A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2)

Tamai, Noriyuki; Myoui, Akira; Hirao, Makoto; Kaito, Takashi; Ochi, Takahiro; Tanaka, Junzo; Takaoka, Kunio; Yoshikawa, Hideki

doi:10.1016/j.joca.2004.12.014

Cited by 141 publications

(99 citation statements)

References 56 publications

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“…Implantation of BMP can elicit new bone formation both in orthotopic and heterotopic sites [13,27], and is used as a bone graft substitute in the clinical setting [8,24,30]. Although it is now possible to generate recombinant human BMPs for medical use, more than 1.5 mg/kg of the recombinant protein has been required for bone induction in primates [1,15], probably due to their reduced capability for tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Yoshikawa

Yoshioka

Nakase

et al. 2009

Clin Orthop Relat Res

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The small GTPase Rho and Rho-associated protein kinase (Rho kinase, ROCK) signal participates in a variety of biological functions including vascular contraction, tumor invasion, and penile erection. Evidence also suggests Rho-ROCK is involved in signaling for mesenchymal cellular differentiation. However, whether it is involved in osteoblastic differentiation is unknown. We therefore asked whether Rho-ROCK signaling participates in recombinant human bone morphogenetic protein (rhBMP-2)-induced osteogenesis both in vitro and in vivo. Continuous delivery of a specific ROCK inhibitor (Y-27632) enhanced ectopic bone formation induced by rhBMP-2 impregnated into an atelocollagen carrier in mice without affecting systemic bone metabolism. Treatment with Y-27632 also enhanced the osteoblastic differentiation of cultured murine neonatal calvarial cells. These effects were associated with increased expression of BMP-4 gene. Expression of a dominant negative mutant of ROCK in ST2 cells promoted osteoblastic differentiation, while a constitutively active mutant of ROCK attenuated osteoblastic differentiation and the ROCK inhibitor reversed this phenotype. Thus, ROCK inhibits osteogenesis, and a ROCK inhibitor in combination with the local delivery of rhBMP/collagen composite may be clinically applicable for stimulating bone formation.

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Section: Introductionmentioning

confidence: 99%

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Yoshikawa

Yoshioka

Nakase

et al. 2009

Clin Orthop Relat Res

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“…Most successful techniques for cartilage regeneration consist of a combination of bioabsorbable materials and growth factors. [5][6][7][8] We have reported that a bioabsorbable synthetic polymer scaffold made of poly(DL-lactide-co-glycolide) (PLG) can repair osteochondral defects in a rabbit model. 9,10 This bioabsorbable scaffold has the capacity to repair full-thickness osteochondral defects of a critical size without using cultured cells.…”

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confidence: 99%

Localization of vascular endothelial growth factor during the early stages of osteochondral regeneration using a bioabsorbable synthetic polymer scaffold

Sakata

Kokubu

Nagura

et al. 2011

Journal Orthopaedic Research

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Vascular endothelial growth factor (VEGF) plays a critical role in chondrogenic differentiation in the growth plate of the epiphysis. This function is necessary for chondrocyte survival in cartilage development. We investigated the localization of VEGF in the osteochondral regeneration process using a bioabsorbable polymer scaffold. Osteochondral defects (5 mm in diameter and 5 mm in depth) were made on the femoral condyle of forty-eight skeletally mature female Japanese white rabbits. In total, twenty-four defects were filled with poly(DL-lactide-co-glycolide) scaffolds and the others were left untreated. The regeneration process was investigated macroscopically, histologically, immunohistochemically, and by gene expression analysis. In the early stages of osteochondral regeneration, bone ingrowth was observed in the deep zone of the scaffold with continuous VEGF expression; cartilage regeneration was observed in the superficial zone of the scaffold with decreased VEGF expression. In contrast, when the defect was left untreated, VEGF localization was observed throughout the entire defect area, and cartilage regeneration at the articular surface was delayed. We conclude that decrease in localization of VEGF at the articular surface in the postoperative early stage is closely related to the progression of cartilage regeneration in osteochondral defects. ß

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“…Tamai et al reported the superior osteoconductivity of the same IP-CHA in an animal model [11]. The same IP-CHA has been used in studies of bone and cartilage regeneration because its interconnected pores can work as a scaffold for cultured cells and growth factors [1,3,4,6,12]. Ito et al reported good bone formation using the same IP-CHA hybridized with cultured BMSCs derived from a transgenic green fluorescent rat [3].…”

