载有生物功能制剂和干细胞的磷酸钙骨水泥在口腔颌面部骨缺损修复中的应用
Calcium phosphate cement with biofunctional agents and stem cell seeding for dental and craniofacial bone repair.
机构信息
Biomaterials & Tissue Engineering Division, Department of Endodontics, Prosthodontics and Operative Dentistry, University of Maryland Dental School, Baltimore, MD 21201, USA.
出版信息
Dent Mater. 2012 Oct;28(10):1059-70. doi: 10.1016/j.dental.2012.06.009. Epub 2012 Jul 17.
OBJECTIVE
Calcium phosphate cement (CPC) can be injected to harden in situ and is promising for dental and craniofacial applications. However, human stem cell attachment to CPC is relatively poor. The objectives of this study were to incorporate biofunctional agents into CPC, and to investigate human umbilical cord mesenchymal stem cell (hUCMSC) seeding on biofunctionalized CPC for osteogenic differentiation for the first time.
METHODS
Five types of biofunctional agents were used: RGD (Arg-Gly-Asp) peptides, human fibronectin (Fn), fibronectin-like engineered polymer protein (FEPP), extracellular matrix Geltrex, and human platelet concentrate. Five biofunctionalized CPC scaffolds were fabricated: CPC-RGD, CPC-Fn, CPC-FEPP, CPC-Geltrex, and CPC-Platelets. The hUCMSC attachment, proliferation, osteogenic differentiation and mineral synthesis were measured.
RESULTS
The hUCMSCs on biofunctionalized CPCs had much better cell attachment, proliferation, actin fiber expression, osteogenic differentiation and mineral synthesis, compared to the traditional CPC control. Cell proliferation was increased by an order of magnitude via incorporation of biofunctional agents in CPC (p<0.05). Mineral synthesis on biofunctionalized CPCs was 3-5 folds of those of control (p<0.05). hUCMSCs differentiated with high alkaline phosphatase, Runx2, osteocalcin, and collagen I gene expressions. Mechanical properties of biofunctionalized CPC matched the reported strength and elastic modulus of cancellous bone.
SIGNIFICANCE
A new class of biofunctionalized CPCs was developed, including CPC-RGD, CPC-Fn, CPC-FEPP, CPC-Geltrex, and CPC-Platelets. hUCMSCs on biofunctionalized CPCs had cell density, cell proliferation, actin fiber density, and bone mineralization that were dramatically better than those on traditional CPC. Novel biofunctionalized CPC scaffolds with greatly enhanced human stem cell proliferation and differentiation are promising to facilitate bone regeneration in a wide range of dental, craniofacial and orthopedic applications.
目的
磷酸钙水泥（CPC）可注射硬化原位，有望用于牙科和颅面应用。然而，CPC 对人干细胞的附着相对较差。本研究的目的是将生物功能剂掺入 CPC 中，并首次研究生物功能化 CPC 上的人脐带间充质干细胞（hUCMSC）接种的成骨分化。
方法
使用了 5 种生物功能剂：RGD（精氨酸-甘氨酸-天冬氨酸）肽、人纤维连接蛋白（Fn）、纤维连接蛋白样工程聚合物蛋白（FEPP）、细胞外基质 Geltrex 和人血小板浓缩物。制备了 5 种生物功能化 CPC 支架：CPC-RGD、CPC-Fn、CPC-FEPP、CPC-Geltrex 和 CPC-Platelets。测量了 hUCMSC 的附着、增殖、成骨分化和矿化合成。
结果
与传统 CPC 对照相比，hUCMSC 在生物功能化 CPC 上具有更好的细胞附着、增殖、肌动蛋白纤维表达、成骨分化和矿化合成。通过在 CPC 中掺入生物功能剂，细胞增殖增加了一个数量级（p<0.05）。生物功能化 CPC 上的矿化合成是对照的 3-5 倍（p<0.05）。hUCMSC 分化后具有高碱性磷酸酶、Runx2、骨钙素和胶原 I 基因表达。生物功能化 CPC 的力学性能与报道的松质骨强度和弹性模量相匹配。
意义
开发了一类新的生物功能化 CPC，包括 CPC-RGD、CPC-Fn、CPC-FEPP、CPC-Geltrex 和 CPC-Platelets。生物功能化 CPC 上的 hUCMSC 具有显著优于传统 CPC 的细胞密度、细胞增殖、肌动蛋白纤维密度和骨矿化。具有显著增强的人干细胞增殖和分化能力的新型生物功能化 CPC 支架有望促进广泛的牙科、颅面和骨科应用中的骨再生。
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