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磷酸钙陶瓷和基于多糖的水凝胶支架与间充质干细胞联合应用对大鼠骨修复的支持作用不同。

Calcium-phosphate ceramics and polysaccharide-based hydrogel scaffolds combined with mesenchymal stem cell differently support bone repair in rats.

作者信息

Frasca Sophie, Norol Françoise, Le Visage Catherine, Collombet Jean-Marc, Letourneur Didier, Holy Xavier, Sari Ali Elhadi

机构信息

Département Soutien Médico-Chirurgical des Forces, Institut de Recherche Biomédicale des Armées (IRBA), BP 73, 91223, Brétigny-sur-Orge cedex, France.

AP-HP, Service de Biothérapie, Hôpital de la Pitié Salpêtrière, Paris, France.

出版信息

J Mater Sci Mater Med. 2017 Feb;28(2):35. doi: 10.1007/s10856-016-5839-6. Epub 2017 Jan 21.

Abstract

Research in bone tissue engineering is focused on the development of alternatives to autologous bone grafts for bone reconstruction. Although multiple stem cell-based products and biomaterials are currently being investigated, comparative studies are rarely achieved to evaluate the most appropriate approach in this context. Here, we aimed to compare different clinically relevant bone tissue engineering methods and evaluated the kinetic repair and the bone healing efficiency supported by mesenchymal stem cells and two different biomaterials, a new hydrogel scaffold and a commercial hydroxyapatite/tricalcium phosphate ceramic, alone or in combination.Syngeneic mesenchymal stem cells (5 × 10) and macroporous biphasic calcium phosphate ceramic granules (Calciresorb C35, Ceraver) or porous pullulan/dextran-based hydrogel scaffold were implanted alone or combined in a drilled-hole bone defect in rats. Using quantitative microtomography measurements and qualitative histological examinations, their osteogenic properties were evaluated 7, 30, and 90 days after implantation. Three months after surgery, only minimal repair was evidenced in control rats while newly mineralized bone was massively observed in animals treated with either hydrogels (bone volume/tissue volume = 20%) or ceramics (bone volume/tissue volume = 26%). Repair mechanism and resorption kinetics were strikingly different: rapidly-resorbed hydrogels induced a dense bone mineralization from the edges of the defect while ceramics triggered newly woven bone formation in close contact with the ceramic surface that remained unresorbed. Delivery of mesenchymal stem cells in combination with these biomaterials enhanced both bone healing (>20%) and neovascularization after 1 month, mainly in hydrogel.Osteogenic and angiogenic properties combined with rapid resorption make hydrogels a promising alternative to ceramics for bone repair by cell therapy.

摘要

骨组织工程研究的重点是开发用于骨重建的自体骨移植替代物。尽管目前正在研究多种基于干细胞的产品和生物材料,但很少有比较研究来评估在这种情况下最合适的方法。在这里,我们旨在比较不同的临床相关骨组织工程方法,并评估间充质干细胞和两种不同生物材料(一种新型水凝胶支架和一种商用羟基磷灰石/磷酸三钙陶瓷)单独或联合使用时的动力学修复和骨愈合效率。将同基因间充质干细胞(5×10)与大孔双相磷酸钙陶瓷颗粒(Calciresorb C35,Ceraver)或多孔支链淀粉/葡聚糖基水凝胶支架单独或联合植入大鼠的钻孔骨缺损中。使用定量显微断层扫描测量和定性组织学检查,在植入后7、30和90天评估它们的成骨特性。手术后三个月,对照大鼠仅表现出最小程度的修复,而在用凝胶(骨体积/组织体积=20%)或陶瓷(骨体积/组织体积=26%)治疗的动物中大量观察到新矿化的骨。修复机制和吸收动力学明显不同:快速吸收的水凝胶从缺损边缘诱导致密的骨矿化,而陶瓷则触发与未吸收的陶瓷表面紧密接触的新编织骨形成。间充质干细胞与这些生物材料联合递送在1个月后增强了骨愈合(>20%)和新血管形成,主要是在水凝胶中。成骨和血管生成特性与快速吸收相结合,使水凝胶成为细胞治疗骨修复中陶瓷的有前途的替代品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76f2/5253158/1a6d695a5cd1/10856_2016_5839_Fig1_HTML.jpg

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