Polymeric mesh and insulin-like growth factor 1 delivery enhance cell homing and graft-cartilage integration.

Polymeric mesh and insulin-like growth factor 1 delivery enhance cell homing and graft-cartilage integration.
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DOI:
10.1111/nyas.14054
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发表时间:
2019-04
影响因子:
5.2
通讯作者:
Lu HH
Lu HH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Boushell MK;Mosher CZ;Suri GK;Doty SB;Strauss EJ;Hunziker EB;Lu HH

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软骨损伤,如全层损伤,容易使患者过早发展为骨关节炎,这是一种退行性关节疾病。虽然软骨损伤的外科治疗有所改善,但由于缺乏透明软骨再生和移植物−宿主整合不足,长期临床疗效停滞不前。这项研究验证了一种假说,即通过从可降解的聚合物网状物中释放趋化因子,促进软骨细胞在移植物−宿主界面上的迁移,可以改善软骨移植物与天然软骨的整合。为此,设计了一种聚乳酸-乙交酯/聚-ε-己内酯网状物来定位胰岛素样生长因子-1(胰岛素样生长因子-1)的传递,胰岛素样生长因子-1是一种公认的软骨细胞诱导剂。IGF-1(100 ng/mg)的释放促进了细胞从软骨移植体内的迁移,网状物是细胞黏附、生长和在体外产生软骨基质的关键结构支撑,与无网状物修复相比,这导致了更高的整合强度。此外,当在活体骨软骨移植模型中进行测试时,这种新型软骨基质在结构上与天然和移植的软骨是连续的。这些结果表明,细胞归巢因子和支持基质的结合将促进细胞介导的整体性软骨修复,并改善软骨移植在骨关节炎治疗中的临床效果。
Cartilage injury, such as full-thickness lesions, predisposes patients to the premature development of osteoarthritis, a degenerative joint disease. While surgical management of cartilage lesions has improved, long-term clinical efficacy has stagnated, owing to the lack of hyaline cartilage regeneration and inadequate graft−host integration. This study tests the hypothesis that integration of cartilage grafts with native cartilage can be improved by enhancing the migration of chondrocytes across the graft−host interface via the release of chemotactic factor from a degradable polymeric mesh. To this end, a polylactide-co-glycolide/poly-ε-caprolactone mesh was designed to localize the delivery of insulin-like growth factor 1 (IGF-1), a well-established chondrocyte attractant. The release of IGF-1 (100 ng/mg) enhanced cell migration from cartilage explants, and the mesh served as critical structural support for cell adhesion, growth, and production of a cartilaginous matrix in vitro, which resulted in increased integration strength compared with mesh-free repair. Further, this neocartilage matrix was structurally contiguous with native and grafted cartilage when tested in an osteochondral explant model in vivo. These results demonstrate that this combined approach of a cell homing factor and supportive matrix will promote cell-mediated integrative cartilage repair and improve clinical outcomes of cartilage grafts in the treatment of osteoarthritis.
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