Ying Lin1, Shuheng Huang2, Rui Zou3, Xianling Gao4, Jianping Ruan5, Michael D Weir6, Mark A Reynolds6, Wei Qin4, Xiaofeng Chang7, Haijun Fu8, Hockin H K Xu9. 1. Department of Stomatology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China. 2. Department of Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510055, China. 3. Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou 510182, China. 4. Department of Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510055, China; Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. 5. Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. 6. Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA. 7. Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases, Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address: changxf@xjtu.edu.cn. 8. Department of Endodontics, Guanghua School and Hospital of Stomatology & Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510055, China. Electronic address: haijunfu76@163.com. 9. Department of Advanced Oral Sciences & Therapeutics, University of Maryland School of Dentistry, Baltimore, MD 21201, USA; Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA; University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. Electronic address: hxu@umaryland.edu.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Entities:
Keywords:
Bone tissue engineering; Calcium phosphate scaffold; Co-culture; Mineral bone cement; Stem cells; Vascularization
Authors: Hong Chen; Hui Yang; Michael D Weir; Abraham Schneider; Ke Ren; Negar Homayounfar; Thomas W Oates; Ke Zhang; Jin Liu; Tao Hu; Hockin H K Xu Journal: RSC Adv Date: 2020-11-04 Impact factor: 4.036
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