title: Bone regeneration in minipigs via calcium phosphate cement scaffold delivering autologous bone marrow mesenchymal stem cells and platelet-rich plasma.
abstract: Macroporous calcium phosphate cement (CPC) with stem cell seeding is promising for bone regeneration. The objective of this study was to investigate the effects of co-delivering autologous bone marrow mesenchymal stem cells (BMSCs) and autologous platelet-rich plasma (PRP) in CPC scaffold for bone regeneration in minipigs for the first time. Twelve female adult Tibet minipigs (12-18 months old) were used. A cylindrical defect with 10 mm height and 8 mm diameter was prepared at the femoral condyle. Two bone defects were created in each minipig, one at each side of the femoral condyle. Three constructs were tested: (1) CPC scaffold (CPC control); (2) CPC seeded with BMSCs (CPC-BMSC); (3) CPC seeded with BMSCs and PRP (CPC-BMSC-PRP). Two time points were tested: 6 and 12 weeks (n = 4). Good integration of implant with surrounding tissues was observed in all groups. At 12 weeks, the CPC-BMSC-PRP group had significantly less residual CPC remaining in the defect than the CPC-BMSC group and the CPC control (p < 0.05). The residual CPC volume for the CPC-BMSC-PRP group was half that of the CPC control. New bone formation for CPC-BMSC-PRP was more than two-fold that of the CPC control (p < 0.05). CPC-BMSC-PRP had new blood vessel density that was nearly two-fold that of the CPC control (p < 0.05). In conclusion, CPC scaffold with autologous BMSC-PRP doubled the new bone regeneration and blood vessel density in minipigs compared with the CPC control. In the present study, the new macroporous CPC system with co-delivered BMSC-PRP has been shown to promote scaffold resorption and bone regeneration in large defects. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Orthopaedic Surgery, Shunde First People Hospital, Shunde, Guangdong, China.
authors.forename: Gengtao
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.|Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.|University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Hockin H K
authors.initials: HHK
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Oral Diseases and Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weir
authors.affiliation: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Department of Orthopaedic Surgery, Deqing Hospital, Huzhou, Zhejiang, China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Li
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Jixing
authors.identifier: 0000-0002-3076-0049
authors.initials: J
authors.lastname: Wang
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.|Biomaterials & Tissue Engineering Division, Department of Endodontics, Periodontics and Prosthodontics, University of Maryland Dental School, Baltimore, MD, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001843:Bone Cements / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D001861:Bone Regeneration / Q000502:physiology*; D002130:Calcium Phosphates / Q000494:pharmacology*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis; D053657:Platelet-Rich Plasma / Q000737:chemistry*; D013552:Swine; D013556:Swine, Miniature; D054457:Tissue Scaffolds / Q000737:chemistry*; D014182:Transplantation, Autologous; D055114:X-Ray Microtomography
chemical_list: D001843:Bone Cements; D002130:Calcium Phosphates; C020243:calcium phosphate
keywords: bone and vessel regeneration; bone marrow mesenchymal stem cells; calcium phosphate cement; large bone defects; minipig; platelet-rich plasma