) or 6 (n=4) months for MRI, histological, and gross evaluation of features of biomaterial performance, including integration, cellular infiltration, surrounding matrix quality, and new matrix in the defect. At 3 months, ELP-filled defects scored significantly higher for integration by histological and gross grading compared to unfilled defects. ELP did not impede cell infiltration but appeared to be partly degraded. At 6 months, new matrix in unfilled defects outpaced that in ELP-filled defects and scored significantly better for MRI evidence of adverse changes, as well as integration and proteoglycan-containing matrix via gross and histological grading. The ELP-crosslinker solution was easily delivered and formed stable, well-integrated gels that supported cell infiltration and matrix synthesis; however, rapid degradation suggests that ELP formulation modifications should be optimized for longer-term benefits in cartilage repair applications.