Cell-free 3D wet-electrospun PCL/silk fibroin/Sr2+ scaffold promotes successful total meniscus regeneration in a rabbit model
Cell-free 3D wet-electrospun PCL/silk fibroin/Sr2+ scaffold promotes successful total meniscus regeneration in a rabbit model
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无细胞 3D 湿电纺 PCL/丝素蛋白/Sr2 支架促进兔模型中半月板成功再生
DOI：
10.1016/j.actbio.2020.06.017
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发表时间：
2020-09-01
影响因子：
9.7
通讯作者：
Guo, Quanyi
中科院分区：
文献类型：
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作者：
Li, Yangyang;Chen, Mingxue;Guo, Quanyi
鉴于半月板自身修复能力差，组织工程技术已成为半月板损伤治疗的新方向。然而，受机械稳定性和生物相容性的影响，大多数半月板植入物不能缓解症状和预防骨关节炎的发展。本研究的目的是开发一种潜在的替代药物用于临床应用。本文以具有良好力学性能和生物相容性的丝素蛋白为材料，锶离子为生物活性因子，与ε-聚己内酯复合，制备了半月板支架（SP-Sr）。通过湿电纺方法，3D SP-Sr提供了合适的孔径（100-200 μ m）和足够的机械支撑（拉伸模量为61.6 +/- 2.9 MPa，压缩模量为0.11 +/- 0.03 MPa）。此外，加入Sr 2+后，SP-Sr接种兔脂肪组织来源的基质细胞（rADSCs）显示出最高的分泌与2.61-和2.98-倍增加胶原蛋白和聚集蛋白聚糖，分别与SF/PCL组相比。SP-Sr细胞外基质相关基因的表达也呈现上调的结果。特别是，胶原蛋白II基因的表达，其中发挥了至关重要的作用，在血管内无血管区的形成，显示了9倍的增加，与纯PCL组相比，在SP-Sr。此外，MRI结果表明，SP-Sr植入兔全半月板切除术6个月的有效防止半月板挤压和减轻关节间隙狭窄与半月板切除术组相比。并通过病理学检查证实了其对软骨保护和延缓骨关节炎发展的作用。特别是，在植入6个月后，新半月板显示出相似的结构组成和力学性能。重要性声明半月板再生面临着巨大的挑战，因为半月板由于其各向异性的结构，其细胞和血供不足而具有有限的愈合潜力。目前的组织工程解决方案由于材料易碎且生物相容性差，无法在体内维持半月板重建的生物学功能，导致长期关节退变。本研究的目的是开发一种具有临床应用潜力的骨替代品。在这里，丝素蛋白和锶被掺入。聚己内酯通过湿法静电纺丝方法制备弯月形支架（SP-Sr）。6个月的植入结果表明，SP-Sr支架能有效防止半月板脱出，保护软骨，延缓骨关节炎的发展，再生半月板具有相似的结构组成和力学性能。(C)2020 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Considering the intrinsic poor self-healing capacity of meniscus, tissue engineering has become a new direction for the treatment of meniscus lesions. However, disturbed by mechanical stability and biocompatibility, most meniscus implants fail to relieve symptoms and prevent the development of osteoarthritis. The goal of this study was to develop a potential meniscal substitute for clinical application. Here, silk fibroin with good mechanical performance and biocompatibility, and strontium ion acting as bioactive factor, were incorporated with epsilon-Polycaprolactone to fabricate a meniscus scaffold (SP-Sr). By the wet-electrospun method, the 3D SP-Sr provided suitable pore size (100-200 mu m) and enough mechanical support (61.6 +/- 2.9 MPa for tensile modulus and 0.11 +/- 0.03 MPa for compressive modulus). Moreover, after addition of Sr2+, the SP-Sr seeded by rabbit adipose tissue-derived stromal cells (rADSCs) showed the highest secretion with 2.61- and 2.98-fold increase in collagen and aggrecan, respectively, compared with SF/PCL group. And the extracellular matrix related genes expression in SP-Sr also showed upregulation results. Particularly, the expression of the collagen II gene, which played a crucial role in the formation of meniscal inner avascular region, showed a 9-fold increase in SP-Sr compared with pure PCL group. Furthermore, the MRI results of SP-Sr implanted in rabbits with total meniscectomy for 6 months demonstrated effective prevention of meniscus extrusion and relieving joint space narrowing compared with meniscectomy group. And the effects of cartilage protection and delaying osteoarthritis development were confirmed by Pathological examination. Especially, after 6-month implantation, the neo-menisci showed similar structural constituent and mechanical performance.Statement of significanceMeniscus regeneration faces great challenge due to the meniscus having limited healing potential owing to its anisotropic structure, its hypocellularity and hypovascularity. The present tissue engineering solutions have failed to maintain the biological function for meniscus reconstruction in vivo because of fragile and poor biocompatible materials, leading to long-term joint degeneration. The goal of this study was to develop a meniscal substitute potential for clinical application. Here, silk fibroin and strontium were incorporated with.-Polycaprolactone by wet-electrospinning method to fabricate a meniscus scaffold (SP-Sr). The 6-month implantation results revealed that SP-Sr scaffold was effective in preventing meniscus extrusion, cartilage protection and delaying osteoarthritis development, and the regenerated menisci showed similar structural constituent and mechanical performance. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.