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干细胞共培养和预血管化的磷酸钙水泥支架在口腔颌面骨组织工程中的应用。

Calcium phosphate cement scaffold with stem cell co-culture and prevascularization for dental and craniofacial bone tissue engineering.

机构信息

Department of Stomatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.

Department of Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510055, China.

出版信息

Dent Mater. 2019 Jul;35(7):1031-1041. doi: 10.1016/j.dental.2019.04.009. Epub 2019 May 7.

DOI:10.1016/j.dental.2019.04.009
PMID:31076156
Abstract

OBJECTIVE

Calcium phosphate cements (CPCs) mimic nanostructured bone minerals and are promising for dental, craniofacial and orthopedic applications. Vascularization plays a critical role in bone regeneration. This article represents the first review on cutting-edge research on prevascularization of CPC scaffolds to enhance bone regeneration.

METHODS

This article first presented the prevascularization of CPC scaffolds. Then the co-culture of two cell types in CPC scaffolds was discussed. Subsequently, to further enhance the prevascularization efficacy, tri-culture of three different cell types in CPC scaffolds was presented.

RESULTS

(1) Arg-Gly-Asp (RGD) incorporation in CPC bone cement scaffold greatly enhanced cell affinity and bone prevascularization; (2) By introducing endothelial cells into the culture of osteogenic cells (co-culture of two different cell types, or bi-culture) in CPC scaffold, the bone defect area underwent much better angiogenic and osteogenic processes when compared to mono-culture; (3) Tri-culture with an additional cell type of perivascular cells (such as pericytes) resulted in a substantially enhanced prevascularization of CPC scaffolds in vitro and more new bone and blood vessels in vivo, compared to bi-culture. Furthermore, biological cell crosstalk and capillary-like structure formation made critical contributions to the bi-culture system. In addition, the pericytes in the tri-culture system substantially promoted stability and maturation of the primary vascular network.

SIGNIFICANCE

The novel approach of CPC scaffolds with stem cell bi-culture and tri-culture is of great significance in the regeneration of dental, craniofacial and orthopedic defects in clinical practice.

摘要

目的

磷酸钙骨水泥 (CPC) 模拟纳米结构的骨矿物质,在牙科、颅面和骨科应用中具有广阔的前景。血管化在骨再生中起着至关重要的作用。本文代表了对 CPC 支架血管预形成以增强骨再生的前沿研究的首次综述。

方法

本文首先介绍了 CPC 支架的血管预形成。然后讨论了两种细胞类型在 CPC 支架中的共培养。随后,为了进一步提高血管预形成效果,提出了三种不同细胞类型在 CPC 支架中的三培养。

结果

(1)在 CPC 骨水泥支架中掺入精氨酸-甘氨酸-天冬氨酸 (RGD) 极大地增强了细胞亲和力和骨血管预形成;(2)通过将内皮细胞引入 CPC 支架中成骨细胞的培养(两种不同细胞类型的共培养或双培养),与单核培养相比,骨缺损区域经历了更好的血管生成和成骨过程;(3)与额外的血管周细胞(如周细胞)的三培养导致 CPC 支架在体外的血管预形成显著增强,并在体内产生更多的新骨和血管,与双培养相比。此外,生物细胞串扰和毛细血管样结构的形成对双培养系统做出了重要贡献。此外,三培养系统中的周细胞显著促进了初级血管网络的稳定性和成熟。

意义

CPC 支架与干细胞双培养和三培养的新方法在临床实践中对牙科、颅面和骨科缺陷的再生具有重要意义。

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