Vurat Murat Taner, Parmaksiz Mahmut, Elçin Ayşe Eser, Elçin Yaşar Murat
Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory, Ankara University Faculty of Science, and Ankara University Stem Cell Institute, Ankara, Turkey.
R&D Division, Biovalda Health Technologies, Inc., Ankara, Turkey.
J Biomed Mater Res A. 2023 Feb;111(2):261-277. doi: 10.1002/jbm.a.37457. Epub 2022 Oct 14.
Although decellularized bone matrix (DBM) has often been used in scaffold form for osteogenic applications, its use as a stem cell encapsulation matrix adaptable to surgical shaping procedures has been neglected. This study aimed to investigate the feasibility of utilizing solubilized DBM and nanohydroxyapatite (nHAp)-incorporated DBM hydrogels as encapsulation matrix for bone marrow-derived MSCs (BM-MSCs). First, DBM and DBM/nHAp hydrogels were assessed by physical, chemical, turbidimetric, thermal, and mechanical methods; then, in vitro cytocompatibility and in vitro hemocompatibility were investigated. An in vivo study was performed to evaluate the osteogenic properties of hydrogels alone or with BM-MSCs encapsulated in them. The findings revealed that hydrogels retained high levels of collagen and glycosaminoglycans after successful decellularization. They were found to be cytocompatible and hemocompatible in vitro, and were able to gel with sufficient mechanical stability at physiological temperature. BM-MSCs survived in culture for at least 2 weeks as metabolically active when encapsulated in both DBM and DBM/nHAp. Preliminary in vivo study showed that DBM-nHAp has higher osteogenicity than DBM. Moreover, BM-MSC encapsulated DMB/nHAp showed predominant bone-like tissue formation at 30 days in the rat ectopic site compared to its cell-free form.
尽管脱细胞骨基质（DBM）常以支架形式用于成骨应用，但其作为一种可适应手术塑形程序的干细胞封装基质的用途却被忽视了。本研究旨在探讨利用溶解的DBM和掺入纳米羟基磷灰石（nHAp）的DBM水凝胶作为骨髓来源间充质干细胞（BM-MSCs）封装基质的可行性。首先，通过物理、化学、比浊、热学和力学方法对DBM和DBM/nHAp水凝胶进行评估；然后，研究其体外细胞相容性和体外血液相容性。进行体内研究以评估水凝胶单独或封装有BM-MSCs时的成骨特性。研究结果表明，水凝胶在成功脱细胞后保留了高水平的胶原蛋白和糖胺聚糖。发现它们在体外具有细胞相容性和血液相容性，并且能够在生理温度下以足够的机械稳定性凝胶化。当封装在DBM和DBM/nHAp中时，BM-MSCs在培养中作为代谢活跃细胞存活至少2周。初步体内研究表明，DBM-nHAp比DBM具有更高的成骨能力。此外，与无细胞形式相比，封装有BM-MSC的DMB/nHAp在大鼠异位部位30天时显示出主要的类骨组织形成。
