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含水凝胶微球和可吸收纤维的非刚性磷酸钙骨水泥,种植脐带干细胞用于骨工程。

Non-rigid calcium phosphate cement containing hydrogel microbeads and absorbable fibres seeded with umbilical cord stem cells for bone engineering.

机构信息

Biomaterials and Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD, USA.

出版信息

J Tissue Eng Regen Med. 2013 Oct;7(10):777-87. doi: 10.1002/term.1466. Epub 2012 Mar 27.

Abstract

The need for bone repair has increased as the population ages. Non-rigid calcium phosphate scaffolds could provide compliance for micro-motions within the tissues and yet have load-supporting strength. The objectives of this study were to: (a) develop a non-rigid calcium phosphate cement (CPC) with microbeads and fibre reinforcement; and (b) investigate human umbilical cord mesenchymal stem cell (hUCMSC) proliferation, osteodifferentiation and mineralization on non-rigid CPC for the first time. Non-rigid CPC was fabricated by adding extra tetracalcium phosphate in the traditional CPC and by incorporating chitosan, absorbable fibres and hydrogel microbeads. The non-rigid CPC-microbead scaffold possessed a strain-at-failure of 10.7%, much higher than the traditional CPC's strain of 0.05% which is typical for brittle bioceramics. Flexural strength of non-rigid CPC-microbead was 4-fold that of rigid CPC-microbead scaffold, while work-of-fracture (toughness) was increased by 20-fold. The strength of non-rigid CPC-microbead-fibre scaffold matched that of cancellous bone. hUCMSCs on non-rigid CPC proliferated from 100 cells/mm(2) at 1 day to 600 cells/mm(2) at 8 days. Alkaline phosphatase, osteocalcin and collagen gene expressions of hUCMSCs were greatly increased, and the cells synthesized bone minerals. hUCMSCs on non-rigid CPC-microbead-fibre constructs had higher bone markers and more mineralization than those on rigid CPC controls. In conclusion, this study developed the first non-rigid, in situ-setting calcium phosphate-microbead-fibre scaffold with a strain-at-failure exceeding 10%. hUCMSCs showed excellent proliferation, osteodifferentiation and mineralization on non-rigid CPC scaffold. The novel non-rigid CPC-hUCMSC construct with good strength, high strain-at-failure and toughness, as well as superior stem cell proliferation, osteodifferentiation and mineralization, is promising for load-bearing bone regeneration applications.

摘要

随着人口老龄化,对骨修复的需求不断增加。非刚性磷酸钙支架可以为组织内的微动提供顺应性,同时具有承载强度。本研究的目的是:(a)开发具有微珠和纤维增强的非刚性磷酸钙水泥(CPC);(b)首次研究人脐带间充质干细胞(hUCMSC)在非刚性 CPC 上的增殖、成骨分化和矿化。非刚性 CPC 通过在传统 CPC 中添加额外的四钙磷酸盐并掺入壳聚糖、可吸收纤维和水凝胶微珠来制备。非刚性 CPC-微珠支架的失效应变为 10.7%,远高于传统 CPC 的 0.05%,这是典型的脆性生物陶瓷。非刚性 CPC-微珠支架的弯曲强度是刚性 CPC-微珠支架的 4 倍,而断裂功(韧性)增加了 20 倍。非刚性 CPC-微珠纤维支架的强度与松质骨相当。hUCMSCs 在非刚性 CPC 上的增殖从第 1 天的 100 个细胞/mm(2)增加到第 8 天的 600 个细胞/mm(2)。hUCMSCs 的碱性磷酸酶、骨钙素和胶原蛋白基因表达显著增加,并且细胞合成了骨矿物质。非刚性 CPC-微珠纤维构建体上的 hUCMSCs 的骨标志物和矿化程度高于刚性 CPC 对照组。总之,本研究开发了第一个失效应变超过 10%的非刚性、原位凝固磷酸钙-微珠纤维支架。hUCMSCs 在非刚性 CPC 支架上表现出良好的增殖、成骨分化和矿化。新型非刚性 CPC-hUCMSC 构建体具有良好的强度、失效应变量和韧性,以及优异的干细胞增殖、成骨分化和矿化,有望用于承重骨再生应用。

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