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将磷酸钙水泥掺入脱细胞细胞外基质中可增强其骨再生性能。

Incorporation of calcium phosphate cement into decellularized extracellular matrix enhances its bone regenerative properties.

机构信息

University of Science and Culture, Faculty of Science & Advanced Technologies in Biology, Tehran, Islamic Republic of Iran; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Islamic Republic of Iran.

Department of Tissue Engineering, Faculty of Basic Sciences and Advanced Technologies in Medicine, Royan Institute, ACECR, Tehran, Islamic Republic of Iran.

出版信息

Colloids Surf B Biointerfaces. 2024 Dec;244:114175. doi: 10.1016/j.colsurfb.2024.114175. Epub 2024 Aug 25.

DOI:10.1016/j.colsurfb.2024.114175
PMID:39216442
Abstract

Decellularized extracellular matrix (dECM) hydrogels are engineered constructs that are widely-used in the field of regenerative medicine. However, the development of ECM-based hydrogels for bone tissue engineering requires enhancement in its osteogenic properties. For this purpose, we initially employed bone-derived dECM hydrogel (dECM-Hy) in combination with calcium phosphate cement (CPC) paste to improve the biological and structural properties of the dECM hydrogel. A decellularization protocol for bovine bone was developed to prepare dECM-Hy, and the mechanically-tuned dECM/CPC-Hy was built based on both rheological and mechanical characteristics. The dECM/CPC-Hy displayed a double swelling ratio and compressive strength. An interconnected structure with distinct hydroxyapatite crystals was evident in dECM/CPC-Hy. The expression levels of Alp, Runx2 and Ocn genes were upregulated in dECM/CPC-Hy compared to the dECM-Hy. A 14-day follow-up of the rats receiving subcutaneous implanted dECM-Hy, dECM/CPC-Hy and mesenchymal stem cells (MSCs)-embedded (dECM/CPC/MSCs-Hy) showed no toxicity, inflammatory factor expression or pathological changes. Radiography and computed tomography (CT) of the calvarial defects revealed new bone formation and elevated number of osteoblasts-osteocytes and osteons in dECM/CPC-Hy and dECM/CPC/MSCs-Hy compared to the control groups. These findings indicate that the dECM/CPC-Hy has substantial potential for bone tissue engineering.

摘要

去细胞细胞外基质(dECM)水凝胶是一种广泛应用于再生医学领域的工程构建体。然而,为了开发用于骨组织工程的基于 ECM 的水凝胶,需要增强其成骨特性。为此,我们最初将骨源性去细胞细胞外基质水凝胶(dECM-Hy)与磷酸钙水泥(CPC)糊剂结合使用,以改善 dECM 水凝胶的生物学和结构特性。开发了一种牛骨去细胞化方案来制备 dECM-Hy,并根据流变学和力学特性构建了机械调谐的 dECM/CPC-Hy。dECM/CPC-Hy 表现出双重溶胀比和压缩强度。在 dECM/CPC-Hy 中可以明显看到具有特征性羟基磷灰石晶体的互连成网络结构。与 dECM-Hy 相比,dECM/CPC-Hy 中的 Alp、Runx2 和 Ocn 基因的表达水平上调。接受皮下植入 dECM-Hy、dECM/CPC-Hy 和间充质干细胞(MSCs)嵌入(dECM/CPC/MSCs-Hy)的大鼠的 14 天随访显示没有毒性、炎症因子表达或病理变化。颅骨缺损的放射学和计算机断层扫描(CT)显示,与对照组相比,dECM/CPC-Hy 和 dECM/CPC/MSCs-Hy 中形成了新骨,成骨细胞-骨细胞和成骨细胞的数量增加。这些发现表明,dECM/CPC-Hy 具有很大的骨组织工程潜力。

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