Delivery of epidermal growth factor receptor inhibitor via a customized collagen scaffold promotes meniscal defect regeneration in a rabbit model
Delivery of epidermal growth factor receptor inhibitor via a customized collagen scaffold promotes meniscal defect regeneration in a rabbit model
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通过定制胶原蛋白支架输送表皮生长因子受体抑制剂可促进兔模型半月板缺损再生
DOI：
10.1016/j.actbio.2017.07.008
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发表时间：
2017
影响因子：
9.7
通讯作者：
Ouyang Hongwei
中科院分区：
文献类型：
--
作者：
Pan Zongyou;Wu Yan;Zhang Xiaolei;Fu Qianbao;Li Jun;Yang Yang;Yu Dongsheng;Xu Yuzi;Lu Xiaolang;Sun Heng;Zhang Xianzhu;Heng Boon Chin;Bunpetch Varitsara;Zhang Shufang;Ouyang Hongwei
半月板损伤是最常见的膝关节损伤之一，迄今为止仍是临床实践中的一个棘手挑战。异常的表皮生长因子受体（EGFR）的激活水平在人类和小鼠踝关节损伤后，促使我们调查EGFR的功能作用，利用诱导软骨特异性EGFR缺陷的小鼠模型。我们证明了小鼠中条件性EGFR缺失导致半月板内部分切除术诱导的ECM产生增加，这与利用小分子EGFR抑制剂吉非替尼阻断EGFR活性相当。在这里，我们结合关节内注射吉非替尼与植入定制的胶原蛋白支架，以取代失去的关节组织，以及促进关节再生和防止骨关节炎（OA）进展在兔关节切除术model.Statement of SignificanceThe主要新奇这项研究是一个新的应用小分子EGFR抑制剂在关节损伤治疗的发现。这项研究还强调了使用定制的胶原蛋白支架提供强大的机械强度和有效促进半月板再生的重要性。总之，我们的研究发现，在兔模型中，关节内递送吉非替尼连同植入定制的多层胶原支架不仅增强了关节再生，而且保护了关节软骨免于退化。这些结果为乳腺组织工程研究和临床实践提供了有价值的见解。
Meniscal injury is one of the most common knee joint injuries, which remains an intractable challenge in clinical practice to date. Aberrant epidermal growth factor receptor (EGFR) activation levels in both human and mice menisci following injury, prompted us to investigate the functional role of EGFR by utilizing an inducible cartilage-specific EGFR-deficient mouse model. We demonstrated that conditional EGFR deletion in mice resulted in increased partial meniscectomy-induced ECM production within the meniscus, which is comparable to utilization of the small molecule EGFR inhibitor, gefitinib, to block EGFR activity. Here, we combined intra-articular delivery of gefitinib with an implanted customized collagen scaffold to substitute for lost meniscal tissue, as well as to promote meniscal regeneration and prevent osteoarthritis (OA) progression in a rabbit meniscectomy model.Statement of SignificanceThe main novelty of this study is the finding of a new application for small molecule EGFR inhibitor in meniscal injury therapy. This study also highlights the importance of using a customized collagen scaffold to provide robust mechanical strength and effectively promote meniscus regeneration. In summary, our study finds that intra-articular delivery of gefitinib together with implantation of a customized, multi-layer collagen scaffold not only enhanced meniscal regeneration, but also protected articular cartilage from degeneration in rabbit model. These results provide valuable insight for meniscal tissue engineering studies and clinical practice.