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具有干细胞工程的锶羟基磷灰石支架促进骨质疏松绵羊模型中的骨整合和骨生成。

Strontium Hydroxyapatite scaffolds engineered with stem cells aid osteointegration and osteogenesis in osteoporotic sheep model.

机构信息

Transmission Electron Microscopy Lab, Sree Chitra Tirunal Institute for Medical Sciences & Technology, India.

Division of In vivo Models & Testing, Sree Chitra Tirunal Institute for Medical Sciences & Technology, India.

出版信息

Colloids Surf B Biointerfaces. 2018 Mar 1;163:346-354. doi: 10.1016/j.colsurfb.2017.12.048. Epub 2017 Dec 28.

DOI:10.1016/j.colsurfb.2017.12.048
PMID:29331906
Abstract

Osteoporotic fracture healing is an orthopaedic challenge due to excessive bone resorption and impaired osteogenesis. Majority of current treatment strategies focus on regulating bone resorption and the potential application of Mesenchymal Stem Cells (MSCs) in promoting osteogenesis has not been explored much. Furthermore, the present study has put forth a novel approach, wherein the synergistic action of Strontium (Sr) and MSCs in a single implant may facilitate osteoporotic bone healing. Strontium Hydroxyapatite (SrHA) synthesized by wet precipitation was fabricated into tissue engineered Strontium incorporated Hydroxyapatite (cSrHA) using sheep adipose tissue derived MSCs (ADMSCs). Porosity, radiopacity and cytocompatibility of SrHA scaffolds were found appropriate for orthopaedic applications. cSrHA scaffolds exhibited an in vitro Alkaline Phosphatase activity of 20 μmol pnp/30 min comparable to that of Hydroxyapatite (HA) - control scaffold, proving its osteogenic efficacy. Implantation studies in sheep osteoporotic model depicted enhanced osteogenic ability with mature lamellar bone formation in cSrHA implanted group, compared to bare HA, SrHA and tissue engineered HA implanted groups. Histomorphometry data substantiated improved osteogenesis on par with material resorption, as cSrHA implanted group exhibited highest regeneration ratio of 0.38 ± 0.05. Density histograms from micro CT further signified the enhanced osteointegrative ability of cSrHA implants. Results of the study depicted the therapeutic potential of cSrHA in osteoporotic bone healing and proposes the use of allogenic ADMSCs for fabricating "Off the Shelf Tissue Engineered Products".

摘要

骨质疏松性骨折愈合是骨科领域的一大挑战,其主要原因是骨吸收过度和成骨作用受损。目前大多数治疗策略主要集中在调节骨吸收上,间充质干细胞(MSCs)在促进成骨方面的潜在应用尚未得到充分探索。此外,本研究提出了一种新方法,即在单个植入物中联合使用锶(Sr)和 MSCs 可能有助于骨质疏松性骨愈合。通过湿沉淀法合成的羟基磷灰石(SrHA)被制成组织工程化的含锶羟基磷灰石(cSrHA),使用绵羊脂肪组织来源的间充质干细胞(ADMSCs)。SrHA 支架的多孔性、放射密度和细胞相容性被认为适合骨科应用。cSrHA 支架的碱性磷酸酶活性为 20μmol pnp/30min,与羟基磷灰石(HA)对照支架相当,证明了其成骨功效。在绵羊骨质疏松模型中的植入研究表明,与 bareHA、SrHA 和组织工程化 HA 植入组相比,cSrHA 植入组具有更强的成骨能力,可形成成熟的板层骨。组织形态计量学数据证实了成骨作用与材料吸收相当,因为 cSrHA 植入组表现出最高的再生率为 0.38±0.05。微 CT 的密度直方图进一步表明了 cSrHA 植入物增强的骨整合能力。该研究结果表明 cSrHA 在骨质疏松性骨愈合中的治疗潜力,并提出使用同种异体 ADMSCs 来制造“现成的组织工程产品”。

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