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用于骨髓干细胞和骨形态发生蛋白-2修复软骨的可注射支架

Injectable Scaffold for Bone Marrow Stem Cells and Bone Morphogenetic Protein-2 to Repair Cartilage.

作者信息

Vayas Raquel, Reyes Ricardo, Arnau María Rosa, Évora Carmen, Delgado Araceli

机构信息

Department of Chemical Engineering and Pharmaceutical Technology, Universidad de La Laguna, La Laguna, Spain.

Servicio de Cirugía Ortopédica y Traumatología, Complejo Hospitalario Universitario Ntra, Sra. de Candelaria, Santa Cruz de Tenerife, Spain.

出版信息

Cartilage. 2021 Jul;12(3):293-306. doi: 10.1177/1947603519841682. Epub 2019 Apr 11.

Abstract

OBJECTIVE

The limits of the microfracture (MFX) treatment in terms of lesion size and long-term tissue functionality makes it necessary to investigate different alternatives to repair focal cartilage lesions. The present study aims at evaluating the efficacy of a minimally invasive approach against the conventional MFX to repair a chondral defect in rabbits. An injectable scaffold of BMP-2 pre-encapsulated in PLGA microspheres dispersed in a Pluronic F-127 solution is proposed as support of cells and controlled delivery system for the growth factor.

DESIGN

MFX was compared versus the injectable system seeded with mesenchymal stem cells (MSCs), both without BMP-2 and under controlled release of BMP-2 at 2 different doses (3 and 12 µg/scaffold). The different treatments were evaluated on a 4-mm diameter chondral defect model using 9 experimental groups of 4 rabbits (8 knees) each, throughout 24 weeks.

RESULTS

Histologically, all the treated groups, except MFX treated, responded significantly better than the control group (nontreated defect). Although no significant differences were found between the treated groups, only BMP(12), MSC-BMP(12), and MFX-BMP(3) groups showed nonsignificant differences when compared with the normal cartilage.

CONCLUSIONS

The hydrogel system proposed to control the release rate of the BMP-2 was safe, easily injectable, and also provided good support for cells. Treatments with MSCs or BMP-2 repaired efficiently the chondral lesion created in rabbits, being less invasive than MFX treatment.

摘要

目的

微骨折(MFX)治疗在损伤大小和长期组织功能方面存在局限性,因此有必要研究修复局灶性软骨损伤的不同替代方法。本研究旨在评估一种微创方法相对于传统MFX修复兔软骨缺损的疗效。提出了一种将BMP-2预包封在分散于泊洛沙姆F-127溶液中的PLGA微球中的可注射支架,作为细胞的支持物和生长因子的控释系统。

设计

将MFX与接种间充质干细胞(MSCs)的可注射系统进行比较,两者均不含BMP-2,并在2种不同剂量(3和12μg/支架)下对BMP-2进行控释。在直径4mm的软骨缺损模型上,使用9个实验组,每组4只兔子(8个膝关节),在24周内对不同治疗方法进行评估。

结果

组织学上,除MFX治疗组外,所有治疗组的反应均明显优于对照组(未治疗的缺损)。虽然治疗组之间未发现显著差异,但与正常软骨相比,只有BMP(12)、MSC-BMP(12)和MFX-BMP(3)组显示出不显著的差异。

结论

所提出的用于控制BMP-2释放速率的水凝胶系统安全、易于注射,并且还为细胞提供了良好的支持。用MSCs或BMP-2治疗可有效修复兔体内形成的软骨损伤,其侵入性小于MFX治疗。

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