Tissue Reactions to Engineered Cartilage Based on Poly-L-Lactic Acid Scaffolds

Tissue Reactions to Engineered Cartilage Based on Poly-L-Lactic Acid Scaffolds
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DOI:
10.1089/ten.tea.2008.0154
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发表时间:
2009-07-01
影响因子:
4.1
通讯作者:
Hoshi, Kazuto
Hoshi, Kazuto
中科院分区:
医学3区
文献类型:
--
作者:
Fujihara, Yuko;Asawa, Yukiyo;Hoshi, Kazuto

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在工程化软骨中对聚-L-乳酸(PLLA)的组织反应可能会影响再生组织的大小或成熟度。为了了解这些反应中的生物学事件,我们将含有或不含有人软骨细胞或去端胶原的PLLA支架的工程化构建物皮下移植到裸鼠中,并评估了新血管形成和巨噬细胞活化,即使在裸鼠中也可以评估。虽然没有显示软骨再生,但单独的PLLA在2周和8周时显示出巨噬细胞和血管的密集定位,以及高水平的白细胞介素-1 β和组织血红蛋白。另外,具有PLLA和具有或不具有去端胶原的软骨细胞(PLLA/细胞/凝胶或PLLA/细胞)的构建体在8周时形成成熟软骨,这在PLLA/细胞/凝胶中更突出。尽管在2周时PLLA/细胞/凝胶和PLLA/细胞中的巨噬细胞和血管的积累与PLLA中的相当,但PLLA/细胞/凝胶中的巨噬细胞和血管的积累在8周时显著减少,血管和巨噬细胞被排除在非软骨区域中。巨噬细胞移动抑制因子可能参与了这些被抑制的组织反应,因为它在工程化软骨的软骨细胞中表达。强烈的组织反应不可避免地发生在单独的生物聚合物中,但有可能是工程化软骨的成熟抑制了这些反应,这可能有助于避免工程化组织的畸形或畸形。
Tissue reactions against poly-L-lactic acid (PLLA) in engineered cartilage may influence the size or maturity of regenerative tissue. To understand the biological events in these reactions, we subcutaneously transplanted engineered constructs of PLLA scaffolds with or without human chondrocytes or atelocollagen in nude mice and evaluated neovascularization and macrophage activation, which can be assessed even in nude mice. Although not showing cartilage regeneration, PLLA alone demonstrated dense localization of macrophages and blood vessels, as well as a high level of interleukin-1 beta and tissue hemoglobin at 2 and 8 weeks. Otherwise, constructs with PLLA and chondrocytes with or without atelocollagen (PLLA/cell/gel or PLLA/cell) formed mature cartilage by 8 weeks, which was more prominent in PLLA/cell/gel. Although accumulation of macrophages and blood vessels in PLLA/cell/gel and PLLA/cell was comparable with that in PLLA at 2 weeks, that in PLLA/cell/gel markedly decreased by 8 weeks, with blood vessels and macrophages excluded into non-cartilage areas. Macrophage migration inhibitory factor could be involved in these suppressed tissue reactions, because it was expressed in chondrocytes of engineered cartilage. Intense tissue reactions inevitably occurred in biopolymers alone, but it is possible that maturation of engineered cartilage suppressed these reactions, which may contribute to circumventing deformity or malformation of engineered tissues.