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三种不同类型支架预先接种人骨髓单核细胞在裸鼠股骨大尺寸缺损模型中对骨愈合的比较。

Comparison of three different types of scaffolds preseeded with human bone marrow mononuclear cells on the bone healing in a femoral critical size defect model of the athymic rat.

机构信息

Department of Trauma, Hand, and Reconstructive Surgery, Hospital of the Goethe University, Frankfurt, Germany.

German Institute for Cell and Tissue Replacement gGmbH (DIZG), Berlin, Germany.

出版信息

J Tissue Eng Regen Med. 2018 Mar;12(3):653-666. doi: 10.1002/term.2484. Epub 2017 Oct 2.

Abstract

Large bone defects often pose major difficulties in orthopaedic surgery. The application of long-term cultured stem cells combined with a scaffold lead to a significant improvement of bone healing in recent experiments but is strongly restricted by European Union law. Bone marrow mononuclear cells (BMC), however, can be isolated and transplanted within a few hours and have been proven effective in experimental models of bone healing. The effectivity of the BMC-supported therapy might be influenced by the type of scaffold. Hence, we compared three different scaffolds serving as a carrier for BMC in a rat femoral critical size defect with regard to the osteogenic activity in the defect zone. Human demineralized bone matrix (DBM), bovine cancellous bone hydroxyapatite ceramic (BS), or β-tricalcium phosphate (β-TCP) were seeded with human BMC and hereafter implanted into critically sized bone defects of male athymic nude rats. Autologous bone served as a control. Gene activity was measured after 1 week, and bone formation was analysed histologically and radiologically after 8 weeks. Generally, regenerative gene expression (BMP2, RUNX2, VEGF, SDF-1, and RANKL) as well as bony bridging and callus formation was observed to be most pronounced in defects filled with autologous bone, followed in descending order by DBM, β-TCP, and BS. Although DBM was superior in most aspects of bone regeneration analysed in comparison to β-TCP and BS, the level of autologous bone could not be attained.

摘要

大骨缺损在骨科手术中常常带来重大困难。长期培养的干细胞与支架的联合应用在最近的实验中显著改善了骨愈合,但受到欧盟法律的严格限制。然而,骨髓单核细胞 (BMC) 可在数小时内分离并移植,并且已在骨愈合的实验模型中被证明有效。BMC 支持的治疗效果可能受到支架类型的影响。因此,我们比较了三种不同的支架,它们在大鼠股骨临界尺寸缺损中作为 BMC 的载体,以评估其在缺损区域的成骨活性。用人 BMC 接种人脱矿骨基质 (DBM)、牛松质骨羟磷灰石陶瓷 (BS) 或β-磷酸三钙 (β-TCP),并将其植入雄性无胸腺裸鼠的临界尺寸骨缺损中。自体骨作为对照。在第 1 周测量基因活性,在第 8 周进行组织学和放射学分析以评估骨形成。总的来说,在填充自体骨的缺损中观察到再生基因表达(BMP2、RUNX2、VEGF、SDF-1 和 RANKL)以及骨桥接和骨痂形成最为明显,其次是 DBM、β-TCP 和 BS。尽管与β-TCP 和 BS 相比,DBM 在大多数分析的骨再生方面都具有优势,但仍无法达到自体骨的水平。

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