使用细胞接种胶原膜的基质诱导自体软骨细胞植入术(MACI)可改善马模型中的软骨愈合。

Matrix-Induced Autologous Chondrocyte Implantation (MACI) Using a Cell-Seeded Collagen Membrane Improves Cartilage Healing in the Equine Model.

作者信息

Nixon Alan J, Sparks Holly D, Begum Laila, McDonough Sean, Scimeca Michael S, Moran Nance, Matthews Gloria L

机构信息

Comparative Orthopaedics Laboratory, Department of Clinical Sciences (A.J.N., H.D.S., L.B., and M.S.S.), and Department of Biomedical Sciences, College of Veterinary Medicine (S.M.), Cornell University, Ithaca, New York.

Histogenics Corporation, Waltham, Massachusetts.

出版信息

J Bone Joint Surg Am. 2017 Dec 6;99(23):1987-1998. doi: 10.2106/JBJS.16.00603.

Abstract

BACKGROUND

Autologous chondrocyte implantation (ACI) using a collagen scaffold (matrix-induced ACI; MACI) is a next-generation approach to traditional ACI that provides the benefit of autologous cells and guided tissue regeneration using a biocompatible collagen scaffold. The MACI implant also has inherent advantages including surgical implantation via arthroscopy or miniarthrotomy, the elimination of periosteal harvest, and the use of tissue adhesive in lieu of sutures. This study evaluated the efficacy of the MACI implant in an equine full-thickness cartilage defect model at 1 year.

METHODS

Autologous chondrocytes were seeded onto a collagen type-I/III membrane and implanted into one of two 15-mm defects in the femoral trochlear ridge of 24 horses. Control defects either were implanted with cell-free collagen type-I/III membrane (12 horses) or were left ungrafted as empty defects (12 horses). An additional 3 horses had both 15-mm defects remain empty as nonimplanted joints. The repair was scored by second-look arthroscopy (12 weeks), and necropsy examination (53 weeks). Healing was assessed by arthroscopic scoring, gross assessment, histology and immunohistology, cartilage matrix component assay, and gene expression determination. Toxicity was examined by prostaglandin E2 formation in joint fluid, and lymph node morphology combined with histologic screening of organs.

RESULTS

MACI-implanted defects had improved gross healing and composite histologic scores, as well as increases in chondrocyte predominance, toluidine blue-stained matrix, and collagen type-II content compared with scaffold-only implanted or empty defects. There was minimal evidence of reaction to the implant in the synovial membrane (minor perivascular cuffing), subchondral bone, or cartilage. There were no adverse clinical effects, signs of organ toxicity, or evidence of chondrocytes or collagen type-I/III membrane in draining lymph nodes.

CONCLUSIONS

The MACI implant appeared to improve cartilage healing in a critical-sized defect in the equine model compared with collagen matrix alone.

CLINICAL RELEVANCE

These results indicate that the MACI implant is quick to insert, provides chondrocyte security in the defect, and improves cartilage healing compared with ACI.

摘要

背景

使用胶原蛋白支架的自体软骨细胞植入术(ACI)(基质诱导ACI;MACI)是传统ACI的一种新一代方法,它利用生物相容性胶原蛋白支架提供自体细胞和引导组织再生的益处。MACI植入物还具有固有优势,包括通过关节镜或小切口关节切开术进行手术植入、无需采集骨膜以及使用组织粘合剂代替缝线。本研究评估了MACI植入物在马全层软骨缺损模型中1年时的疗效。

方法

将自体软骨细胞接种到I/III型胶原膜上,并植入24匹马股骨滑车嵴上两个15毫米缺损中的一个。对照缺损要么植入无细胞的I/III型胶原膜(12匹马),要么留作未移植的空缺损(12匹马)。另外3匹马的两个15毫米缺损均作为未植入关节保持为空。通过二次关节镜检查(12周)和尸检(53周)对修复情况进行评分。通过关节镜评分、大体评估、组织学和免疫组织学、软骨基质成分分析以及基因表达测定来评估愈合情况。通过关节液中前列腺素E2的形成以及淋巴结形态结合器官组织学筛查来检查毒性。

结果

与仅植入支架或空缺损相比,MACI植入的缺损在大体愈合和综合组织学评分方面有所改善,软骨细胞优势、甲苯胺蓝染色基质和II型胶原含量也有所增加。在滑膜(轻微血管周围套袖状)、软骨下骨或软骨中对植入物的反应证据极少。没有不良临床影响、器官毒性迹象,也没有在引流淋巴结中发现软骨细胞或I/III型胶原膜的证据。

结论

与单独的胶原基质相比,MACI植入物似乎能改善马模型中临界尺寸缺损的软骨愈合。

临床意义

这些结果表明,MACI植入物插入迅速,能在缺损中提供软骨细胞稳定性,与ACI相比可改善软骨愈合。

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