A critical size bony defect (CSD) is defined as the smallest intra-osseous wound characterized by an absence of spontaneous healing, which would not heal by bone formation during the lifetime (Schmitz

ABSTRACT TAK-778 [(2R,4S)-(Ϫ)-N-(4-diethoxyphosphorylmethylphenyl)- 1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; mw 505.53], a novel osteoblast differentiation promoting compound, was characterized in vitro and in vivo models. TAK-778 at doses of 10 Ϫ6 M and higher promoted potently bone-like nodule formation in the presence of dexamethasone in rat bone marrow stromal cell culture. This was accompanied by increases in cellular alkaline phosphatase activity, soluble collagen release, and osteocalcin secretion. Under the culture conditions, TAK-778 also stimulated the secretion of transforming growth factor-␤ and insulin-like growth factor-I, indicating that TAK-778 may exert regulatory effects on osteoblast differentiation via autocrine/paracrine mechanisms. Furthermore, the in vivo osteogenic potential of TAK-778 was studied in bony defect and osteotomy animal models, using sustained release microcapsules consisted of a biodegradable polymer, poly (dl-lactic/glycolic) acid (PLGA). Single local injection of TAK-778/PLGA-microcapsules (PLGA-MC) (0.2-5 mg/site) to rat skull defects resulted in a dose-dependent increase in new bone area within the defects after 4 weeks. When the pellet containing TAK-778/PLGA-MC (4 mg/pellet) was packed into place to fill the tibial segmental defect in rabbit, this pellet induced osseous union within 2 months, whereas the placebo pellet did not. In addition, single local application of TAK-778/PLGA-MC (10 mg/site) to rabbit tibial osteotomy site enhanced callus formation accompanied by an increase in breaking force after 30 days. These results reveal for the first time that a nonendogenous chemical compound promotes potently osteogenesis in vitro and enhances new bone formation during skeletal regeneration and bone repair in vivo and should be useful for the stimulation of fracture healing. Fracture healing is a special form of wound healing characterized by regeneration of the normal osseous anatomy. Bone represents the only organ in the body capable of complete repair without the presence of an intervening fibrous scar Fracture healing involves a complex cascade of several cellular events. These events include immediate injury response, intramembranous ossification, chondrogenesis, and endochondral ossification, resulting in the formation of a fracture callus Received for publication January 26, 1999. ABBREVIATIONS: TAK-778, (2R,4S)-(Ϫ)-N-(4-diethoxyphosphorylmethylphenyl)-1,2,4,5-tetrahydro-4-methyl-7,8-methylenedioxy-5-oxo-3-benzothiepin-2-carboxyamide; BMPs, bone morphogenetic proteins; IGFs, insulin-like growth factors; FGFs, fibroblast growth factors; ALP, alkaline phosphatase; MEM, minimum essential medium; FBS, fetal bovine serum; CM, conditioned media; bFGF, basic fibroblast growth factor.

Spontaneous healing capacity of rabbit cranial

Purpose: Fibronectin (FN) has been shown to stimulate bone regeneration in animal models. The aim of this study was to evaluate the capacity of bovine bone mineral coated with synthetic oligopeptides to enhance bone regeneration in rabbit calvarial defects. Methods: Oligopeptides including fibrin-binding sequences of FN repeats were synthesized on the basis of primary and tertiary human plasma FN structures. Peptide coated and uncoated bone minerals were implanted into 10 mm calvarial defects in New Zealand white rabbits, and the animals were sacrificed at 4 or 8 weeks after surgery. After specimens were prepared, histologic examination and histomorphometric analysis were performed. Results: At 4 weeks after surgery, the uncoated groups showed a limited amount of osteoid formation at the periphery of the defect and the oligopeptide coated groups showed more osteoid formation and new bone formation in the center of the defect as well as at the periphery. At 8 weeks, both sites showed increased new bone formation. However, the difference between the two sites had reduced. Conclusions: Fibrin-binding synthetic oligopeptide derived from FN on deproteinized bovine bone enhanced new bone formation in rabbit calvarial defects at the early healing stage. This result suggests that these oligopeptides can be beneficial in reconstructing oral and maxillofacial deformities or in regenerating osseous bone defects.

Comparative study on the results of non-surgical periodontal treatment according to the location of the affected site

pISSN 2093-2278 eISSN 2093-2286Tomographic and histometric analysis of autogenous bone block and synthetic hydroxyapatite block grafts without rigid fixation on rabbit calvaria

Repair of critical size defects in the rat cranium using ceramic-reinforced PLA scaffolds obtained by supercritical gas foaming

Abstract not found