Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells

Malavosklish Bikram; Christine Fouletier-Dilling; John A. Hipp; Francis Gannon; Alan R. Davis; Elizabeth A. Olmsted-Davis; Jennifer L. West

doi:10.1007/s10439-007-9263-4

Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells

Malavosklish Bikram, Christine Fouletier-Dilling, John A. Hipp, Francis Gannon, Alan R. Davis, Elizabeth A. Olmsted-Davis, Jennifer L. West

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 ± 25.0 mm³ mineralized tissue and 31.8 ± 7.8 mm³ for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals.

Original language	English (US)
Pages (from-to)	796-807
Number of pages	12
Journal	Annals of Biomedical Engineering
Volume	35
Issue number	5
DOIs	https://doi.org/10.1007/s10439-007-9263-4
State	Published - May 2007

Keywords

Adenovirus
Biomaterials
Bone
Bone morphogenetic protein
Cell encapsulation
Gene therapy
Hydrogel
Tissue engineering
Tissue repair

ASJC Scopus subject areas

Biomedical Engineering

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10.1007/s10439-007-9263-4

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@article{98d804b4694a41da89087c60e57076fe,

title = "Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells",

abstract = "The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 ± 25.0 mm3 mineralized tissue and 31.8 ± 7.8 mm3 for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals.",

keywords = "Adenovirus, Biomaterials, Bone, Bone morphogenetic protein, Cell encapsulation, Gene therapy, Hydrogel, Tissue engineering, Tissue repair",

author = "Malavosklish Bikram and Christine Fouletier-Dilling and Hipp, {John A.} and Francis Gannon and Davis, {Alan R.} and Olmsted-Davis, {Elizabeth A.} and West, {Jennifer L.}",

note = "Funding Information: We thank James J. Moon, Melissa K. McHale, Jessica A. Shafer and Rachel E. Whitmire for technical assistance. This work was supported by Department of Defense award W81XWH-04-1-0068.",

year = "2007",

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doi = "10.1007/s10439-007-9263-4",

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T1 - Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells

AU - Bikram, Malavosklish

AU - Fouletier-Dilling, Christine

AU - Hipp, John A.

AU - Gannon, Francis

AU - Davis, Alan R.

AU - Olmsted-Davis, Elizabeth A.

AU - West, Jennifer L.

N1 - Funding Information: We thank James J. Moon, Melissa K. McHale, Jessica A. Shafer and Rachel E. Whitmire for technical assistance. This work was supported by Department of Defense award W81XWH-04-1-0068.

PY - 2007/5

Y1 - 2007/5

N2 - The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 ± 25.0 mm3 mineralized tissue and 31.8 ± 7.8 mm3 for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals.

AB - The success of ex vivo viral gene therapy systems for promoting bone formation could be improved through the development of systems to spatially localize gene expression. Towards this goal, we have encapsulated adenovirus-transduced human diploid fetal lung fibroblasts (MRC-5) expressing bone morphogenetic protein-type 2 (BMP-2) within non-degradable poly(ethylene glycol)-diacrylate (PEG-DA) hydrogels and implanted these intramuscularly to promote endochondral bone formation. To optimize BMP-2 secretion, the molecular weight of the polymers and cell densities were varied. Polymers with molecular weights of 6, 10, and 20 kDa were used to prepare hydrogels containing 1, 5, or 10 million transduced cells. The results showed that 10 million transduced fibroblasts that was the maximum number of cells feasible for encapsulation within PEG-DA 10 and 20 kDa hydrogels produced the highest amount of secreted BMP-2 protein. Encapsulation of MRC-5 and transduced fibroblasts resulted in 71 and 58% cell viability, respectively. The bioactivity of secreted BMP-2 protein from the hydrogels was confirmed with an alkaline phosphatase assay. Micro-CT of the lower limb muscles of NOD/SCID mice following implantation with hydrogels showed 39.5 ± 25.0 mm3 mineralized tissue and 31.8 ± 7.8 mm3 for the cell-injected mice, and the bone was localized to the hydrogel surfaces. Histology revealed bone as well as cartilage for both hydrogel implanted and cell-injected animals.

KW - Adenovirus

KW - Biomaterials

KW - Bone

KW - Bone morphogenetic protein

KW - Cell encapsulation

KW - Gene therapy

KW - Hydrogel

KW - Tissue engineering

KW - Tissue repair

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SN - 0090-6964

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JO - Annals of Biomedical Engineering

JF - Annals of Biomedical Engineering

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ER -

Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells

Abstract

Keywords

ASJC Scopus subject areas

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