Biological activity of recombinant human growth factors released from biocompatible bone implants

Ziegler, J.; Anger, Dominique; Krummenauer, Frank; Breitig, D.; Fickert, Stefan; Guenther, Klaus-Peter

doi:10.1002/jbm.a.31625

Cited by 29 publications

(26 citation statements)

References 52 publications

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“…Previously, chitosan has been used to prepare microparticles by several methods including emulsification, freeze-drying, and cross-linking. Most of these studies so far have used chemicals and conditions, which are not favorable for the stability of the growth factors [15,16]. There are also a number of surrounding environmental parameters which regulate the release of growth factor from the microparticles as well as its stability that needs to be studied in order to better understand the controlled release kinetics.…”

Section: Introductionmentioning

confidence: 99%

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

Mantripragada

Jayasuriya

2014

J. Biomed. Mater. Res.

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This study investigates the influence of the controlled release of bone morphogenetic protein 7 (BMP-7) from cross-linked chitosan microparticles on pre-osteoblasts (OB-6) in vitro. BMP-7 was incorporated into microparticles by encapsulation during the particle preparation and coating after particle preparation. Chitosan microparticles had an average diameter of 700 μm containing ~100 ng of BMP-7. The release study profile indicates that nearly 98% of the BMP-7 coated on the microparticles was released in a period of 18 days while only 36% of the BMP-7 encapsulated in the microparticles was released in the same time period. Cell attachment study indicated that the BMP-7 coated microparticles have many cells adhered on the microparticles in comparison with microparticles without growth factors on day 10. DNA assay indicated a statistical significant increase (p<0.05) in the amount of DNA obtained from BMP-7 encapsulated and coated microparticles in comparison with microparticles without any growth factors. A real time RT-PCR experiment was performed to determine the expression of a few osteoblast specific genes - Dlx5, runx2, osterix, osteopontin, osteocalcin, and bone sialoprotein. The results thus suggest that chitosan microparticles obtained by coacervation method are biocompatible and helps in improving the encapsulation efficiency of BMP-7. Also BMP-7 incorporated in the microparticles is being released in a controlled fashion to support attachment, proliferation and differentiation of pre-osteoblasts, thus acting as a good scaffold for bone tissue regeneration.

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Section: Introductionmentioning

confidence: 99%

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

Mantripragada

Jayasuriya

2014

J. Biomed. Mater. Res.

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“…Second, the bound growth factors inside CPC may become inactivated over time. For example, a previous study investigating the bioactivity of growth factors showed that the growth factor released after 24 h did not increase the osteogenesis, but the growth factor released after 1 h did increase the osteogenesis [57]. Therefore, due to the high retention of growth factors in CPC, the portion of released growth factors may have a concentration that was too low for cells to sense, and the growth factors released after an initial time period may have lost the bioactivity.…”

Section: Discussionmentioning

confidence: 99%

Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats

et al. 2014

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Objectives Calcium phosphate cement (CPC) is promising for dental and craniofacial applications due to its ability to be injected or filled into complex-shaped bone defects and molded for esthetics, and its resorbability and replacement by new bone. The objective of this study was to investigate bone regeneration via novel macroporous CPC containing absorbable fibers, hydrogel microbeads and growth factors in critical-sized cranial defects in rats. Methods Mannitol porogen and alginate hydrogel microbeads were incorporated into CPC. Absorbable fibers were used to provide mechanical reinforcement to CPC scaffolds. Six CPC groups were tested in rats: (1) Control CPC without macropores and microbeads; (2) Macroporous CPC + large fiber; (3) Macroporous CPC + large fiber + nanofiber; (4) Same as (3), but with rhBMP2 in CPC matrix; (5) Same as (3), but with rhBMP2 in CPC matrix + rhTGF-β1 in microbeads; (6) Same as (3), but with rhBMP2 in CPC matrix + VEGF in microbeads. Rats were sacrificed at 4 and 24 weeks for histological and micro-CT analyses. Results The macroporous CPC scaffolds containing porogen, absorbable fibers and hydrogel microbeads had mechanical properties similar to cancellous bone. At 4 weeks, the new bone area fraction (mean ± sd; n = 5) in CPC control group was the lowest at (14.8 ± 3.3)%, and that of group 6 (rhBMP2 + VEGF) was (31.0 ± 13.8)% (p < 0.05). At 24 weeks, group 4 (rhBMP2) had the most new bone of (38.8 ± 15.6)%, higher than (12.7 ± 5.3)% of CPC control (p < 0.05). Micro-CT revealed nearly complete bridging of the critical-sized defects with new bone for several macroporous CPC groups, compared to much less new bone formation for CPC control. Significance Macroporous CPC scaffolds containing porogen, fibers and microbeads with growth factors were investigated in rat cranial defects for the first time. Macroporous CPCs had new bone up to 2-fold that of traditional CPC control at 4 weeks, and 3-fold that of traditional CPC at 24 weeks, and hence may be useful for dental, craniofacial and orthopedic applications.

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“…Human recombinant bone morphogenetic protein 2 belongs to the transforming growth factor-beta (TGF-β) superfamily of proteins [8]. It is a key molecule in bone metabolism owing to its ability to induce differentiation of mesenchymal cells into osteoblasts [8].…”

Section: Introductionmentioning

confidence: 99%

“…It is a key molecule in bone metabolism owing to its ability to induce differentiation of mesenchymal cells into osteoblasts [8]. TGF-β ligands are involved in tumor suppression or progression [9]; a previous report indicated that recombinant human bone morphogenetic protein-2 is also associated with cancer [10].…”

Section: Introductionmentioning

confidence: 99%

Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model

et al. 2016

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The effect of porous alpha-tricalcium phosphate (α-TCP) with immobilized basic fibroblast growth factor (bFGF) on bone regeneration was evaluated in a canine mandibular bone defect model. Identical bone defects were made in the canine mandible; six defects in each animal were filled with porous α-TCP with bFGF bound via heparin (bFGF group), whereas the other was filled with unmodified porous α-TCP (control group). Micro-computed tomography and histological evaluation were performed two, four and eight weeks after implantation. The bone mineral density of the bFGF group was higher than that of the control group at each time point (p < 0.05), and the bone mineral content of the bFGF group was higher than that of the control group at four and eight weeks (p < 0.05). Histological evaluation two weeks after implantation revealed that the porous α-TCP had degraded and bone had formed on the surface of α-TCP particles in the bFGF group. At eight weeks, continuous cortical bone with a Haversian structure covered the top of bone defects in the bFGF group. These findings demonstrate that porous α-TCP with immobilized bFGF can promote bone regeneration.

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Biological activity of recombinant human growth factors released from biocompatible bone implants

Cited by 29 publications

References 52 publications

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

Injectable chitosan microparticles incorporating bone morphogenetic protein-7 for bone tissue regeneration

Bone regeneration via novel macroporous CPC scaffolds in critical-sized cranial defects in rats

Porous Alpha-Tricalcium Phosphate with Immobilized Basic Fibroblast Growth Factor Enhances Bone Regeneration in a Canine Mandibular Bone Defect Model

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