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Woo, Byung Ho; Fink, Betsy F.; Page, Richard C.; Schrier, Jay A.; Jo, Young Tak; Ge, Jingping; DeLuca, Michelle; Vásconez, Henry C.; DeLuca, Patrick P.

doi:10.1023/a:1013382832091

Cited by 140 publications

(27 citation statements)

References 28 publications

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“…Sustained delivery vehicles for recombinant proteins have been studied previously, primarily using 125 I-labeled proteins [15, 50, 52–57]. In this study, the protein release kinetics from the collagen sponge were similar to those reported previously in ectopic bone formation models, in which the retention half-life ranged from several hours to several days [58–61].…”

Section: Discussionsupporting

confidence: 76%

Effects of protein dose and delivery system on BMP-mediated bone regeneration

et al. 2011

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Delivery of recombinant proteins is a proven therapeutic strategy to promote endogenous repair mechanisms and tissue regeneration. Bone morphogenetic protein-2 (rhBMP-2) has been used to promote spinal fusion and repair of challenging bone defects; however, the current clinically-used carrier, absorbable collagen sponge, requires high doses and has been associated with adverse complications. We evaluated the hypothesis that the relationship between protein dose and regenerative efficacy depends on delivery system. First, we determined the dose-response relationship for rhBMP-2 delivered to 8-mm rat bone defects in a hybrid nanofiber mesh/alginate delivery system at six doses ranging from 0 to 5 μg. Next, we directly compared the hybrid delivery system to the collagen sponge at 0.1 and 1.0 μg. Finally, we compared the in vivo protein release properties of the two delivery methods. In the hybrid delivery system, bone volume, connectivity and mechanical properties increased in a dose-dependent manner to rhBMP-2. Consistent bridging of the defect was observed for doses of 1.0 μg and greater. Compared to collagen sponge delivery at the same 1.0 μg dose, the hybrid system yielded greater connectivity by week 4 and 2.5-fold greater bone volume by week 12. These differences may be explained by the significantly greater protein retention in the hybrid system compared to collagen sponge. This study demonstrates a clear dose-dependent effect of rhBMP-2 delivered using a hybrid nanofiber mesh/alginate delivery system. Furthermore, the effective dose was found to vary with delivery system, demonstrating the importance of biomaterial carrier properties in the delivery of recombinant proteins.

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Section: Discussionsupporting

confidence: 76%

Effects of protein dose and delivery system on BMP-mediated bone regeneration

et al. 2011

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“…Direct application is via delivery of BMP2 either locally or systemically. The local and sustained in vivo release of BMP2 based on the biodegradable PLGA microsphere system [35] and apatite-coated PLGA/nanohydroxyapatite particulates [36] resulted in faster and more complete bone healing in critical-size calvarial defects. Subcutaneous injection of BMP2 for three days post-operatively enhanced undifferentiated human ASC-seeded PLGA constructs in the repair of critical-size calvarial defects in a nude mouse model [15].…”

Section: Discussionmentioning

confidence: 99%

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

Pei

McConda

et al. 2015

Bone

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Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly (lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici’s collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats.

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“…During bone repair, BMP-2 is expressed early during the early inflammatory phase, and later in the process during osteogenesis[37]. Thus, it is not surprising that many reports have shown that bone regeneration can be enhanced by sustained release of BMP-2[38, 39]. The data presented here showed sustained release of each growth factor for over 30 days (figures 6b, 7b, and 8b), and the ability to modulate the release profiles based on the properties of the mineral coating.…”

Section: Discussionmentioning

confidence: 99%

Controllable mineral coatings on PCL scaffolds as carriers for growth factor release

et al. 2012

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In this study, we have developed mineral coatings on polycaprolactone scaffolds to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite, the major inorganic constituent of human bone tissue in coatings formed in all HCO3 concentrations. Mineral coatings with increased HCO3 substitution showed more rapid dissolution kinetics in an environment deficient in calcium and phosphate but showed re-precipitation in an environment with the aforementioned ions. The mineral coating provided an effective mechanism for growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral mineral-coated PCL scaffolds. We also demonstrated sustained release of all growth factors with release kinetics that were strongly dependent in the solubility of the mineral coating.

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Abstract: The sustained delivery of BMP-2 based on the biodegradable PLGA microsphere system resulted in faster and more complete bone healing in the animal model.

Cited by 140 publications

References 28 publications

Effects of protein dose and delivery system on BMP-mediated bone regeneration

Effects of protein dose and delivery system on BMP-mediated bone regeneration

A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

Controllable mineral coatings on PCL scaffolds as carriers for growth factor release

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