Promotion of Osteogenesis and Angiogenesis in Vascularized Tissue-Engineered Bone Using Osteogenic Matrix Cell Sheets.
The regeneration of large, poorly vascularized bone defects remains a significant challenge. Although vascularized bone grafts promote osteogenesis, the required tissue harvesting causes problematic donor-site morbidity. Artificial bone substitutes are promising alternatives for regenerative medicine applications, but the incorporation of suitable cells and/or growth factors is necessary for their successful clinical application. The inclusion of vascular bundles can further enhance the bone-forming capability of bone substitutes by promoting tissue neovascularization. Little is known about how neovascularization occurs and how new bone extends within vascularized tissue-engineered bone, because no previous studies have used tissue-engineered bone to treat large, poorly vascularized defects.



In this study, the authors developed a novel vascularized tissue-engineered bone scaffold composed of osteogenic matrix cell sheets wrapped around vascular bundles within β-tricalcium phosphate ceramics.



Four weeks after subcutaneous transplantation in rats, making use of the femoral vascular bundle, vascularized tissue-engineered bone demonstrated more angiogenesis and higher osteogenic potential than the controls. After vascularized tissue-engineered bone implantation, abundant vascularization and new bone formation were observed radially from the vascular bundle, with increased mRNA expression of alkaline phosphatase, bone morphogenetic protein-2, osteocalcin, and vascular endothelial growth factor-A.



This novel method for preparing vascularized tissue-engineered bone scaffolds may promote the regeneration of large bone defects, particularly where vascularization has been compromised.
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Kenichi
K
Nakano
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Keiichi
K
Murata
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Shohei
S
Omokawa
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Manabu
M
Akahane
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Takamasa
T
Shimizu
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Kenji
K
Kawamura
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Kenji
K
Kawate
Kashihara, Nara, Japan.|From the Departments of Orthopaedic Surgery and Artificial Joint and Regenerative Medicine for Bone and Cartilage, Nara Medical University, and the Department of Public Health, Health Management and Policy, Nara Medical University School of Medicine.
Yasuhito
Y
Tanaka
D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D002130:Calcium Phosphates; D008297:Male; D018919:Neovascularization, Physiologic; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D010012:Osteogenesis; D019736:Prostheses and Implants; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D017154:Stromal Cells / Q000637:transplantation; D023822:Tissue Engineering; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D002130:Calcium Phosphates; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C485817:beta-tricalcium phosphate; D015675:Osteocalcin; D000469:Alkaline Phosphatase