Capillary Vessel Network Integration by Inserting a Vascular Pedicle Enhances Bone Formation in Tissue-Engineered Bone Using Interconnected Porous Hydroxyapatite Ceramics

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Abstract
The aim of the present study was to investigate the possibility of integrating porous hydroxyapatite (HA) ceramics with a capillary vessel network via insertion of a vascular pedicle, and to determine whether this procedure enhances new bone formation in tissue engineering of bone. First, synthetic interconnected porous HA (IP-CHA) was implanted subcutaneously into rat groin with or without insertion of superficial inferior epigastric vessels. At 6 weeks, IP-CHA with vascular insertion contained thick fibrous connective tissue with a number of large blood vessels that seemed to derive from the inserted vascular bundle. Next, IP-CHA loaded with recombinant human bone morphogenetic protein 2 (BMP, 2 or 10 μg/block) was implanted with or without vascular insertion. At 3 weeks, IP-CHA/BMP (10 μg) composite with vascular insertion exhibited abundant new bone formation in the pores of the deep portion close to the inserted vessels. In contrast, IP-CHA/BMP (10 μg) without vascular insertion showed poor bone formation. Histomorphometric analysis demonstrated that vascular insertion significantly increased new bone formation. In IP-CHAs with a lower dose of BMP (2 μg), no bone formation was found, with or without vascular insertion. These results suggest that the present system of integrating a vascular network with IP-CHA is a useful technique for bone tissue engineering.