In vivo structural and cellular remodeling of engineered bone-ligament-bone constructs used for anterior cruciate ligament reconstruction in sheep.
In vivo structural and cellular remodeling of engineered bone-ligament-bone constructs used for anterior cruciate ligament reconstruction in sheep.
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DOI：
10.1080/03008207.2016.1187141
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发表时间：
2016-11
影响因子：
2.9
通讯作者：
Larkin LM
中科院分区：
文献类型：
--
作者：
Florida SE;VanDusen KW;Mahalingam VD;Schlientz AJ;Wojtys EM;Wellik DM;Larkin LM
前交叉韧带（ACL）断裂是最常见和最昂贵的运动相关损伤之一。目前用于ACL重建的肌腱移植物受到次优生物力学性能的限制。我们已经解决了这些问题的工程多相骨-韧带-骨（BLB）的结构和机械性能类似于天然ACL的建设。本研究的目的是检查急性重建过程中发生的BLB移植物推进到成人韧带表型在体内。因此，我们将由雄性细胞制造的BLB构建体植入雌性宿主绵羊中，并允许3、7、14或28天（每个时间点n=4）恢复。为了解决移植物衍生的细胞是否甚至是必要的，将BLB构建体的子集（n=3）去细胞化，植入并允许28天的恢复。在每个恢复时间点，进行以下组织学分析：苦味酸天狼星红染色以评估胶原排列，免疫组织化学以评估移植物发育和宿主免疫应答。使用对每个接种的BLB进行的PCR分析来检测是否存在残留在构建体中的移植物衍生的雄性细胞和/或迁移到周围宿主组织中。PCR和组织学样品的分析显示，在3天时宿主来源的巨噬细胞和中性粒细胞快速迁移到移植物中，随后在28天内增加胶原密度和排列、血管化、神经支配和移植物与宿主细胞的接近完全的再增殖。这项研究提供了一个更好的理解的过程中，韧带再生在我们的BLB结构，因为他们对成人韧带表型重塑。
Anterior cruciate ligament (ACL) ruptures rank among the most prevalent and costly sports-related injuries. Current tendon grafts used for ACL reconstruction are limited by suboptimal biomechanical properties. We have addressed these issues by engineering multiphasic bone-ligament-bone (BLB) constructs which develop structural and mechanical properties similar to native ACL. The purpose of this study was to examine the acute remodeling process that occurs as the BLB grafts advance toward the adult ligament phenotype in vivo. Thus, we implanted BLB constructs fabricated from male cells into female host sheep and allowed 3,7,14 or 28 days (n=4 at each time point) for recovery. To address whether or not graft-derived cells were even necessary, a subset of BLB constructs (n=3) were acellularized, implanted and allowed 28 days for recovery. At each recovery time point, the following histological analyses were performed: Picrosirius red staining to assess collagen alignment and immunohistochemistry to assess both graft development and host immune response. PCR analysis, performed on every explanted BLB, was used to detect the presence of graft-derived male cells remaining in the constructs and/or migration into surrounding host tissue. The analysis of the PCR and histology samples revealed a rapid migration of host-derived macrophages and neutrophils into the graft at 3 days, followed by increased collagen density and alignment, vascularization, innervation and near complete repopulation of the graft with host cells within 28 days. This study provides a greater understanding of the processes of ligament regeneration in our BLB constructs as they remodel towards the adult ligament phenotype.
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影响因子：
3.1
作者：
Kim HS;Seon JK;Jo AR
通讯作者：
Jo AR
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Syed-Picard, Fatima N.;Larkin, Lisa M.;Arruda, Ellen M.
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