Section: Discussionmentioning

confidence: 99%

“…Akita et al reported that vascular bundle insertion into the same IP-CHA produced a vascular network within the porous structure and that vascular bundle insertion enhanced new bone formation in tissue-engineered bone using recombinant human bone morphogenetic protein-2 (rhBMP-2) and IP-CHA [1]. For cartilage regeneration, Tamai et al reported that the triple composite of rhBMP-2, poly-D , L -lactic acid/polyethylene glycol (PLA-PEG) and the same IP-CHA promoted the repair of full-thickness articular defects [12]. Thus, we decided to evaluate the regeneration of a bone defect including tendon attachment in tissue engineering using IP-CHA as a scaffold and BMSCs as a cell source.…”

Section: Discussionmentioning

confidence: 99%

“…Interconnected porous calcium hydroxyapatite ceramic (IP-CHA) has good osteoconductivity because the interconnection of pores allows cells to invade deeply into the material [11]. Recently, IP-CHA has been used in studies of bone and joint regeneration by tissue engineering because the interconnected pores work as a scaffold for cultured cells and growth factors [1,3,4,6,12]. We have been doing animal studies to regenerate a bone defect including tendon attachment using IP-CHA as a scaffold.…”

Section: Introductionmentioning

confidence: 99%

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Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model

Omae

Mochizuki

Yokoya

et al. 2006

International Orthopaedics (SICOT)

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Tendon attachment to interconnected porous calcium hydroxyapatite ceramics (IP-CHA) with cultured bone marrow stromal cells (BMSC) was analysed. The purpose of this study was to evaluate whether BMSC in IP-CHA could augment the tendon attachment to IP-CHA histologically and biomechanically. Eighteen Japanese white rabbits were used. Cultured BMSCs were subcultured in IP-CHA. The grafted tendon and IP-CHA with BMSC complex were implanted in a bone defect of the knee [BMSC(+) group]. In the contralateral knee, a tendon and IP-CHA without BMSC complex were implanted [BMSC(-) group]. Histological findings of the interface between the tendon and IP-CHA were similar in the two groups 3 weeks after the operation. However, 6 weeks after the operation, more abundant bone formation around the tendon was observed in the BMSC (+) group. The direct apposition of the tendon to bone in pores and collagen fibre continuity between the tendon and fibrous tissue in pores were observed. In biomechanical evaluation, the maximum pull-out load of the tendon from the IP-CHA in the BMSC(+) group was significantly higher than that in the BMSC(-) group 6 weeks after the operation. BMSCs cultured in IP-CHA could augment tendon attachment to IP-CHA. Résumé Le propos de cette étude est de déterminer si l'utilisation de culture cellulaire de moelle osseuse (BMSC) avec l'utilisation de calcium d'hydroxyapatite (IP-CHA) augmente la résistance de l'attachement osseux du tendon sur le plan histologique et biomécanique. Dix-huit lapins blancs du Japon ont été utilisés pour ce travail. Les tendons greffés avec hydroxyapatite et culture de la cellule de moelle osseuse ont été implantés dans une defect au niveau du genou. Sur le genou opposé, le tendon a été implanté sans culture cellulaire. Sur le plan histologique les résultats sont identiques dans les deux groupes, 3 semaines après intervention, cependant 6 semaines après l'intervention la progression de la formation osseuse est plus importante autour du tendon ayant bénéficié d'une culture cellulaire de moelle osseuse. Il en est de même en ce qui concerne la résistance biomécanique du tendon qui est significativement plus importante dans le groupe culture cellulaire, 6 semaines après l'intervention.

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A new biotechnology for articular cartilage repair: subchondral implantation of a composite of interconnected porous hydroxyapatite, synthetic polymer (PLA-PEG), and bone morphogenetic protein-2 (rhBMP-2)

Cited by 141 publications

References 56 publications

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Stimulation of Ectopic Bone Formation in Response to BMP-2 by Rho Kinase Inhibitor: A Pilot Study

Localization of vascular endothelial growth factor during the early stages of osteochondral regeneration using a bioabsorbable synthetic polymer scaffold

Augmentation of tendon attachment to porous ceramics by bone marrow stromal cells in a rabbit model

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