Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA.
J Tissue Eng Regen Med. 2012 Mar;6(3):214-24. doi: 10.1002/term.419. Epub 2011 Mar 27.
Stem cell-based tissue engineering offers immense promise for bone regeneration. The objective of this study was to develop a self-setting, mannitol-containing calcium phosphate cement (CPC) encapsulating human umbilical cord mesenchymal stem cells (hUCMSCs) for bone tissue engineering. hUCMSCs could be an inexhaustible and low-cost alternative to the gold-standard bone marrow MSCs, which require an invasive procedure to harvest. hUCMSCs were encapsulated in alginate beads and mixed into the CPC paste. Water-soluble mannitol porogen was incorporated into CPC to create macropores. The porosity was increased from 49% for the hUCMSC-encapsulating CPC to 64% after adding mannitol and absorbable-fibres (p < 0.05). Flexural strength of the construct was increased from 0.3 MPa to 2.0 MPa via fibres. Live cell percentage was > 80% for all constructs. The ALP and OC gene expressions were low at 1 day and greatly increased at 14 days. The constructs that contained mannitol had significantly higher ALP and OC expressions than that without mannitol. ALP activity of hUCMSCs inside CPC with mannitol and fibre was significantly higher than that without mannitol. At 14 days, mineralization by the encapsulated hUCMSCs was eight-fold higher than that at 1 day. In conclusion, a novel mannitol-containing porous CPC-hUCMSC construct was developed for bone tissue engineering. Its advantages include cell delivery inside a load-bearing CPC that has injectable and in situ setting capabilities. hUCMSCs inside CPC had good viability and successfully osteodifferentiated. The self-setting and strong hUCMSC-encapsulating CPC scaffold is promising for bone tissue engineering in a wide range of orthopaedic and craniofacial applications.
基于干细胞的组织工程为骨再生提供了巨大的前景。本研究旨在开发一种自凝、含甘露醇的磷酸钙骨水泥（CPC），用于骨组织工程，其中包封人脐带间充质干细胞（hUCMSCs）。hUCMSCs 可以替代金标准骨髓间充质干细胞，作为一种取之不尽、成本低廉的替代物，因为后者需要进行侵入性的采集程序。hUCMSCs 被包封在藻酸盐珠中，并与 CPC 糊混合。将水溶性甘露醇造孔剂掺入 CPC 中以制造大孔。加入甘露醇和可吸收纤维后，多孔性从包封 hUCMSC 的 CPC 的 49%增加到 64%（p<0.05）。通过纤维，构建体的弯曲强度从 0.3 MPa 增加到 2.0 MPa。所有构建体的活细胞百分比均>80%。ALP 和 OC 基因表达在第 1 天较低，在第 14 天显著增加。含甘露醇的构建体的 ALP 和 OC 表达明显高于不含甘露醇的构建体。含甘露醇和纤维的 CPC 内 hUCMSCs 的 ALP 活性明显高于不含甘露醇的构建体。在第 14 天，包封的 hUCMSCs 的矿化作用比第 1 天增加了 8 倍。总之，开发了一种新型的含甘露醇多孔 CPC-hUCMSC 构建体用于骨组织工程。其优点包括在具有可注射和原位设定能力的承重 CPC 内输送细胞。CPC 内的 hUCMSCs 具有良好的生存能力，并成功地成骨分化。自凝且强韧的 hUCMSC 包封 CPC 支架有望在广泛的骨科和颅面应用中用于骨组织工程。
