Development of vascularized artificial bone using micro-engineering technology

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K16622
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyoto University
• Principal Investigator: Kawai Toshiyuki 京都大学, 医学研究科, 特定病院助教 (80806828)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: bone defect / angiogenesis / vascularization / polycaprolactone / BMP2

Outline of Final Research Achievements

Vascularization is currently considered the biggest challenge in bone tissue engineering due to necrosis in the center of large scaffolds. We established a new expendable vascular bundle model to vascularize a 3D printed channelled scaffold with and without BMP2 for improved healing of large segmental bone defects. Bone formation and angiogenesis in an 8 mm critical sized bone defect in the rat femur were significantly promoted by inserting a bundle consisting of the superficial epigastric artery and vein into the central channel of a large porous polycaprolactone scaffold. BMP-2 delivery was found to promote not only bone formation, but also angiogenesis in the critical sized bone defects. Both insertion of the vascular bundle alone and BMP-2 loading alone induced comparable levels of angiogenesis and when used in combination, significantly greater vascular volume was observed. These findings suggest a promising new modality of treatment in large bone defects.

Free Research Field

整形外科学

Academic Significance and Societal Importance of the Research Achievements

骨欠損に対し、近年自身の骨の移植を行わず組織工学的手法により、細胞・足場・成長因子などを組み合わせて硬組織再生を行う方法が有望視されている。人工物内部で組織再生が起こるには、インプラント深部まで自身の細胞が進入して生存する必要があるが、細胞は栄養の供給源から数百マイクロメートル以上離れてしまうと生存することができない。そのためインプラント全体を栄養する微小血行路の再生が必要となる。我々は近年著しい進歩を遂げている微小造形の技術を利用してインプラント内に三次元微小血管ネットワークの誘導をおこなった。この技術によりこれまで不可能であった巨大骨欠損部の再建が可能となる。