A new recombinant human bone morphogenetic protein-2 carrier for bone regeneration

Yokota, Shoji; Sonohara, S.; Yoshida, Mutsumi; Murai, Masakazu; Shimokawa, Seitaro; Fujimoto, Ryuhei; Fukushima, Shinji; Kokubo, Satoshi; Nozaki, Kazutoshi; Takahashi, Koichiro; Uchida, Tomoyuki; Yokohama, Shigeharu; Sonobe, Takashi

doi:10.1016/s0378-5173(01)00728-1

Cited by 25 publications

(24 citation statements)

References 14 publications

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“…30,41 Several kinds of polymer systems have been used as a carrier for BMP-2 to be stored and released. 30,42 In this study, BMP-2 was loaded on scaffolds using blend electrospinning so that growth factors could be mixed with the PCL-Gel polymer solution containing BCP particles, and the mixed solution was used directly in the electrospinning process. The matrix scaffold was a hybrid system containing ceramic/polymer and growth factors.…”

Section: Discussionmentioning

confidence: 99%

In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

Kim

Linh

Min

et al. 2014

Tissue Engineering Part A

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To confirm the effect of recombinant human bone morphogenetic protein-2 (BMP-2) for bone regeneration, BMP-2-loaded polycaprolactone (PCL)-gelatin (Gel)-biphasic calcium phosphate (BCP) fibrous scaffolds were fabricated using the electrospinning method. The electrospinning process to incorporate BCP nanoparticles into the PCL-Gel scaffolds yielded an extracellular matrix-like microstructure that was a hybrid system composed of nano-and micro-sized fibers. BMP-2 was homogeneously loaded on the PCL-Gel-BCP scaffolds for enhanced induction of bone growth. BMP-2 was initially released at high levels, and then showed sustained release behavior for 31 days. Compared with the PCL-Gel-BCP scaffold, the BMP-2-loaded PCL-Gel-BCP scaffold showed improved cell proliferation and cell adhesion behavior. Both scaffold types were implanted in rat skull defects for 4 and 8 weeks to evaluate the biological response under physiological conditions. Remarkable bone regeneration was observed in the BMP-2/PCL-Gel-BCP group. These results suggest that BMP-2-loaded PCL-Gel-BCP scaffolds should be considered for potential bone tissue engineering applications.

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Section: Discussionmentioning

confidence: 99%

In VitroandIn VivoStudies of BMP-2-Loaded PCL–Gelatin–BCP Electrospun Scaffolds

Kim

Linh

Min

et al. 2014

Tissue Engineering Part A

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“…Previously several bioabsorbable carriers for rhBMP-2 were developed and tested, e.g., demineralized bone matrix, 19,31 biophasic calcium phosphate (BCP), 17,28 absorbable collagen sponge (ACS), 33 and PGS. 12,40 Most carrier materials for rhBMP-2 showed some advantages and disadvantages and it has not yet been determined what the ideal delivery system for rhBMP-2 is. For example, collagen sponge performed well as a carrier for bone formation, but it has risks associated with transplantation of allogeneic and xenogeneic tissues.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Augments Recombinant Human Bone Morphogenetic Protein-2-Induced Osteoinductive Activity

et al. 2006

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The osteoinductive activity induced by recombinant human BMP-2 (rhBMP-2) blunts proportionately as the recipient ages. In order to compensate for this bluntness administration of fibroblast growth factor-2 (FGF-2) has been considered. The aim of this study was to determine whether FGF-2 administration augments osteoinductive activity caused by rhBMP-2 and to evaluate the effect of aging on bone formation induced by coadministration of rhBMP-2 and FGF-2. Sixty-four Wistar strain male rats of 8-week-old (prepubertal) and 16-week-old (postpubertal) received bone defects bilaterally in the parietal bone and the defects were filled by a polylactic acid polyglycolic acid copolymer/gelatin sponge (PGS) impregnated with rhBMP-2 plus 0 ng, 25 ng, and 250 ng FGF-2 (n=10 in each). At 2 weeks after grafting, the new bone volume seemed to be larger in the rhBMP-2+FGF-2 groups than in the rhBMP-2 alone group. At 4 weeks, the new bone formation was linked to the adjacent original bone. In the prepubertal rats, all newly formed bone was similarly calcified. In the postpubertal rats, only the rhBMP-2+25 ng FGF-2 group showed this higher degree of calcification. At 2 weeks, alkaline phosphatase (ALP) activity in the rhBMP-2+25 ng FGF-2 group was significantly (p<0.05) larger than that in the rhBMP-2 group in both prepubertal and postpubertal rats. This result shows that low-dose administration of FGF-2 enhanced the degree of calcification and ALP activity in the rhBMP-2 grafting site especially in the postpubertal rats. Therefore, FGF-2 would be a candidate to compensate for the reduction of osteoinductive activity of rhBMP-2 with aging.

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“…Moreover, PLGA is most often used in combination other ceramic or polymeric materials that interact with PLGA, thereby enhancing the difficulty to draw unambiguous conclusions on the specific effects of physicochemical characteristics of PLGA on ultimate performance in bone regeneration. In this regard, it is important to notice that relevant information on, for example, polymer molecular weight, [30][31][32][33][34][35] stereochemistry, [31][32][33][34] or end-group functionalization, [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] are often missing, which complicates scientific progress even further.…”

Section: Degradationmentioning

confidence: 99%

“…Nevertheless, PLGA-coated chitosan scaffolds were shown to enhance bone formation in comparison to plain chitosan scaffolds after implantation in a rat calvarial defect. 39,40 PLGA coatings have been applied even into cortical bone allografts in an attempt to maintain bone structural architecture immediately after implantation. Despite the biocompatibility of bone allografts, an improved subsequent host bone response was reported.…”

mentioning

confidence: 99%